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Sample records for pyrazole compound bpr1p0034

  1. Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity

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    Yeh Jiann-Yih

    2010-02-01

    that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus. Conclusions To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.

  2. Pyrazole-based compounds in chitosan liposomal emulsion for antimicrobial cotton fabrics.

    Science.gov (United States)

    Nada, Ahmed; Al-Moghazy, Marwa; Soliman, Ahmed A F; Rashwan, Gehan M T; Eldawy, Taghreed Hosny Ahmed; Hassan, Ashraf Abd Elhakim; Sayed, Galal Hosni

    2017-09-13

    The chemistry of pyrazoles has gained increasing attention due to its diverse pharmacological properties such as antiviral, antagonist, antimicrobial, anticancer, anti-inflammatory, analgesic, anti-prostate cancer, herbicidal, acaricidal and insecticidal activities. 1-Phenyl pyrazole-3, 5-diamine, 4-[2-(4-methylphenyl) diazenyl] and 1H- pyrazole-3 (1), 5-diamine, 4-[2-(4-methylphenyl) diazenyl] (2) were synthesized, characterized and encapsulated into liposomal chitosan emulsions for textile finishing. The chemical modifications of cotton fabrics were demonstrated by infrared analysis. Retention of the fabric mechanical properties was investigated by reporting the tensile strength values. Synthesized pyrazole-based compounds were screened for cytotoxicity against skin fibroblast cell line and showed very limited toxicity for both compounds. Antimicrobial potentials of the treated cotton fabrics were tested against bacterial strains E. coli ATCC 8379 and Staphylococcus aureus ATCC 25923. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Well-defined, nanometer-sized LiH cluster compounds stabilized by pyrazolate ligands.

    Science.gov (United States)

    Stasch, Andreas

    2014-01-27

    The assembly of well-defined large cluster compounds of ionic light metal hydrides is a synthetic challenge and of importance for synthesis, catalysis, and hydrogen storage. The synthesis and characterization of a series of neutral and anionic pyrazolate-stabilized lithium hydride clusters with inorganic cores in the nanometer region is now reported. These complexes were prepared in a bottom-up approach using alkyl lithium and lithium pyrazolate mixtures with silanes in hydrocarbon solutions. Structural characterization using synchrotron radiation revealed isolated cubic clusters that contain up to 37 Li(+) cations and 26 H(-) ions. Substituted pyrazolate ligands were found to occupy all corners and some edges for the anionic positions. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Compound Derived from Anthracene and Pyrazol for a Light-Emitting Diode

    Institute of Scientific and Technical Information of China (English)

    王明亮; 张俊祥; 刘举正; 徐春祥

    2001-01-01

    A new compound, 5-(9-anthryl)-1,3-diphenyl-1H-pyrazol (ADPP), with an anthryl moiety as an emissive groupand a diphenylpyrazoline moiety as a charge transporting group is designed and synthesized. The absorption,photoluminescence, electroluminescence, and electrochemistry are measured. Absorption of ADPP is similar tothat of anthracene in the vibonic structure but shows slight redshifts because anthryl moiety twists strongly withrespect to pyrazol moiety although delocalization still exists between the two moieties. Light-emitting devicesfabricated with ADPP show a bright blue emission at 470nm. The turn-on voltage is 12 V and the light emissionfollows the current closely, indicating an efficient charge injection and transport for both electrons and holes.

  5. Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound.

    Science.gov (United States)

    Mitchell, Lorna H; Drew, Allison E; Ribich, Scott A; Rioux, Nathalie; Swinger, Kerren K; Jacques, Suzanne L; Lingaraj, Trupti; Boriack-Sjodin, P Ann; Waters, Nigel J; Wigle, Tim J; Moradei, Oscar; Jin, Lei; Riera, Tom; Porter-Scott, Margaret; Moyer, Mikel P; Smith, Jesse J; Chesworth, Richard; Copeland, Robert A

    2015-06-11

    A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.

  6. Design, Synthesis, and Biological Activities of Novel Pyrazole Oxime Compounds Containing a Substituted Pyridyl Moiety

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    Cuili Chen

    2017-05-01

    Full Text Available In this paper, in order to find novel biologically active pyrazole oximes, a series of pyrazole oxime compounds bearing a substituted pyridyl unit were prepared. Bioassays showed that some target compounds were found to have good acaricidal activity against Tetranychus cinnabarinus at a concentration of 500 μg/mL, compound 9q especially displayed potent acaricidal activity against T. cinnabarinus when the concentration was reduced to 100 μg/mL. Interestingly, most target compounds possessed excellent insecticidal activities against Oriental armyworm at 500 μg/mL. Moreover, some compounds were active against Aphis medicaginis and Nilaparvata lugens at 500 μg/mL. Additionally, compounds 9b, 9g, 9l, 9p, 9q, 9r, 9s, 9t, 9u, and 9v displayed significant antiproliferative activities against HepG2 cells with IC50 values of 1.53–17.27 μM, better than that of the control 5-fluorouracil (IC50 = 35.67 μM.

  7. 2D-QSAR Studies on Pyrazole Compounds Containing Pyrimidine Amino

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The quantitative structure-activity relationship (QSAR) of 16 pyrazole compounds was studied by ab initio method at the HF/3-21G level using Guassian03 soft. The optimized structures together with some characteristic and electric parameters of the title compounds were obtained; some stereo-parameters were calculated by HyperChem software.Stepwise multiple regression method was adopted to establish bi- and tri-parametric models between biological activity and some parameters. The lager ΔE and logP, the higher biological activity; and the biological activity would be promoted with the smaller μ, QN and QPYRA. It provided a theory direction to synthesize some compounds with high activity.

  8. Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

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    Li Zizhong [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Liu Qian [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Ding Yushin [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S. John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)]. E-mail: s.gatley@neu.edu

    2005-05-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

  9. Phenol-pyrazole ligands in the design of manganese(III) compounds : synthesis, structural characterization and study of the magnetic properties

    NARCIS (Netherlands)

    Viciano Chumillas, Marta

    2009-01-01

    In this thesis project, new manganese(III) compounds containing phenol-pyrazole ligands are presented. Small variations on the phenol-pyrazole ligand have been performed to investigate the role of the ligand in the formation of new complexes. The reaction conditions are also crucial to determine the

  10. Magnetocaloric effect in M-pyrazole-[Nb(CN)(8)] (M = Ni, Mn) molecular compounds.

    Science.gov (United States)

    Fitta, Magdalena; Bałanda, Maria; Mihalik, Marian; Pełka, Robert; Pinkowicz, Dawid; Sieklucka, Barbara; Zentkova, Maria

    2012-12-19

    We report a study of magnetocaloric effect (MCE) in cyanido-bridged {[M(II)(pyrazole)(4)](2)[Nb(IV)(CN)(8)]·4H(2)O}(n) molecular compounds where M = Ni, Mn, pyrazole = C(3)H(4)N(2). The substances show a sharp phase transition to a long range magnetically ordered state, with ferromagnetic coupling between M and Nb sublattices in the case of the Ni-based sample 1 (T(c) = 13.4 K) and ferrimagnetic coupling for the Mn-based sample 2 (T(c) = 23.8 K). The magnetic entropy change ΔS due to applied field change ΔH as a function of temperature was determined by the magnetization and heat capacity measurements. The maximum value of ΔS at μ(0)ΔH = 5 T is 6.1 J mol(-1) K(-1) (5.9 J kg(-1) K(-1)) for 1 at T = 14 K and 6.7 J mol(-1) K(-1) (6.5 J kg(-1) K(-1)) for 2 at T = 25 K. MCE data at different applied fields have been presented as one universal curve, which confirms magnetic transitions in 1 and 2 to be of second order. The temperature dependences of the n exponent characterizing the dependence of ΔS on ΔH have been obtained. The n(T(c)) values, consistent with the shape of the magnetization curves, pointed to the 3D Heisenberg behaviour for 2 and some anisotropy, probably of the XY type, for 1. The (H/T(c))(2/3) dependence of the maximum entropy change has been tested in the ferrimagnetic Mn(2)-L-[Nb(CN)(8)] (L = C(3)H(4)N(2), C(4)H(4)N(2)) series.

  11. Reusable manganese compounds containing pyrazole-based ligands for olefin epoxidation reactions.

    Science.gov (United States)

    Manrique, Ester; Poater, Albert; Fontrodona, Xavier; Solà, Miquel; Rodríguez, Montserrat; Romero, Isabel

    2015-10-28

    We describe the synthesis of new manganese(ii) and manganese(iii) complexes containing the bidentate ligands 2-(3-pyrazolyl)pyridine, pypz-H, and 3(5)-(2-hydroxyphenyl)pyrazole, HOphpz-H, with formula [MnX2(pypz-H)2] (X = Cl(-), 1, CF3SO3(-), 2, OAc(-), 3 or NO3(-) (4)), [MnCl2(pypz-H)(H2O)2], 5, or [MnCl(Ophpz-H)2], 6. All the complexes have been characterized through analytical, spectroscopic and electrochemical techniques. Single X-ray structure analysis revealed a six-coordinated Mn(ii) ion in complexes 1-5, and a five-coordinated Mn(iii) ion in complex 6. Compound 5 is the first co-crystal of Mn(ii) containing Cl and H2O ligands together with bidentate nitrogen ligands. The catalytic activity of complexes 1-6 has been tested with regard to the epoxidation of styrene and, in the case of 1, 5 and 6, other alkenes have been epoxidized using peracetic acid as oxidant in different media, among which glycerol, a green solvent never used in epoxidation reactions using peracetic acid as oxidant. The catalysts show moderate to high conversions and selectivities towards the corresponding epoxides. For complexes 1, 5 and 6, a certain degree of cis→trans isomerization is observed in the case of cis-β-methylstyrene. These observations have been explained through computational calculations. The reutilization of catalysts 1 and 6 for the epoxidation of alkenes has been evaluated in [bmim] : acetonitrile mixture (bmim = 1-butyl-3-methylimidazolium), allowing the effective recyclability of the catalytic system and keeping high conversion and selectivity values up to 12 successive runs, in all cases.

  12. Pharmacological and toxicological evaluations of the new pyrazole compound (LQFM-021) as potential analgesic and anti-inflammatory agents.

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    Florentino, Iziara F; da Silva, Daiany P B; Martins, José Luís R; da Silva, Taciane S; Santos, Fernanda C A; Tonussi, Carlos R; Vasconcelos, Géssica A; Vaz, Boniek G; Lião, Luciano M; Menegatti, Ricardo; Costa, Elson A

    2016-10-01

    Chronic inflammation is a world health problem. There is a need to develop new anti-inflammatory and analgesic drugs with improved activity and reduced side effects. In this context, the aim of this study was to evaluate the antinociceptive and anti-inflammatory effects of the pyrazole compound LQFM-021 after acute and sub-chronic administration in rats submitted to a CFA-induced chronic arthritis model, as well as compare the toxicity of this compound to that of dipyrone, given throughout 7 days. Firstly, we observed that acute oral administration of the higher dose (130 µmol/kg) of LQFM-021 reduced paw lifting time (PET) and edema formation. These effects disappeared on the following day, requiring another dose to maintain the effects. This dose also promoted reduction of the polymorphonuclear recruitment in the synovial fluid. In another experiment, both treatments with LQFM-021, 65 µmol/kg twice a day and 130 µmol/kg once a day, produced a progressive and permanent reduction of the PET and edema, also reducing polymorphonuclear recruitment. However, the single treatment with 130 µmol/kg was more effective than the double treatment with 65 µmol/kg. LQFM-021 did not produce toxicity signs. However, dipyrone (130 µmol/kg once a day) promoted erosion of the epithelial cells and decreased mucus in the gastric mucosa. These data indicate that LQFM-021 produced antinociceptive and anti-inflammatory effects in CFA-induced arthritis in rats. These effects occurred in the absence of apparent toxic effects, indicating that the pyrazole compound LQFM-021 may be considered a good prototype for development of new analgesic/anti-inflammatory drug.

  13. Design and synthesis of novel complexes containing N-phenyl-1H-pyrazole moiety: Ni complex as potential antifungal and antiproliferative compound

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    El-Gamel, Nadia E. A.; Farghaly, Thoraya A.

    2013-11-01

    Cu(II) (1), Ni(II) (2), Cr(III) (3) and Fe(III) (4) complexes with 3-acetyl-4-benzoyl-1-phenyl-1H-pyrazole (L1) were prepared and structurally characterized. Usual coordination of L1 was achieved through nitrogen of pyrazole moiety and carbonyl acetyl group. Electronic spectra of the complexes indicate that the geometry of the metal center was six coordinate octahedral. In vitro antimicrobial activity of the ligand and complex compounds was screened in terms of antibacterial effect on Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative) and antifungal effect on the fungi Aspergillus flavus and candida albicans using the modified Kirby-Bauer disc diffusion and minimum inhibitory concentrations (MIC) methods. Ni(II) complex (2) exhibited remarkable antifungal inhibition against Candida albicans equal to the standard antifungal agent. To continue our study some structural modifications are formed by adding 4-fluoro-benzoyl moiety to L1 in different forms to produce different ligands, 3-acetyl-4-(4-flourobenzoyl)-1-phenyl-1H-pyrazole (L2) and 3-[(3-acetyl-1-phenyl-1H-4-pyrazolyl)carbonyl]-1-phenyl-4-(4-flourobenzoyl)-1H-pyrazole (L3), Ni complexes (5 and 6) are prepared and comparable in vitro antimicrobial study is evaluated. In vitro cytotoxicity of the Ni(II) complex (2) is studied using MTT assay. The analysis of the cell test showed that (2) displayed quite small cytotoxic response at the higher concentration level which indeed would further enable us for more opportunities in therapeutic and biomedical challenges. Both of the capability as a potent in vitro antifungal agent and the cell test analysis show Ni(II) complex (2) as a promising material in the translation of observed in vitro biological phenomenon into clinical therapies settings.

  14. Therapeutic outlook of pyrazole analogs: A mini review.

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    Ganguly, Swastika; Sony Jacob, K

    2015-11-19

    Pyrazole is one of the excellent structural motifs in medicinal chemistry. Various physiological and therapeutic possibilities have been exploited by incorporating different pharmacophoric groups in the pyrazole moiety. This has opened a new arena of pyrazole analogs that can be developed into medicinal agents such as anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticancer, anticonvulsant, hypoglycemic, carbonic anhydrase inhibitors, mono amino oxidase (MAO) inhibitors, etc. Though, pyrazole analogs have proven their clinical efficacy as different pharmacological agents, a few of them have been withdrawn from the market due to their side effects. Thus, research on potential new drug candidates bearing the pyrazole moiety with lesser side effects has fairly increased over the last few years. This review explores diverse pharmacological activities exhibited by pyrazole analogs reported recently, which may be of great help for researchers in the area of drug discovery to understand the current scenario of pyrazole based compounds and to design and develop newer drug candidates with improved efficacy.

  15. Preparation and Investigation of Monodentate and Bridging Pyrazole Complexes

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    Evans, Wynne

    2004-01-01

    Complexes of pyrazole-derived ligands are very popular due to the ability of the pyrazolato anion to form bridged polymetallic compounds in which the metals are held close enough to react with small molecules or facilitate magnetic exchange. The preparation of monodentate pyrazole and 3,5-dimethylpyrazole (DMHpz) nickel species and the…

  16. Synthesis and Antifungal Activity of the Derivatives of Novel Pyrazole Carboxamide and Isoxazolol Pyrazole Carboxylate

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    Jialong Sun

    2015-03-01

    Full Text Available A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy. Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

  17. Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

    Science.gov (United States)

    Sun, Jialong; Zhou, Yuanming

    2015-03-09

    A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

  18. Lead optimization of a pyrazole sulfonamide series of Trypanosoma brucei N-myristoyltransferase inhibitors: identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human African trypanosomiasis.

    Science.gov (United States)

    Brand, Stephen; Norcross, Neil R; Thompson, Stephen; Harrison, Justin R; Smith, Victoria C; Robinson, David A; Torrie, Leah S; McElroy, Stuart P; Hallyburton, Irene; Norval, Suzanne; Scullion, Paul; Stojanovski, Laste; Simeons, Frederick R C; van Aalten, Daan; Frearson, Julie A; Brenk, Ruth; Fairlamb, Alan H; Ferguson, Michael A J; Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D

    2014-12-11

    Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood-brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT.

  19. Progress of the synthesis of condensed pyrazole derivatives (from 2010 to mid-2013).

    Science.gov (United States)

    Li, Meng; Zhao, Bao-Xiang

    2014-10-06

    Condensed pyrazole derivatives are important heterocyclic compounds due to their excellent biological activities and have been widely applied in pharmaceutical and agromedical fields. In recent years, numerous condensed pyrazole derivatives have been synthesized and advanced to clinic studies with various biological activities. In this review, we summarized the reported synthesis methods of condensed pyrazole derivatives from 2010 until now. All compounds are divided into three parts according to the rings connected to pyrazole-ring, i.e. [5, 5], [5,F 6], and [5, 7]-condensed pyrazole derivatives. The biological activities and applications in pharmaceutical fields are briefly introduced to offer an orientation for the design and synthesis of condensed pyrazole derivatives with good biological activities.

  20. Pyrazoles and imidazoles as ligands. X. electron paramagnetic resonance spectra of MnII in a tetragonal environment of four pyrazoles and two anions

    NARCIS (Netherlands)

    Dowsing, R.D.; Nieuwenhuijse, B.; Reedijk, J.

    1971-01-01

    Electron Paramagnetic Resonance Spectra have been recorded for some compounds of the type Mn(ligand)4- (anion)2, with pyrazole and 3(5)-methyl pyrazole as the ligands, and Cl−, Br−, I−, and NO3−, as the anions. The spectra show absorptions far from geff=2 for all compounds at both X- and Q-band fre

  1. A dinuclear manganese(III) and a rare pentanuclear manganese(III) compound with a phenol-pyrazole ligand

    NARCIS (Netherlands)

    Viciano-Chumillas, M.; Tanase, S.; Mutikainen, I.; Turpeinen, U.; de Jongh, L.J.; Reedijk, J.

    2012-01-01

    Reacting Mn(ClO4)2·6H2O and H2phpzEt (H2phpzEt = 5(3)-(2-hydroxyphenyl)-3(5)-ethylpyrazole) in methanol in the presence of sodium hydroxide yields the compound [Mn2(HphpzEt)4(H2O)2](ClO4)2 (1). The pentanuclear [Mn5(μ3-O)2(HphpzEt)3(phpzEt)3(OCH3)(HOCH3)2(O2CPh)] (2) is obtained when performing a si

  2. Synthesis and structural characterization of pyrazole and pyrazole niobocene complexes

    Energy Technology Data Exchange (ETDEWEB)

    Carrillo-Hermosilla, F.; Jalon, F.A.; Otero, A.; Villasenor, E. [Departamento de Quimica Inorganica. Organica y Bioquimica, Facultad de Quimicas. Universidad de Castilla-La Mancha (Spain)

    1996-12-31

    The first pyrazolyl niobocene complexes were prepared by reacting the trihydride complex Nb/eta``5-C{sub 5}H{sub 4}(SiMe{sub 3}){sub 2}H{sub 3} with pyrazole. 3-methyl pyrazole and tetrafluoroborate salt of protonated bis (pyrazole-1-il)methane. (Author) 20 refs.

  3. Design and Synthesis of Pyrazole-3-one Derivatives as Hypoglycaemic Agents

    Directory of Open Access Journals (Sweden)

    Prasanna A. Datar

    2015-01-01

    Full Text Available Pyrazole-3-one compounds were designed on the basis of docking studies of previously reported antidiabetic pyrazole compounds. The amino acid residues found during docking studies were used as guidelines for the modification of aromatic substitutions on pyrazole-3-one structure. Depending on the docking score, the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to in vivo hypoglycemic activity using alloxan induced diabetic rats and metformin as a standard. Compound 4 having sulphonamide derivative was found to be the most potent compound among the series.

  4. [Study on derivatives of 5-amino-4-acylamino-1H-pyrazole as inhibitors of furin].

    Science.gov (United States)

    Kibirev, V K; Osadchuk, T V; Vadziuk, O B; Shablykin, O V; Kozachenko, A P; Chumachenko, S A; Popil'nichenko, S V; Brovarets, V S

    2011-01-01

    A series of 5-amino-1H-pyrazoles was synthesized and studied as inhibitors of furin. The most potent compound, 5-amino-4-acetylamino-3-(4-methylphenylamino)1H-pyrazole, was found to retard the activity of furin by mixed-type inhibition with K = 288 microM. These findings permit to plan new ways for chemical modifications of the 5-amino-1H-pyrazole structure and design more potent furin inhibitors of non-peptide nature.

  5. Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity.

    Science.gov (United States)

    Shi, Jing Bo; Tang, Wen Jian; Qi, Xing Bao; Li, Rong; Liu, Xin Hua

    2015-01-27

    A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 ± 0.08 μM. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity.

  6. Toxicological evaluation of a novel cooling compound: 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethylacetamide

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    Donald S. Karanewsky

    2015-01-01

    Full Text Available A toxicological evaluation of a novel cooling agent, 2-(4-methylphenoxy-N-(1H-pyrazol-3-yl-N-(2-thienylmethyl acetamide (S2227; CAS 1374760-95-8, was completed for the purpose of assessing its safety for use in food and beverage applications. S2227 undergoes rapid oxidative metabolism in vitro, and in rat and dog pharmacokinetic studies is rapidly converted to its component carboxylic acid and secondary amine. S2227 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. The secondary amine hydrolysis product, N-(2-thienylmethyl-1H-pyrazol-3-amine (M179, was also evaluated for genotoxicity. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL for S2227 was 100 mg/kg/day (highest dose tested when administered by oral gavage for 90 consecutive days. Furthermore, S2227 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

  7. Tris{4-[(1,3-diphenyl-1H-pyrazol-4-ylmethylene]-41-aminobiphenyl}amine

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    Sandhya P. Veettil

    2010-04-01

    Full Text Available Tris{4-[(1,3-diphenyl-1H-pyrazol-4-ylmethylene]-41-aminobiphenyl}amine was synthesized from N-(4-bromophenyl-N-[(1,3-diphenyl-1H-pyrazol-4-ylmethylene]amine and tris(4-bromophenylamine based on Ullmann coupling reaction. The synthesized compound was characterized by NMR, IR, MS and elemental analysis.

  8. Pyrazole complexes as anion receptors: effects of changing the metal, the pyrazole substitution pattern, and the number of pyrazole ligands.

    Science.gov (United States)

    Nieto, Sonia; Pérez, Julio; Riera, Lucía; Riera, Víctor; Miguel, Daniel; Golen, James A; Rheingold, Arnold L

    2007-04-16

    Compound cis,fac-[Mo(eta3-allyl)(CO)2(Hdmpz)3]BAr'4 (1) (Hdmpz = 3,5-dimethylpyrazole, Ar' = 3,5-bis(trifluoromethyl)phenyl) undergoes rapid substitution of one of the pyrazole ligands by anions, including the low nucleophilic ReO4-, a reaction that afforded [Mo(OReO3)(eta3-allyl)(CO)2(Hdmpz)2] (2), structurally characterized by X-ray diffraction. The new compounds fac-[Mn(CO)3(Hdmpz)3]BAr'4 (4a) and fac-[Mn(CO)3(HtBupz)3]BAr'4 (4b) (HtBupz = 3(5)-tert-butylpyrazole) also undergo pyrazole substitution with most anions, and the product from the reaction with nitrate was crystallographically characterized. Compounds 4a,b were found to be substitutionally stable toward perrhenate, and the adducts [Mn(CO)3(Hdmpz)3].[ReO4] (7a) and [Mn(CO)3(HtBupz)3].[ReO4].[Bu4N].[BAr'4] (7b), crystallographically characterized, display hydrogen bonds between one of the perrhenate oxygens and the N-H groups of two of the pyrazole ligands. The structurally similar adduct [Re(CO)3(Hdmpz)3].[ReO4] (8) was found to result from the interaction of [Re(CO)3(Hdmpz)3]BAr'4 with perrhenate. The reaction of [Re(OTf)(CO)5] with 3,5-dimethylpyrazole (Hdmpz) afforded [Re(CO)5(Hdmpz)]OTf (9). The reaction of 9 with Hdmpz and NaBAr'4 yielded [Re(CO)4(Hdmpz)2]BAr'4 (10), which was found to be unstable toward chloride anion. In contrast, the new compound fac,cis-[Re(CO)3(CNtBu)(Hdmpz)2]BAr'4 (11) is stable in solution in the presence of different anions. Binding constants for 11 with chloride, bromide, and nitrate are 1-2 orders of magnitude lower than those found for these anions and rhenium tris(pyrazole) hosts, indicating that the presence of the third pyrazole ligand is crucial. Compounds fac-[Re(CO)3(HPhpz)3]BAr'4 (14) (HPhpz = 3(5)-phenylpyrazole) and fac-[Re(CO)3(HIndz)3]BAr'4 (15) (HIndz = indazole) are, in terms of anion binding strength and selectivity, inferior to those with dimethylpyrazole or tert-butylpyrazole ligands.

  9. Synthesis and anti-TMV activity of novel N-(3-alkyl-1H-pyrazol-4-yl)-3-alkyl-4-substituted- 1H-pyrazole-5-carboxamides

    Institute of Scientific and Technical Information of China (English)

    Da Qiang Zhang; Gao Fei Xu; Zhi Jin Fan; Dao Quan Wang; Xin Ling Yang; De Kai Yuan

    2012-01-01

    In oraer to investigate the biological activity of novel bis-pyrazole compounds,a series of N-(3-alkyl-5-(N-methylcarbamyl)-1H-pyrazol-4-yl)-3-alkyl-4-substituted-1H-pyrazole-5-carboxamides were designed and synthesized with ethyl 3-alkyl-1H-pyrazole-5-carboxylate 1 as starting materials.N-Methyl-3-alkyl-4-amino-1H-pyrazole-5-carboxamides 6 were obtained from 1 via 5 steps.3-Alkyl-4-substitued-1H-pyrazole-5-carboxyl chlorides 4a,4b,11a,11b,11c or 12 were also obtained from 1 via several steps.Target compounds 7a-7g were obtained after the reaction of 6 with the above 1H-pyrazole-5-carboxyl chlorides.Preliminary bioassay showed some compounds possessing good inactivation effect against TMV (tobacco mosaic virus).Compound 7a showed higher activity superior to ningnanmycin at a concentration of 5.0 × 10-4 g/mL and equal acdvity at 1.0 × 10-4 g/nL; 7b and 7c showed equal activity to virazole both at concentrations of 5.0 × 10-4 g/mL and 1.0 × 10-4 g/mL.

  10. Differential modulation of TWIK-related K(+) channel (TREK) and TWIK-related acid-sensitive K(+) channel 2 (TASK2) activity by pyrazole compounds.

    Science.gov (United States)

    Kim, Hyun Jong; Woo, Joohan; Nam, Yuran; Nam, Joo Hyun; Kim, Woo Kyung

    2016-11-15

    Pyrazole derivatives were originally suggested as selective blockers of the transient receptor potential cation 3 (TRPC3) and channel. In particular, pyr3 and 10 selectively inhibit TRPC3, whereas pyr2 (BTP2) and 6 inhibit ORAI1. However, their effects on background K(+) channel activity have not been elucidated. In this study, the effects of BTP2, pyr3, pyr6, and pyr10 were studied on cloned human TWIK-related K(+) channels (TREKs) and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) channels, which modulate Ca(2+) signaling by controlling membrane potential, in HEK293T-overexpressing cells by using a whole-cell patch clamp technique. Pyr3 potently inhibited TREK-1 (ITREK1), TREK-2 (ITREK2), and TASK2 current (ITASK-2) with half-maximal inhibitory concentrations (IC50) of 0.89±0.27, 1.95±1.44, and 2.42±0.39µM, respectively. BTP2 slightly inhibited ITASK-2 (80.3±2.5% at 100μM). In contrast, pyr6 at 100µM potentiated ITREK1 and ITREK2 by approximately 2.6- and 3.6-fold compared to the control and inhibited ITASK2 (38.7±9.2%). Pyr10 showed a subtype-specific inhibition of ITREK1 but not ITREK2. It also inhibited ITASK2 (70.9±3.1% at 100μM). To the best of our knowledge, this study is the first to describe the differential modulation of TREKs and TASK2 channels by pyrazole derivatives, previously used as inhibitors of TRPC3 and ORAI1. Therefore, studies using these drugs should consider their modulation of other channels such as TREK and TASK-2.

  11. Synthetic routes to 3(5)-phosphonylated pyrazoles

    Science.gov (United States)

    Goulioukina, N. S.; Makukhin, N. N.; Beletskaya, I. P.

    2016-07-01

    This review comprehensively covers the currently available synthetic routes to 3(5)-phosphonylated pyrazoles. There are demonstrated significant advances in this field over the last 10-15 years caused by the use of the Bestmann-Ohira reagent [as well as (diazomethyl)phosphonates and phosphonylated hydrazonoyl halides] in reactions with diverse dipolarophiles. 1,3-Dipolar cycloaddition of diazo compounds to α,β-unsaturated phosphonates as well as intramolecular heterocyclization of (1-diazoallyl)phosphonates and (3--diazo-1-propenyl)phosphonates are discussed. Synthetic potential of cyclocondensation of organophosphorus 1,3-dielectrophilic compounds with hydrazines is shown. Ways to introduce a phosphonate group into the pyrazole ring are considered. Examples of chemical transformations of 3(5)-phosphonylated pyrazoles are reported. The bibliography includes 88 references.

  12. New pyrazole derivative 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole: synthesis and assessment of some biological activities.

    Science.gov (United States)

    de Oliveira, Lanussy Porfiro; da Silva, Daiany Priscilla Bueno; Florentino, Iziara Ferreira; Fajemiroye, James Oluwagbamigbe; de Oliveira, Thiago Sardinha; Marcelino, Renato Ivan de Ávila; Pazini, Francine; Lião, Luciano Morais; Ghedini, Paulo César; de Moura, Soraia Santana; Valadares, Marize Campos; de Carvalho, Verônica Vale; Vaz, Boniek Gontijo; Menegatti, Ricardo; Costa, Elson Alves

    2017-01-01

    The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also blocked CaCl2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K(+) channels observed in the vasorelaxant effect.

  13. An iron(III) complex salt containing pyrazole as both ligand and counter-ion: bis(1H-pyrazol-2-ium) pentacyanido(1H-pyrazole-κN(2))ferrate(III).

    Science.gov (United States)

    Wang, Yu-Feng; Yu, Chun-Hua; Zhu, Run-Qiang

    2014-05-01

    The title compound, (C3H5N2)2[Fe(CN)5(C3H4N2)], is composed of a mononuclear [Fe(CN)5(pyrazole)](2-) dianion and two 1H-pyrazol-2-ium cations. A three-dimensional supramolecular network is formed through a rich scheme of N-H...N hydrogen bonds and C-H...π interactions among the cations and anions.

  14. Synthesis and Biological Activity of 3-Methyl-1H-pyrazole-4-carboxylic Ester Derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHAO Wei-Guang; LI Zheng-Ming; YUAN Ping-Wei; WANG Wen-Yan

    2001-01-01

    In search of novel pyrazole derivatives with bioactivity,a se-ries of 3-methyl- 1H-pyrazole-4-caboxylic ester derivatives were synthesized via α-oxoketene dithioacetals as starting ma-terial.The structures of al1 compounds prepared were con-firmed by 1HNMR, IR, MS and elemental analyses.Prelimi-nary bioassays indicated that some compounds showed fungici-dal activity against wheat rust,phoma asparagi and antiviral activity against TMV.

  15. Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening.

    Science.gov (United States)

    Miller, Zachary; Kim, Keun-Sik; Lee, Do-Min; Kasam, Vinod; Baek, Si Eun; Lee, Kwang Hyun; Zhang, Yan-Yan; Ao, Lin; Carmony, Kimberly; Lee, Na-Ra; Zhou, Shou; Zhao, Qingquan; Jang, Yujin; Jeong, Hyun-Young; Zhan, Chang-Guo; Lee, Wooin; Kim, Dong-Eun; Kim, Kyung Bo

    2015-02-26

    We performed a virtual screen of ∼340 000 small molecules against the active site of proteasomes followed by in vitro assays and subsequent optimization, yielding a proteasome inhibitor with pyrazole scaffold. The pyrazole-scaffold compound displayed excellent metabolic stability and was highly effective in suppressing solid tumor growth in vivo. Furthermore, the effectiveness of this compound was not negatively impacted by resistance to bortezomib or carfilzomib.

  16. Diethyl 2-[phenyl(pyrazol-1-ylmethyl]propanedioate

    Directory of Open Access Journals (Sweden)

    Ihssan Meskini

    2010-05-01

    Full Text Available There are two independent molecules in the asymmetric unit of the title compound, C17H20N2O4, which differ slightly in the orientation of the phenyl ring and carbonyl groups with respect to the pyrazole unit. In the first molecule, the dihedral angle between the phenyl and pyrazole rings is 68.99 (13° while the two carbonyl groups make a dihedral angle of 72.1 (4°. The corresponding values in the second molecule are 68.54 (14 and 71.5 (4°, respectively.

  17. Design, synthesis and structure-activity relationship study of novel pyrazole-based heterocycles as potential antitumor agents.

    Science.gov (United States)

    Farag, Ahmad M; Ali, Korany A K; El-Debss, Taha M A; Mayhoub, Abdelrahman S; Amr, Abdel-Galil E; Abdel-Hafez, Naglaa A; Abdulla, Mohamed M

    2010-12-01

    The versatile hitherto unreported 3-[(E)-3-(dimethylamino)acryloyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (3) was prepared via the reaction of 3-acetyl-1,5-diphenyl-1H-pyrazole-4-carbonitrile (1) with dimethylformamid-dimethylacetal (DMF-DMA). The latter product and 3-((E)-3-morpholin-4-yl-acryloyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (4) underwent regioselective 1,3-dipolar cycloaddition with nitrilimines to afford the corresponding pyrazole derivatives. In vivo anti-estrogenic activity and acute toxicity after single oral dose of the newly synthesized compounds were evaluated. In vitro disease-oriented primary antitumor screening utilizing 14 cell lines of breast and ovarian tumor subpanels has been also carried out. All tested compounds showed anti-estrogenic properties equipotent or superior to the reference drug, letrozole. 3-[3-(4-Cyano-1,5-diphenyl-1H-pyrazole-3-yl)-1-(4-methylphenyl)-1H-pyrazole-4-carbonyl]-1,5-diphenyl-1H-pyrazole-4-carbonitrile (27c) and 3-(3-acetyl-1-phenyl-1H-pyrazole-4-carbonyl)-1,5-diphenyl-1H-pyrazole-4-carbonitrile (8a) showed a significant cytotoxic activity in a nanomolar range against certain types of breast and ovarian tumors with tolerable toxicity.

  18. 2,2,2-Tris(pyrazol-1-ylethanol

    Directory of Open Access Journals (Sweden)

    Craig C. McLauchlan

    2011-05-01

    Full Text Available The title compound TPE, C11H12N6O, was prepared by slow evaporation from diethyl ether. In the crystal, there is a hydrogen bond between the alcohol H atom and an N in the pyrazole ring of a neighboring molecule.

  19. 4-Bromo-3-methoxy-1-phenyl-1H-pyrazole

    Directory of Open Access Journals (Sweden)

    Algirdas Šačkus

    2009-11-01

    Full Text Available The title compound was prepared by treatment of 4-bromo-1-phenyl-1H-pyrazol-3-ol with sodium hydride/methyl iodide in good yield. Detailed spectroscopic data (1H NMR, 13C NMR, 15N NMR, IR, MS are presented.

  20. Ultrasound-promoted iodination of pyrazoles in aqueous medium

    Directory of Open Access Journals (Sweden)

    Jéssica Kunsminskas

    2012-06-01

    Full Text Available Several pharmacological activities have been devoted to pyrazole containing molecules. In particular, 4-iodopyrazoles have been employed as key starting materials in cross-coupling chemistry and metal-iodine exchange reactions that focus on the synthesis of such biologically important compounds. Unfortunately, existing methods for the synthesis of 4-iodopyrazoles are not in agreement with the environmental requirements due to a series of drawbacks including the use of large excess of reagents, the generation of toxic waste and long reaction times. Recently, we developed a fast and mild reaction condition for the iodination of aromatic compounds using an I2/H2O2 system water as a nonflammable and innocuous solvent and ultrasonic irradiation as energy source. In this work, we present the application of this methodology for the iodination of pyrazoles (Scheme. Initially, a series of pyrazoles were efficiently prepared starting from 1,3-dicarbonyl compounds and hydrazines under ultrasonic irradiation. Three examples from the pyrazoles were subjected to the iodination condition shown above. Iodopyrazoles were obtained in 63-65% yields.

  1. Microwave assisted regioselective synthesis of novel pyrazoles and pyrazolopyridazines via fluorine containing building blocks

    Science.gov (United States)

    Althagafi, Ismail I.; Shaaban, Mohamed R.

    2017-08-01

    A facile regioselective synthesis of novel pyrazole derivatives containing a fluorophenyl moiety via the 1,3-dipolar cycloaddition of nitrileimines and enamines using conventional as well as microwave irradiation conditions have been achieved. Fluorine-containing building blocks methodology was used in order to access the targeted fluorinated compounds. The structures of the synthesized products were confirmed by 1H NMR, FT-IR, mass spectrometry, and elemental analyses. Furthermore, the synthesized pyrazoles have been used in the synthesis of some new pyrazolo pyidazines containing pendent to fluorophenyl moiety. An unambiguous structural assignment of the obtained pyrazole regioisomers was determined using the 1H NMR analysis as a valuable tool.

  2. 1-{3-[1-(Hydroxyiminoethyl]-4-methyl-1H-pyrazol-5-yl}ethanone

    Directory of Open Access Journals (Sweden)

    Matti Haukka

    2011-10-01

    Full Text Available In the title compound, C8H11N3O2, the oxime and the acetyl groups adopt a transoid conformation, while the pyrazole H atom is localized in the proximity of the acetyl group and is cis with respect to the acetyl O atom. In the crystal, dimers are formed as the result of hydrogen-bonding interactions involving the pyrazole NH group of one molecule and the carbonyl O atom of another. The dimers are associated into sheets via O—H...N hydrogen bonds involving the oxime hydroxyl and the unprotonated pyrazole N atom, generating a macrocyclic motif with six molecules.

  3. Synthesis, Characterization and Biological activity of Some Novel Sulphur Bridged Pyrazoles

    Directory of Open Access Journals (Sweden)

    Singaravel Mohan,

    2010-10-01

    Full Text Available Mercaptoheterocyclic compounds on treatment with ethyl bromoacetate in the presence of base afforded thioacetate derivative of mercaptoheterocyclic compounds. These on subsequent treatment with hydrazine hydrate yielded acylated hydrazine derivative of ercaptoheterocyclic compounds. Reaction of these acylated hydrazinederivatives of mercaptoheterocyclic compounds with ketene dithioacetal derivative afforded sulphur bridged pyrazole derivatives.

  4. Pyrazoles as potential anti-angiogenesis agents: A contemporary overview

    Science.gov (United States)

    Kasiotis, Konstantinos; Tzanetou, Evangelia; Haroutounian, Serkos

    2014-09-01

    Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research.

  5. Synthesis of Fluorescent Indazoles by Palladium-Catalyzed Benzannulation of Pyrazoles with Alkynes.

    Science.gov (United States)

    Kim, Og Soon; Jang, Jin Hyeok; Kim, Hyun Tae; Han, Su Jin; Tsui, Gavin Chit; Joo, Jung Min

    2017-03-17

    The synthesis of indazoles from pyrazoles and internal alkynes is described. Instead of complex benzenoid compounds, readily available pyrazoles were used for the preparation of indazoles by reaction of the C-H bonds of the heterocyclic ring. Oxidative benzannulation was also applied to imidazoles, providing benzimidazoles. This convergent strategy enabled alteration of the photochemical properties of benzo-fused diazoles by varying the substituents at the benzene ring, thus leading to the development of tetraarylindazoles as new fluorophores.

  6. 3-(4-Bromophenyl-1-phenyl-1H-pyrazole-4-carbaldehyde

    Directory of Open Access Journals (Sweden)

    Mahmoud Elkady

    2012-12-01

    Full Text Available The asymmetric unit of the title compound, C16H11BrN2O, contains two independent molecules with slightly different geometries. The 4-bromobenzene ring forms dihedral angles of 26.0 (2 and 39.9 (7° with the pyrazole ring in the two molecules while the phenyl ring is oriented at 19.7 (5 and 7.3 (0° with respect to the pyrazole ring.

  7. 2-[1-(9-Anthrylmethyl-1H-pyrazol-3-yl]pyridine

    Directory of Open Access Journals (Sweden)

    Shi-Lu Zhang

    2009-11-01

    Full Text Available The title compound, C23H17N3, can be used in coordination chemistry. The anthracene ring makes dihedral angles of 86.08 (5 and 76.63 (6°, respectively, with the pyridine and pyrazole rings. The dihedral angle between the pyrazole and pyrimidine rings is 11.79 (7°. In the structure, weak intermolecular C—H...N hydrogen bonds are observed.

  8. Synthesis, characterization, and anticancer activity of ruthenium-pyrazole complexes.

    Science.gov (United States)

    David, Solene; Perkins, Richard S; Fronczek, Frank R; Kasiri, Sahba; Mandal, Subhrangsu S; Srivastava, Radhey S

    2012-06-01

    A series of new water soluble Ru(III) pyrazole complexes mer-[RuCl(3)(DMSO-S)(pyz)(2)] 1, mer-[RuCl(3)(DMSO-S)(DMSO-O)(pyz)] 2, mer-[RuCl(3)(bpy)(dmpyz)] 3, and mer-[RuCl(3)(DMSO-S)(dmpyz)(2)] 4 (pyz=pyrazole; dmpyz=3,5-dimethylpyrazole, bpy=2,2'-bipyridine) have been synthesized and characterized by use of a combination of spectroscopy (IR and UV-visible), X-ray diffraction, and cyclic voltammetry. The molecular X-ray structure of all reported compounds (1-4) revealed distorted octahedral coordination around ruthenium. The cytotoxicity assay on human breast cancer cells (MCF7) demonstrated that compounds 1 and 4 affect cell viability, whereas compounds 2 and 3 do not show appreciable activity. The IC(50) values for 1 and 4 lie within the range of 71-32μM in MCF7 cells.

  9. Synthesis and antimicrobial evaluation of some new pyrazole, pyrazoline and chromeno[3,4-c]pyrazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Abunada, Nada M.; Miqdad, Omar A. [Al-Aqsa University, Gaza (Palestinian Territory, Occupied). Faculty of Applied Sciences. Dept. of Chemistry; Hassaneen, Hamdi M. [Cairo University, Cairo (Egypt). Faculty of Science. Dept. of Chemistry; Samaha, Ahmed S. M. Abu [Al-Aqsa University, Gaza (Palestinian Territory, Occupied). Faculty of Applied Sciences. Dept. of Biology

    2009-07-01

    Some new pyrazole-5-carbonitrile derivatives 8,9 and pyrazole-5-carboxamide 13 were synthesized by the cycloaddition reaction of nitrilimines 3,4 to alpha-cyanocinnamonitriles 5a-f and alpha-cyanocinnamamide 12a,b respectively. On the other hand 3,4 add to ethyl alpha-cyanocinnamate 14a-f to give ethyl 2-pyrazoline-5-carboxylate derivatives 15,16. Also, cycloaddition of 3,4 to 3-cyanocoumarin 19a or 3-phenylsulphonylcoumarin 19b or 3-bromocoumarin 19c give chromeno[3,4-c]pyrazol-4(3H)-one derivatives 20. In the same direction, the cycloaddition of 3,4 to 3-acetylcoumarin 22 and 3-benzoylcoumarin 23 gives the corresponding dihydrochromeno[3,4-]pyrazol-4(3H)-one 24 and 25 respectively. Oxidation of 24 and 25 give 20. Most of the prepared compounds showed good to moderate antibacterial and antifungal activities. (author)

  10. Syntheses of 1,3,4-Thia(oxa)diazole-substituted Pyrazole Derivatives and Their Fungicidal Activities

    Institute of Scientific and Technical Information of China (English)

    WANG Wen-yan; ZHAO Wei-guang; LI Zheng-ming

    2004-01-01

    A series of 1,3,4-oxadiazole or 1,3,4-thiadiazole-substituted pyrazole derivatives were synthesized from 4-pyrazole formhydrazide; their biological activities were studied. The structures of all the new compounds were confirmed by means of spectroscopic methods and mieroanalyses. The preliminary bioassay results indicate that some compounds of them have a good fungicidal activity against Phoma asparagi and Physalospora piricola Nose.

  11. Novel anticancer compound [trifluoromethyl-substituted pyrazole N-nucleoside] inhibits FLT3 activity to induce differentiation in acute myeloid leukemia cells.

    Science.gov (United States)

    Saleh, Ayman M; Taha, Mutasem O; Aziz, Mohammad A; Al-Qudah, Mahmoud A; AbuTayeh, Reem F; Rizvi, Syed A

    2016-06-01

    Anticancer properties of chemically synthesized compounds have continuously been optimized for better efficacy and selectivity. Derivatives of heterocyclic compounds are well known to have selective antiproliferative effect against many types of cancer. In this study, we investigated the ability of an indigenously synthesized anticancer molecule, G-11 [1-(2",3",4",6"-Tetra-O-acetyl-β-D-glucopyranosyl)-4-(3'-trifluoromethylphenylhydrazono)-3-trifluoromethyl-1,4-dihydropyrazol-5-one], to cause selective cytotoxicity and induce differentiation in the acute myeloid leukemia HL-60 cells. G-11 was able to exert cytotoxic effect on hematological (Jurkat, U937, K562, HL-60, CCRF-SB) and solid tumor (MCF-7, HepG2, HeLa, Caco-2) cell lines, with IC50 values significantly lower than noncancerous cells (HEK-293, BJ and Vero) and normal peripheral blood mononuclear cells. G-11 induced differentiation of HL-60 cells to granulocytes and monocytes/macrophages by inhibiting the activation of FLT3 (CD135 tyrosine kinase). ITD-FLT3 mutation found in many acute myeloid leukemia patients could also be targeted by G-11 as exhibited by its inhibitory effect on MOLM-13 and MV4-11 cell lines. Molecular docking studies suggest the involvement of Leu616, Asp698, Cys694 and Cys828 residues in binding of G-11 to FLT3. The ability of G-11 to cause selective cytotoxicity and induce differentiation in cancer cells could be clinically relevant for therapeutic gains.

  12. Efficient ultrasound-assisted synthesis, spectroscopic, crystallographic and biological investigations of pyrazole-appended quinolinyl chalcones

    Science.gov (United States)

    Prasath, R.; Bhavana, P.; Sarveswari, S.; Ng, Seik Weng; Tiekink, Edward R. T.

    2015-02-01

    Two series of new quinolinyl chalcones containing a pyrazole group, 3a-f and 4a-r, have been synthesized by Claisen-Schmidt condensation of the derivatives of 2-methyl-3-acetylquinoline with either substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde or 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde in 76-93% yield under ultrasonic method. The compounds were characterized using IR, 1H NMR and ESI-MS spectroscopic methods and, for representative compounds, by X-ray crystallography. An E-configuration about the Cdbnd C ethylene bond has been established via 1H NMR spectroscopy and X-ray crystallography. These compounds show promising anti-microbial properties, with 4a and 3e being the most potent against bacterial and fungal strains, respectively and the methoxy substituted compounds showed moderate anti-oxidant activity.

  13. Design, synthesis and anti-tobacco mosaic virus (TMV) activity of 5-chloro-N-(4-cyano-1-aryl-1H-pyrazol-5-yl)-1-aryl-3-methyl-1H-pyrazole-4-carboxamide derivatives.

    Science.gov (United States)

    Xiao, Jin-Jing; Liao, Min; Chu, Ming-Jie; Ren, Zi-Li; Zhang, Xin; Lv, Xian-Hai; Cao, Hai-Qun

    2015-01-07

    A series of novel pyrazole amide derivatives 3a-3p which take TMV PC protein as the target has been designed and synthesized by the reactions of 5-chloro-1-aryl-3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4-carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy and elemental analysis. Preliminary bioassays indicated that all the compounds acted against the tobacco mosaic virus (TMV) with different in vivo and in vitro modes at 500 μg/mL and were found to possess promising activity. Especially, compound 3p showed the most potent biological activity against tobacco mosaic virus (TMV) compared to ningnanmycin, and a molecular docking study was performed and the binding model revealed that the pyrazole amide moiety was tightly embedded in the binding sites of TMV PC (PDB code: 2OM3).

  14. Intramolecular cyclization of steroidal semicarbazones to pyrazoles using Vilsmeier reagent

    Institute of Scientific and Technical Information of China (English)

    Mahboob Alam; M.Mushfiq

    2008-01-01

    The preparation of hitherto unknown steroidal heterocycles containing pyrazole fused to 6,7-position of the steroidal nucleus is described.These heterocycles were prepared by the action of Vilsmeier reagent with steroidal semicarbazones in DMF.The slructure of the compounds has been established on the basis of their elemental analysis and spectral data.A general mechanistic scheme for these reactions is also suggested based on current and previous results.

  15. 1-{3-[1-(Hydroxyimino)ethyl]-4-methyl-1H-pyrazol-5-yl}ethanone.

    Science.gov (United States)

    Malinkin, Sergey; Penkova, Larysa; Pavlenko, Vadim A; Haukka, Matti; Pavlova, Svetlana V

    2011-10-01

    In the title compound, C(8)H(11)N(3)O(2), the oxime and the acetyl groups adopt a transoid conformation, while the pyrazole H atom is localized in the proximity of the acetyl group and is cis with respect to the acetyl O atom. In the crystal, dimers are formed as the result of hydrogen-bonding inter-actions involving the pyrazole NH group of one mol-ecule and the carbonyl O atom of another. The dimers are associated into sheets via O-H⋯N hydrogen bonds involving the oxime hydroxyl and the unprotonated pyrazole N atom, generating a macrocyclic motif with six mol-ecules.

  16. Synthesis and in vitro biological evaluation of new pyrazole chalcones and heterocyclic diamides as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Sankappa Rai U.

    2015-05-01

    Full Text Available Synthesis and characterization of new heterocyclic pyrazole chalcones (4a–e and diamide (6a–e derivatives are described. Pyrazole chalcones were synthesized by the reaction of pyrazole aldehydes and suitable aromatic ketones. Diamides were synthesized by the reaction of phthalic acid and amines. Newly synthesized compounds were characterized by spectral studies and their biological activity was assessed in vitro using MCF-7 (human breast adenocarcinoma and HeLa (human cervical tumor cells cell lines. Few of the synthesized molecules inhibited the growth of the human breast cancer cell lines and human cervical tumor cell lines at low micromolar to nanomolar concentrations.

  17. Synthesis, spectroscopy (IR, multinuclear NMR, ESI-MS), diffraction, density functional study and in vitro antiproliferative activity of pyrazole-beta-diketone dihalotin(IV) compounds on 5 melanoma cell lines.

    Science.gov (United States)

    Pettinari, Claudio; Caruso, Francesco; Zaffaroni, Nadia; Villa, Raffaella; Marchetti, Fabio; Pettinari, Riccardo; Phillips, Christine; Tanski, Joseph; Rossi, Miriam

    2006-01-01

    Novel 4-acylpyrazolon-5-ato-dihalotin(IV) complexes, [Q2SnX2], (X = F, Cl, Br or I); HQ = HQ(CHPh2) (1,2-dihydro-3-methyl-1-phenyl-4-(2,2-diphenylacetyl)pyrazol-5-one), HQ(Bn) (1,2-dihydro-3-methyl-1-phenyl-4-(2-phenylacetyl)pyrazol-5-one) or HQ(CF3,py) (4-(2,2,2-trifluoroacetyl)-1,2-dihydro-3-methyl-1-(pyridin-2-yl)pyrazol-5-one) have been synthesized and characterized by spectroscopic (IR, 1H, 13C, 19F and 119Sn NMR, electrospray ionisation mass spectrometry (ESI-MS)), analytical and structural methods (X-ray and density functional theory). 119Sn chemical shifts depend on the nature of the halides bonded to tin. Isomer conversion, detected in solution by NMR spectroscopy, is related to the acyl moiety bulkiness while the cis(Cl)-cis(acyl)-trans(pyrazolonato) scheme is found in the solid state. The in vitro antiproliferative tests of three derivatives on three human melanoma cell lines (JR8, SK-MEL-5, MEL501) and two melanoma cell clones (2/21 and 2/60) show dose-dependent decrease of cell proliferation in all cell lines. The activity correlates with the nature of the substituent on position 1 of pyrazole, decreasing in the order pyridyl>Ph>methyl. The activity for (Q(CF3,py))2SnCl2 on the SK-MEL-5 cell line is IC50 = 50 microM.

  18. 5-Pentyl-4-phenylsulfonyl-1H-pyrazol-3-ol

    Directory of Open Access Journals (Sweden)

    Tara Shahani

    2010-06-01

    Full Text Available In the title compound, C14H18N2O3S, the 1H-pyrazole ring is approximately planar, with a maximum deviation of 0.005 (1 Å. The dihedral angle formed between the 1H-pyrazole and phenyl rings is 79.09 (5°. Pairs of intermolecular N—H...O and O...H...N hydrogen bonds form dimers between neighboring molecules, generating R22(10 ring motifs. These dimers are further linked byintermolecular N—H...O and O—H...N hydrogen bonds into a two-dimensional array parallel to the ac plane. The crystal structure is also stabilized by C—H...π interactions.

  19. Novel thiol-based histone deacetylase inhibitors bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold as surface recognition motif: Design, synthesis and SAR study.

    Science.gov (United States)

    Wen, Jiachen; Niu, Qun; Liu, Jiang; Bao, Yu; Yang, Jinyu; Luan, Shenglin; Fan, Yinbo; Liu, Dan; Zhao, Linxiang

    2016-01-15

    A series of novel thiol-based histone deacetylase (HDAC) inhibitors bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold as surface recognition motif was designed, synthesized, and evaluated for their HDAC inhibition activity. Among them, 15j (IC50=0.08μM) was identified as a better inhibitor than Vorinostat (IC50=0.25μM) against total HDACs. In addition, Structure-activity relationships (SAR) analyses indicated that (i) compounds with different substituents on pyrazole N-1 position exhibited superior activities than those on pyrazole N-2 position, (ii) variation of functional groups on N-1'-alkyl chain terminus followed the trends of carboxyl group>hydroxyl group≫alkyl group, and (iii) methylation on pyrazole C-4 position diminished the HDAC inhibition activity. The SAR will guide us to further refine compounds bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold to achieve better HDAC inhibitors.

  20. Synthesis, DNA binding and in-vitro cytotoxicity studies on novel bis-pyrazoles.

    Science.gov (United States)

    Indrasena Reddy, K; Aruna, C; Manisha, M; Srihari, K; Sudhakar Babu, K; Vijayakumar, V; Sarveswari, S; Priya, R; Amrita, A; Siva, R

    2017-03-01

    A new series of bis-pyrazoles 6a-t were synthesized from 3,5-dimethyl pyrazole using sequential approach. All these compounds were characterized by IR, (1)H NMR, (13)C NMR and mass spectral data. The interaction of newly synthesized bis-pyrazoles with DNA was investigated through molecular docking and absorption spectroscopic technique. Among all bis-pyrazoles compounds, the 6h compound showed lower conformational energy through in silico analysis. The interaction of each molecule in this series 6a-t with the various concentrations of DNA was examined through the UV-visible spectroscopic studies. The UV-visible spectroscopy studies on the specific binding of compound 6a, 6b, 6g, 6h, 6d, 6i, 6k, 6n, 6s with DNA have exhibited spectral shifts and the results were discussed. In further the compounds 6a-t were subjected to the in-vitro cytotoxicity studies against human pancreatic adenocarcinoma, human non-small cell lung carcinoma cell lines. Among the screened compounds, N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-1H-pyrazol-5-yl)cyclobutane carboxamide and N-(5'-Isopropoxy-2'-isopropyl-3,5-dimethyl-2'H-[1,4'] bipyrazolyl-3'-yl)-dimethane sulfonamide were found as lead molecules since they have exhibited promising activity against both the cancer cell lines used in this study, whereas the compounds 4-(trifluoromethyl)-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-pyrazol-5-yl)benzamide and 2,6-difluoro-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-pyrazol-5-yl) benzamide were found to be active against the pancreatic cell line only. Rest all the other compounds were found to exhibit moderate to good activity towards both the cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 5-Amino-pyrazoles as potent and selective p38[alpha] inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Das, Jagabandhu; Moquin, Robert V.; Dyckman, Alaric J.; Li, Tianle; Pitt, Sidney; Zhang, Rosemary; Shen, Ding Ren; McIntyre, Kim W.; Gillooly, Kathleen; Doweyko, Arthur M.; Newitt, John A.; Sack, John S.; Zhang, Hongjian; Kiefer, Susan E.; Kish, Kevin; McKinnon, Murray; Barrish, Joel C.; Dodd, John H.; Schieven, Gary L.; Leftheris, Katerina (BMS)

    2012-02-07

    The synthesis and structure-activity relationships (SAR) of p38{alpha} MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38{alpha} MAP kinase with excellent cellular potency toward the inhibition of TNF{alpha} production. Compound 2j was highly efficacious in vivo in inhibiting TNF{alpha} production in an acute murine model of TNF{alpha} production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38{alpha} is also disclosed.

  2. Synthesis and Herbicidal Activity of Substituted Pyrazole Isothiocyanates

    Directory of Open Access Journals (Sweden)

    Xing Zhang

    2012-10-01

    Full Text Available Isothiocyanates and substituted pyrazoles were combined to form a series of novel isothiocyanates with highly effective herbicidal activity. The target compounds were analyzed by elemental analysis, 1H-NMR, EI-MS and IR spectroscopy. The synthesized compounds, particularly compounds 3-1 and 3-7, exhibited good herbicidal activities against four weeds. The EC50 values of compound 3-1 against Echinochloa crusgalli L., Cyperus iria L., Dactylis glomerata L., and Trifolium repens L. were 64.32, 65.83, 62.42, and 67.72 µg/mL, respectively. The EC50 values of compound 3-7 against E. crusgalli L., C. iria L., D. glomerata L., T. repens L. were 65.33, 64.90, 59.41 and 67.41 µg/mL, respectively. Compounds 3-1 and 3-7 may be further optimized as lead compounds for new herbicides.

  3. Syntheses of Some 3-[1'( 1' H )-Substituent-pyrazol-5'-yl ] benzo [5,6] coumarins

    Institute of Scientific and Technical Information of China (English)

    EL-DEEN, Ibrahim Mohey; AL-WAKEEL, El-Sayed Ismail; El-MAWLA, Ahmed Gad

    2002-01-01

    3-[1' (1' H)-Substitueut-pyrazol-5'-yl] benzo [ 5, 6] coumarins and 3-(1' , 2 '-oxazol- 5 '- yl ) benzo [ 5 , 6 ] coumarin were prepared via condensation of 3-(2'-formyl-1'-chlorovinyl) benzo [ 5, 6]coumarin with hydrazine derivatives or hydroxylamine. Reaction of 3-[1' (1'H)-pyrazol-5'-yl] benzo[5, 6] coumarin with alkyl halides, olefinic compounds or acid chlorides are described.

  4. 4-(1,3-Diphenyl-4,5-dihydro-1H-pyrazol-5-yl-1,3-diphenyl-1H-pyrazole

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-11-01

    Full Text Available The title compound, C30H24N4, contains two pyrazole rings and four phenyl rings. The pyrazole rings are essentially planar, with maximum deviations of 0.003 (1 and 0.066 (1 Å and make a dihedral angle of 73.43 (6°. The two pyrazole rings make dihedral angles of 40.08 (6, 9.28 (6, 15.78 (8 and 17.25 (7° with their attached phenyl rings. In the crystal, there are no significant intermolecular hydrogen-bonding interactions. The crystal structure is stabilized by C—H...π interactions.

  5. Synthesis and Antimicrobial Studies of Pyrimidine Pyrazole Heterocycles

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2014-01-01

    Full Text Available Prompted from the diversity of the wider use and being an integral part of genetic material, an effort was made to synthesize pyrimidine pyrazole derivatives of pharmaceutical interest by oxidative cyclization of chalcones with satisfactory yield and purity. A novel series of 1,3-dimethyl-6-hydroxy-2,4-dioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl-1,2,3,4-tetrahydropyrimidines (5a–d and 1,3-diaryl-6-hydroxy-4-oxo-2-thioxo-5-(1′-phenyl-3′-aryl-1H-pyrazol-5′-yl-1,2,3,4-tetrahydropyrimidines (5e–l has been synthesized. The structures of these compounds were established on the basis of FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. All the synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. Among all the compounds, 5g was found to be the most active as its MIC was 31.25 µg/mL against S. aureus and B. cereus. The compounds 5h, 5c, and 5e also possess antibacterial activity with MIC values as 62.50, 125.00, and 500.00 µg/mL, respectively. The compounds 5c and 5j were found to have antifungal activity against Aspergillus spp. As antifungal drugs lag behind the antibacterial drugs, therefore we tried in vitro combination of these two compounds with standard antifungal drugs (polyene and azole against Aspergillus spp. The combination of ketoconazole with 5c and 5j showed synergy at 1 : 8 (6.25 : 50.00 µg/mL and 1 : 4 (25 : 100 µg/mL against A. fumigatus (ITCC 4517 and A. fumigatus (VPCI 190/96, respectively.

  6. Design, Synthesis and Fungicidal Activities of Some Novel Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Xue-Ru Liu

    2014-09-01

    Full Text Available In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS, and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank Donk, Fusarium oxysporum (S-chl f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27–32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.

  7. Synthesis and Bioactivities of Novel Pyrazole Oxime Derivatives Containing a 5-Trifluoromethylpyridyl Moiety

    Directory of Open Access Journals (Sweden)

    Hong Dai

    2016-02-01

    Full Text Available In this study, in order to find novel biologically active pyrazole oxime compounds, a series of pyrazole oxime derivatives containing a 5-trifluoromethylpyridyl moiety were synthesized. Preliminary bioassays indicated that most title compounds were found to display good to excellent acaricidal activity against Tetranychus cinnabarinus at a concentration of 200 μg/mL, and some designed compounds still showed excellent acaricidal activity against Tetranychus cinnabarinus at the concentration of 10 μg/mL, especially since the inhibition rates of compounds 8e, 8f, 8l, 8m, 8n, 8p, and 8q were all 100.00%. Interestingly, some target compounds exhibited moderate to good insecticidal activities against Plutella xylostella and Aphis craccivora at a concentration of 200 μg/mL; furthermore, compounds 8e and 8l possessed outstanding insecticidal activities against Plutella xylostella under the concentration of 50 μg/mL.

  8. Ultrasound Promoted Synthesis of Bis(substituted pyrazol-4-ylcarbonyl-Substituted Thioureas

    Directory of Open Access Journals (Sweden)

    Li Xiao

    2009-03-01

    Full Text Available A series of novel bis(substituted pyrazol-4-ylcarbonyl-substituted thioureas have been synthesized by the reactions of substituted pyrazol-4-ylcarbonyl isothiocyanates with different diamines under ultrasound irradiation and classical heating method at 20-25 °C. In general, substantial improvement in rates and modest yields increases were observed when reactions were carried out under sonication, compared with the classical heating method. The structures of these compounds have been elucidated by elemental and spectral (IR, 1H-NMR analysis.

  9. Crystal structure of 1-methoxy-2,2,2-tris(pyrazol-1-ylethane

    Directory of Open Access Journals (Sweden)

    Ganna Lyubartseva

    2014-09-01

    Full Text Available The title compound, C12H14N6O, consists of three pyrazole rings bound via nitrogen to the distal ethane carbon of methoxy ethane. The dihedral angles between the three pyrazole rings are 67.62 (14, 73.74 (14, and 78.92 (12°. In the crystal, molecules are linked by bifurcated C—H,H...N hydrogen bonds, forming double-stranded chains along [001]. The chains are linked via C—H...O hydrogen bonds, forming a three-dimensional framework structure. The crystal was refined as a perfect (0.5:0.5 inversion twin.

  10. 5-Dimethylamino-1-phenylchromeno[2,3-c]pyrazol-4(1H-one

    Directory of Open Access Journals (Sweden)

    Wolfgang Holzer

    2010-11-01

    Full Text Available The title compound was prepared by treatment of 5-fluoro-1-phenylchromeno [2,3-c]pyrazol-4(1H-one with aqueous dimethylamine. Detailed spectroscopic data (1H NMR, 13C NMR, 15N NMR, IR, MS are presented.

  11. (2E-3-(3-Methoxy-1-phenyl-1H-pyrazol-4-yl-2-propenal

    Directory of Open Access Journals (Sweden)

    Algirdas Šačkus

    2009-12-01

    Full Text Available The palladium-catalyzed reaction of 4-bromo-3-methoxy-1-phenyl-1H-pyrazole with acrolein diethyl acetal gives the title compound in good yield. Detailed spectroscopic data (1H NMR, 13C NMR, 15N NMR, IR, MS are presented.

  12. Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xuqing; Song, Fengbing; Kuo, Gee-Hong; Xiang, Amy; Gibbs, Alan C.; Abad, Marta C.; Sun, Weimei; Kuo, Lawrence C.; Sui, Zhihua (J); (J-PRD)

    2013-11-20

    A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties.

  13. 3-(Piperidin-1-yl-6-(1H-pyrazol-1-ylpyridazine

    Directory of Open Access Journals (Sweden)

    Abdul Qayyum Ather

    2010-06-01

    Full Text Available In the title compound, C12H15N5, the piperidine ring adopts a chair conformation with the substituent C atom in an equatorial site and the dihedral angle between the pyridazine and pyrazole ring planes is 10.36 (2°.

  14. Design, Synthesis and Biological Activities of Novel Benzoyl Hydrazines Containing Pyrazole

    Institute of Scientific and Technical Information of China (English)

    闫涛; 于淑晶; 刘鹏飞; 刘卓; 王宝雷; 熊丽霞; 李正名

    2012-01-01

    In search of environmentally benign compounds with high biological activity, low toxicity and low resistance, 8 novel benzoyl hydrazines containing pyrazole were designed and synthesized. All compounds were characterized by I H NMR spectra and HRMS. The preliminary results of biological activity assessment indicated that most of title compounds exhibited certain insecticidal activities against M),thimna separata Walker at 200 mg L-1 but excellent fungicidal activities against six fungus at 50 mg L-1, which were better than the control.

  15. Regioselective Synthesis and Base Catalyzed Transacylation of Substituted 1H-Pyrazole-4-carboxamides

    Institute of Scientific and Technical Information of China (English)

    REN,Jun(任军); ZHANG,Xiao-Hong(张晓弘); LIU,Ying(刘莹); CHEN,Wei-Qiang(陈卫强); JIN,Gui-Yu(金桂玉)

    2002-01-01

    New type of substituted 1H-pyrazole-4-carboxamides were obtained by regioselective synthesis under the catalysis of different bases. The structures of the title compounds were confirmed by elemental analysis, 1H NMR, IR, MS and X-ray crystallogaphy. Compounds 1 were transacylated into their corresponding amides 3 in the presence of sodium hydride.Preliminary bioassays indicated that some compounds showed fungicidal activities against Rhizoctonia solani and Sclerotinia sclerotiorum.

  16. Synthesis and Biological Evaluation of Novel Aryl-2H-pyrazole Derivatives as Potent Non-purine Xanthine Oxidase Inhibitors.

    Science.gov (United States)

    Sun, Zhi-Gang; Zhou, Xiao-Jing; Zhu, Ming-Li; Ding, Wen-Ze; Li, Zhen; Zhu, Hai-Liang

    2015-01-01

    A series of aryl-2H-pyrazole derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro as potent xanthine oxidase inhibitors. Among them, 2 aryl-2H-pyrazole derivatives showed significant inhibitory activities against xanthine oxidase. Compound 19 emerged as the most potent xanthine oxidase inhibitor (IC50=9.8 µM) in comparison with allopurinol (IC50=9.5 µM). The docking study revealed that compound 19 might have strong interactions with the active site of xanthine oxidase. This compound is thus a new candidate for further development for the treatment of gout.

  17. Design, Synthesis and Bioactivities of Novel Dichloro-Allyloxy-Phenol-Containing Pyrazole Oxime Derivatives.

    Science.gov (United States)

    Dai, Hong; Ye, Linyu; Zhuang, Huiyang; Dai, Baojiang; Fang, Yuan; Shi, Yujun

    2015-12-08

    In this study, in order to find novel biologically active pyrazole oxime compounds, a number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized according to the method of active group combination. All of the target compounds were confirmed by ¹H-NMR, (13)C-NMR and elemental analysis. In addition, bioassays showed that all of the newly synthesized compounds had no acaricidal activity against Tetranychus cinnabarinus and low insecticidal activity against Aphis craccivora at tested concentrations. However, most of them displayed excellent insecticidal activity against Oriental armyworm at a concentration of 500 μg/mL, and some designed compounds still exhibited potent insecticidal activity against Oriental armyworm even at the dose of 20 μg/mL, especially compounds 7f, 7n and 7p had 100%, 90% and 90% inhibition rates, respectively, which were comparable to that of the control pyridalyl.

  18. Novel pyrazole integrated 1,3,4-oxadiazoles: synthesis, characterization and antimicrobial evaluation.

    Science.gov (United States)

    Ningaiah, Srikantamurthy; Bhadraiah, Umesha K; Doddaramappa, Shridevi D; Keshavamurthy, Shubakara; Javarasetty, Chethan

    2014-01-01

    A novel series of 2-(5-methyl-1,3-diphenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazoles 7(a-m) were synthesized either by cyclization of N'-benzoyl-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 4a using POCl3 at 120°C or by oxidative cyclization of hydrazones derived from various arylaldehyde and (E)-N'-benzylidene-5-methyl-1,3-diphenyl-1H-pyrazole-4-carbohydrazide 5(a-d) using chloramine-T as oxidant. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Among the synthesized compounds, compound 7m emerged as an effective antimicrobial agent, while compounds 7d, 7f, 7i and 7l showed good to moderate activity. The minimum inhibitory concentration of the compounds was in the range of 20-50μgmL(-1) against bacteria and 25-55μgmL(-1) against fungi. The title compounds represent a novel class of potent antimicrobial agents.

  19. Synthesis, Characterization and Biological Activities of N-Acyl-3-(3-pyridyl)-5-aryl-pyrazoles

    Institute of Scientific and Technical Information of China (English)

    KANG Yan-fang; WANG Dun-jia; XU Ben-po; WEI Xian-hong; ZHENG Jing

    2013-01-01

    Ten novel N-acyl-3-(3-pyridyl)-5-aryl-pyrazoles were synthesized by Claisen condensation of the aryl methyl ketones with ethyl nicotinate,the cyclization with hydrazine hydrate and the N-acylation with acyl chloride in turn.The structures of all the compounds synthesized were confirmed by means of Fourier transform infrared(FTIR),1H NMR,mass spectroscopy and elemental analysis.The biological activities of the title compounds were examined by disc diffusion method against Escherichia coli,Staphylococcus aureus,Pyricularia oryzae and Rhizoctnia solani.All the N-acyl-3-(3-pyridyl)-5-aryl-pyrazoles exhibited a certain degree of antibacterial and antifungal activities.Comparatively,compounds 3c and 3d exhibited much significant antibacterial and antifungal activities than the other pyrazole derivatives.

  20. Chemical consequences of pyrazole orientation in Ru(II) complexes of unsymmetric quinoline-pyrazole ligands.

    Science.gov (United States)

    Hedberg Wallenstein, Joachim; Fredin, Lisa A; Jarenmark, Martin; Abrahamsson, Maria; Persson, Petter

    2016-08-07

    A series of homoleptic Ru(II) complexes including the tris-bidentate complexes of a new bidentate ligand 8-(1-pyrazol)-quinoline (Q1Pz) and bidentate 8-(3-pyrazol)-quinoline (Q3PzH), as well as the bis-tridentate complex of bis(quinolinyl)-1,3-pyrazole (DQPz) was studied. Together these complexes explore the orientation of the pyrazole relative to the quinoline. By examining the complexes structurally, photophysically, photochemically, electrochemically, and computationally by DFT and TD-DFT, it is shown that the pyrazole orientation has a significant influence on key properties. In particular, its orientation has noticeable effects on oxidation and reduction potentials, photostability and proton sensitivity, indicating that [Ru(Q3PzH)3](2+) is a particularly good local environment acidity-probe candidate.

  1. Facile Route to Tetrasubstituted Pyrazoles Utilizing Ceric Ammonium Nitrate.

    Science.gov (United States)

    Devery, James J; Mohanta, Pramod K; Casey, Brian M; Flowers, Robert A

    2009-01-01

    A convenient approach for the synthesis of tetrasubstituted pyrazoles is described. The method involves the treatment of 1,3-diketones and allyltrimethylsilane with CAN followed by cerium-catalyzed addition of substituted hydrazines to construct pyrazoles in good yields.

  2. Zeolite-catalyzed methylation of pyrazole with dimethyl carbonate

    Energy Technology Data Exchange (ETDEWEB)

    Born, S.; Weichert, J.; Hartmann, M.; Ernst, S. [Dept. of Chemistry, Chemical Technology, Kaiserslautern Univ. (Germany)

    2002-07-01

    The present paper describes our attempts to explore the potential of acidic and nonacidic zeolites for the alkylation of pyrazole with dimethyl carbonate to 1-methyl pyrazole, which is a useful intermediate in the manufacture of pharmaceuticals and pesticides. (orig.)

  3. Synthesis and Antimicrobial Evaluation of Some Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed Mahrous Hamada

    2012-04-01

    Full Text Available Reaction of a series of (E-3-phenyl-4-(p-substituted phenyl-3-buten-2-ones with p-sulfamylphenyl hydrazine in glacial acetic acid gave the corresponding hydrazones, subsequent treatment of which with 30% HCl afforded pyrazole-1-sulphonamides. On the other hand, refluxing of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide in ethanol containing a few drops of acetic acid gave pyrazoline-1-thiocarboxamides and isonicotinoyl pyrazolines, respectively. The structures of the synthesized compounds were determined on the basis of their elemental analyses and spectroscopic data. The antimicrobial activity of the newly isolated heterocyclic compounds was evaluated against Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed a moderate degree of potent antimicrobial activity.

  4. Synthesis and Crystal Structure of 5-Diazo-4-ethoxycarbonyl-3-methylthio Pyrazol

    Institute of Scientific and Technical Information of China (English)

    邹小毛; 胡方中; 杨华铮

    2004-01-01

    The crystal of the title compound, 5-diazo-4-ethoxycarbonyl-3-methylthio pyrazole, has been prepared and determined by X-ray diffraction. The crystal belongs to the monoclinic system, space group C2/c with a = 29.174(8), b = 4.7592(12), c = 15.956(4) A, β =117.632(4)°, C7H8N4O2S, Mr = 212.23, V = 1962.7(9) A3, Z = 8, Dx = 1.436 g/cm3, S = 1.000,μ(MoKα) = 0.31 mm-1, T = 298(2) K, F(000) = 880, R = 0.0658 and wR = 0.1741 for 1091independent reflections with I ≥ 2σ(I). The crystal of the title compound is formed with π-πinteractions through electrostatic attractions. Moreover, no HSO4- exists in the crystal structure.Therefore, only diazo pyrazole was obtained rather than either diazonium salt of the corresponding pyrazole or diazoaminopyrazole when 5-amino-4-ethoxycarbonyl-3-methylthio pyrazole was diazotized with sodium nitrite, catalyzed by sulfuric acid at 0 ℃.

  5. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Mauricio S. dos; Gomes, Adriana O.; Bernardino, Alice M.R.; Souza, Marcos C. de, E-mail: alicerolim@globo.co [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Programa de Pos-Graduacao em Quimica Organica; Khan, Misbahul A. [The Islamia University of Bahawalpur (Pakistan). Chemistry Dept.; Brito, Monique A. de [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Fac. de Farmacia. Lab. de Quimica Medicinal Computacional; Castro, Helena C.; Abreu, Paula A. [Universidade Federal Fluminense (LABioMol/GCM/UFF), Niteroi, RJ (Brazil). Inst. de Biologia. Lab. de Antibioticos, Bioquimica e Modelagem Molecular; Rodrigues, Carlos R. [Universidade Federal do Rio de Janeiro (ModMol/UFRJ), RJ (Brazil). Fac. de Farmacia. Lab. de Modelagem Molecular e QSAR; Leo, Rosa M.M. de; Leon, Leonor L.; Canto-Cavalheiro, Marilene M. [Fundacao Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto Oswaldo Cruz. Lab. de Bioquimica de Tripanosomatideos

    2011-07-01

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  6. Current status of pyrazole and its biological activities.

    Science.gov (United States)

    Naim, Mohd Javed; Alam, Ozair; Nawaz, Farah; Alam, Md Jahangir; Alam, Perwaiz

    2016-01-01

    Pyrazole are potent medicinal scaffolds and exhibit a full spectrum of biological activities. This review throws light on the detailed synthetic approaches which have been applied for the synthesis of pyrazole. This has been followed by an in depth analysis of the pyrazole with respect to their medical significance. This follow-up may help the medicinal chemists to generate new leads possessing pyrazole nucleus with high efficacy.

  7. Discovery of pyrazole as C-terminus of selective BACE1 inhibitors.

    Science.gov (United States)

    Zou, Yiquan; Xu, Lei; Chen, Wuyan; Zhu, Yiping; Chen, Tiantian; Fu, Yan; Li, Li; Ma, Lanping; Xiong, Bing; Wang, Xin; Li, Jian; He, Jianhua; Zhang, Haiyan; Xu, Yechun; Li, Jia; Shen, Jingkang

    2013-10-01

    We recently discovered and reported dual inhibitor 5 of AChE and BACE1 with N-benzylpiperidine ethyl as C-terminus. Compound 5 showed potent inhibitory activities for BACE1, and could reduce endogenous Aβ1-40 production in APP transgenic mice. In present work, we rapidly identified substituted triazole as the C-terminus of compound 5 by replacing the benzylpiperidine ethyl group with click chemistry and tested these synthesized compounds by in situ screening assay. As revealed by the crystal structures of BACE1 in complex with our triazole compound 12, we found that Pro70 and Thr72 located in the flap region were the critical components for binding with these inhibitors. With the aid of the crystal structure, a new series of five-membered heterocyclic compounds was prepared in order to explore the structure-activity relationship (SAR) of this class of molecules. From these efforts, pyrazole was discovered as a novel C-terminus of BACE1 inhibitors. After further modification of pyrazole with variable substituents, compound 37 exhibited good potency in enzyme inhibition assay (IC50=0.025 μM) and compound 33 showed moderate inhibition effects on Aβ production of APP transfected HEK293 cells. Moreover, these pyrazole derivatives demonstrated good selectivity versus cathepsin D. Our results indicated that the vicinity of Pro70 and Thr72 might be utilized as a subsite, and the discovered pyrazole derivatives might provide useful hints for developing novel BACE1 inhibitors as anti-AD drugs.

  8. Synthesis and Biological Activity of New Pyrethroid Acid Oxime-esters Containing Pyrazole Ring

    Institute of Scientific and Technical Information of China (English)

    MA Jun-an; HUANG Run-qiu; FENG Lei; SONG Jian; QIU De-wen

    2003-01-01

    A series of compounds containing oxime-ester linkage and pyrazole ring(in place of the ester linkage and the alcohol moiety in pyrethroid ester) was designed and synthesized. The structures of all the compounds prepared were confirmed by 1H NMR and MS spectroscopy as well as elemental analyses. The bioassay data of those compounds against tobacco mosaic virus(TMV), cucumber mosaic virus(CMV), potato virus X(PVX) and potato virus Y(PVY) were presented. Among them compound 6i was found to possess significant plant antiviral activities. But all the compounds showed low insecticidal and acaricidal activities.

  9. Synthesis and Herbicidal Activity of 5-Heterocycloxy-3-substituted-1-(3-trifluoromethyl)phenyl-1H-pyrazole

    Institute of Scientific and Technical Information of China (English)

    XU Han; HU Xu-hong; ZOU Xiao-mao; ZHU You-quan; LIU Bin; HU Fang-zhong; YANG Hua-zheng

    2012-01-01

    The authors synthesized a series of novel 5-heterocycloxy-3-substituted-1-(3-trifluoromethyl)phenyl-1H- pyrazole derivatives.Herbicidal activities of the two intermediate compounds and thirteen target compounds were evaluated via Brassica napus and Echinochloa crusgalli(L.) Beauv tests.Bioassay results show that some of the compounds exhibit better inhibiting activities against Brassica napus and some of the compounds exhibit bleaching activities against Echinochloa crusgalli(L.) Beauv at 100 μg/mL.

  10. Discovery of a novel series of phenyl pyrazole inner salts based on fipronil as potential dual-target insecticides.

    Science.gov (United States)

    Jiang, Dingxin; Zheng, Xiaohua; Shao, Guang; Ling, Zhang; Xu, Hanhong

    2014-04-23

    A series of novel phenyl pyrazole inner salt derivatives based on fipronil were designed and synthesized in the search for dual-target insecticides. These compounds were designed to target two families of nicotinic acetylcholine receptors and γ-aminobutyric acid receptors. The insecticidal activities of the new compounds against diamondback moth (Plutella xylostella) were evaluated. The results of bioassays indicated that most of the inner salts showed moderate to high activities, of which the phenyl pyrazole inner salts containing quinoline had excellent biological activity. Previous structure-activity relationship studies revealed that a suitable structure of the quaternary ammonium salts was critical for the bioactivity of phenyl pyrazole inner salts, which contribute to exposing the cationic nitrogen to bind to the receptor (for instance, nicotinic acetylcholine receptors) and possibly interact with the receptor via hydrogen bonding and cooperative π-π interaction. The present work demonstrates that the insecticidal potency of phenyl pyrazole inner salts holds promise for the development new dual-target phenyl pyrazole insecticides.

  11. Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist/inverse agonist properties.

    Science.gov (United States)

    Deiana, Valeria; Gómez-Cañas, María; Pazos, M Ruth; Fernández-Ruiz, Javier; Asproni, Battistina; Cichero, Elena; Fossa, Paola; Muñoz, Eduardo; Deligia, Francesco; Murineddu, Gabriele; García-Arencibia, Moisés; Pinna, Gerard A

    2016-04-13

    Previous studies have investigated the relevance and structure-activity relationships (SARs) of pyrazole derivatives in relation with cannabinoid receptors, and the series of tricyclic 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent CB2 receptor ligands. In the present study, novel 1,4-dihydroindeno[1,2-c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl or a cyclohexyl substituent were designed and synthesized to evaluate the influence of these structural modifications towards CB1 and CB2 receptor affinities. Among these derivatives, compound 15 (6-cyclopropyl-1-(2,4-dichlorophenyl)-N-(adamantan-1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide) showed the highest CB2 receptor affinity (Ki = 4 nM) and remarkable selectivity (KiCB1/KiCB2 = 2232), whereas a similar affinity, within the nM range, was seen for the fenchyl derivative (compound 10: Ki = 6 nM), for the bornyl analogue (compound 14: Ki = 38 nM) and, to a lesser extent, for the aminopiperidine derivative (compound 6: Ki = 69 nM). Compounds 10 and 14 were also highly selective for the CB2 receptor (KiCB1/KiCB2 > 1000), whereas compound 6 was relatively selective (KiCB1/KiCB2 = 27). The four compounds were also subjected to GTPγS binding analysis showing antagonist/inverse agonist properties (IC50 for compound 14 = 27 nM, for 15 = 51 nM, for 10 = 80 nM and for 6 = 294 nM), and this activity was confirmed for the three more active compounds in a CB2 receptor-specific in vitro bioassay consisting in the quantification of prostaglandin E2 release by LPS-stimulated BV2 cells, in the presence and absence of WIN55,212-2 and/or the investigated compounds. Modelling studies were also conducted with the four compounds, which conformed with the structural requirements stated for the binding of antagonist compounds to the human CB2 receptor.

  12. Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines.

    Science.gov (United States)

    Nitulescu, George Mihai; Draghici, Constantin; Olaru, Octavian Tudorel; Matei, Lilia; Ioana, Aldea; Dragu, Laura Denisa; Bleotu, Coralia

    2015-09-01

    We designed and synthesized new pyrazole thiourea chimeric derivatives and confirmed their structures by NMR and IR spectra. Apoptotic effects were studied in human cancer cells. The N-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-N'-(3-bromophenyl)-thiourea compound (4b) exhibited the highest apoptosis-inducing effect. Compound 4b and the thiazole derivatives, 5b and 6b, increased the expression of tumor necrosis factor receptors TRAIL-R2 and TRAIL-R1, accompanied by down-modulation of pro-caspase 3 levels, and the augmentation of cleaved caspase 3. They also reduced the levels of apoptosis inhibitory proteins and the expression of the heat-shock proteins Hsp27 and Hsp70. All the tested pyrazole derivatives induced a concentration-dependent increase of cells in G2/M phases. The analysis of the experimental data indicates the reduction of Akt phosphorylation as the most probable cellular mechanism of action for the tested compounds. The in vitro study indicated that compound 4b could be a promising anti-cancer drug, to be further developed in animal models of cancer.

  13. Synthesis and Liquid Crystalline Properties of 3-Substituted Pentane-2,4-dione, Pyrazole and Isoxazole Derivatives

    Institute of Scientific and Technical Information of China (English)

    HAN,Jie; GUO,Hui; WANG,Xiao-Guang; PANG,Mei-Li; MENG,Ji-Ben

    2007-01-01

    The γ-substituted β-diketonate 2,4-dioxo-3-pentyl 4-[4-(n-octyloxy)cinnamoyl]oxybenzoate 1 and its pyrazole and isoxazole derivatives (2 and 3 respectively) have been synthesized and characterized by the spectroscopic methods and elemental analysis. The mesogenic properties of these compounds have been studied by polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). A monotropic nematic mesophase was observed for theβ-diketonate 1, in contrast, the pyrazole 2 displays an enantiotropic smectic A and isoxazole 3 exhibits an enantiotropic nematic mesophase. The relationship between the structure and liquid crystalline properties has also been discussed.

  14. Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4-Hydroxyphenylpyruvate dioxygenase inhibitors.

    Science.gov (United States)

    Xu, Yu-Ling; Lin, Hong-Yan; Ruan, Xu; Yang, Sheng-Gang; Hao, Ge-Fei; Yang, Wen-Chao; Yang, Guang-Fu

    2015-03-06

    4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia. Inhibition of HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione (NTBC), has been available for clinical use so far. In the present study, a series of novel pyrazole-benzimidazolone hybrids were designed, synthesized and evaluated as potent human HPPD inhibitors. Most of the new compounds displayed significant inhibitory activity against the recombinant human HPPD. Moreover, compound 9l was identified as the most potent candidate with IC50 value of 0.021 μM against recombinant human HPPD, about 3-fold more potent than NTBC. Thus the pyrazole-benzimidazolone hybrid has great potential to be further developed for the treatment of type I tyrosinemia.

  15. 3-Dimensional quantitative structure-activity relationship and molecular docking studies of tetrasubstituted pyrazole derivatives as inhibitors of cyclooxygenase-2

    Directory of Open Access Journals (Sweden)

    Kulwinder Singh

    2014-04-01

    Conclusion: The present study shall help in rational drug design and synthesis of new selective COX-2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between COX-2 and the novel tetrasubstituted pyrazole derivative compounds. [Int J Res Med Sci 2014; 2(2.000: 612-619

  16. Crystal structure of [1-(3-chlorophenyl-5-hydroxy-3-methyl-1H-pyrazol-4-yl](p-tolylmethanone

    Directory of Open Access Journals (Sweden)

    Balbir Kumar

    2015-05-01

    Full Text Available In the title compound C18H15ClN2O2, the dihedral angles between the central pyrazole ring and the pendant chlorobenzene and p-tolyl rings are 17.68 (10 and 51.26 (12°, respectively. An intramolecular O—H...O hydrogen bond is observed, which closes an S(6 ring.

  17. 1-[2,6-Dichloro-4-(trifluoromethylphenyl]-5-iodo-4-trifluoromethylsulfinyl-1H-pyrazole-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Ding-Xin Jiang

    2009-08-01

    Full Text Available In the title compound, C12H2Cl2F6IN3OS, the dihedral angle between the planes of the benzene and pyrazole rings is 77.8 (2°. In the crystal, a short I...N contact of 2.897 (5 Å occurs.

  18. Ethyl 3-bromo-1-(3-chloro-2-pyridyl-4,5-dihydro-1H-pyrazole-5-carboxylate

    Directory of Open Access Journals (Sweden)

    Bin Li

    2009-12-01

    Full Text Available The title compound, C11H11BrClN3O2, contains two molecules in the asymmetric unit in which the dihedral angles between the pyrazole and pyridine rings are 30.0 (2 and 22.3 (2°.

  19. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities

    OpenAIRE

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M.; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-01-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values o...

  20. Synthetic approaches, structure activity relationship and biological applications for pharmacologically attractive pyrazole/pyrazoline-thiazolidine-based hybrids.

    Science.gov (United States)

    Havrylyuk, Dmytro; Roman, Olexandra; Lesyk, Roman

    2016-05-04

    The features of the chemistry of 4-thiazolidinone and pyrazole/pyrazolines as pharmacologically attractive scaffolds were described in a number of reviews in which the main approaches to the synthesis of mentioned heterocycles and their biological activity were analyzed. However, the pyrazole/pyrazoline-thiazolidine-based hybrids as biologically active compounds is poorly discussed in the context of pharmacophore hybrid approach. Therefore, the purpose of this review is to summarize the data about the synthesis and modification of heterocyclic systems with thiazolidine and pyrazoline or pyrazole fragments in molecules as promising objects of modern bioorganic and medicinal chemistry. The description of biological activity was focused on SAR analysis and mechanistic insights of mentioned hybrids.

  1. Pyrazole carboxamides and carboxylic acids as protein kinase inhibitors in aberrant eukaryotic signal transduction

    DEFF Research Database (Denmark)

    Persson, Tobias; Yde, Christina W.; Rasmussen, Jakob Ewald

    2007-01-01

    Densely functionalised pyrazole carboxamides and carboxylic acids were synthesised in an expedient manner through saponification and transamidation, respectively, of ester-functionalised pyrazoles. This synthetic protocol allowed for three diversifying steps in which appendages on the pyrazole...

  2. 3-Methyl-5-(4-methylpiperazin-1-yl-1-phenyl-1H-pyrazole-4-carbaldehyde

    Directory of Open Access Journals (Sweden)

    V. M. Sunitha

    2016-11-01

    Full Text Available In the title compound, C16H20N4O, the dihedral angle between the pyrazole and phenyl rings is 53.86 (12°. The piperazine ring adopts a chair conformation with the exocyclic N—C bonds in equatorial orientations. In the crystal, molecules are linked by very weak C—H...O hydrogen bonds to generate [010] C(8 chains, with adjacent molecules related by translation.

  3. N′-[(1E-4-Bromobenzylidene]-5-phenyl-1H-pyrazole-3-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Khalid Karrouchi

    2016-05-01

    Full Text Available In the title compound, C17H13BrN4O, the dihedral angles between the pyrazole ring and the pedant phenyl and bromobenzene rings are 21.61 (11 and 28.09 (11°, respectively. In the crystal, N—H...O hydrogen bonds link the molecules into [010] chains, which are reinforced by C—H...O interactions.

  4. Crystal structure of N′-diphenylmethylidene-5-methyl-1H-pyrazole-3-carbohydrazide

    Directory of Open Access Journals (Sweden)

    Khalid Karrouchi

    2015-11-01

    Full Text Available In the title compound, C18H16N4O, the planes of the phenyl rings are approximately perpendicular to each other [dihedral angle = 78.07 (8°] and form dihedral angles of 56.43 (8 and 24.59 (8° with the pyrazole ring. In the crystal, molecules are linked by N—H...O hydrogen bonds to form one-dimensional chains parallel to the [010] direction.

  5. Bis[bis(3,5-dimethyl-1H-pyrazol-1-ylborato]cobalt(II

    Directory of Open Access Journals (Sweden)

    Moayad Hossaini Sadr

    2011-07-01

    Full Text Available The asymmetric unit of the title compound, [Co(C10H16BN42], comprises one unit of the complex. The geometry around the CoII ion is a distorted tetrahedron. The dihedral angles between the pyrazole rings in the two ligands are 47.19 (15 and 47.20 (16°, while that between the coordination planes is 79.77 (7°.

  6. (4-Bromo-3,5-dimethyl-1H-pyrazol-1-yl(2,6-difluorophenylmethanone

    Directory of Open Access Journals (Sweden)

    Xiang-Dong Mei

    2010-01-01

    Full Text Available There are two molecules in the asymmetric unit of the title compound, C12H9BrF2N2O. They have very similar conformations: the dihedral angles between their pyrazole and benzene ring systems are 78.4 (3 and 78.6 (4°. In the crystal, weak aromatic π–π stacking [centroid–centroid separation = 3.696 (5 Å] helps to establish the packing.

  7. 2-[3-(4-Methoxyphenyl-1-phenyl-1H-pyrazol-5-yl]phenol

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available The title compound, C22H18N2O2, was derived from 1-(2-hydroxyphenyl-3-(4-methoxyphenylpropane-1,3-dione. The central pyrazole ring forms dihedral angles of 16.83 (5, 48.97 (4 and 51.68 (4°, respectively, with the methoxyphenyl, phenyl and hydroxyphenyl rings. The crystal packing is stabilized by O—H...N hydrogen bonding.

  8. A novel, potent, oral active and safe antinociceptive pyrazole targeting kappa opioid receptors.

    Science.gov (United States)

    Trevisan, Gabriela; Rossato, Mateus F; Walker, Cristiani I B; Oliveira, Sara M; Rosa, Fernanda; Tonello, Raquel; Silva, Cássia R; Machado, Pablo; Boligon, Aline A; Martins, Marcos A P; Zanatta, Nilo; Bonacorso, Hélio G; Athayde, Margareth L; Rubin, Maribel A; Calixto, João B; Ferreira, Juliano

    2013-10-01

    Pyrazole compounds are an intriguing class of compounds with potential analgesic activity; however, their mechanism of action remains unknown. Thus, the goal of this study was to explore the antinociceptive potential, safety and mechanism of action of novel 1-pyrazole methyl ester derivatives, which were designed by molecular simplification, using in vivo and in vitro methods in mice. First, tree 1-pyrazole methyl ester derivatives (DMPE, MPFE, and MPCIE) were tested in the capsaicin test and all presented antinociceptive effect; however the MPClE (methyl 5-trichloromethyl-3-methyl-1H-pyrazole-1-carboxylate) was the most effective. Thus, we selected this compound to assess the effects and mechanisms in subsequent pain models. MPCIE produced antinociception when administered by oral, intraperitoneal, intrathecal and intraplantar routes and was effective in the capsaicin and the acetic acid-induced nociception tests. Moreover, this compound reduced the hyperalgesia in diverse clinically-relevant pain models, including postoperative, inflammatory, and neuropathic nociception in mice. The antinociception produced by orally administered MPClE was mediated by κ-opioid receptors, since these effects were prevented by systemically pre-treatment with naloxone and the κ-opioid receptor antagonist nor-binaltorphimine. Moreover, MPCIE prevented binding of the κ-opioid ligand [(3)H]-CI-977 in vitro (IC₅₀ of 0.68 (0.32-1.4) μM), but not the TRPV1 ([(3)H]-resiniferatoxin) or the α₂-adrenoreceptor ([(3)H]-idazoxan) binding. Regarding the drug-induced side effects, oral administration of MPClE did not produce sedation, constipation or motor impairment at its active dose. In addition, MPCIE was readily absorbed after oral administration. Taken together, these results demonstrate that MPClE is a novel, potent, orally active and safe analgesic drug that targets κ-opioid receptors.

  9. Discovery of a series of 2-(1H-pyrazol-1-yl)pyridines as ALK5 inhibitors with potential utility in the prevention of dermal scarring.

    Science.gov (United States)

    Boys, Mark L; Bian, Feng; Kramer, James B; Chio, Christopher L; Ren, Xiao-Dan; Chen, Huifen; Barrett, Stephen D; Sexton, Karen E; Iula, Donna M; Filzen, Gary F; Nguyen, Maria N; Angell, Paul; Downs, Victoria L; Wang, Zhi; Raheja, Neil; Ellsworth, Edmund L; Fakhoury, Stephen; Bratton, Larry D; Keller, Paul R; Gowan, Richard; Drummond, Elena M; Maiti, Samarendra N; Hena, Mostofa A; Lu, Leroy; McConnell, Patrick; Knafels, John D; Thanabal, Venkataraman; Sun, Fang; Alessi, Diane; McCarthy, Ann; Zhang, Erli; Finzel, Barry C; Patel, Sneha; Ciotti, Susan M; Eisma, Rone; Payne, N A; Gilbertsen, Richard B; Kostlan, Catherine R; Pocalyko, David J; Lala, Deepak S

    2012-05-15

    A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Synthesis and biofilm formation reduction of pyrazole-4-carboxamide derivatives in some Staphylococcus aureus strains.

    Science.gov (United States)

    Cascioferro, Stella; Maggio, Benedetta; Raffa, Demetrio; Raimondi, Maria Valeria; Cusimano, Maria Grazia; Schillaci, Domenico; Manachini, Barbara; Plescia, Fabiana; Daidone, Giuseppe

    2016-11-10

    The ability of several N-phenyl-1H-pyrazole-4-carboxamide derivatives and other pyrazoles opportunely modified at the positions 3, 4 and 5, to reduce the formation of the biofilm in some Staphylococcus aureus strains (ATCC 29213, ATCC 25923 and ATCC 6538) were investigated. All the tested compounds were able, although to a different extent, to reduce the biofilm formation of the three bacterial strains considered. Among these, the 1-(2,5-dichlorophenyl)-5-methyl-N-phenyl-1H-pyrazole-4-carboxamide 14 resulted as the best inhibitor of biofilm formation showing an IC50 ranging from 2.3 to 32 μM, against all the three strains of S. aureus. Compound 14 also shows a good protective effect in vivo by improving the survival of wax moth larva (Galleria mellonella) infected with S. aureus ATCC 29213. These findings indicate that 14d is a potential lead compound for the development of new anti-virulence agents against S. aureus infections.

  11. Structure-activity relationships of pyrazole derivatives as potential therapeutics for immune thrombocytopenias.

    Science.gov (United States)

    Purohit, Meena K; Chakka, Sai Kumar; Scovell, Iain; Neschadim, Anton; Bello, Angelica M; Salum, Noruê; Katsman, Yulia; Bareau, Madeleine C; Branch, Donald R; Kotra, Lakshmi P

    2014-05-01

    Idiopathic or immune thrombocytopenia (ITP) is a serious clinical disorder involving the destruction of platelets by macrophages. Small molecule therapeutics are highly sought after to ease the burden on current therapies derived from human sources. Earlier, we discovered that dimers of five-membered heterocycles exhibited potential to inhibit phagocytosis of human RBCs by macrophages. Here, we reveal a structure-activity relationship of the bis-pyrazole class of molecules with -C-C-, -C-N- and -C-O- linkers, and their evaluation as inhibitors of phagocytosis of antibody-opsonized human RBCs as potential therapeutics for ITP. We have uncovered three potential candidates, 37, 47 and 50, all carrying a different linker connecting the two pyrazole moieties. Among these compounds, hydroxypyrazole derivative 50 is the most potent compound with an IC50 of 14 ± 9 μM for inhibiting the phagocytosis of antibody-opsonized human RBCs by macrophages. None of the compounds exhibited significant potential to induce apoptosis in peripheral blood mononuclear cells (PBMCs). Current study has revealed specific functional features, such as up to 2-atom spacer arm and alkyl substitution at one of the N(1) positions of the bivalent pyrazole core to be important for the inhibitory activity.

  12. Novel pyrazole derivatives as neutral CB₁ antagonists with significant activity towards food intake.

    Science.gov (United States)

    Manca, Ilaria; Mastinu, Andrea; Olimpieri, Francesca; Falzoi, Matteo; Sani, Monica; Ruiu, Stefania; Loriga, Giovanni; Volonterio, Alessandro; Tambaro, Simone; Bottazzi, Mirko Emilio Heiner; Zanda, Matteo; Pinna, Gérard Aimè; Lazzari, Paolo

    2013-04-01

    In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1 antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead CB1 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((±)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(Z)-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake.

  13. Design and Synthesis of Novel Pyrazole-based Lp-PLA2 Inhibitors%Design and Synthesis of Novel Pyrazole-based Lp-PLA2 Inhibitors

    Institute of Scientific and Technical Information of China (English)

    王毅; 徐为人; 邵华; 谢亚非; 王建武

    2011-01-01

    A series of novel pyrazole-based lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors have been de- signed and synthetized by a variety of acetophenones via a 10-step convergent approach. The synthetic approach is carefully optimized, and an unsuccessful alternative route is also discussed. The in vitro biological activity reveals that all the synthesized compounds are potent Lp-PLA2 inhibitors with compound 13b being the most potent one (Lp-PLA2, IC50= 1.5 nmol/L).

  14. Synthesis and biological evaluation of novel formyl-pyrazoles bearing coumarin moiety as potent antimicrobial and antioxidant agents.

    Science.gov (United States)

    Nagamallu, Renuka; Kariyappa, Ajay Kumar

    2013-12-01

    A series of coumarin appended formyl-pyrazoles 14-18 were synthesized by a simple and accessible approach. The reaction of 8-acetyl-4-methyl-7-hydroxy coumarin 3 and phenyl hydrazine hydrochlorides 4-8 produces the intermediate compounds 8-acetyl-4-methyl-7-hydroxy coumarin hydrazones 9-13. The reaction of compounds 9-13 and DMF in the presence of POCl3 yielded formyl-pyrazoles bearing coumarin moiety 14-18 in good yield. The synthesized new compounds 14-18 and the intermediates 8-acetyl-4-methyl-7-hydroxy coumarin hydrazones 9-13 prepared were screened in vitro for their antibacterial, antifungal antioxidant activities. The compounds 12 and 17 having chloro substitution exhibited promising antifungal and antibacterial activity against the different organisms tested. The compound 17 showed remarkable DPPH radical scavenging ability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. 4-Methyl-5-phenyl-1H-pyrazol-3-ol

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    Tara Shahani

    2010-07-01

    Full Text Available The title compound, C10H10N2O, crystallizes with two independent molecules in the asymmetric unit, having closely comparable geometries. The dihedral angles between the 1H-pyrazole and benzene rings in the two molecules are 39.57 (14 and 41.95 (13°. The two molecules are each connected to neighbouring molecules by pairs of intermolecular O—H...N hydrogen bonds, forming dimers with R22(8 ring motifs. These dimers are further linked into R44(10 ring motifs by intermolecular N—H...O hydrogen bonds, forming chains along [101]. The crystal structure is further stabilized by a C—H...π interaction.

  16. Excited state tautomerization of 7-azaindole catalyzed by pyrazole

    Science.gov (United States)

    Karmakar, Shreetama; Mukherjee, Moitrayee; Chakraborty, Tapas

    2013-03-01

    Pyrazole, a five member cyclic azole, is reported here as an efficient catalyst for excited state tautomeric conversion of 7-azaindole. In hydrocarbon solution the two compounds efficiently form a doubly hydrogen-bonded 1:1 cyclic complex whose association constant value is found comparable with 7-azaindole dimerization constant, and according to B3LYP/6-311G++∗∗ calculation the binding energies of the complex and dimer are nearly same. In the excited state (S1), the TDDFT calculation predicts tautomer of the complex to be 13.4 kcal/mol more stable than normal form. Fluorescence spectra reveal that upon UV excitation the complex emits exclusively from the tautomeric form.

  17. Syntheses, Characterization and Antimicrobial Evaluation of Some 1, 3, 5-Trisubustituted Pyrazole Derivatives

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    Vertika Gautam

    2010-01-01

    Full Text Available A series of 1, 3, 5-trisubustituted pyrazole derivatives were synthesized and screened for antimicrobial activity. The compounds (2j-o were evaluated against two gram-positive and two gram-negative bacteria and one fungus, at concentrations of 10 µg/mL and 50 µg/mL. The compounds were founds to be inactive against P. aeruginosa and A. niger but exhibited moderate activity against B. subtilis, E. coli and S. aureus. It can be concluded that the newly synthesized compounds possess promising antimicrobial activity.

  18. Synthesis, characterization, electrochemical studies and antitumor activity of some new chalcone analogues containing ferrocenyl pyrazole moiety.

    Science.gov (United States)

    Ratković, Zoran; Juranić, Zorica D; Stanojković, Tatjana; Manojlović, Dragan; Vukićević, Rastko D; Radulović, Niko; Joksović, Milan D

    2010-02-01

    A series of new alpha,beta-unsaturated conjugated ketones containing ferrocenyl pyrazole unit were synthesized and fully characterized by IR and NMR spectroscopy. Electrochemical characterization of subject compounds was performed by means of cyclic voltametry. The in vitro cytotoxic activity of all the synthesized compounds was studied against cervix adenocarcinoma HeLa, melanoma Fem-x and myelogenous leukemia K562 cell lines by the MTT method. Derivative 1l containing 3-pyridyl moiety exhibited a better cytotoxic activity in the cell growth inhibition of K562 cell lines in comparison with cisplatin as a reference compound.

  19. Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory, antioxidant and antimicrobial agents.

    Science.gov (United States)

    Bandgar, Babasaheb P; Gawande, Shrikant S; Bodade, Ragini G; Gawande, Nalini M; Khobragade, Chandrahasya N

    2009-12-15

    A novel series of 1-(2,4-dimethoxy-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (3) have been prepared by the Claisen-Schmidt condensation of 1-(2,4-dimethoxy-phenyl)-ethanone (1) and substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (2). Substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (2) were prepared by Vilsmeir-Haack reaction on acetophenonephenylhydrazones to offer the target compounds. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory (TNF-alpha and IL-6 inhibitory assays), antioxidant (DPPH free radical scavenging assay) and antimicrobial activities (agar diffusion method) against some pathogenic bacteria and fungi. Of 10 compounds screened, compounds 3a, 3c and 3g exhibited promising IL-6 inhibitory (35-70% inhibition, 10 microM), free radical scavenging (25-35% DPPH activity) and antimicrobial activities (MIC 100 microg/mL and 250 microg/mL) at varied concentrations. The structure-activity relationship (SAR) and in silico drug relevant properties (HBD, HBA, PSA, cLogP, molecular weight, E(HOMO) and E(LUMO)) further confirmed that the compounds are potential lead compounds for future drug discovery study. Toxicity of the compounds was evaluated theoretically and experimentally and revealed to be nontoxic except 3d and 3j.

  20. Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents.

    Science.gov (United States)

    Liu, Jia-Jia; Zhao, Meng-Yue; Zhang, Xin; Zhao, Xin; Zhu, Hai-Liang

    2013-11-01

    Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

  1. Synthesis, crystal structures, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives

    Science.gov (United States)

    Qi, De-Qiang; Yu, Chuan-Ming; You, Jin-Zong; Yang, Guang-Hui; Wang, Xue-Jie; Zhang, Yi-Ping

    2015-11-01

    A series of pyrazole-based 1,3,4-oxadiazole derivatives were rationally designed and synthesized in good yields by following a convenient route. All the newly synthesized molecules were fully characterized by IR, 1H NMR and elemental analysis. Eight compounds were structurally determined by single crystal X-ray diffraction analysis. The fluorescence properties of all the compounds were investigated in dimethyl sulfoxide media. In addition, these newly synthesized compounds were evaluated for in vitro inhibitory activity against commercial enzyme xanthine oxidase (XO) by measuring the formation of uric acid from xanthine. Among the compounds synthesized and tested, 3d and 3e were found to be moderate inhibitory activity against commercial XO with IC50 = 72.4 μM and 75.6 μM. The studies gave a new insight in further optimization of pyrazole-based 1,3,4-oxadiazole derivatives with excellent fluorescence properties and XO inhibitory activity.

  2. 4-[5-(Furan-2-yl-3-trifluoromethyl-1H-pyrazol-1-yl]benzenesulfonamide

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    Abdullah M. Asiri

    2012-04-01

    Full Text Available In the title compound, C14H10F3N3O3S, there are significant twists in the molecule, as seen in the values of the dihedral angles between the pyrazole ring and each of the furan [31.1 (2°] and benzene rings [55.58 (10°]. The amino N atom occupies a position almost normal to the benzene ring [N—S—Car—Car (ar = aromatic torsion angle = 83.70 (19°]. One amino H atom forms a hydrogen bond to the tricoordinate pyrazole N atom and the other interacts with a sulfonamide O atom, forming a supramolecular chain along [010]. The chains are consolidated into a supramolecular layers via C—H...O interactions involving the second sulfonamide O atom; layers stack along [10-1]. The furan ring was found to be disordered over two diagonally opposite orientations of equal occupancy.

  3. Experimental and theoretical investigation of optical nonlinearities in (nitrovinyl)-1H-pyrazole derivative

    Science.gov (United States)

    Dwivedi, Y.; de Boni, L.; Gonçalves, P. J.; Mairink, L. M.; Menegatti, R.; Fonseca, T. L.; Zilio, S. C.

    2013-03-01

    This work reports on the optical nonlinearities of a newly synthesized pyrazole derivative, namely (E)-1-(4-chlorophenyl)-4-(2-nitrovinyl)-1H-pyrazole. The Z-scan technique with femtosecond laser pulses was used to determine the two-photon absorption (2PA) cross-section spectrum, which presents a maximum of 67 GM at 690 nm. We have combined hyper-Rayleigh scattering (HRS) experiments and second-order Møller-Plesset perturbation theory (MP2) calculations to study the first hyperpolarizability (βHRS). It was found that the MP2/6-311+G(d) model, taking into account solvent and dispersion effects, provides the βHRS value of 40 × 10-30 cm5/esu for the compound, in good agreement with the experimental result of 45 ± 2 × 10-30 cm5/esu.

  4. Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety.

    Science.gov (United States)

    Karrouchi, K; Chemlal, L; Taoufik, J; Cherrah, Y; Radi, S; El Abbes Faouzi, M; Ansar, M

    2016-11-01

    A series of Schiff bases of 4-amino-1,2,4-triazole derivatives containing pyrazole (5a-h) were synthesized from condensation of 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (3) derivative with various aromatic aldehydes (4a-h). The structures of the synthesized compounds were elucidated by IR, (1)H NMR, (13)C NMR, and mass spectrometry. All the synthesized compounds (5a-h) were screened for their in vivo analgesic and in vitro antioxidant activities revealing significant analgesic and antioxidant properties.

  5. Synthesis and Anti-inflammatory Activity of Some Novel Pyrazole Derivatives of Gallic Acid

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    S. Arunkumar

    2009-01-01

    Full Text Available In the present study, a new series of [5-substituted-3-(phenylamino-1H-pyrazol-1yl] (3,4,5-trihydroxyphenyl-methanone (4a-j have been synthesized. 3, 4, 5-Trihydroxy benzohydrazide (1 was synthesized from propyl gallate and hydrazine hydrate in presence of ethanol. Chalcones (2a-j were synthesized from acetanilide and various aromatic aldehydes in presence of ethanol and sodium hydroxide solution. By refluxing the compound (1 and compounds (2a-j in presence of ethanol yielded [5-substituted-3-(phenylamino-4.5-dihydropyrazol-1yl] (3,4,5-trihydroxy phenyl-methanone (3a-j. The final compounds [5-substituted-3-(phenylamino-1H-pyrazol-1yl] (3,4,5-trihydroxyphenyl-methanone (4a-j were synthesized by treating compounds (3a-j with bromine water. The synthesized compounds have been characterized by IR, 1HNMR and Mass spectral data. The compounds were evaluated for in vivo anti-inflammatory activity by carrageenan induced paw edema test. In general all compounds were found to exhibit good anti-inflammatory activity.

  6. Synthesis and characterization of selected fused isoxazole and pyrazole derivatives and their antimicrobial activity

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    VIJAY V. DABHOLKAR

    2009-11-01

    Full Text Available New potent antibacterials, fused isoxazole and pyrazole derivatives, were synthesized using 5,5-dimethylcyclohexane-1,3-dione (1 and 3-[(4-chlorobenzylideneamino]-2-thioxoimidazolidin-4-one (2 as synthons. Aromatic aldehydes on condensation with 1 and 2 gave 2-arylidene-5,5-dimethylcyclohexane-1,3-dione (3 and 5-arylidene-3-[(4-chlorobenzylideneamino]-2-thioxoimidazolidin-4-one (4, respectively. Compounds 3 and 4 were forced to undergo heterocyclization reaction with nucleophilic reagents to give the title compounds. The newly synthesized heterocyles (5–8 were characterized based on their chemical properties and spectroscopic data, and were found to inhibit Staphylococcus aureus and Corynebacterium diphtheriae.

  7. Pyrazole phenylcyclohexylcarbamates as inhibitors of human fatty acid amide hydrolases (FAAH).

    Science.gov (United States)

    Aghazadeh Tabrizi, Mojgan; Baraldi, Pier Giovanni; Ruggiero, Emanuela; Saponaro, Giulia; Baraldi, Stefania; Romagnoli, Romeo; Martinelli, Adriano; Tuccinardi, Tiziano

    2015-06-05

    Fatty acid amide hydrolase (FAAH) inhibitors have gained attention as potential therapeutic targets in the management of neuropathic pain. Here, we report a series of pyrazole phenylcyclohexylcarbamate derivatives standing on the known carbamoyl FAAH inhibitor URB597. Structural modifications led to the recognition of compound 22 that inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM). The most active compounds of this series showed significant selectivity toward monoacylglycerol lipase (MAGL) enzyme. In addition, molecular modeling and reversibility behavior of the new class of FAAH inhibitors are presented in this article.

  8. Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives.

    Science.gov (United States)

    Zhang, Hengyuan; Zhu, Peiqing; Liu, Jie; Lin, Yan; Yao, Hequan; Jiang, Jieyun; Ye, Wencai; Wu, Xiaoming; Xu, Jinyi

    2015-02-01

    A collection of pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited significant antiproliferative activity. Especially compound 15e displayed the most potent activity with the IC50 values of 5.58 and 6.13μM against B16 and SF763 cancer cell lines, respectively. Furthermore, the significant in vivo antitumor activity of 15e was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

  9. Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5-aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide derivatives.

    Science.gov (United States)

    Koç, G Ş; Tan, O U; Uçar, G; Yildirim, E; Erol, K; Palaska, E

    2014-11-01

    28 new 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives were synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. The derivatives substituted by halogen on the fifth position of pyrazole ring, inhibited MAO-A enzyme with a high selectivity index. On the other hand, compounds substituted with 2-naphthyl inhibited MAO-B enzyme with a moderate selectivity index. Docking studies were done to highlight the interactions of the most active derivative with the active site of MAO-A. In addition, in vivo antidepressant and anxiolytic activities of the compounds having selective MAO-A inhibitory effects, were investigated by using Porsolt forced swimming and elevated plus-maze tests respectively. 3-(4-Fluorophenyl)-5-(4-chloro-phenyl)-N-allyl-4,5-dihydro-1H-pyrazole-1-carbothio-amide has antidepressant, 3-(4-fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide and 3-(4-fluoro-phenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H-pyrazole-1-carbothioamide have anxiolytic activity.

  10. Bis{4-[(3,5-dimethyl-1H-pyrazol-4-ylselanyl]-3,5-dimethyl-1H-pyrazol-2-ium} chloride monohydrate

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    Maksym Seredyuk

    2012-07-01

    Full Text Available In the title compound, 2C10H15N4Se+·Cl−·OH−, a singly protonated molecule of the organic selenide participates in hydrogen bonding with neighboring molecules, forming zigzag chains along [001]. The molecule adapts a cis bridging mode with a C—Se—C angle of 102.13 (15°. π–π stacking interactions are observed between the closest pyrazole rings of neighboring chains [centroid–centroid distance = 3.888 (1 Å] and hydrogen bonding occurs through bridging chloride anions and hydroxide groups. Additionally, O—H...Cl hydrogen bonds are formed.

  11. Bis{4-[(3,5-dimethyl-1H-pyrazol-4-yl)selan-yl]-3,5-dimethyl-1H-pyrazol-2-ium} chloride monohydrate.

    Science.gov (United States)

    Seredyuk, Maksym; Pavlenko, Vadim A; Znovjyak, Kateryna O; Gumienna-Kontecka, Elzbieta; Penkova, Larysa

    2012-07-01

    In the title compound, 2C(10)H(15)N(4)Se(+)·Cl(-)·OH(-), a singly protonated mol-ecule of the organic selenide participates in hydrogen bonding with neighboring mol-ecules, forming zigzag chains along [001]. The molecule adapts a cis bridging mode with a C-Se-C angle of 102.13 (15)°. π-π stacking inter-actions are observed between the closest pyrazole rings of neighboring chains [centroid-centroid distance = 3.888 (1) Å] and hydrogen bonding occurs through bridging chloride anions and hydroxide groups. Additionally, O-H⋯Cl hydrogen bonds are formed.

  12. 3,6-Dinitropyrazolo[4,3-c]pyrazole-Based Multipurpose Energetic Materials through Versatile N-Functionalization Strategies.

    Science.gov (United States)

    Yin, Ping; Zhang, Jiaheng; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2016-10-04

    A family of 3,6-dinitropyrazolo[4,3-c]pyrazole-based energetic compounds was synthesized by using versatile N-functionalization strategies. Subsequently, nine ionic derivatives of the N,N'-(3,6-dinitropyrazolo[4,3-c]pyrazole-1,4-diyl)dinitramidate anion were prepared by acid-base reactions and fully characterized by infrared, multinuclear NMR spectra, and elemental analysis. The structures of four of these compounds were further confirmed by single-crystal X-ray diffraction. Based on their different physical and detonation properties, these compounds exhibit promising potential as modern energetic materials and can be variously classified as green primary explosives, high-performance secondary explosives, fuel-rich propellants, and propellant oxidizers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Syntheses and Antibacterial Studies of Some 1-Phenyl-3-(4-(2-ethanoloxy phenyl-5-aryl-1H-pyrazoles

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    Anju Goyal

    2013-01-01

    Full Text Available A series of 1-phenyl-3-(4-(2-ethanoloxy phenyl-5-aryl-1H-pyrazoles were synthesized from chalcones, that is, 3-aryl-1-(4-hydroxyphenyl prop-2-en-1-ones and studied for their in vitro antibacterial activity. Chalcones 1 on reaction with phenyl hydrazine in the presence of acetic acid and few drops of hydrochloric acid yielded the corresponding 1-phenyl-3-(4-hydroxyphenyl-5-aryl-1H-pyrazoles 2 which on further reaction with 2-chloroethanol furnished the title compounds 3. These compounds were characterized by CHN analyses, IR, mass and 1H NMR spectral data. All the compounds were evaluated for their in vitro antibacterial activity against two Gram positive strains (Bacillus subtilis and Staphylococcus aureus and two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa, and their minimum inhibitory concentration (MIC was determined.

  14. Structural Basis of Transcription Inhibition by CBR Hydroxamidines and CBR Pyrazoles.

    Science.gov (United States)

    Feng, Yu; Degen, David; Wang, Xinyue; Gigliotti, Matthew; Liu, Shuang; Zhang, Yu; Das, Deepankar; Michalchuk, Trevor; Ebright, Yon W; Talaue, Meliza; Connell, Nancy; Ebright, Richard H

    2015-08-04

    CBR hydroxamidines are small-molecule inhibitors of bacterial RNA polymerase (RNAP) discovered through high-throughput screening of synthetic-compound libraries. CBR pyrazoles are structurally related RNAP inhibitors discovered through scaffold hopping from CBR hydroxamidines. CBR hydroxamidines and pyrazoles selectively inhibit Gram-negative bacterial RNAP and exhibit selective antibacterial activity against Gram-negative bacteria. Here, we report crystal structures of the prototype CBR hydroxamidine, CBR703, and a CBR pyrazole in complex with E. coli RNAP holoenzyme. In addition, we define the full resistance determinant for CBR703, show that the binding site and resistance determinant for CBR703 do not overlap the binding sites and resistance determinants of other characterized RNAP inhibitors, show that CBR703 exhibits no or minimal cross-resistance with other characterized RNAP inhibitors, and show that co-administration of CBR703 with other RNAP inhibitors results in additive antibacterial activities. The results set the stage for structure-based optimization of CBR inhibitors as antibacterial drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Thermally stable 3,6-dinitropyrazolo[4,3-c]pyrazole-based energetic materials.

    Science.gov (United States)

    Zhang, Jiaheng; Parrish, Damon A; Shreeve, Jean'ne M

    2014-10-01

    3,6-Dinitropyrazolo[4,3-c]pyrazole was prepared using an efficient modified process. With selected cations, ten nitrogen-rich energetic salts and three metal salts were synthesized in high yield based on the 3,6-dinitropyrazolo[4,3-c]pyrazolate anion. These compounds were fully characterized by IR and multinuclear NMR spectroscopies, as well as elemental analyses. The structures of the neutral compounds 4 and its salt 16 were confirmed by single-crystal X-ray diffraction showing extensive hydrogen-bonding interactions. The neutral pyrazole precursor and its salts are remarkably thermally stable. Based on the calculated heats of formation and measured densities, detonation pressures (22.5-35.4 GPa) and velocities (7948-9005 m s(-1)) were determined, and they compare favorably with those of TNT and RDX. Their impact and friction sensitivities range from 12 to >40 J and 80 to 360 N, respectively. These properties make them competitive as insensitive and thermally stable high-energy density materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. On the Interactions of Fused Pyrazole Derivative with Selected Amino Acids: DFT Calculations

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    Kornelia Czaja

    2017-01-01

    Full Text Available Due to the increasing prevalence of neoplasms, there is a permanent need for new selective cytostatic compounds. Anticancer drugs can act in different ways, affecting protein expression and synthesis, including disruption of signaling pathways within cells. Continuing our previous research aiming at elucidating the mechanism of pyrazole’s anticancer activity, we carried out in silico studies on the interactions of fused pyrazole derivative with alanine, lysine, glutamic acid, and methionine. The objective of the study is to improve our understanding of the possible interactions of pyrazole derivatives with the above-mentioned amino acids. For this purpose, we apply the DFT formalism (optimization using the B3LYP, CAM-B3LYP, PBE0, and M06L functionals and interaction energy calculations (counterpoise corrected method based on the basis set superposition error, BSSE together with QTAIM approach and estimation of the 1H NMR chemical shifts of analyzed pyrazole derivative using different basis sets and DFT functionals in CPCM solvation model (and water used as a solvent.

  17. [3-(5-Nitro-2-furyl-1-phenyl-1H-pyrazol-4-yl](phenylmethanone

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    Jia Hao Goh

    2010-05-01

    Full Text Available In the title pyrazole compound, C20H13N3O4, an intramolecular C—H...O hydrogen bond generates a seven-membered ring, producing an S(7 ring motif. The essentially planar furan and pyrazole rings [maximum deviations of 0.002 (1 and 0.007 (1 Å, respectively] are coplanar with each other, forming a dihedral angle of 3.06 (10°. The pyrazole ring forms dihedral angles of 8.51 (9 and 56.81 (9° with the two benzene rings. The nitro group is coplanar with the attached furan ring, as indicated by the dihedral angle of 2.5 (3°. In the crystal packing, intermolecular C—H...O hydrogen bonds link adjacent molecules into two-molecule-wide chains along the a axis. The crystal packing is further stabilized by weak intermolecular C—H...π and π–π interactions [centroid–centroid distance = 3.4441 (10 Å].

  18. Discovery of N-benzoxazol-5-yl-pyrazole-4-carboxamides as nanomolar SQR inhibitors.

    Science.gov (United States)

    Xiong, Li; Zhu, Xiao-Lei; Shen, Yan-Qing; Wishwajith, Wickramabahu Kandergama Wasala Mudiyanselage; Li, Kui; Yang, Guang-Fu

    2015-05-05

    Succinate-ubiquinone oxidoreductase (SQR, EC 1.3.5.1, complex II), an essential component of cellular respiratory chain and tricarboxylic acid (or Krebs) cycle, has been identified as one of the most significant targets for pharmaceutical and agrochemical. Herein, with the aim of discovery of new antibacterial lead structure, a series of N-benzoxazol-5-yl-pyrazole-4-carboxamides were designed, synthesized, and evaluated for their SQR inhibitory effects. Very promisingly, one candidate (Ki = 11 nM, porcine SQR) was successfully identified as the most potent synthetic SQR inhibitor so far. The further inhibitory kinetics studies revealed that the candidate is non-competitive with respect to the substrate cytochrome c and DCIP. Computational simulations revealed that the titled compounds have formed hydrogen bond with D_Y91 and B_W173 and the pyrazole ring formed cation-π interaction with C_R46. In addition, in R(1) position, -CHF2 group has increased the binding affinity and decreased the entropy contribution, while -CF3 group displayed completely opposite effect when bound with SQR. The results of the present work showed that N-benzoxazol-5-yl-pyrazole-4-carboxamide is a new scaffold for discovery of SQR inhibitors and worth further study.

  19. Sulfate-bridged dimeric trinuclear copper(II)-pyrazolate complex with three different terminal ligands.

    Science.gov (United States)

    Mezei, Gellert

    2016-08-01

    The reaction of CuSO4·5H2O, 4-chloro-pyrazole (4-Cl-pzH) and tri-ethyl-amine (Et3N) in di-methyl-formamide (DMF) produced crystals of di-aqua-hexa-kis-(μ-4-chloro-pyrazolato-κ(2) N:N')bis-(N,N-di-methyl-formamide)di-μ3-hydroxido-bis-(μ4-sulfato-κ(4) O:O':O'':O'')hexa-copper(II) N,N-di-methyl-formamide tetra-solvate dihydrate, [Cu3(OH)(SO4)(C3H2ClN2)3(C3H7NO)(H2O)]2·4C3H7NO·2H2O. The centrosymmetric dimeric molecule consists of two trinuclear copper-pyrazolate units bridged by two sulfate ions. The title compound provides the first example of a trinuclear copper-pyrazolate complex with three different terminal ligands on the Cu atoms, and also the first example of such complex with a strongly binding basal sulfate ion. Within each trinuclear unit, the Cu(II) atoms are bridged by μ-pyrazolate groups and a central μ3-OH group, and are coordinated by terminal sulfate, H2O and DMF ligands, respectively. Moreover, the sulfate O atoms coordinate at the apical position to the Cu atoms of the symmetry-related unit, providing square-pyramidal coordination geometry around each copper cation. The metal complex and solvent mol-ecules are involved in O-H⋯O hydrogen bonds, leading to a two-dimensional network parallel to (10-1).

  20. Design and synthesis of pyrazole/isoxazole linked arylcinnamides as tubulin polymerization inhibitors and potential antiproliferative agents.

    Science.gov (United States)

    Kamal, Ahmed; Shaik, Anver Basha; Rao, Bala Bhaskara; Khan, Irfan; Bharath Kumar, G; Jain, Nishant

    2015-10-28

    As pyrazole and isoxazole based derivatives are well-known for displaying a considerable biological profile, an attempt has been made to unravel their cytotoxic potential. In this context, a number of pyrazole/isoxazole linked arylcinnamide conjugates (15a-o and 21a-n) have been synthesized by employing a straight forward route. The basic structure comprised three ring scaffolds (A, B and C): methoxyphenyl rings as A and C rings and a five membered heterocyclic ring (pyrazole or isoxazole) as the B-ring. To achieve clear understanding, these derivatives are categorized as pyrazole-phenylcinnamides (PP) and isoxazole-phenylcinnamides (IP). These compounds have been evaluated for their ability to inhibit the growth of various human cancer cell lines such as HeLa, DU-145, A549 and MDA-MB231 and most of them exhibit considerable cytotoxic effects. Some of them like 15a, 15b, 15e, 15i and 15l exhibit promising cytotoxicity in HeLa cells (IC50 = 0.4, 1.8, 1.2, 2.7 and 1.7 μM). Amongst them 15a, 15b and 15e were taken up for detailed biological studies, they were found to arrest the cells in the G2/M phase of the cell cycle. Moreover, they were investigated for their effect on the microtubular cytoskeletal system by using a tubulin polymerization assay, immunofluroscence and molecular docking studies; interestingly they demonstrate a significant inhibition of tubulin polymerization.

  1. Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors.

    Science.gov (United States)

    Li, Ya-Sheng; Tian, Hao; Zhao, Dong-Sheng; Hu, De-Kun; Liu, Xing-Yu; Jin, Hong-Wei; Song, Gao-Peng; Cui, Zi-Ning

    2016-08-01

    A series of pyrazole and triazole derivatives containing 5-phenyl-2-furan functionality were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. The bioassay results showed that title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Meanwhile, the activity of compounds containing 1,2,4-triazole (series II) was higher than that of pyrazole-attached derivatives (series I). The primary structure-activity relationship study and docking results showed that the 1,2,4-triazole moiety of compound IIk played a key role to form integral hydrogen bonds and π-π stacking interaction with PDE4B protein while the rest part of the molecule extended into the catalytic domain to block the access of cAMP and formed the foundation for inhibition of PDE4. Compound IIk would be great promise as a hit compound for further study based on the preliminary structure-activity relationship and molecular modeling studies.

  2. Regioselective synthesis and biological studies of novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives as potential antiproliferative agents.

    Science.gov (United States)

    Ananda, Hanumappa; Sharath Kumar, Kothanahally S; Nishana, Mayilaadumveettil; Hegde, Mahesh; Srivastava, Mrinal; Byregowda, Raghava; Choudhary, Bibha; Raghavan, Sathees C; Rangappa, Kanchugarakoppal S

    2017-02-01

    Pyrazole moiety represents an important category of heterocyclic compound in pharmaceutical and medicinal chemistry. The novel 1-aryl-3, 5-bis (het) aryl pyrazole derivatives were synthesized with complementary regioselectivity. The chemical structures were confirmed by IR, (1)H NMR, (13)C NMR, and mass spectral analysis. The chemical entities were screened in various cancer cell lines to assess their cell viability activity. Results showed that the compound 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl) pyridine (5d) possessed maximum cytotoxic effect against breast cancer and leukemic cells. The cytotoxicity was confirmed by live-dead cell assay and cell cycle analysis. Mitochondrial membrane potential, Annexin V-FITC staining, DNA fragmentation, Hoechst staining, and western blot assays revealed the ability of compound 5d to induce cell death by activating apoptosis in cancer cells. Thus, the present study demonstrates that compound 5d could be an attractive chemical entity for the development of small molecule inhibitors for treatment of leukemia and breast cancer.

  3. Experimental and theoretical studies of a pyrazole-thiazolidin-2,4-di-one hybrid

    Science.gov (United States)

    Mushtaque, Md.; Avecilla, Fernando; Haque, Ashanul; Perwez, Ahmad; Khan, Md. Shahzad; Rizvi, M. Moshahid Alam

    2017-08-01

    The present work describes synthesis, characterization and biological evaluations of a hybrid compound 10 composed of two intriguing scaffolds pyrazole and thiazolidin-2,4-di-one. The title compound was obtained via multi-step reaction and characterized by a number of techniques (viz. IR, UV-Visible, 1H-NMR, 13C-NMR and MS) including X-ray crystallography. The structural and photophysical data of compound 10 were well supported by theoretical calculations performed at density functional (DFT) level. In-vitro anticancer studies on different human cancer cell lines indicated moderate to low activity of the compounds. The molecular target of the compound was predicted through in-silico studies. Finding of the studies are presented herein.

  4. (E-5-[(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yliminomethyl]-2-methoxyphenyl 4-chlorobenzenesulfonate

    Directory of Open Access Journals (Sweden)

    Tian-Xiang Lei

    2012-07-01

    Full Text Available In the title compound, C25H22ClN3O5S, the two N atoms in the pyrazole ring have a pyramidal environment, with the sums of the valence angles around them being 349.3 (2 and 357.5 (2°. The phenyl ring is twisted by 50.97 (12° from the pyrazole mean plane. In the crystal, pairs of weak C—H...O hydrogen bonds link the molecules into inversion dimers.

  5. N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-benzene-sulfonamide.

    Science.gov (United States)

    da Silva, Luiz Everson; de Sousa, Paulo Teixeira; Dall'oglio, Evandro Luiz; Foro, Sabine

    2007-12-06

    In the title compound, C(18)H(19)N(3)O(3)S, the phenyl ring and the pyrazole ring are twisted with respect to each other by an angle of 49.11 (7)°. The C-N-S-C torsion angle is -122.5 (2)°. The methyl group bonded to the N atom of the pyrazole ring has a large deviation from the mean ring plane of 0.603 (3) Å. One inter-molecular N-H⋯O and two non-classical inter-molecular C-H⋯O hydrogen bonds are observed in the crystal structure.

  6. Biaryl ethers as potent allosteric inhibitors of reverse transcriptase and its key mutant viruses: aryl substituted pyrazole as a surrogate for the pyrazolopyridine motif.

    Science.gov (United States)

    Su, Dai-Shi; Lim, John J; Tinney, Elizabeth; Tucker, Thomas J; Saggar, Sandeep; Sisko, John T; Wan, Bang-Lin; Young, Mary Beth; Anderson, Kenneth D; Rudd, Deanne; Munshi, Vandna; Bahnck, Carolyn; Felock, Peter J; Lu, Meiquing; Lai, Ming-Tain; Touch, Sinoeun; Moyer, Gregory; Distefano, Daniel J; Flynn, Jessica A; Liang, Yuexia; Sanchez, Rosa; Perlow-Poehnelt, Rebecca; Miller, Mike; Vacca, Joe P; Williams, Theresa M; Anthony, Neville J

    2010-08-01

    Biaryl ethers were recently reported as potent NNRTIs. Herein, we disclose a detailed effort to modify the previously reported compound 1. We have designed and synthesized a series of novel pyrazole derivatives as a surrogate for pyrazolopyridine motif that were potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells.

  7. Consecutive Three-Component Synthesis of 3-(HeteroAryl-1H-pyrazoles with Propynal Diethylacetal as a Three-Carbon Building Block

    Directory of Open Access Journals (Sweden)

    Thomas J. J. Müller

    2011-11-01

    Full Text Available A novel consecutive three-component synthesis of 3-(heteroaryl-1H-pyrazoles via room temperature Sonogashira arylation of propynal diethylacetal used as a propargyl aldehyde synthetic equivalent has been disclosed. The final acetal cleavage-cyclocondensation with hydrazine hydrochloride at 80 °C rapidly furnishes the title compounds in a one-pot fashion.

  8. Synthesis and biological evaluation of novel 2,4,5-triaryl-1 H-pyrazol-3(2H)-ones as inhibitors of ALK5

    Institute of Scientific and Technical Information of China (English)

    Xing Zhou Li; Xian Ping Dai; Kang Ying Lai; Li Li Wang; Zhi Bing Zheng; Song Li

    2008-01-01

    A series of 2,4,5-triaryl substituted 1H-pyrazol-3(2H)-ones,as ALK5 inhibitors,were desigened,synthesized and evaluated in vitro.Most compounds exhibited noticeable ALK5 inhibition activities at 1 μmol/L and displayed no significant cytotoxicities at 30 μmol/L.

  9. Synthesis of 2-Alkyl(aryl)-3-methylthio-6-methyl-6-arylpyrano-[4, 3-c] pyrazol-4(2H)-ones

    Institute of Scientific and Technical Information of China (English)

    Yu Xin LI; You Ming WANG; Xiao Ping YANG; Su Hua WANG; Zheng Ming LI

    2004-01-01

    The synthesis of 2-alkyl(aryl)-3-methylthiopyrano[4,3-c]pyrazol-4(2H)-ones via 5, 6-dihydro-2H-pyran-2, 4-dione-3-dithioacetals with (un)substituted hydrazines is described and the mechanism of the formation of title compounds is discussed. Their structures were confirmed by 1HNMR spectra and elemental analysis.

  10. 2-(2,4-Dichlorophenyl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylacetamide

    Directory of Open Access Journals (Sweden)

    B. Narayana

    2013-01-01

    Full Text Available In the crystal structure of the title compound, C19H17Cl2N3O2, the molecules form dimers of the R22(10 type through N—H...O hydrogen bonding. As a result of steric repulsion, the amide group is rotated with respect to both the dichlorophenyl and 2,3-dihydro-1H-pyrazol-4-yl rings, making dihedral angles of 80.70 (13 and 64.82 (12°, respectively. The dihedral angle between the dichlorophenyl and 2,3-dihydro-1H-pyrazol-4-yl rings is 48.45 (5° while that between the 2,3-dihydro-1H-pyrazol-4-yl and phenyl rings is 56.33 (6°.

  11. Energetic N-Nitramino/N-Oxyl-Functionalized Pyrazoles with Versatile π-π Stacking: Structure-Property Relationships of High-Performance Energetic Materials.

    Science.gov (United States)

    Yin, Ping; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2016-11-07

    N-Nitramino/N-oxyl functionalization strategies were employed to investigate structure-property relationships of energetic materials. Based on single-crystal diffraction data, π-π stacking of pyrazole backbones can be tailored effectively by energetic functionalities, thereby resulting in diversified energetic compounds. Among them, hydroxylammonium 4-amino-3,5-dinitro-1H-pyrazol-1-olate and dipotassium N,N'-(3,5-dinitro-1H-pyrazol-1,4-diyl)dinitramidate, with unique face-to-face π-π stacking, can be potentially used as a high-performance explosive and an energetic oxidizer, respectively. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. 2-[3-(4-Chlorophenyl-5-(4-fluorophenyl-4,5-dihydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thiazole

    Directory of Open Access Journals (Sweden)

    Bakr F. Abdel-Wahab

    2013-04-01

    Full Text Available In the title compound, C24H17ClFN3S, the pyrazole ring is almost planar (r.m.s. deviation = 0.030 Å. With the exception of the methine-bound benzene ring, which forms a dihedral angle of 85.77 (13° with the pyrazole ring, the remaining non-C atoms lie in an approximate plane (r.m.s. deviation = 0.084 Å so that overall the molecule has a T-shape. In the crystal, centrosymmetrically related molecules are connected via π–π interactions between pyrazole rings [centroid–centroid distance = 3.5370 (15 Å] and these stack along the a axis with no specific interactions between them.

  13. Structure of Pyrazole Derivatives Impact their Affinity, Stoichiometry, and Cooperative Interactions for CYP2E1 Complexes

    Science.gov (United States)

    Hartman, Jessica H.; Bradley, Amber M.; Laddusaw, Ryan M; Perry, Martin D.; Miller, Grover P.

    2013-01-01

    CYP2E1 plays a critical role in detoxication and carcinogenic activation of drugs, pollutants, and dietary compounds; however, these metabolic processes can involve poorly characterized cooperative interactions that compromise the ability to understand and predict CYP2E1 metabolism. Herein, we employed an array of ten azoles with an emphasis on pyrazoles to establish the selectivity of catalytic and cooperative CYP2E1 sites through binding and catalytic studies. Spectral binding studies for monocyclic azoles suggested two binding events, while bicyclic azoles suggested one. Pyrazole had moderate affinity toward the CYP2E1 catalytic site that improved when a methyl group was introduced at either position 3 or 4. The presence of methyl groups simultaneously at positions 3 and 5 blocked binding, and a phenyl group at position 3 did not improve binding affinity. In contrast, pyrazole fusion to a benzene or cyclohexane ring greatly increased affinity. The consequences of these binding events on CYP2E1 catalysis were studied through inhibition studies with 4-nitrophenol, a substrate known to bind both sites. Most pyrazoles shared a common mixed cooperative inhibition mechanism in which pyrazole binding rescued CYP2E1 from substrate inhibition. Overall, inhibitor affinities toward the CYP2E1 catalytic site were similar to those reported in binding studies, and the same trend was observed for binding at the cooperative site. Taken together, these studies identified key structural determinants in the affinity and stoichiometry of azole interactions with CYP2E1 and consequences on catalysis that further advance an understanding of the relationship between structure and function for this enzyme. PMID:23811196

  14. Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands.

    Science.gov (United States)

    Silva, Francisco; Marques, Fernanda; Santos, I C; Paulo, António; Rodrigues, António Sebastião; Rueff, José; Santos, Isabel

    2010-05-01

    Reactions of GaCl(3) with pyrazole-containing ligands of the pyrazole-imine-phenol (HL(1)-HL(3)) or pyrazole-amine-phenol (HL(4)-HL(6)) types led to the synthesis of well-defined [GaL(2)](+) homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL(1)-HL(6)) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL(1) and HL(6). The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways.

  15. Solvent-Free Synthesis of Some1-Acetyl Pyrazoles

    Energy Technology Data Exchange (ETDEWEB)

    Thirunarayanan, Ganesamoorthy [Annamalai Univ., Tamil Nadu (India); Sekar, Krishnamoorthy Guna [National College, Tiruchirappalli (India)

    2013-10-15

    Some N-acetyl pyrazoles including 1-(3-(3,4-dichlorophenyl)-5-(substituted phenyl)-4,5-dihydro-{sup 1}H-pyrazole-1-yl) ethanones have been synthesised by solvent free cyclization cum acetylation of chalcones like substituted styryl 3,4-dichlorophenyl ketones using hydrazine hydrate and acetic anhydride in presence of catalytic amount of fly-ash: H{sub 2}SO{sub 4} catalyst. The yield of these N-acetyl pyrazole derivatives are more than 75%. The synthesised N-acetyl pyrazoline derivatives were characterized by their physical constants and spectral data.

  16. Pyrazole Based Inhibitors against Enzymes of Staphylococcus aureus

    DEFF Research Database (Denmark)

    Jagadeesan, G.; Vijayakuma, Vinodhkumar; Palayam, Malathy

    2015-01-01

    Pyrazole derivatives display a wide variety of biological activities such as antimicrobial, anti-inflammatory and anti-tumor activities. Its biological prominence has intrigued chemists and biologists in recent years to synthesize new pyrazole derivatives as antiviral, antibacterial and anticancer...... agents. The current study focuses on molecular docking and dynamics studies of pyrazole derivatives against Nucleosidase and DNA gyrase B of Staphylococcus aureus. Molecular docking and dynamics studies reveal that some of these derivatives show better binding abilities than some of the current drugs...

  17. Structure of Pyrazole Derivatives Impact their Affinity, Stoichiometry, and Cooperative Interactions for CYP2E1 Complexes

    OpenAIRE

    2013-01-01

    CYP2E1 plays a critical role in detoxication and carcinogenic activation of drugs, pollutants, and dietary compounds; however, these metabolic processes can involve poorly characterized cooperative interactions that compromise the ability to understand and predict CYP2E1 metabolism. Herein, we employed an array of ten azoles with an emphasis on pyrazoles to establish the selectivity of catalytic and cooperative CYP2E1 sites through binding and catalytic studies. Spectral binding studies for m...

  18. Structure of Pyrazole Derivatives Impact their Affinity, Stoichiometry, and Cooperative Interactions for CYP2E1 Complexes

    OpenAIRE

    Hartman, Jessica H.; Bradley, Amber M.; Laddusaw, Ryan M.; Perry, Martin D.; Miller, Grover P.

    2013-01-01

    CYP2E1 plays a critical role in detoxication and carcinogenic activation of drugs, pollutants, and dietary compounds; however, these metabolic processes can involve poorly characterized cooperative interactions that compromise the ability to understand and predict CYP2E1 metabolism. Herein, we employed an array of ten azoles with an emphasis on pyrazoles to establish the selectivity of catalytic and cooperative CYP2E1 sites through binding and catalytic studies. Spectral binding studies for m...

  19. Crystal structure of 1-acetyl-3-(4-methylphenyl)-5-phenyl-4,5-dihydro-1 H-pyrazole

    Science.gov (United States)

    Bülbül, H.; Tinmaz, F.; Dege, N.; Özer İlhan, İ.; Sarıpınar, E.

    2014-12-01

    In the title compound, C18H18N2O, the whole molecule is not planar but the phenyl ring systems are planar individually. The central pyrazole ring system is twisted with puckering parameters Q = 0.1610(18) Å and φ = 82.2(6)°. The crystallographic structure is stabilized by C-H⋯N type intramolecular hydrogen bond, generating ring motif R(5).

  20. 3-Methyl-1-phenyl-4-[(Z-phenyl(4-acetamidoanilinomethylidene]-1H-pyrazol-5(4H-one

    Directory of Open Access Journals (Sweden)

    Li-Hua Zhi

    2012-07-01

    Full Text Available In the title compound, C25H22N4O2, the dihedral angles between the central pyrazole ring and the phenyl and benzene rings are 37.01 (3, 75.58 (7 and 49.67 (8°. An intramolecular N—H...O hydrogen bond generates an S(6 motif. In the crystal, N—H...O hydrogen bonds link molecules into a zigzag chain extended along the b axis.

  1. trans-Bis(perchlorato-κOtetrakis(1H-pyrazole-κN2copper(II

    Directory of Open Access Journals (Sweden)

    Viktor Zapol'skii

    2008-10-01

    Full Text Available The title compound, [Cu(ClO42(C3H4N24], was obtained unexpectedly by the reaction of copper(II perchlorate hexahydrate with equimolar amounts of 1-chloro-1-nitro-2,2,2-tripyrazolylethane in methanol solution. The crystal structure comprises octahedrally coordinated Cu2+ ions, located on an inversion centre, with four pyrazole ligands in the equatorial plane. The average Cu—N distance is 2.000 (1 Å. Two perchlorate ions are coordinated to copper in trans positions [Cu—O = 2.4163 (11 Å].

  2. Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c.

    Science.gov (United States)

    Esvan, Yannick J; Giraud, Francis; Pereira, Elisabeth; Suchaud, Virginie; Nauton, Lionel; Théry, Vincent; Dezhenkova, Lyubov G; Kaluzhny, Dmitry N; Mazov, Vsevolod N; Shtil, Alexander A; Anizon, Fabrice; Moreau, Pascale

    2016-07-15

    A derivative of the staurosporine aglycon (K252c), in which the lactam ring was replaced by a pyrazole moiety, was synthesized. The resulting indolopyrazolocarbazole (3) inhibited Pim isoforms 1-3 whereas it did not impair the activity of two known targets of K252c, protein kinase C isoforms α and γ. Compound 3 exhibited moderate cytotoxic activity toward human leukemia and colon carcinoma cell lines (K562 and HCT116), strongly suggesting that this new scaffold deserves further investigations for treatment of malignancies associated with Pim activity.

  3. N-[(3,5-Dimethyl­pyrazol-1-yl)meth­yl]phthalimide

    OpenAIRE

    Wang, Su-qing; Jian, Fang-Fang; Liu, Huan-Qiang

    2008-01-01

    The title compound {systematic name: 2-[(3,5-dimenthylpyrazol-1-yl)meth­yl]isoindole-1,3-dione}, C14H13N3O2, was prepared by reaction of N-(bromo­meth­yl)phthalimide and 3,5-dimethyl­pyrazole in chloro­form solution. The mol­ecular structure and packing are stabilized by intra­molecular C—H⋯O hydrogen-bonding and C—H⋯π inter­actions.

  4. N-{2-[2-(5-Methyl-1H-pyrazol-3-ylacetamido]phenyl}benzamide monohydrate

    Directory of Open Access Journals (Sweden)

    Karim Chkirate

    2017-02-01

    Full Text Available The asymmetric unit of the title compound, C19H18N4O2·H2O, comprises the U-shaped pyrazole derivative and a solvent water molecule. The molecular conformation is partly determined by an intramolecular N—H...O hydrogen bond. The crystal packing is directed by an extensive network of O—H...O, N—H...O, N—H...N and C—H...O hydrogen bonds together with C—H...π(ring contacts that generate a three-dimensional network.

  5. 5-(2,4-Dichlorophenoxy-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde

    Directory of Open Access Journals (Sweden)

    S. Madan Kumar

    2016-07-01

    Full Text Available In the crystal structure of the title compound, C17H12Cl2N2O2, the pyrazole ring makes dihedral angles of 65.0 (2 and 43.9 (2° with the dichlorophenyl and phenyl rings, respectively. The dihedral angle between the chlorophenyl and phenyl rings is 59.1 (2°. In the crystal, the molecules are linked by C—H...O hydrogen bonds and weak C—Cl...π and C—H...π interactions, generating a three-dimensional network.

  6. 2-(2,4-Dichlorophenoxy-1-(1H-pyrazol-1-ylethanone

    Directory of Open Access Journals (Sweden)

    Abdul Qayyum Ather

    2010-10-01

    Full Text Available In the title compound, C11H8Cl2N2O2, the 2,4-dichlorophenoxy and 1H-pyrazole groups are almost planar [r.m.s. deviations of 0.0157 and 0.0008 Å, respectively] and are oriented at a dihedral angle of 64.17 (5° with respect to one another. In the crystal, the molecules are stabilized in the form of dimers due to inversion-related C—H...O hydrogen bonds, with R22(10 ring motifs.

  7. 3,5-Bis(4-methoxyphenyl-1-phenyl-4,5-dihydro-1H-pyrazole

    Directory of Open Access Journals (Sweden)

    Zeliha Baktır

    2011-02-01

    Full Text Available In the title compound, C23H22N2O2, the central pyrazole ring is nearly planar (r.m.s. deviation = 0.046 Å and it makes a dihedral angle of 18.5 (2° with the phenyl ring. The dihedral angles between the phenyl and the two methoxy-substituted phenyl rings are 26.2 (2 and 80.6 (2°. The crystal structure is stabilized by C—H...π stacking interactions and weak π–π interactions [centriod–centroid distance = 3.891 (2 Å].

  8. The therapeutic voyage of pyrazole and its analogs: A review.

    Science.gov (United States)

    Khan, Mohemmed Faraz; Alam, Mohammad Mumtaz; Verma, Garima; Akhtar, Wasim; Akhter, Mymoona; Shaquiquzzaman, Mohammad

    2016-09-14

    Pyrazole, a five membered heteroaromatic ring with two nitrogen atoms is of immense significance. Presence of this nucleus in the pharmacological agents of diverse therapeutic categories viz. antianxiety, anti-inflammatory, antipsychotic, anticancer, antiobesity, analgesic, antipyretic etc. has made it an indispensable anchor for design and development of new pharmacological agents. Owing to the development of novel and new pyrazole based therapeutic agents at a faster pace, there is a need to couple the latest information with previously available information to understand status of this moiety in medicinal chemistry research. The review herein highlights the therapeutic worth of pyrazole derivatives. Several therapeutically active pyrazole based derivatives developed by numerous scientists across the globe are reported here.

  9. An Improved Synthesis And Biological Evaluation Of Some New 4,5-dihydro-pyrazole-1-Carbaldehyde Derivatives

    Directory of Open Access Journals (Sweden)

    S. B. Zangade

    2012-03-01

    Full Text Available An improved condensation of substituted chalcones 1a-g with hydrazine hydrate and formic acid in 2-methoxyethanol to afford new series of 4,5-dihydro-pyrazole-1-carbaldehyde derivatives 2a-g. Clean reaction conditions, simple workup procedure and short reaction time giving high yields of product are notable advantages of method. All newly synthesized compounds characterized by chemical test, spectral and elemental analysis. Further, all newly synthesized compounds were screened for their antimicrobial activity. Most of these title compounds exhibited potent activity.

  10. {2,6-Bis[(2,6-diisopropylphosphanyloxy]-4-fluorophenyl-κ3P,C1,P′}(1H-pyrazole-κN2nickel(II hexafluorophosphate

    Directory of Open Access Journals (Sweden)

    Man-Lung Kwan

    2012-10-01

    Full Text Available The title compound, [Ni(C18H30FO2P2(C3H4N2]PF6, was prepared by halide abstraction with TlPF6 in the presence of CH3CN in CDCl3 from the respective neutral pincer chlorido analogue followed by addition of pyrazole. The PO—C—OP pincer ligand acts in typical trans-P2 tridentate fashion to generate a distorted square-planar nickel structure. The Ni—N(pyrazole distance is 1.925 (2 Å and the plane of the pyrazole ligand is rotated 56.2 (1° relative to the approximate square plane surrounding the NiII center in which the pyrazole is bound to the NiII atom through its sp2-hybridized N atom. This Ni—N distance is similar to bond lengths in the other reported NiII pincer-ligand square-planar pyrazole complex structures; however, its dihedral angle is significantly larger than any of those for the latter set of pyrazole complexes.

  11. {2,6-Bis[(2,6-diisopropyl-phosphan-yl)-oxy]-4-fluoro-phenyl-κ(3)P,C(1),P'}(1H-pyrazole-κN(2))nickel(II) hexa-fluoro-phosphate.

    Science.gov (United States)

    Kwan, Man-Lung; Conry, Sara J; Carfagna, Charles S; Press, Loren P; Ozerov, Oleg V; Hoffman, Norris W; Sykora, Richard E

    2012-10-01

    The title compound, [Ni(C(18)H(30)FO(2)P(2))(C(3)H(4)N(2))]PF(6), was prepared by halide abstraction with TlPF(6) in the presence of CH(3)CN in CDCl(3) from the respective neutral pincer chlorido analogue followed by addition of pyrazole. The PO-C-OP pincer ligand acts in typical trans-P(2) tridentate fashion to generate a distorted square-planar nickel structure. The Ni-N(pyrazole) distance is 1.925 (2) Å and the plane of the pyrazole ligand is rotated 56.2 (1)° relative to the approximate square plane surrounding the Ni(II) center in which the pyrazole is bound to the Ni(II) atom through its sp(2)-hybridized N atom. This Ni-N distance is similar to bond lengths in the other reported Ni(II) pincer-ligand square-planar pyrazole complex structures; however, its dihedral angle is significantly larger than any of those for the latter set of pyrazole complexes.

  12. Synthesis of some new carbonitriles and pyrazole coumarin derivatives with potent antitumor and antimicrobial activities.

    Science.gov (United States)

    Hafez, Omiama M Abdel; Nassar, Mahmoud I; El-Kousy, Salah M; Abdel-Razik, Ayman F; Sherien, M M Atalla; El-Ghonemy, Mai M

    2014-01-01

    3-Acetyl-4-hydroxycoumarin (2) was reacted with some aldehydes (4-chlorobenzaldehyde, 4-bromobenzaldehyde, 5-methylfurfural) to afford the chalcones (3a-c). Cyclization of these chalcones with malononitrile in the presence of ammonium acetate afforded pyridine carbonitriles (4a-c), while the cyclization reaction of chalcones (3a-c) with ethyl cyanoacetate afforded the oxopyridine carbonitriles (5a-c). On the other hand, the chalcones (3a-c) reacted with hydrazine hydrate in alcohol to yield pyrazoles (6a-c), but when the same reaction is carried out in the presence of acetic acid, the acetyl pyrazole derivatives (7a-c) were obtained. Finally, the reaction of the chalcones (3a-c) with phenylhydrazine afforded phenylpyrazole derivatives (8a-c). The structures of synthesized compounds were confirmed by their micro analysis and spectral data (IR, NMR and MS). Twelve samples were evaluated for the human breast adenocarcinoma cytotoxicity, three of them showed moderate activity, the rest of the samples showed weak cytotoxic activity (very high IC50), but for the hepatocarcinoma cell lines four samples showed weak cytotoxic effect, while the rest of the compounds showed very weak effect. For antimicrobial study, three compounds proved to be the most promising against tested bacterial organisms.

  13. 3-Isobutyl-4-phenylsulfanyl-1H-pyrazol-5-ol

    Directory of Open Access Journals (Sweden)

    Tara Shahani

    2011-02-01

    Full Text Available The asymmetric unit of the title compound, C13H16N2OS, contains two independent molecules (A and B. The pyrazole ring [maximum deviations = 0.0049 (17 Å in molecule A and 0.0112 (19 Å in molecule B] makes a dihedral angle of 70.23 (11 and 73.18 (12° with the phenyl ring in molecules A and B, respectively. The isobutyl group in molecule B is disordered over two sets of sites with a ratio of refined occupancies of 0.858 (5:0.142 (5. In the crystal, molecules A and B are linked via a pair of intermolecular N—H...O hydrogen bonds, generating an R22(8 ring motif. These ring motifs are further linked into two-dimensional arrays parallel to the bc plane by intermolecular N—H...O and weak C—H...S hydrogen bonds. The crystal is further stablized by weak π–π interactions [centroid–centroid distances = 3.5698 (13 and 3.5287 (12 Å].

  14. Synthesis and Crystal Structure of 1-[(1-Phenyl-4-cyano)pyrazol-5-yliminomethyl]- 2-nitroiminoimidazolidine

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The title compound 1-[(1-Phenyl-4-cyano)pyrazol-5-yliminomethyl]-2-nitroiminoimidazolidine 2 (C14H14N8O2, Mr=326.33) was obtained by the reaction of (1-Phenyl-4-cyano)pyrazol-5-yliminomethyl ethylether with 2-nitroiminoimidazoli-dine in the presence of sodium hydride. The crystal is monoclinic, space group P21/n, with unit cell constants a =7.310(1), b =17.218(2), c =11.669(1), β=92.552(2)°, Z=4, V=1467.2(3)3, Dc=1.477g/cm3, F(000)=680, μ(MoKα)=0.107 mm-1, R=0.0506, wR=0.1398 for 2593 observed reflections(I>2σ(I)). In this compound the nitroimino group is coplanar with the imidazolidine ring and pyrazole ring plane; shorter C-N bond lengths and longer exocyclo C=N bond length were observed, suggesting a formation of a fully delocalized system. The dihedral angles between the plane formed by the O(1), O(2), N(1), N(2), C(1), N(4), C(4), N(5), C(5), N(6), N(7), C(7), C(6) atoms and phenyl ring is 48.5°. The interatomic distance for N(4)-N(6) is 4.61.The intermolecular hydrogen bonding N(3)-H...N(8) is observed.

  15. Discovery of pyrazole carboxylic acids as potent inhibitors of rat long chain L-2-hydroxy acid oxidase.

    Science.gov (United States)

    Barawkar, Dinesh A; Bandyopadhyay, Anish; Deshpande, Anil; Koul, Summon; Kandalkar, Sachin; Patil, Pradeep; Khose, Goraksha; Vyas, Samir; Mone, Mahesh; Bhosale, Shubhangi; Singh, Umesh; De, Siddhartha; Meru, Ashwin; Gundu, Jayasagar; Chugh, Anita; Palle, Venkata P; Mookhtiar, Kasim A; Vacca, Joseph P; Chakravarty, Prasun K; Nargund, Ravi P; Wright, Samuel D; Roy, Sophie; Graziano, Michael P; Cully, Doris; Cai, Tian-Quan; Singh, Sheo B

    2012-07-01

    Long chain L-2-hydroxy acid oxidase 2 (Hao2) is a peroxisomal enzyme expressed in the kidney and the liver. Hao2 was identified as a candidate gene for blood pressure (BP) quantitative trait locus (QTL) but the identity of its physiological substrate and its role in vivo remains largely unknown. To define a pharmacological role of this gene product, we report the development of selective inhibitors of Hao2. We identified pyrazole carboxylic acid hits 1 and 2 from screening of a compound library. Lead optimization of these hits led to the discovery of 15-XV and 15-XXXII as potent and selective inhibitors of rat Hao2. This report details the structure activity relationship of the pyrazole carboxylic acids as specific inhibitors of Hao2.

  16. Experimental and calculated structural parameters of 5-trihalomethyl-4,5-dihydro-1 H-pyrazole derivatives, novel analgesic agents

    Science.gov (United States)

    Machado, Pablo; Campos, Patrick T.; Lima, Glauber R.; Rosa, Fernanda A.; Flores, Alex F. C.; Bonacorso, Helio G.; Zanatta, Nilo; Martins, Marcos A. P.

    2009-01-01

    The crystal structures of four novel analgesic agents, methyl 5-hydroxy-3- or 4-methyl-5-trichloro[trifluoro]methyl-4,5-dihydro-1 H-pyrazole-1-carboxylate, have been determined by X-ray diffractometry. The data demonstrated that the molecular packing was stabilized mainly by O sbnd H⋯O hydrogen bonds of the 5-hydroxy and 1-carboxymethyl groups. The 4,5-dihydro-1 H-pyrazole rings were obtained as almost planar structures showing RMS deviation at a range of 0.0052-0.0805 Å. Additionally, computational investigation using semi-empirical AM1 and PM3 methods were performed to find a correlation between experimental and calculated geometrical parameters. The data obtained suggest that the structural data furnished by the AM1 method is in better agreement with those experimentally determined for the above compounds.

  17. Soluble Polymer-Supported Synthesis of Pyrazoles via 1,3-Dipolar Cycloaddition Strategy

    Institute of Scientific and Technical Information of China (English)

    LIN,Xu-Feng(林旭锋); WANG,Yan-Guang(王彦广); DING,Han-Feng(丁寒锋)

    2004-01-01

    Rapid parallel liquid-phase synthesis of pyrazoles has first been developed.The 1,3-dipolar cycloaddition between nitrilimines generated in situ and soluble polymer-supported alkynyl or alkenyl dipolarophiles in parallel one-pot fashion gave the corresponding PEG-supported regioisomeric pyrazoles or regiospecific pyrazolines.The latter was assuredly oxidated by DDQ to PEG-supported regiospecific pyrazoles.Cleavage from the support under mild conditions afforded pyrazoles in good yields and high purity.

  18. Combinatorial Libraries on Rigid Scaffolds: Solid Phase Synthesis of Variably Substituted Pyrazoles and Isoxazoles

    Directory of Open Access Journals (Sweden)

    Eduard R. Felder

    1997-01-01

    Full Text Available The synthesis of combinatorial compound libraries has become a powerful lead finding tool in modern drug discovery. The ability to synthesize rapidly, in high yield, new chemical entities with low molecular weight on a solid support has a recognized strategic relevance (“small molecule libraries”. We designed and validated a novel solid phase synthesis scheme, suitable to generate diversity on small heterocycles of the pyrazole and isoxazole type. Appropriate conditions were worked out for each reaction, and a variety of more or less reactive agents (building blocks was utilized for discrete conversions, in order to exploit the system’s breadth of applicability. Four sequential reaction steps were validated, including the loading of the support with an acetyl bearing moiety, a Claisen condensation, an a-alkylation and a cyclization of a b-diketone with monosubstituted hydrazines. In a second stage, the reaction sequence was applied in a split and mix approach, in order to prepare a combinatorial library built-up from 4 acetyl carboxylic acids (R1, 35 carboxylic esters (R2 and 41 hydrazines (R4 (and 1 hydroxylamine to yield a total of 11,760 compounds divided into 41 pyrazole sublibraries with 140 pairs of regioisomers and 1 isoxazole sublibrary of equal size.

  19. Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles

    Directory of Open Access Journals (Sweden)

    Nagwa Mohamed Mahrous Hamada

    2015-06-01

    Full Text Available The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.

  20. Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles.

    Science.gov (United States)

    Hamada, Nagwa Mohamed Mahrous; Abdo, Nadia Yousef Megally

    2015-06-08

    The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.

  1. Design, Synthesis and Structure-activity of N-Glycosyl-1-pyridyl-1H-pyrazole-5-carboxamide as Inhibitors of Calcium Channels

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yun-yun; LI Yu-xin; LI Yi-ming; YANG Xiao-ping; MAO Ming-zhen; LI Zheng-ming

    2013-01-01

    Carbohydrates,with broad-spectrum structures and biological functions,are key organic compounds in nature,along with nucleic acids and proteins.As part of our ongoing efforts to develop a new class of pesticides with novel mechanism of action,a series of novel N-glycosyl-l-pyridyl-lH-pyrazole-5-carboxamide was designed and synthesized via the reactions of glycosyl methanamides and pyridyl-pyrazole acid.The compounds were characterized by 1H NMR and 13C NMR.The bioassay results indicate that some of these compounds exhibit moderate insecticidal activities and assessed as potential inhibitors of calcium channels.The modulation of voltage-gated calcium channels by compounds 4a and 5a in the central neurons isolated from the third instar larvae of Spodoptera exigua was studied by whole-cell patch-clamp technique.In addition,compound 5a inhibits the recorded calcium currents reversible on washout.Experimental results also indicate that compound 5a did not release stored calcium from the Endoplasmic Reticulum.The present work demonstrates that N-glycosyl-l-pyridyl-lH-pyrazole-5-carboxamides cannot be used as possible inhibitors of calcium channels for developing novel pesticides.

  2. Sulfate-bridged dimeric trinuclear copper(II–pyrazolate complex with three different terminal ligands

    Directory of Open Access Journals (Sweden)

    Gellert Mezei

    2016-08-01

    Full Text Available The reaction of CuSO4·5H2O, 4-chloropyrazole (4-Cl-pzH and triethylamine (Et3N in dimethylformamide (DMF produced crystals of diaquahexakis(μ-4-chloropyrazolato-κ2N:N′bis(N,N-dimethylformamidedi-μ3-hydroxido-bis(μ4-sulfato-κ4O:O′:O′′:O′′hexacopper(II N,N-dimethylformamide tetrasolvate dihydrate, [Cu3(OH(SO4(C3H2ClN23(C3H7NO(H2O]2·4C3H7NO·2H2O. The centrosymmetric dimeric molecule consists of two trinuclear copper–pyrazolate units bridged by two sulfate ions. The title compound provides the first example of a trinuclear copper–pyrazolate complex with three different terminal ligands on the Cu atoms, and also the first example of such complex with a strongly binding basal sulfate ion. Within each trinuclear unit, the CuII atoms are bridged by μ-pyrazolate groups and a central μ3-OH group, and are coordinated by terminal sulfate, H2O and DMF ligands, respectively. Moreover, the sulfate O atoms coordinate at the apical position to the Cu atoms of the symmetry-related unit, providing square–pyramidal coordination geometry around each copper cation. The metal complex and solvent molecules are involved in O—H...O hydrogen bonds, leading to a two-dimensional network parallel to (10-1.

  3. Copper(II) complexes with pyrazole derivatives - Synthesis, crystal structure, DFT calculations and cytotoxic activity

    Science.gov (United States)

    Kupcewicz, Bogumiła; Ciolkowski, Michal; Karwowski, Boleslaw T.; Rozalski, Marek; Krajewska, Urszula; Lorenz, Ingo-Peter; Mayer, Peter; Budzisz, Elzbieta

    2013-11-01

    The series of pyrazole derivatives (1a-4a) were used as bidentate N,N' ligands to obtain neutral Cu(II) complexes of ML2Cl2 type (1b-4b). The molecular structures of ligand 1a and Cu(II) complex 4b were determined by X-ray crystallography and theoretical DFT calculations. In this study, three functionals B3LYP, BP86 and mPW1PW91 with different basis sets and two effective core potentials Los Alamos and Stuttgart/Dresden were performed. The DFT study disclosed the usefulness of BP86 functional with SDD-ECP for Cu(II) ion and dedicated D95 basis set for other non-transition metal atoms, with the exclusion of Cl for which 6-31++G(2df,2pd) were used. The structural analysis shows that the presence of phenyl substituent in a pyrazole ring contributed to Cu-N bond elongation, which can result in different reactivity of complexes 1b and 3b. The cytotoxicity of the obtained compounds was evaluated on three cancer cells lines: HL-60, NALM-6 and WM-115. The complexes have exhibited similar moderate antiproliferative activity. All the complexes, except for 1b, were found to be more active against three cancer cell lines than uncomplexed pyrazoles. The lipophilicity and electrochemical properties of ligands and complexes was also studied. For complexes with ligand 1a and 3a only one reduction process at the metal centre occurs (Cu(II) → Cu(I)) with oxidization of Cu(I)-Cu(II) in the backward step.

  4. Synthesis and Properties of a New Explosive, 4-Amino-3,5-Dinitro-lH-Pyrazole (LLM-116)

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, R D; Lee, G S; Pagoria, P F; Mitchell, A R; Gilardi, R

    2001-05-22

    A novel synthesis of the title compound was achieved by direct amination using Vicarious Nucleophilic Substitution (VNS) methodology. Reaction of 1,1,1-trimethylhydrazinium iodide with 3,5-dinitropyrazole in DMSO produces 4-amino-3,s-dinitro-1H-pyrazole as a 1:1 crystal solvate with DMSO. Recrystallization from water yields the monohydrated crystal. Recrystallization of the monohydrate from butyl acetate yields the compound in pure form. Crystallographic data and results of small-scale safety tests are reported. These data indicate that LLM-116 is a promising candidate as an insensitive high explosive.

  5. Antimycobacterial evaluation of novel [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives synthesized by microwave-mediated Michael addition.

    Science.gov (United States)

    Sedighi, Vida; Azerang, Parisa; Sardari, Soroush

    2015-06-01

    The focus of this study is the synthesis and biological activity evaluation of a series of dibenzalaceton derivatives (3a-3n) and novel [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives (5a-5g) against Mycobacterium bovis, Bacillus Calmette-Guerin (BCG). Dibenzalacetone derivatives were synthesized by benzaldehyde derivatives. The [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives were synthesized by Michael addition reaction and using green chemistry microwave-mediated method. All compounds were evaluated against BCG and the activity expressed as minimum inhibitory concentration (MIC) in μM. The result showed good activity for all the compounds especially compounds (3a), (3n), and (5a) illustrated high activity (7.03, 8.10 and 5.37 μM, respectively).

  6. Bis{4-[(3,5-dimethyl-1H-pyrazol-4-yl)selan­yl]-3,5-dimethyl-1H-pyrazol-2-ium} chloride monohydrate

    Science.gov (United States)

    Seredyuk, Maksym; Pavlenko, Vadim A.; Znovjyak, Kateryna O.; Gumienna-Kontecka, Elzbieta; Penkova, Larysa

    2012-01-01

    In the title compound, 2C10H15N4Se+·Cl−·OH−, a singly protonated mol­ecule of the organic selenide participates in hydrogen bonding with neighboring mol­ecules, forming zigzag chains along [001]. The molecule adapts a cis bridging mode with a C—Se—C angle of 102.13 (15)°. π–π stacking inter­actions are observed between the closest pyrazole rings of neighboring chains [centroid–centroid distance = 3.888 (1) Å] and hydrogen bonding occurs through bridging chloride anions and hydroxide groups. Additionally, O—H⋯Cl hydrogen bonds are formed. PMID:22807889

  7. Synthesis, characterization and anticancer studies of new steroidal oxadiazole, pyrrole and pyrazole derivatives

    Directory of Open Access Journals (Sweden)

    Shamsuzzaman

    2015-07-01

    Full Text Available In the present study steroidal derivatives, 3β-[5′-mercapto-1′,3′,4′-oxadiazole-2-yl]methoxy cholest-5-ene 2, 3β-[2′,5′-dimethylpyrrole-1-yl]aminocarbonylmethoxycholest-5-ene 3 and 3β-[3′,5′-dimethyl pyrazole-1-yl]carbonylmethoxycholest-5-ene 4 have been synthesized from cholest-5-en-3β-O-acetyl hydrazide 1 using CS2/KOH, acetonyl acetone and acetyl acetone, respectively as reagents and are characterized by IR, 1H NMR,13C NMR, MS and elemental analysis. Compounds 2–4 were also evaluated for anticancer activity against human leukemia cell line (HL-60 by MTT assay and compound 4 displayed the promising behavior by showing better anticancer activity.

  8. Novel ethyl-5-amino-3-methylthio-1H-pyrazole-4-carboxylates: Synthesis and pharmacological activity

    Directory of Open Access Journals (Sweden)

    S.N. Thore

    2016-05-01

    Full Text Available A series of novel ethyl-5-amino-3-methylthio-1H-pyrazole-4-carboxylates 3a–j were synthesized from condensation of various hydrazides 2a–j with ketene dithioacetal. The synthesized compounds were screened for in vivo analgesic and anti-inflammatory activities using acetic acid writhing test in mice and carrageenan-induced paw edema test in rat, respectively. Diclofenac sodium was used as a standard drug for comparison. Compounds 3a, 3c and 3d exhibited significant analgesic and anti-inflammatory activities at a dose of 25 mg/kg and showed quite less ulcerogenic index in the range of 0.9–1.12 whereas diclofenac sodium showed 3.10.

  9. Synthesis and bactericidal activities of novel pyrazole-l-carbothioamide derivatives

    Institute of Scientific and Technical Information of China (English)

    LIU Xinhua; WANG Shifan; SONG Baoan

    2007-01-01

    4-(2-Hydroxy-phenyl)-but-3-en-2-one (1) was prepared via condensation of salicylaldehyde with acetone,and then reaction of the ketone 1 with thiosemicarbazide was accompanied by cyclization to give substituted pyrazole (2).Seven new 5-(2-hydroxy-phenyl)-3-methyl-4,5-dihydropyrazole- 1-carbothioamide derivatives (3a-3g) were synthesized by the acylation of 2 and characterized by means of elemental analysis,infrared (IR),and 1H nuclear magnetic resonance (NMR).The compounds 3c,3d,and 3g showed certain bactericidal activity against E.coli;while compound 3g showed certain bactericidal activity against P.vulgaris.

  10. Aqua(4-nitrophthalato-κO1bis[2-(1H-pyrazol-3-yl-κN2pyridine-κN]manganese(II hemihydrate

    Directory of Open Access Journals (Sweden)

    Lei Ni

    2010-12-01

    Full Text Available In the title compound, [Mn(C8H3NO6(C8H7N32(H2O]·0.5H2O, the Mn2+ ion is octahedrally coordinated by two 2-(1H-pyrazol-3-ylpyridine ligands, one 4-nitrophthalate ligand and one coordinated water molecule leading to an overall MnN4O2 coordination environment. The two 2-(1H-pyrazol-3-ylpyridine ligands, which deviate from planarity by 0.0187 (2 and 0.0601 (2 Å, make a dihedral angle of 81.90 (6°. An intramolecular N—H...O hydrogen bond occurs. Intermolecular π–π stacking interactions with a face-to-face separation of 3.61 (1 Å between the 2-(1H-pyrazol-3-ylpyridine ligands is observed. Additionally, O—H...O hydrogen bonding involving the uncoordinated water (which is situated on an inversion center, coordinated water molecules and 2-(1H-pyrazol-3-ylpyridine ligands leads to a three-dimensional network in the crystal structure.

  11. A Convenient Approach to Heterocyclic Building Blocks: Synthesis of Novel Ring Systems Containing a [5,6]Pyrano[2,3-c]pyrazol-4(1H-one Moiety

    Directory of Open Access Journals (Sweden)

    Wolfgang Holzer

    2007-01-01

    Full Text Available Starting from commercially available educts, a straightforward synthetic route to new heterocyclic building blocks is exemplified with the one- or two-step synthesis of tri-, tetra-, or pentacyclic ring systems. Representatives of the following novel ring systems are prepared from 3-methyl-1-phenyl-2-pyrazolin-5-one and the corresponding o-halo-arenecarbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane: pyrimidino[4',5':5,6]pyrano[2,3-c]pyrazol-4(1H-one, thieno[3',2':5,6]pyrano[2,3c]pyrazol- 4-(1H-one, thieno[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H-one, thieno[3'',2'':4',5']thieno[2',3':5,6]-pyrano[2,3-c]pyrazol-4(1H-one, [1,3]dioxolo[5',6'][1]benzothieno[2',3':5,6]pyrano-[2,3-c]- pyrazol-4(1H-one, pyridazino[4',3':5,6]pyrano[2,3-c]pyrazol-4(1H-one and pyrazolo-[4'',3'':5',6']pyrido[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H-one. While the latter two ring systems are directly obtained due to a spontaneous intramolecular substitution reaction, in the other reactions uncyclised 4-aroylpyrazol-5-ols are produced, which are cyclised into the target heterocycles in a subsequent synthetic step (i.e. treatment with NaH in DMF. Detailed NMR spectroscopic investigations (1H-, 13C-, 15N- with the obtained compounds were undertaken to unambiguously prove the new structures.

  12. Synthesis, Antibacterial and Antifungal Activity of Some New Pyrazoline and Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Seham Y. Hassan

    2013-02-01

    Full Text Available A series of 2-pyrazolines 5–9 have been synthesized from α,β-unsaturated ketones 2–4. New 2-pyrazoline derivatives 13–15 bearing benzenesulfonamide moieties were then synthesized by condensing the appropriate chalcones 2–4 with 4-hydrazinyl benzenesulfonamide hydrochloride. Ethyl [1,2,4] triazolo[3,4-c][1,2,4]triazino[5,6-b]-5H-indole-5-ethanoate (26 and 1-(5H-[1,2,4]triazino[5,6-b] indol-3-yl-3-methyl-1H-pyrazol-5(4H-one (32 were synthesized from 3-hydrazinyl-5H-[1,2,4]triazino[5,6-b]indole (24. On the other hand ethyl[1,2,4]triazolo[3,4-c][1,2,4]triazino[5,6-b]-5,10-dihydroquinoxaline- 5-ethanoate (27 and 1-(5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxalin-3-yl-3-methyl-1H-pyrazol-5(4H-one (33 were synthesized from 3-hydrazinyl-5,10-dihydro-[1,2,4]triazino[5,6-b]quinoxaline (25 by reaction with diethyl malonate or ethyl acetoacetate, respectively. Condensation of 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde (1' with compound 24 or 25 afforded the corresponding Schiff's bases 36 and 37, respectively. Reaction of the Schiff's base 37 with benzoyl hydrazine or acetic anhydride afforded benzohydrazide derivative 39 and the cyclized compound 40, respectively. Furthermore, the pyrazole derivatives 42–44 were synthesized by cyclization of hydrazine derivative 25 with the prepared chalcones 2–4. All the newly synthesized compounds have been characterized on the basis of IR and 1H-NMR spectral data as well as physical data. Antimicrobial activity against the organisms E. coli ATCC8739 and P. aeruginosa ATCC 9027 as examples of Gram-negative bacteria, S. aureus ATCC 6583P as an example of Gram-positive bacteria and C. albicans ATCC 2091 as an example of a yeast-like fungus have been studied using the Nutrient Agar (NA and Sabouraud Dextrose Agar (SDA diffusion methods. The best performance was found for the compounds 16, 17, 19 and 20.

  13. Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin

    Directory of Open Access Journals (Sweden)

    Carla I. Nieto

    2015-08-01

    Full Text Available A series of new (E-3(5-[β-(aryl-ethenyl]-5(3-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H, 13C, 19F and 15N spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent as well as iNOS (calcium-calmodulin independent isoenzymes is presented. A qualitative structure–activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E-3(5-[β-(3-Fluoro-4-hydroxyphenyl-ethenyl]-5(3-phenyl-1H-pyrazole (13, is the best inhibitor of iNOS, being also more selective towards the other two isoforms.

  14. Pyrazole derived ultra-short antimicrobial peptidomimetics with potent anti-biofilm activity.

    Science.gov (United States)

    Ahn, Mija; Gunasekaran, Pethaiah; Rajasekaran, Ganesan; Kim, Eun Young; Lee, Soo-Jae; Bang, Geul; Cho, Kun; Hyun, Jae-Kyung; Lee, Hyun-Ju; Jeon, Young Ho; Kim, Nam-Hyung; Ryu, Eun Kyoung; Shin, Song Yub; Bang, Jeong Kyu

    2017-01-05

    In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin. Besides its higher selectivity (therapeutic index) toward bacterial cells than LL-37, Py11 showed highly increased proteolytic stability against trypsin digestion and maintained its antimicrobial activity in the presence of physiological salts. Interestingly, Py11 exhibited higher anti-biofilm activity against MDRPA compared to LL-37. The results from fluorescence spectroscopy and transmission electron microscopy (TEM) suggested that Py11 kills bacterial cells possibly by integrity disruption damaging the cell membrane, leading to the cytosol leakage and eventual cell lysis. Furthermore, Py11 displayed significant anti-inflammatory (endotoxin-neutralizing) activity by inhibiting LPS-induced production of nitric oxide (NO) and TNF-α. Collectively, our results suggest that Py11 may serve as a model compound for the design of antimicrobial and antisepsis agents.

  15. Synthesis and biological evaluation of a novel series of chalcones incorporated pyrazole moiety as anticancer and antimicrobial agents.

    Science.gov (United States)

    Mohamed, Magda F; Mohamed, Mervat S; Shouman, Samia A; Fathi, Mohamed M; Abdelhamid, Ismail Abdelshafy

    2012-11-01

    A newly synthesized series of chalcone derivatives containing pyrazole rings were synthesized and evaluated for their cytotoxic activities in vitro against several human cancer cell lines. Most of the prepared compounds showed potential cytotoxicity against human breast cancer cell lines MCF-7, HEPG-2, and HCT-116. Also the compounds were evaluated as antimicrobial agents. The three compounds 3, 4, and 5 were proved to be better anticancer agents than the positive standard doxorubicin with IC50 values (4.7, 4.4, and 3.9 μg/ml) against the same human cancer cell lines, whereas compounds 5 and 6 showed the most active antimicrobial compounds in comparison to the other chalcones.

  16. Crystal structure of 5-[4-(di-methyl-amino)-phen-yl]-3-(4-methyl-phen-yl)-4,5-di-hydro-1H-pyrazole-1-carbaldehyde.

    Science.gov (United States)

    Adam, Farook; Samshuddin, Seranthimata; Ameram, Nadiah; Subramaya; Samartha, Laxminarayana

    2015-12-01

    The title compound, C19H21N3O, comprises a central pyrazole ring which is N-connected to an aldehyde group and C-connected twice to substituted benzene rings. The pyrazole ring is twisted on the C-C single bond, and the least-squares plane through this ring forms dihedral angles of 82.44 (5) and 4.52 (5)° with the (di-methyl-amino)-benzene and p-tolyl rings, respectively. In the crystal, weak C-H⋯O hydrogen bonds link mol-ecules into supra-molecular tubes along the b axis.

  17. Synthesis and in vitro antimicrobial screening of new pyrano[4,3-b]pyrane derivatives of 1H-pyrazole

    Institute of Scientific and Technical Information of China (English)

    Chetan B. Sangani; Divyesh C. Mungra; Manish P. Patel; Ranjan G. Patel

    2012-01-01

    A new series of pyrano[4,3-b]pyrane 4a-(I) bearing 1H-pyrazole has been synthesized by one pot base catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde 1a-(1),malononitrile 2 and 4-hydroxy-6-methylpyrone 3.All the synthesized compounds were screened against six bacterial pathogens,namely B.subtilis,C.tetani,S.pneumoniae,S.typhi,V.cholerae,E.coli and antifungal activity against,two fungal pathogens,A.fumigatus and C.albicans using broth microdilution MIC method.Some of the compounds are found to be equipotent or more potent than that of commercial drugs,against most of employed strains.

  18. Conformationally restricted novel pyrazole derivatives: synthesis of 1,8-disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g]indazoles as a new class of PDE4 inhibitors.

    Science.gov (United States)

    Reddy, T Shyamsunder; Kumar, K Shiva; Meda, Chandana L T; Kandale, Ajit; Rambabu, D; Krishna, G Rama; Hariprasad, C; Rao, V Venugopala; Venkataiah, S; Reddy, C Malla; Naidu, A; Dubey, P K; Parsa, Kishore V L; Pal, Manojit

    2012-05-01

    A number of novel 1,8-disubstituted 5,5-dimethyl-4,5-dihydro-1H-benzo[g]indazoles based on a conformationally restricted pyrazole framework have been designed as potential inhibitors of PDE4. All these compounds were readily prepared by using simple chemistry strategy. The in vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized along with the X-ray single crystal data of a representative compound is presented.

  19. Synthesis and anti-inflammatory activity of some new thiadiazole linked pyrazole benzene sulphonamides as cyclooxygenase inhibitors

    Directory of Open Access Journals (Sweden)

    Jahangir Alam

    2015-12-01

    Full Text Available A new series of thiadiazole linked pyrazole benzenesulfonamide derivatives were synthesized by the condensation of aldehydic pyrazole with aryl substituted thiadiazole amine followed by Schiff base reaction. The synthesized compounds (6a-o were characterized by IR, NMR, and Mass spectral data, further evaluated their in-vivo anti-inflammatory, analgesic and in-vitro COX-II inhibition assay. The compounds 6b and 6m showed most significant in-vivo anti-inflammatory with 72.33 and 71.17% inhibition along analgesic activity having 67.89% and 71.37 % respectively. Their selectivity against COX-II enzyme with selectivity index 67.81 and 66.38 was established for 6b and 6m, which is compared with Celecoxib. During the gastric ulceration study, selected compounds couldn’t observed any ulcerogenic effect on gastric mucosa.The in-silico pharmacokinetic profile and molecular docking study exposed very good binding affinity towards the cycloxygenase (COX-II enzyme (PDB Id: 3PGH, therefore the compounds 6b and 6m are used as promising lead candidates for the support of drug development.

  20. Formation of a dinuclear copper(II) complex through the cleavage of CN bond of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole

    Science.gov (United States)

    Shardin, Rosidah; Pui, Law Kung; Yamin, Bohari M.; Kassim, Mohammad B.

    2014-09-01

    A simple mononuclear octahedral copper(II) complex was attempted from the reaction of three moles of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole and one mole of copper(II) perchlorate hexahydrate in methanol. However, the product of the reaction was confirmed to be a dinuclear copper(II) complex with μ-{3-(pyridin-2-yl)-pyrazolato} and 3-(pyridin-2-yl)-1H-pyrazole ligands attached to each of the Cu(II) centre atom. The copper(II) ion assisted the cleavage of the CbenzoylN bond afforded a 3-(pyridin-2-yl)-1H-pyrazole molecule. Deprotonation of the 3-(pyridin-2-yl)-1H-pyrazole gave a 3-(pyridin-2-yl)-pyrazolato, which subsequently reacted with the Cu(II) ion to give the {3-(pyridin-2-yl)-pyrazolato}{3-(pyridin-2-yl)-1H-pyrazole}Cu(II) product moiety. The structure of the dinuclear complex was confirmed by x-ray crystallography. The complex crystallized in a monoclinic crystal system with P2(1)/n space group and cell dimensions of a = 12.2029(8) Å, b = 11.4010(7) Å, c = 14.4052(9) Å and β = 102.414(2)°. The compound was further characterized by mass spectrometry, CHN elemental analysis, infrared and UV-visible spectroscopy and the results concurred with the x-ray structure. The presence of d-d transition at 671 nm (ɛ = 116 dm3 mol-1 cm-1) supports the presence of Cu(II) centres.

  1. 2-[5-(4-Methoxyphenyl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-6-methyl-1,3-benzothiazole

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-09-01

    Full Text Available In the title compound, C24H21N3OS, the pyrazole ring makes dihedral angles of 5.40 (7 and 6.72 (8° with the benzo[d]thiazole ring system and the benzene ring, respectively, and a dihedral angle of 85.72 (8° with the methoxy-substituted benzene ring. In the crystal structure, the molecules are linked by C—H...π interactions.

  2. Crystal structure of 3-methyl-1-phenyl-5-(1H-pyrrol-1-yl-1H-pyrazole-4-carbaldehyde

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2014-10-01

    Full Text Available In the title compound, C15H13N3O, the pyrrolyl and phenyl rings make dihedral angles of 58.99 (5 and 34.95 (5°, respectively, with the central pyrazole ring. In the crystal, weak, pairwise C—H...O interactions across centers of symmetry form dimers, which are further associated into corrugated sheets running approximately parallel to (100 via weak C—H...N interactions.

  3. 1,5-Dimethyl-4-(1-methyl-3-oxo-3-phenylprop-1-enylamino-2-phenyl-1H-pyrazol-3(2H-one

    Directory of Open Access Journals (Sweden)

    Hualing Zhu

    2011-07-01

    Full Text Available In the title compound, C21H21N3O2, an intramolecular N—H...O interaction generates an S(6 ring, which stablizes the enamine–keto tautomer. The S(6 ring makes dihedral angles of 33.07 (7, 56.50 (8 and 38.59 (8°, respectively, with the benzoylacetone benzene ring and the antipyrine pyrazole and benzene rings.

  4. NMR and theoretical study on interactions between diperoxovanadate complex and pyrazole-like ligands.

    Science.gov (United States)

    Yu, Xianyong; Liu, Ronghua; Peng, Hongliang; Huang, Haowen; Li, Xiaofang; Zheng, Baishu; Yi, Pinggui; Chen, Zhong

    2010-03-01

    To understand the effects of pyrazole substitution on reaction equilibrium, the interactions between a series of pyrazole-like ligands and [OV(O(2))(2)(D(2)O)](-)/[OV(O(2))(2)(HOD)](-) were explored by using multinuclear ((1)H, (13)C, and (51)V) magnetic resonance, HSQC, and variable temperature NMR in 0.15 mol/L NaCl ionic medium mimicking physiological conditions. These results show that the relative reactivities among the pyrazole-like ligands are 3-methyl-1H-pyrazole approximately 4-methyl-1H-pyrazole approximately 1H-pyrazole>1-methyl-1H-pyrazole. As a result, the main factor which affects the reaction equilibrium is the steric effect instead of the electronic effect of the methyl group of these ligands. A pair of isomers has been formed resulting from the coordination of 3-methyl-1H-pyrazole and a vanadium complex, which is attributed to different types of coordination between the vanadium atom and the ligands. Thus, the competitive coordination leads to the formation of a series of six-coordinate peroxovanadate species [OV(O(2))(2)L](-) (L, pyrazole-like ligands). Moreover, the results of density functional calculations provided a reasonable explanation on the relative reactivity of the pyrazole-like ligands as well as the important role of solvation in these reactions.

  5. Pyrazole synthesis under microwave irradiation and solvent-free conditions

    Energy Technology Data Exchange (ETDEWEB)

    Buriol, Lilian; Frizzo, Clarissa P.; Marzari, Mara R.B.; Moreira, Dayse N.; Prola, Lizie D.T.; Zanatta, Nilo; Bonacorso, Helio G.; Martins, Marcos A.P., E-mail: mmartins@base.ufsm.b [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Quimica. Nucleo de Quimica de Heterociclos

    2010-07-01

    This paper presents a study of solvent-free reaction conditions using microwave irradiation (MW) to obtain 4,5-dihydro-{sup 1}H-pyrazoles and dehydrated pyrazoles by the cyclocondensation reaction of 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones [CF{sub 3}C(O)CH=C(R{sup 1})OR, where R/R{sup 1} Et/H, Me/Me and Me/Ph] with hydrazines [NH{sub 2}NH-R{sub 2}, where R{sub 2} = CO{sub 2}Me, Ph, CH{sub 2}CH{sub 2}OH]. Some reactions were performed under the same reaction conditions using methanol as solvent. The results obtained using MW equipment for synthesis under solvent-free conditions were also compared with those described in literature for conventional thermal heating and heating with a domestic MW oven. In general, the products furnished by reaction in MW equipment for synthesis presented better yields and shorter reaction times. In addition, it was demonstrated that the reaction temperature altered the formation of products for each hydrazine showing that MW equipment for synthesis is efficient for reacting hydrazines and 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones to procedure the products 4,5-dihydro-{sup 1}H-pyrazoles and dehydrated pyrazoles. (author)

  6. Recent progress on pyrazole scaffold-based antimycobacterial agents.

    Science.gov (United States)

    Keri, Rangappa S; Chand, Karam; Ramakrishnappa, Thippeswamy; Nagaraja, Bhari Mallanna

    2015-05-01

    New and reemerging infectious diseases will continue to pose serious global health threats well into the 21st century and according to the World Health Organization report, these are still the leading cause of death among humans worldwide. Among infectious diseases, tuberculosis claims approximately 2 million deaths per year worldwide. Also, agents that reduce the duration and complexity of the current therapy would have a major impact on the overall cure rate. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat Mycobacterium tuberculosis. Subsequently, there is an urgent need for the development of new drug candidates with newer targets and alternative mechanism of action. In this perspective, pyrazole, one of the most important classes of heterocycles, has been the topic of research for thousands of researchers all over the world because of its wide spectrum of biological activities. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on the pyrazole core to provide an insight so that its full therapeutic potential can be utilized for the treatment of tuberculosis. In this article, the possible structure-activity relationship of pyrazole analogs for designing better antituberculosis (anti-TB) agents has been discussed and is also helpful for new thoughts in the quest for rational designs of more active and less toxic pyrazole-based anti-TB drugs.

  7. Water mediated synthesis of pyrano[2, 3-c]pyrazoles using L-histidine as an effective catalyst

    Science.gov (United States)

    Khatri, Taslimahemad Talab; Khursheed, Aadil; Kumar, Pushpendra

    2017-07-01

    Pyranopyrazoles are known to show various biological activities, hence is an important class of heterocyclic compounds. Herein we are reporting very first time a convenient and reliable L-histidine catalyzed one pot synthesis of a series of pyrano[2,3-c]pyrazoles from hydrazines, ethyl acetoacetate, malano nitrile and aromatic aldehydes. The reaction presumably involves a sequence of hydrazine formation, arylidine formation, Michael addition followed by cyclization. The yields are high and the reaction takes 1-2 hours for completion, moreover reusability of the catalyst is four times without effecting much on the percentage yield formation.

  8. 1-(6-Fluoro-1,3-benzothiazol-2-yl-3-phenyl-1H-pyrazole-4-carbaldehyde

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-12-01

    Full Text Available The asymmetric unit of the title compound, C17H10FN3OS, consists of two crystallographically independent molecules. In one molecule, the pyrazole ring makes dihedral angles of 6.51 (7 and 34.02 (9°, respectively, with the terminal 1,3-benzothiazole ring system and the phenyl ring, while in the other molecule these values are 6.41 (8 and 23.06 (9°. In the crystal, the molecules are linked by weak π–π [centroid–centroid distance = 3.7069 (10 Å] and C—H...π interactions.

  9. (2E-3-(1,3-Diphenyl-1H-pyrazol-4-yl-1-phenylprop-2-en-1-one

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-07-01

    Full Text Available In the title compound, C24H18N2O, the pyrazole ring is essentially planar [maximum deviation = 0.004 (1 Å] and makes dihedral angles of 18.07 (4, 48.60 (4 and 9.13 (5° with the phenyl rings. In the crystal, adjacent molecules are connected via intermolecular C—H...O hydrogen bonds, forming dimers. Furthermore, the crystal structure is stabilized by weak C—H...π and π–π interactions, with centroid–centroid distances of 3.6808 (5 Å.

  10. Synthesis and crystal structure studies of ethyl 5-methyl-1, 3-diphenyl-1H-pyrazole-4-carboxylate

    Science.gov (United States)

    Chandra, Srikantamurthy, N.; Babu, E. A. Jithesh; Umesha, K. B.; Mahendra, M.

    2014-04-01

    The title compound, C19H18N2O2, was investigated by single crystal X-ray diffraction method. It crystallizes in monoclinic class under the space group P21/c with cell parameters a= 8.4593(4) Å, b=15.6284(6) Å, c=12.4579(5) Å, α=90°, β=98.241(3)°, γ=90° and Z=2. The ethoxycarbonyl group is slightly twisted from the pyrazole ring, and adopts syn-periplanar conformation. The crystal structure is stabilized by intermolecular C-H….O hydrogen bonds, which help in stabilizing the crystal structure.

  11. 1-[(6-Chloro-3-pyridylmethyl]-N-(4-ethoxyphenyl-3-phenyl-1H-pyrazole-5-carboxamide

    Directory of Open Access Journals (Sweden)

    Zheng Tang

    2009-04-01

    Full Text Available In the title compound, C24H21ClN4O2, the pyrazole ring makes dihedral angles of 7.70 (11, 89.17 (11 and 40.68 (11° with the phenyl, pyridine and ethoxyphenyl rings, respectively. There are some intramolecular C—H...O and C—H...π bonds giving rigidity to the molecule, while weak intermolecular N—H...N and C—H...π hydrogen bonds link the molecules into a two-dimensional structure.

  12. 4-[2-(4-Chlorophenylhydrazinylidene]-3-methyl-1H-pyrazol-5(4H-one

    Directory of Open Access Journals (Sweden)

    Balakrishna Kalluraya

    2011-10-01

    Full Text Available In the title compound, C10H9ClN4O, the pyrazole ring [maximum deviation = 0.014 (2 Å] forms a dihedral angle of 7.06 (14° with the chlorobenzene ring. The molecular conformation is stabilized by an intramolecular N—H...O hydrogen bond, which generates an S(6 ring motif. In the crystal, inversion dimers linked by pairs of C—H...O hydrogen bonds generate R22(16 ring motifs. The dimers are further connected by N—H...N hydrogen bonds, thereby forming layers lying parallel to the bc plane.

  13. Cycloisomerization of acetylenic oximes and hydrazones under gold catalysis: Synthesis and cytotoxic evaluation of isoxazoles and pyrazoles

    Indian Academy of Sciences (India)

    J C Jeyaveeran; Chandrasekar Praveen; Y Arun; A A M Prince; P T Perumal

    2016-01-01

    The synthesis of substituted isoxazoles and pyrazoles through a general cycloisomerization methodology has been reported. The capability of gold(III) chloride to promote cycloisomerization of both , -acetylenic oximes and , -acetylenic hydrazones is the centrepiece of the strategy. A range of acetylenic precursors were investigated to afford 28 examples of the products with good to excellent chemical yields. Selected compounds were screened for their cytotoxic potential towards COLO320 cancer cell lines. The IC50 values of the tested compounds were in the micromolar range, with the best compound, 5-(6-Methoxy-naphthalen-2-yl)-3-phenyl-isoxazole (3h) displaying an IC50 of 38.9 M. For this compound, the crystal structure in complex with Aurora-A kinase was obtained which revealed details of its binding mode within the active site with a free energy of binding -9.54 kcal/mol.

  14. 5-Methyl-1-[(4-methylphenylsulfonyl]-1H-pyrazol-3-yl 4-methylbenzenesulfonate

    Directory of Open Access Journals (Sweden)

    Shahzad Murtaza

    2012-07-01

    Full Text Available In the title compound, C18H18N2O5S2, the tolyl rings are oriented at a dihedral angle of 16.15 (11° with respect to one another. The 5-methyl-1H-pyrazol-3-ol ring is roughly planar (r.m.s. deviation = 0.0231 Å and subtends angles of 73.82 (8 and 89.85 (8° with the tolyl rings. In the crystal, very weak π–π interactions between tolyl groups, with centroid–centroid distances of 4.1364 (19 and 4.0630 (16 Å, together with a C—H...π contact generate a three-dimensional network.

  15. Tris(ethylenediaminenickel(II 1H-pyrazole-3,5-dicarboxylate 1.67-hydrate

    Directory of Open Access Journals (Sweden)

    Güneş Demirtaş

    2010-08-01

    Full Text Available The asymmetric unit of the title compound, [Ni(C2H8N23](C5H2N2O4·1.67H2O, consists of three [Ni(en3]2+ dications (en is ethylenediamine, three [(pzdc3]2− dianions (pzdc is pyrazole-3,5-dicarboxylate and five water molecules. In each complex dication, the NiII atom is coordinated by six N atoms from three en ligands forming a distorted octahedral coordination geometry. In the crystal, the ions and water molecules are linked into a three-dimensional framework by a large number of N—H...O and O—H...O hydrogen bonds.

  16. Tetra-μ-oxido-tetrakis{dioxido[3-(2-pyridyl-1H-pyrazole]molybdenum(VI}

    Directory of Open Access Journals (Sweden)

    Dacheng Li

    2009-09-01

    Full Text Available In the title compound, [Mo4O12(C8H7N34], the MoVI ion has a distorted octahedral coordination completed by two terminal O atoms, two μ-oxide atoms and two N atoms from one 3-(2-pyridyl-1H-pyrazole ligand. It is noteworthy that in the tetranuclear unit (overline4 symmetry, any three MoVI atoms define a plane, and the fourth lies 1.8 (1 Å out of that plane. The degree of linearity of the oxide bridges between two Mo atoms is 175.38 (13°. Moreover, the N—H group forms an intramolecular hydrogen bond (four per molecule.

  17. Octaaquabis(μ2-1H-pyrazole-3,5-dicarboxylatotricopper(II tetrahydrate

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Li

    2010-02-01

    Full Text Available In the trinucler CuII complex molecule of the title compound, [Cu3(C5HN2O42(H2O8]·4H2O, the central CuII atom is located on an inversion centre and is coordinated in a distorted octahedral geometry. The equatorial sites are occupied by two N and two O atoms from two pyrazole-3,5-dicarboxylate ligands and the axial positions are occupied by two water molecules. The two other symmetry-related CuII atoms are pentacoordinated and assume a square-pyramidal geometry. In the crystal structure, coordinated and uncoordinated water molecules and carboxylate O atoms are linked by O—H...O hydrogen bonds.

  18. Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents.

    Science.gov (United States)

    Kamal, Ahmed; Shaik, Anver Basha; Jain, Nishant; Kishor, Chandan; Nagabhushana, Ananthamurthy; Supriya, Bhukya; Bharath Kumar, G; Chourasiya, Sumit S; Suresh, Yerramsetty; Mishra, Rakesh K; Addlagatta, Anthony

    2015-03-06

    A series of twenty one compounds with pyrazole and oxindole conjugates were synthesized by Knoevenagel condensation and investigated for their antiproliferative activity on different human cancer cell lines. The conjugates are comprised of a four ring scaffold; the structural isomers 12b and 12c possess chloro-substitution in the D ring. Among the congeners 12b, 12c, and 12d manifested significant cytotoxicity and inhibited tubulin assembly. Treatments with 12b, 12c and 12d resulted in accumulation of cells in G2/M phase, disruption of microtubule network, and increase in cyclin B1 protein. Zebrafish screening revealed that 12b, and 12d caused developmental defects. Docking analysis demonstrated that the congeners occupy the colchicine binding pocket of tubulin.

  19. Solvatochromic and single crystal studies of 3-(4-bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde

    Science.gov (United States)

    Singh, Pramod; Rawat, B. S.; Negi, Jagmohan S.; Pant, Geeta Joshi nee; Rawat, M. S. M.; Joshi, G. C.; Thapliyal, K.

    2013-04-01

    The structure of 3-(4-bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde was determined by using X-ray diffraction analysis. Photophysical studies of the title compound were investigated in the solvents with different polarities. The emission spectrum of the compound was recorded in polar solvent DMSO (356 nm). In different solvents the extinction coefficients and quantum yield of the compound vary from 1.88 × 104 to 3.53 × 104 and 0.01 to 0.25, respectively. The ratio of the dipole moment of excited state to the dipole moment of ground state was calculated by using solvatochromic shift methods.

  20. Isatin-pyrazole benzenesulfonamide hybrids potently inhibit tumor-associated carbonic anhydrase isoforms IX and XII.

    Science.gov (United States)

    Ibrahim, Hany S; Abou-Seri, Sahar M; Tanc, Muhammet; Elaasser, Mahmoud M; Abdel-Aziz, Hatem A; Supuran, Claudiu T

    2015-10-20

    New series of benzenesulfonamide derivatives incorporating pyrazole and isatin moieties were prepared using celecoxib as lead molecule. Biological evaluation of the target compounds was performed against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more precisely against the human isoforms hCA I, II (cytosolic), IX and XII (transmembrane, tumor-associated enzymes). Most of the tested compounds efficiently inhibited hCA I, II and IX, with KIs of 2.5-102 nM, being more effective than the reference drug acetazolamide. Compounds 11e, 11f, 16e and 16f were found to inhibit hCA XII with Ki of 3.7, 6.5, 5.4 and 7.2 nM, respectively. Compounds 11e and 16e, with 5-NO2 substitution on the isatin ring, were found to be selective inhibitors of hCA IX and hCA XII. Docking studies revealed that the NO2 group of both compounds participate in interactions with Asp132 within the hCA IX active site, and with residues Lys67 and Asp130 in hCA XII, respectively.

  1. Inhibition of 3(17)beta-hydroxysteroid dehydrogenase from Pseudomonas testosteroni by steroidal A ring fused pyrazoles.

    Science.gov (United States)

    Levy, M A; Holt, D A; Brandt, M; Metcalf, B W

    1987-04-21

    Several 2,3- and 3,4-steroidal fused pyrazoles have been investigated as potential inhibitors of NAD(P)H-dependent steroid oxidoreductases. These compounds are proven to be potent, specific inhibitors for 3(17) beta-hydroxysteroid dehydrogenase from Pseudomonas testosteroni with Ki values of 6-100 nM. In contrast, the activities of 3 alpha,20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans, steroid 5 alpha-reductase from rat prostate, and 3 alpha-hydroxysteroid dehydrogenase from rat liver were unaffected by micromolar concentrations of these compounds. Product and dead-end inhibition studies indicate an ordered association to the beta-dehydrogenase with the cofactor binding prior to substrate or inhibitor. From the results of double inhibition experiments, it is proposed that inhibition occurs through formation of an enzyme-NAD+-inhibitor ternate. On the basis of pH profiles of Vm/Km, Vm, and 1/Ki and of absorbance difference spectra, a hypothetical mechanism of inhibition by the steroidal pyrazoles, drawn by analogy from the inhibition of liver alcohol dehydrogenase by alkylpyrazoles [Theorell, H., & Yonetani, T. (1963) Biochem. Z. 338, 537-553; Andersson, P., Kvassman, J. K., Lindström, A., Oldén, B., & Pettersson, G. (1981) Eur. J. Biochem. 113, 549-554], is reconsidered. The pH studies and enzyme modification experiments by diethyl pyrocarbonate suggest the involvement of histidine in binding of the inhibitor. A modified proposal for the structure of the enzyme-NAD+-steroidal pyrazole complex is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. POMA analyses as new efficient bioinformatics' platform to predict and optimise bioactivity of synthesized 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.

    Science.gov (United States)

    Ahsan, Mohamed Jawed; Govindasamy, Jeyabalan; Khalilullah, Habibullah; Mohan, Govind; Stables, James P

    2012-12-01

    A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chlorophenyl)-N-(4-fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D07) was found to be the most active with IC(50)>4.83 μM and CC(50) 4.83 μM. 3-(4-Fluorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carbothioamide (D41) was found to be the most active compound against bacterial strains with MIC of 4 μg/ml, comparable to the standard drug ciprofloxacin while 3-(4-methoxyphenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D38) was found to be the most active compound against fungal strains with MIC 2-4 μg/ml, however less active than standard fluconazole. Toxicities prediction by Osiris were well supported and experimentally verified with exception of some compounds. In anticonvulsant screening, 3-(4-fluorophenyl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (D09) showed maximum activity showing 100% (4/4, 0.25-0.5h) and 75% (3/4, 1.0 h) protection against minimal clonic seizure test without any toxicity.

  3. Asymmetric synthesis of pyrazoles and pyrazolones employing the reactivity of pyrazolin-5-one derivatives.

    Science.gov (United States)

    Chauhan, Pankaj; Mahajan, Suruchi; Enders, Dieter

    2015-08-21

    Due to the frequent occurrence of the pyrazole core in many important naturally occurring and synthetic molecules, tremendous efforts have been made for their synthesis. The pyrazolin-5-one derivatives have emerged as the most effective substrates for the synthesis of useful pyrazoles and their corresponding pyrazolone derivatives. Recently, the reactivity of pyrazolin-5-ones has been used for the asymmetric synthesis of highly functionalised pyrazole and pyrazolone derivatives by employing organo- and metal-catalysts. This feature article focuses on the progress in the catalytic asymmetric synthesis of pyrazoles and pyrazolones using pyrazolin-5-one derivatives.

  4. Methylation of 5-Amino-3-methylthio-1H-pyrazole Derivatives and Two Related Crystal Structures

    Institute of Scientific and Technical Information of China (English)

    REN, Xue-Ling(任雪玲); WU, Chao(吴超); HU, Fang-Zhong(胡方中); ZOU, Xiao-Mao(邹小毛); YANG, Hua-Zheng(杨华铮)

    2004-01-01

    5-Amino-3-methylthio-1H-pyrazoles are very important building blocks from which a wide variety of pyrazole derivatives can be prepared. When substituted 5-amino-3-methylthio-1H-pyrazole was treated with CH3I, the methylation occurres at endocyclic two nitrogens at the same time. The ratio of isomers in products was depended upon the nature of 4-position substituent in the pyrazole ring. The products were characterized by X-ray diffraction analysis, and the ratios of isomer were explained by means of the results of ab inito calculation.

  5. Synthesis, photoluminescence properties and theoretical insights on 1,3-diphenyl-5-(9-anthryl)-2-pyrazoline and -1H-pyrazole.

    Science.gov (United States)

    Dong, Baoli; Wang, Mingliang; Xu, Chunxiang

    2013-01-01

    1,3-Diphenyl-5-(9-anthryl)-2-pyrazoline and 1,3-diphenyl-5-(9-anthryl)-1H-pyrazole with an anthryl chromophore were synthesized and characterized using (1) H NMR, (13) C NMR, FT-IR, mass spectrometry and elemental analysis. Their optical properties were characterized by UV-vis absorption and fluorescence spectroscopy. It was observed that the absorption and fluorescence spectra of the two compounds showed a red shift with respect to that of anthracene. Pyrazole exhibited high fluorescent quantum yields (Φf  = 0.90 in toluene) while pyrazoline showed nearly no fluorescence in solution. The significant fluorescence divergence of the two similar compounds was investigated theoretically through density functional theory (DFT) calculations. The energetically lowest-lying state S1 in the pyrazoline exhibited both characteristics of locally excited and electron-transfer states that resulted in the fluorescence quenching of anthryl chromophore whereas the S1 state in the pyrazole corresponded to an optically allowed state that led to high fluorescence quantum yields in solutions.

  6. Synthesis, structure-activity relationships, and in vitro antibacterial and antifungal activity evaluations of novel pyrazole carboxylic and dicarboxylic acid derivatives.

    Science.gov (United States)

    Mert, Samet; Kasımoğulları, Rahmi; İça, Tuba; Çolak, Ferdağ; Altun, Ahmet; Ok, Salim

    2014-05-06

    A series of pyrazole-3-carboxylic acid and pyrazole-3,4-dicarboxylic acid derivatives were synthesized, the structures were confirmed by their NMR ((1)H and (13)C) and FT-IR spectra, and elemental analyses. The antibacterial and antifungal activities of the compounds against five bacterial and five fungal pathogens were screened using modified agar well diffusion assay. Most of the molecules have inhibitory effects on both standard and clinical Candida albicans strains. However, only the molecules 8, 10, 21, and 22 demonstrate some inhibitory effects on Candida parapsilosis, Candida tropicalis, and Candida glabrata strains. The structure-antifungal activity relationships of the compounds on the C. albicans strains were investigated by electron-conformational method. The pharmacophores and antipharmacophores responsible for the inhibition and non-inhibition of the C. albicans strains were obtained by electronic and geometrical characteristics of the reactive fragments of the molecules. These fragments along with the associated parameters can be used in designing the future more potent antifungal agents. It has been shown that both the positions of electronegative atoms like F and O in the pyrazole substituents and the amount of the associated charges on such atoms are crucial in regulating the strength of antifungal activity for the C. albicans strain.

  7. Vibrational spectroscopic investigations, molecular dynamic simulations and molecular docking studies of N‧-diphenylmethylidene-5-methyl-1H-pyrazole-3-carbohydrazide

    Science.gov (United States)

    Pillai, Renjith Raveendran; Menon, Vidya V.; Mary, Y. Shyma; Armaković, Stevan; Armaković, Sanja J.; Panicker, C. Yohannan

    2017-02-01

    FT-IR and FT-Raman spectra of N‧-diphenylmethylidene-5-methyl-1H-pyrazole-3-carbohydrazide were recorded and analyzed. Due to the industrial and biological importance of pyrazole derivatives, we have carried out an extensive quantum chemical study on N‧-diphenylmethylidene-5-methyl-1H-pyrazole-3-carbohydrazide. The theoretical ground state geometry and electronic structure of the title molecule were optimized by DFT/B3LYP/6-311G++(d,p) method and compared with those of the crystal data. The wave numbers obtained are assigned by potential energy distribution. The ring breathing modes of the benzene rings are assigned theoretically at 1009 cm-1 for the mono substituted phenyl rings. The first order hyperpolarizability is comparable with that of similar derivatives and 16 times that of the standard NLO material urea. Conformational analysis was conducted in order to locate all possible conformations of the title compound, followed by investigation of local reactivity properties by MEP and ALIE surfaces. Natural bond orbital analysis has been carried out to analyse the stability of the molecule arising from hyper-conjugative interactions and charge delocalization. Further, reactive properties via autoxidation and hydrolysis mechanisms have been assessed through calculations of bond dissociation energies and radial distribution functions. Docking results confirmed that the compound was a potential inhibitor of CDK2s and were in agreement with the previous reported studies.

  8. Infrared spectrum, structural and optical properties and molecular docking study of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde

    Science.gov (United States)

    Mary, Y. Sheena; Panicker, C. Yohannan; Sapnakumari, M.; Narayana, B.; Sarojini, B. K.; Al-Saadi, Abdulaziz A.; Van Alsenoy, C.; War, Javeed Ahmad; Fun, H. K.

    2015-03-01

    The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde have been investigated experimentally and theoretically. The title compound was optimized using at HF and DFT levels of calculations. The B3LYP/6-311++G(d,p) (5D,7F) results and in agreement with experimental infrared bands. The normal modes are assigned using potential energy distribution. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. From molecular electrostatic potential map, it is evident that the negative electrostatic potential regions are mainly localized over the carbonyl group and mono substituted phenyl ring and are possible sites for electrophilic attack and, positive regions are localized around all para substituted phenyl and pyrazole ring, indicating possible sites for nucleophilic attack. First hyperpolarizability is calculated in order to find its role in nonlinear optics. The geometrical parameters are in agreement with experimental data. From the molecular docking studies, it is evident that the fluorine atom attached to phenyl ring and the carbonyl group attached to pyrazole ring are crucial for binding and the results draw us to the conclusion that the compound might exhibit phosphodiesterase inhibitory activity.

  9. Experimental (XRD, IR and NMR) and theoretical investigations on 1-(2-nitrobenzoyl)3,5-bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole

    Science.gov (United States)

    Evecen, Meryem; Tanak, Hasan; Tinmaz, Feyza; Dege, Necmi; Özer İlhan, İlhan

    2016-12-01

    The pyrazole compound 1-(2-nitrobenzoyl)3,5-bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole (I) has been synthesized and characterized by IR, NMR and X-ray diffraction methods. The compound crystallizes in the monoclinic space group C2/c with a = 36.126(5) Ǻ, b = 8.1963(7) Ǻ, c = 14.3983(18) Ǻ, β = 100.825(10)° and Z = 8. The molecular geometry, vibrational frequencies and Gauge-Independent Atomic Orbital (GIAO) 1H and 13C NMR chemical shift values of 1-(2-nitrobenzoyl)3,5-bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole in the ground state have been calculated using the density functional method (B3LYP) with the 6-311++G(d,p) basis set. The optimized parameters are in agreement with X-ray data. The calculated vibrational frequencies and chemical shift values were compared with experimental IR and NMR values. In addition, frontier molecular orbitals, molecular electrostatic potential and NBO analysis of (I) were investigated by DFT calculations.

  10. Synthesis and anticonvulsant activity of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.

    Science.gov (United States)

    Ahsan, Mohamed Jawed; Khalilullah, Habibullah; Stables, James P; Govindasamy, Jeyabalan

    2013-06-01

    A series of fourteen 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues were synthesized and evaluated for anticonvulsant activity according to the Antiepileptic Drug Development Programme (ADD) protocol. Some of the synthesized compounds showed significant activity in minimal clonic seizure model (6 Hz psychomotor seizure test). 3-(4-Fluorophenyl)-N-(4-bromophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4c) was found to be the most active compound of the series showing 75% (3/4, 0.25-2.0 h) and 50% (2/4, 4.0 h) protection against minimal clonic seizure at 100 mg/kg without any toxicity. 3-(Pyridin-4-yl)-N-(4-chlorophenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide (4f) showed protection in maximal electroshock (MES) seizure and subcutaneous metrazol (scMET) seizure at 300 mg/kg.

  11. Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

    Directory of Open Access Journals (Sweden)

    Shijie Du

    2015-05-01

    Full Text Available A series of novel 3-(difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-ylphenyl-3-(difluoro-methyl-1-methyl-1H-pyrazole-4-carboxamide (9m exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

  12. Crystal structure of ethyl N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-di­hydro-1H-pyrazol-4-yl)carbamate

    Science.gov (United States)

    Danish, Muhammad; Tahir, Muhammad Nawaz; Anwar, Uzma; Raza, Muhammad Asam

    2015-01-01

    In the title compound, C14H17N3O3, the dihedral angle between the benzene ring and the five-membered di­hydro­pyrazole ring is 52.26 (9)°. The ethyl ester group is approximately planar (r.m.s. deviation 0.0568 Å) and subtends an angle 67.73 (8)° to the pyrazole ring. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(10) ring motif. Weaker C—H⋯O contacts link these dimers into a three-dimensional network of mol­ecules stacked along the a-axis direction. Offset π–π stacking inter­actions between the benzene rings [centroid-to-centroid distance = 3.8832 (12) Å] further stabilize the crystal packing. PMID:26029449

  13. Bis(acetato-κ2O,O′bis(3,5-dimethyl-1H-pyrazole-κN2copper(II

    Directory of Open Access Journals (Sweden)

    Yuliya M. Davydenko

    2009-06-01

    Full Text Available In the title compound, [Cu(C2H3O22(C5H8N22], the CuII atom has a distorted tetragonal–bipyramidal geometry, with the equatorial plane formed by two N atoms belonging to two 3,5-dimethyl-1H-pyrazole ligands and two O atoms from two acetate anions. The second O atoms of the acetate groups provide elongated Cu—O axial contacts, so that the acetates appear to be coordinated in a pseudo-chelate fashion. The pyrazole ligands are situated in cis positions with respect to each other. In the crystal structure, molecules are linked through intermolecular N—H...O hydrogen bonds, forming a one-dimensional chain.

  14. Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines.

    Science.gov (United States)

    Bertuzzi, G; Locatelli, E; Colecchia, D; Calandro, P; Bonini, B F; Chandanshive, J Z; Mazzanti, A; Zani, P; Chiariello, M; Comes Franchini, M

    2016-07-19

    In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,β-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15-60 μM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.

  15. N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl­benzene­sulfonamide

    Science.gov (United States)

    da Silva, Luiz Everson; de Sousa Jr, Paulo Teixeira; Dall’Oglio, Evandro Luiz; Foro, Sabine

    2008-01-01

    In the title compound, C18H19N3O3S, the phenyl ring and the pyrazole ring are twisted with respect to each other by an angle of 49.11 (7)°. The C—N—S—C torsion angle is −122.5 (2)°. The methyl group bonded to the N atom of the pyrazole ring has a large deviation from the mean ring plane of 0.603 (3) Å. One inter­molecular N—H⋯O and two non-classical inter­molecular C—H⋯O hydrogen bonds are observed in the crystal structure. PMID:21200928

  16. Rhenium-mediated coupling of acetonitrile and pyrazoles. New molecular clefts for anion binding.

    Science.gov (United States)

    Arroyo, Marta; Miguel, Daniel; Villafañe, Fernando; Nieto, Sonia; Pérez, Julio; Riera, Lucía

    2006-08-21

    The reaction of fac-[ReBr(CO)3(NCMe)2] (1) with either pyrazole (Hpz) or 3,5-dimethylpyrazole (Hdmpz) in a 1:2 Re/pyrazole ratio affords the known complexes fac-[ReBr(CO)3(Hpz)2] (2) and [ReBr(CO)3(Hdmpz)2] (3). Using a 1:1 ratio, MeCN as solvent, and longer reaction times led to a mixture in which the major components are the pyrazolylamidino complexes fac-[ReBr(CO)3(HN=C(CH3)pz-kappa2N,N)] (4) and fac-[ReBr(CO)3(HN=C(CH3)dmpz-kappa2N,N)] (5). The complexes fac-[ReBr(CO)3(Hpz)(NCMe)] (6) and fac-[ReBr(CO)3(Hdmpz)(NCMe)] (7) (along with 2 and 3) were found to be minor components of these reactions. Analogous reactions of fac-[Re(OClO3)(CO)3(NCMe)2] yielded fac-[Re(NCCH3)(CO)3(HN=C(CH3)pz-kappa2N,N)]ClO4 (8), fac-[Re(NCCH3)(CO)3(HN=C(CH3)dmpz-kappa2N,N)]ClO4 (9), fac-[Re(Hpz)(CO)3(HN=C(CH3)pz-kappa2N,N)]ClO4 (10), and fac-[Re(Hdmpz)(CO)3(HN=C(CH3)dmpz-kappa2N,N)]ClO4 (11). The X-ray structure of 11 showed the perchlorate anion to be hydrogen-bonded by the N-H groups of the pyrazole and pyrazolylamidino ligands. The behavior of the compound fac-[Re(Hdmpz)(CO)3(HN=C(CH3)dmpz-kappa2N,N)]BAr'4 (13) (synthesized by reaction of [ReBr(CO)3(Hdmpz)2] (3) with (i) AgOTf and (ii) NaBAr'(4)/MeCN) as an anion receptor has been studied in CD3CN solution. In addition, the structure of the supramolecular adduct fac-[Re(CO)3(Hdmpz)(HN=C(CH3)dmpz-kappa2N,N)].Cl (14), featuring chloride binding by the two N-H groups, was determined by X-ray diffraction.

  17. Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities.

    Science.gov (United States)

    Tzanetou, Evangelia; Liekens, Sandra; Kasiotis, Konstantinos M; Fokialakis, Nikolas; Haroutounian, Serkos A

    2012-10-01

    The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values of 1.5 ± 0.4 µM and 5.6 ± 2.5 µM, respectively, against MCF-7 cells. In addition, the indazole derivative 16 was assessed as a competent inhibitor of endothelial tube formation at 30 µM.

  18. Design, synthesis and hypoglycemic activity of 3-methyl-1-phe nyl-4-{ 4-[ ( 5-m et hyl-2-phenyloxazol-4-yl) methoxy ] benzylene (benzyl) }-2-pyrazol-5-one

    Institute of Scientific and Technical Information of China (English)

    Xing LIU; Yalou WANG; Guanzhong WU; Jiangchuan LI; Xiaoyan WU

    2008-01-01

    Based on the SAR (structure activity relation-ship) of TZDs (thiazolidinediones), 3-methyl-1-phenyl-2-pyrazoline-5-one was selected as a substitute for TZD. Compounds of 3-methyl- 1-phenyl-4- {4-[(5-methyl-2-phe-nyloxazol-4-yl)methoxy]benzylene(benzyl) }-2-pyrazol-5-one were designed and synthesized to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. Butanedione monoxime reacted with (substituted) benzaldehyde via cyclization and chlorination to give 4-(chloromethyl)-5-methyl-2-phenyloxazole derivatives, which condensed with 4-hydroxybenzaldehyde or vanillin, and was followed by the Knoevenagel reaction with 3-methyl-1-phenyl-2-pyrazol-5-one to give compounds Ⅰa-Ⅰh. Compounds Ⅰa-Ⅰh were hydrogenated with Pd-C to giveⅡa-Ⅱh, and their hypoglycemic activity was evaluated with a glucose oxidase kit and insulin load test on normal mice. Sixteen new target compounds were synthesized. All the com-pounds were characterized by 1H NMR, IR, MS and elemental analysis. The preliminary pharmacological tests show that the compounds have good hypoglycemic activity and can enhance the action of insulin, especially Ib, Id and If.

  19. Structure elucidation of the designer drug N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide and the relevance of predicted (13) C NMR shifts - a case study.

    Science.gov (United States)

    Girreser, Ulrich; Rösner, Peter; Vasilev, Andrej

    2016-07-01

    The detailed structure elucidation process of the new cannabimimetic designer drug, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, with a highly substituted pyrazole skeleton, using nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric (MS) techniques is described. After a first analysis of the NMR spectra and comparison with 48 possible pyrazole and imidazole structures, a subset of six positional isomeric pyrazoles and six imidazoles remained conceivable. Four substituents of the heterocyclic skeleton were identified: a proton bound to a pyrazole ring carbon atom; a 5-fluoropentyl group; a 4-fluorophenyl substituent; and a carbamoyl group, which is N-substituted with a methyl residue carrying a tert.-butyl and a carbamoyl substituent. The 5-fluoropentyl residue is situated at the nitrogen ring atom. Additional NMR experiments like the (1) H,(13) C HMBC were performed, but due to the small number of signals based on long-range couplings, the comparison of predicted and observed (13) C chemical shifts became necessary. The open access Internet shift prediction programs NMRDB, NMRSHIFTDB2, and CSEARCH were employed for the prediction of (13) C shift values which allowed an efficient and unambiguous structure determination. For the identified N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide, the best agreement between predicted (13) C shifts and the observed chemical shifts and long-range couplings for the pyrazole ring carbon atoms, with a standard error of about 2 ppm, was found with each of the predictions. For the comparison of measured and predicted chemical shifts model compounds with simple substituents proved helpful. The identified compound is a homologue of AZ-037 which is offered by Internet suppliers. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells.

    Science.gov (United States)

    Kosikowska, Urszula; Malm, Anna; Pitucha, Monika; Rajtar, Barbara; Polz-Dacewicz, Malgorzata

    2014-01-01

    During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49-31.25 μg ml(-1)) and H. influenzae (MIC = 0.24-31.25 μg ml(-1)) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24-31.25 μg ml(-1)) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml(-1)). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.

  1. SYNTHESIS, CHARACTERIZATION AND BIOCIDAL ACTIVITY OF NOVEL HALOGENATED - 4-[(SUBSTITUTED-BENZOTHIAZOL-2-YL HYDRAZONO]-2-(SUBSTITUTED-PHENYL-5-METHYL /ETHOXY -2,4-DIHYDRO-PYRAZOL-3-ONE DERIVATIVES Synthese, Charakterisierung und biozide Aktivität NOVEL HALOGENIERTEN - 4 - [(substituiertes-benzothiazol-2-YL hydrazono] -2 -(Substituiertes Phenyl-5-Methyl / ETHOXY -2,4-DIHYDRO-pyrazol-3-ONE DERIVATE

    Directory of Open Access Journals (Sweden)

    V. Khatri, K. Sharma, V. Sareen, D. Shinde and S. Sareen

    2012-04-01

    Full Text Available Some new 4-[(substituted-benzothiazol-2-ylhydrazono]-2-(substituted-phenyl-5- methyl/ethoxy-2,4-dihydro-pyrazol-3-one(4 have been synthesized by reacting substituted 2- amino benzothiazol (1 with acetoacetic ester and malonic ester (2. 2-[(substituted-benzothiazol- 2-ylhydrazono]-3-oxo-butyric acid ethyl ester and 2-[(substituted-benzothiazol-2- ylhydrazono]- malonic acid diethyl ester (3 react with different hydrazines to give the title compounds(4. These compounds are evaluated for their antifungal and insecticidal activity. The structures of all these compounds have been confirmed by IR, 1H NMR, mass spectra and elemental analysis data.

  2. Studies on magnetic properties of unique molecular magnet {[FeII(pyrazole)4]2[NbIV(CN)8]•4H2O}n

    Science.gov (United States)

    Konieczny, P.; Pełka, R.; Zieliński, P. M.; Wasiutyński, T.; Pinkowicz, D.; Sieklucka, B.

    2013-01-01

    In this paper magnetic properties of hybrid inorganic-organic compound {[FeII(pyrazole)4]2[NbIV(CN)8]•4H2O}n are presented. This is a three dimensional molecular magnet with well localized magnetic moments, which make it a suitable candidate for testing magnetic models. In order to characterize the magnetic properties of the above compound we performed the AC/DC magnetometry in the range 0-5 T. The special attention was paid to the phase transition at 7.9 K. The study in magnetic field supports magnetic ordering below 7.9 K.

  3. Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

    Directory of Open Access Journals (Sweden)

    Denisa Tarabová

    2014-04-01

    Full Text Available Activated enol ethers derived from esters or the dinitrile of malonic acid, or from pentane-2,4-dione were treated with hydrazine hydrate. The structures of the obtained products – pyrazoles 5 – were studied with a focus on tautomerism and supramolecular structure. A reverse addition of the reagents led to the isolation of two novel products, namely bis-enehydrazines 6 with an unsymmetrical arrangement of the formally equivalent subunits.

  4. 40 CFR 721.987 - Dialkylaminophenyl imino pyrazole acid ester (generic).

    Science.gov (United States)

    2010-07-01

    ... ester (generic). 721.987 Section 721.987 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.987 Dialkylaminophenyl imino pyrazole acid ester (generic). (a) Chemical... as dialkylaminophenyl imino pyrazole acid ester (PMN P-98-45) is subject to reporting under...

  5. Copper-mediated pyrazole synthesis from 2,3-allenoates or 2-alkynoates, amines and nitriles.

    Science.gov (United States)

    Chen, Bo; Zhu, Can; Tang, Yang; Ma, Shengming

    2014-07-21

    An efficient copper-mediated three-component reaction of 2,3-allenoates or 2-alkynoates, amines, and nitriles affording fully substituted pyrazoles with a very nice diversity has been developed. A tandem conjugate addition, 1,2-addition, and N-N bond formation mechanism has been proposed for this diverse synthesis of pyrazoles based on mechanistic studies.

  6. Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates.

    Science.gov (United States)

    Babinski, David J; Aguilar, Hector R; Still, Raymond; Frantz, Doug E

    2011-08-05

    The synthesis of 3,4,5-trisubstituted pyrazoles via a tandem catalytic cross-coupling/electrocyclization of enol triflates and diazoacetates is presented. The initial scope of this methodology is demonstrated on a range of differentially substituted acyclic and cyclic enol triflates as well as an elaborated set of diazoacetates to provide the corresponding pyrazoles with a high degree of structural complexity.

  7. 5-(2-Chlorophenoxy-1,3-dimethyl-1H-pyrazole-4-carbaldehyde oxime

    Directory of Open Access Journals (Sweden)

    Hai-Jun Zhang

    2012-07-01

    Full Text Available In the title molecule, C12H12ClN3O2, the benzene and pyrazole rings are inclined to each other at a dihedral angle of 83.3 (3°. In the crystal, molecules are linked into [010] chains via O—H...N hydrogen bonds with the unsubstituted pyrazole N atom acting as the acceptor.

  8. Pyrazole antagonists of the CB1 receptor with reduced brain penetration.

    Science.gov (United States)

    Fulp, Alan; Zhang, Yanan; Bortoff, Katherine; Seltzman, Herbert; Snyder, Rodney; Wiethe, Robert; Amato, George; Maitra, Rangan

    2016-03-01

    Type 1 cannabinoid receptor (CB1) antagonists might be useful for treating obesity, liver disease, metabolic syndrome, and dyslipidemias. Unfortunately, inhibition of CB1 in the central nervous system (CNS) produces adverse effects, including depression, anxiety and suicidal ideation in some patients, which led to withdrawal of the pyrazole inverse agonist rimonabant (SR141716A) from European markets. Efforts are underway to produce peripherally selective CB1 antagonists to circumvent CNS-associated adverse effects. In this study, novel analogs of rimonabant (1) were explored in which the 1-aminopiperidine group was switched to a 4-aminopiperidine, attached at the 4-amino position (5). The piperidine nitrogen was functionalized with carbamates, amides, and sulfonamides, providing compounds that are potent inverse agonists of hCB1 with good selectivity for hCB1 over hCB2. Select compounds were further studied using in vitro models of brain penetration, oral absorption and metabolic stability. Several compounds were identified with predicted minimal brain penetration and good metabolic stability. In vivo pharmacokinetic testing revealed that inverse agonist 8c is orally bioavailable and has vastly reduced brain penetration compared to rimonabant.

  9. Crystal structure of 3-(thio-phen-2-yl)-5-p-tolyl-4,5-di-hydro-1H-pyrazole-1-carbo-thio-amide.

    Science.gov (United States)

    Naveen, S; Pavithra, G; Abdoh, Muneer; Ajay Kumar, K; Warad, Ismail; Lokanath, N K

    2015-07-01

    In the title compound, C15H15N3S2, the central pyrazole ring adopts a twisted conformation on the -CH-CH2- bond. Its mean plane makes dihedral angles of 7.19 (12) and 71.13 (11)° with those of the thio-phene and toluene rings, respectively. The carbothi-amide group [C(=S)-N] is inclined to the pyrazole ring mean plane by 16.8 (2)°. In the crystal, mol-ecules are linked by N-H⋯S hydrogen bonds, forming chains propagating along [010]. Within the chains, there are N-H⋯π inter-actions present. Between the chains there are weak parallel slipped π-π inter-actions involving inversion-related thio-phene and pyrazole rings [inter-centroid distance = 3.7516 (14) Å; inter-planar distance = 3.5987 (10) Å; slippage = 1.06 Å].

  10. A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents.

    Science.gov (United States)

    Nassar, Ibrahim F; Atta-Allah, Saad R; Elgazwy, Abdel-Sattar S Hamad

    2015-06-01

    An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, d-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.

  11. Evidence of Polymorphism on the Antitrypanosomal Naphthoquinone (4E)-2-(1H-Pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one

    Science.gov (United States)

    Sperandeo, Norma R.; Faudone, Sonia N.

    2013-01-01

    The aim of this study was to characterize the solid state properties of (4E)-2-(1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a compound with a significant inhibitory activity against Trypanosoma cruzi, the etiological agent of Chagas disease (American trypanosomiasis). Methods used included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by crystallization from absolute methanol and 2-propanol-water that exhibited different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on heating desolvated leading to the anhydrous modification BiPNQ-I. It was determined that FTIR, DSC, and PXRD are useful techniques for the characterization and identification of the crystalline modifications of BiPNQ. PMID:24106678

  12. Synthesis of New Substituted Chromen[4,3-c]pyrazol-4-ones and Their Antioxidant Activities

    Directory of Open Access Journals (Sweden)

    Abdullah Sulaiman Al-Ayed

    2011-12-01

    Full Text Available A series of new coumarin derivatives 4 containing a 4-arylbut-3-en-2-one moiety were synthesized by condensation of 3-acetylcoumarin 1 with aryl aldehydes 2 in chloroform in the presence of piperidine. The interactions of 3-formyl-4-chlorocoumarin (3 with nitrogen-containg nucleophiles leading to the corresponding substituted chromen-[4,3-c]pyrazol-4-ones 5 are described. The structures of the obtained compounds were established on the basis of 1D NMR, 2D NMR and IR and further the compounds were evaluated for possible antioxidant activities. The coumarinic chalcone 4a has been found to be the most active (IC50 = 2.07 μM in this study.

  13. Enamine Configuration of 5-Methyl-2-phenyl-4-[(Z)-3-tolylamino-phenylmethylene]pyrazol-3(2H)-one

    Institute of Scientific and Technical Information of China (English)

    QIAO Yu-Qin; Lü Xing-Qiang; BAO Feng; KANG Bei-Sheng

    2005-01-01

    Compound 5-methyl-2-phenyl-4-[(Z)-3-tolylamino-phenylmethylene]pyrazol-3(2H)-c = 12.035(4)(。A), α = 97.896(6), β = 103.865(6), γ = 107.950(6)°, Mr= 367.44, Z = 2, V= 993.2(6)(。A)3,Dc = 1.229 g/cm3,μ(MoKα) = 0.077 mm 1 and F(000) = 388.The structure was refined to R =0.0444 and wR = 0.1199 for 2903 observed reflections (I > 2σ(I)).The results of 1H NMR and single-crystal X-ray diffraction studies showed the enamine character of the compound.The strong intramolecular hydrogen bonds in the large conjugate system, together with weak intermolecular supramolecular network.

  14. Synthesis, molecular docking, and biological evaluation of some novel hydrazones and pyrazole derivatives as anti-inflammatory agents.

    Science.gov (United States)

    Mohammed, Khaled O; Nissan, Yassin M

    2014-10-01

    2-Hydrazinyl-N-(4-sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4-10 and pyrazole derivatives 11-17. All compounds were tested for their in vivo anti-inflammatory activity and their ability to inhibit the production of PGE(2) in serum samples of rats. IC(50) values for the most active compounds for inhibition of COX-1 and COX-2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti-inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15-17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17. Compound 17 showed good selectivity index value of 11.1 for COX-1/COX-2 inhibition in vitro.

  15. Evidence of the in vitro genotoxicity of methyl-pyrazole pesticides in human cells.

    Science.gov (United States)

    Graillot, Vanessa; Tomasetig, Florence; Cravedi, Jean-Pierre; Audebert, Marc

    2012-10-09

    Consumers are exposed daily to several pesticide residues in food, which can be of potential concern for human health. Based on a previous study dealing with exposure of the French population to pesticide residues via the food, we selected 14 pesticides frequently found in foodstuffs, on the basis of their persistence in the environment or their bioaccumulation in the food chain. In a first step, the objective of this study was to investigate if the 14 selected pesticides were potentially cytotoxic and genotoxic. For this purpose, we used a new and sensitive genotoxicity assay (the γH2AX test, involving phosphorylation of histone H2AX) with four human cell lines (ACHN, SH-SY5Y, LS-174T and HepG2), each originating from a potential target tissue of food contaminants (kidney, nervous system, colon, and liver, respectively). Tebufenpyrad was the only compound identified as genotoxic and the effect was only observed in the SH-SY5Y neuroblastoma cell-line. A time-course study showed that DNA damage appeared early after treatment (1h), suggesting that oxidative stress could be responsible for the induction of γH2AX. In a second step, three other pesticides were studied, i.e. bixafen, fenpyroximate and tolfenpyrad, which - like tebufenpad - also had a methyl-pyrazole structure. All these compounds demonstrated genotoxic activity in SH-SY5Y cells at low concentration (nanomolar range). Complementary experiments demonstrated that the same compounds show genotoxicity in a human T-cell leukemia cell line (Jurkat). Moreover, we observed an increased production of reactive oxygen species in Jurkat cells in the presence of the four methyl-pyrazoles. These results demonstrate that tebufenpyrad, bixafen, fenpyroximat and tolfenpyrad induce DNA damage in human cell lines, very likely by a mode of action that involves oxidative stress. Nonetheless, additional in vivo data are required before a definitive conclusion can be drawn regarding hazard prediction to humans. © 2012

  16. Modulating structural dimensionality of cadmium(II) coordination polymers by means of pyrazole, tetrazole and pyrimidine derivative ligands

    Science.gov (United States)

    Seco, Jose Manuel; Calahorro, Antonio; Cepeda, Javier; Rodríguez-Diéguez, Antonio

    2015-06-01

    Six new compounds with functionalized pyrazole, tetrazole, and pyrimidine ligands, namely [Cd(μ-4-Hampz)(μ-Cl)2]n(1), [Cd(μ3-pzdc)(μ-H2O)(H2O)]n(2), [Cd(μ-5-amtz)2(eda)]n(3), {[Cd9(μ4-5-amtz)8(μ-Cl)10(H2O)2]ṡxH2O}n(4), {[Cd2(μ-dm2-pmc)2Cl2(H2O)2]ṡH2O}n(5), and [Cd2(μ-Br2-pmc)(μ-Cl)3(H2O)2]n(6) (where 4-Hampz = 4-aminopyrazole, pzdc = 3,5-pyrazoledicarboxylate, 5-amtz = 5-aminotetrazolate, eda = ethylenediamine, dm2-pmc = 4,6-dimethoxy-2-pyrimidinecarboxylate, Br2-pmc = 5-bromopyrimidine-2-carboxylate) have been synthesized under hydrothermal conditions and structurally characterized by single crystal X-ray diffraction. Compounds 1 and 2 share the structural feature of being constructed from dinuclear building units that are further connected through the pyrazole based ligands, rendering a compact and a potentially open 3D frameworks, respectively. On the other hand, 5-amtz ligand exhibits two different coordination modes in compounds 3 and 4 as a result of the presence or absence of an additional blocking ligand. In this way, the μ-κ4N,N‧,N″,N‴ mode in 4 affords robust clusters that are joined in a topologically novel 3D open architecture containing two types of channels, whereas a simple bidentate bridging mode is limited for 5-amtz in 3 due to the presence of the chelating eda ligand. 1D and 3D structures are obtained with pyrimidine ligands in compounds 5 and 6 according to the steric hindrance of the substituents.

  17. PEG mediated synthesis and biological evaluation of asymmetrical pyrazole curcumin analogues as potential analgesic, anti-inflammatory and antioxidant agents.

    Science.gov (United States)

    Jadhav, Shravan Y; Bhosale, Raghunath B; Shirame, Sachin P; Patil, Sandeep B; Kulkarni, Suresh D

    2015-03-01

    The new series of asymmetrical pyrazole curcumin analogues 4a-g were synthesized by using polyethylene glycol (PEG-400) as a green reaction medium and evaluated for their in vivo analgesic and in vitro antioxidant (H2 O2 , DPPH, Ferrous reducing power and Nitric oxide scavenging activity) and anti-inflammatory activities. All the compounds synthesized 4a-g showed the potential to demonstrate analgesic activity as compared to the standard ibuprofen. Among the tested series, compounds 4e and 4b exhibited good hydrogen peroxide scavenging activity as compared to the standard butylated hydroxy toluene (BHT). Compounds 4b, 4d, 4f, and 4g showed good DPPH free radical scavenging activity. Compounds 4b, 4c, 4d, 4e and 4g showed excellent ferrous-reducing power activity, whereas all the compounds showed better nitric oxide scavenging activity than standard ascorbic acid. Additionally, all the synthesized compounds were also screened for their in vitro anti-inflammatory activity. Compounds 4b, 4d, 4f and 4g showed good anti-inflammatory activity as compared to standard diclofenac sodium.

  18. New heterocyclic hybrids of pyrazole and its bioisosteres: design, synthesis and biological evaluation as dual acting antimalarial-antileishmanial agents.

    Science.gov (United States)

    Bekhit, Adnan A; Hassan, Ahmed M M; Abd El Razik, Heba A; El-Miligy, Mostafa M M; El-Agroudy, Eman J; Bekhit, Alaa El-Din A

    2015-04-13

    A new series of pyrazole derivatives were synthesized by hybridization with five-membered heterocyclic moieties such as thiazoles, thiazolidinones, 1,3,4-thiadiazoles and pyrazolines. The compounds were evaluated for their in vivo antimalarial activity against Plasmodium berghei infected mice and the most active derivatives were further examined for their in vitro antimalarial activity against chloroquine resistant (RKL9) strain of Plasmodium falciparum. Compounds 2c, 2d, 4b, 4c, 4d, 5a, 6c, 8c and 9b had more than 90% parasite suppression activity of that found with the antimalarial reference standard drug, chloroquine phosphate and had lower IC50 values than chloroquine. Compounds 4b and 9b were the most active derivatives, and their activities were 5-fold higher than chloroquine. All the newly synthesized compounds were evaluated for their in vitro antileishmanial activity against Leishmania aethiopica promastigotes and amastigote. The results showed that compounds 2c, 2d, 3d, 4b, 4c, 4d and 5a had lower or similar IC50 values than the reference standard drugs, amphotericin B and miltefosine. Compound 3d had the highest antileishmanial activity. Collectively, compounds 2c, 2d, 4b, 4c, 4d and 5a exhibited dual activity against malaria and leishmaniasis and were safe and well tolerated by the experimental animals orally up to 300 mg/kg and parenterally up to 100 mg/kg.

  19. Synthesis, in vitro anticancer evaluation and in silico studies of novel imidazo[2,1-b]thiazole derivatives bearing pyrazole moieties.

    Science.gov (United States)

    Ali, Ahmed R; El-Bendary, Eman R; Ghaly, Mariam A; Shehata, Ihsan A

    2014-03-21

    A series of imidazo[2,1-b]thiazoles bearing pyrazole moieties 4-6(a-c) was synthesized through the reaction of 6-hydrazinylimidazo[2,1-b]thiazoles 3a-c with different β-dicarbonyl compounds. Eleven compounds were screened at the National Cancer Institute (NCI), USA for anticancer activity at a single dose (10 μM). The in vitro anticancer evaluation revealed that compounds 2a and 4-6(a) exhibited increased potency towards CNS SNB-75 and Renal UO-31 cancer cell lines. COMPARE analyses showed strong to considerable correlations with rapamycin (mTOR inhibitor). The results of assessment of toxicities, druglikeness, and drug score profiles of compounds 2a and 4-6(a) are promising. Some of the target compounds showed good docking scores with potential anticancer targets, chosen based on pharmacophore mapping of the established derivatives.

  20. Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines.

    Science.gov (United States)

    Cankara Pirol, Şeyma; Çalışkan, Burcu; Durmaz, Irem; Atalay, Rengül; Banoglu, Erden

    2014-11-24

    We synthesized a series of novel amide derivatives of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid and assessed their antiproliferative activities against three human cancer cell lines (Huh7, human liver; MCF7, breast and HCT116, colon carcinoma cell lines) with the sulforhodamine B assay. Compound 4j with 2-chloro-4-pyridinyl group in the amide part exhibited promising cytotoxic activity against all cell lines with IC50 values of 1.6 μM, 3.3 μM and 1.1 μM for Huh7, MCF7 and HCT116 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G1 phase as an indicator of apoptotic cell death induction. On the basis of their high potency in cellular environment, these straightforward pyrazole-3-carboxamide derivatives may possess potential in the design of more potent compounds for intervention with cancer cell proliferation.

  1. Synthesis, Crystal Structure and Fungicidal Activity of 3- ( 4- Chloro- 3- ethyl- 1 -methyl- 1 H- pyrazol- 5-yl ) - 6- (E) phenylvinyltriazolo [ 3, 4-b ] - 1,3, 4-thiadiazole

    Institute of Scientific and Technical Information of China (English)

    陈寒松; 李正名; 杨小平; 王宏根; 姚心侃

    2000-01-01

    The crystal structure of the title compound 3-(4-Chloro-3-ethyl-1-methyl-1H-pyrazol-5-yl)-6- (E) phenylvinyltriazolo [ 3, 4-b ]-1, 3, 4-thiadiazole ( C17 H15ClN6S, Mr = 370.87) was determined by single crystal X-ray diffraction. The crystal ismonoclinic, space group P21/n, a = 10.862(2), b = 11.541(2), c = 14.994(3) A,β=108.41(3)°, V=1783(1) A, Z=4, Dx =1.381g/cm-3, μ=0.3361 mm-1, andF(000) = 768. The results confirmed that the title compound belongs to type E of ste-reochemistry. The dihedral angle between triazole and 1, 3, 4-thiadiaole ring is 3° andthe torsion angle between 1,3, 4-thiadiazole and pyrazole ring is 134.0°.

  2. Synthesis of diversely 1,3,5-trisubstituted pyrazoles via 5-exo-dig cyclization.

    Science.gov (United States)

    Borkin, Dmitry A; Puscau, Mirela; Carlson, Alena; Solan, Agnes; Wheeler, Kraig A; Török, Béla; Dembinski, Roman

    2012-06-21

    5-Exo-dig cyclocondensation of alk-3-yn-1-ones with hydrazines, in the presence of montmorillonite K-10, provides an effective method with a high atom economy for the synthesis of diversely 1,3,5-trisubstituted pyrazoles. The microwave-accelerated reaction proceeds in the absence of solvent and leads to 5-benzyl substituted pyrazoles with good yields (72-91%). The regiochemistry of the process was confirmed by the X-ray crystallographic structure determination of 1-(2-fluorophenyl)-5-(4-methylbenzyl)-3-phenyl-1H-pyrazole.

  3. Surface, morphology and X-ray diffraction studies of Co (II) complexes of pyrazole ligands

    Science.gov (United States)

    Mishra, A.; Jain, Garima; Ninama, S.

    2014-09-01

    Pyrazole based complexes of the cobalt (II) Bis-(diethyl 4-amino-1-(P-nitrophenyl) 1H-pyrazole-3,5dicarboxylate) [Co (D4A1(P-N)1HP35D)] and cobalt (II) Bis-(diethyl 4- amino-1-(3-chlorophenyl) 1H-pyrazole-3,5dicarboxylate) [Co (D4A1(3-Cl)1HP35D)] were synthesized by chemical root method and characterized by different method viz. X-ray diffraction, Fourier transform infrared spectroscopy and Transmission electron microscopy studies. All these studies were in good agreement with the synthesized complexes.

  4. Complete assignment of NMR data of 22 phenyl-1H-pyrazoles' derivatives.

    Science.gov (United States)

    de Oliveira, Aline Lima; Alves de Oliveira, Carlos Henrique; Mairink, Laura Maia; Pazini, Francine; Menegatti, Ricardo; Lião, Luciano Morais

    2011-08-01

    Complete assignment of (1)H and (13)C NMR chemical shifts and J((1)H/(1)H and (1)H/(19)F) coupling constants for 22 1-phenyl-1H-pyrazoles' derivates were performed using the concerted application of (1)H 1D and (1)H, (13)C 2D gs-HSQC and gs-HMBC experiments. All 1-phenyl-1H-pyrazoles' derivatives were synthesized as described by Finar and co-workers. The formylated 1-phenyl-1H-pyrazoles' derivatives were performed under Duff's conditions.

  5. Crystal structure of 4-amino-3-(3-methyl-5-phenyl-1H-pyrazol-1-yl-1H-1,2,4-triazole-5(4H-thione

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2015-06-01

    Full Text Available In the title compound, C12H12N6S, the dihedral angles between the central pyrazole ring and the pendant triazole and benzene rings are 68.01 (4 and 59.83 (9°, respectively. In the crystal, molecules are linked by N—H...N and N—H...S hydrogen bonds, generating (10-1 sheets.

  6. A New Approach to Ethyl 1-Aroyl/Aroylmethyl-5-methyl-3-methylthiopyrazole-4-carboxylates: High Regioselectivity in Alkylation and Acylation Reactions between N-1 and N-2 of a Pyrazole Derivative

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Two series, totalizing twelve, of new compounds, ethyl 1-aroyl/aroylmethyl-5-methyl-3-methylthiopyrazole-4-carboxylates 5/6, have been synthesized via highly regioselective acylation and alkylation of ethyl 3-methyl-5-methylthio-1H- pyrazole-4-carboxylate 2a with aroyl chloride 3and alpha-tosyloxysubstitutedacetophenones 4. Unexpected structures of the product have been unambiguously determined by both X-ray crystallographic analysis and 2D NMR.

  7. Ligand effects on the structure and magnetic properties of alternating copper(II) chains with 2,2'-bipyrimidine- and polymethyl-substituted pyrazolates as bridging ligands.

    Science.gov (United States)

    Castro, Isabel; Calatayud, M Luisa; Barros, Wdeson P; Carranza, José; Julve, Miguel; Lloret, Francesc; Marino, Nadia; De Munno, Giovanni

    2014-06-02

    A novel series of heteroleptic copper(II) compounds of formulas {[Cu2(μ-H2O)(μ-pz)2(μ-bpm)(ClO4)(H2O)]ClO4·2H2O}n (1), {[Cu2(μ-H2O)(μ-3-Mepz)2(μ-bpm)](ClO4)2·2H2O}n (2), and {[Cu2(μ-OH)(μ-3,5-Me2pz)(μ-bpm)(H-3,5-Me2pz)2](ClO4)2}n (3) [bpm = 2,2'-bipyrimidine, Hpz = pyrazole, H-3-Mepz = 3-methylpyrazole, and H-3,5-Me2pz = 3,5-dimethylpyrazole] have been synthesized and structurally characterized by X-ray diffraction methods. The crystal structures of 1 and 2 consist of copper(II) chains with regular alternating bpm and bis(pyrazolate)(aqua) bridges, whereas that of 3 is made up of copper(II) chains with regular alternating bpm and (pyrazolate)(hydroxo) bridges. The copper centers are six- (1) or five-coordinate (2) in axially elongated, octahedral (1) or square-pyramidal (2) environments in 1 and 2, whereas they are five-coordinate in distorted trigonal-bipyramidal surroundings in 3. The values of the copper-copper separations across the bpm/pyrazolate bridges are 5.5442(7)/3.3131(6) (1), 5.538(1)/3.235(1) (2), and 5.7673(7)/3.3220(6) Å (3). The magnetic properties of 1-3 have been investigated in the temperature range of 25-300 K. The analysis of their magnetic susceptibility data through the isotropic Hamiltonian for an alternating antiferromagnetic copper(II) chain model [H = -J∑i=1-n/2 (S2i·S2i-1 + αS2i·S2i+1), with α = J'/J and Si = SCu = 1/2] reveals the presence of a strong to moderate antiferromagnetic coupling through the bis(pyrazolate)(aqua) [-J = 217 (1) and 215 cm(-1) (2)] and (pyrazolate)(hydroxo) bridges [-J = 153 cm(-1) (3)], respectively, whereas a strong to weak antiferromagnetic coupling occurs through the bis-bidentate bpm [-J' = 211 (1), 213 (2), and 44 cm(-1) (3)]. A simple orbital analysis of the magnetic exchange interaction within the bpm- and pyrazolate-bridged dicopper(II) fragments of 1-3 visualizes the σ-type pathways involving the (dx(2)-y(2)) (1 and 2) or d(z(2)) (3) magnetic orbitals on each metal ion, which account

  8. Tetra­kis(3,5-dimethyl-1H-pyrazole-κN 2)(nitrato-κ2 O,O′)cadmium(II) nitrate

    OpenAIRE

    Wang, Su-qing; Jian, Fang-Fang

    2008-01-01

    The title compound, [Cd(NO3)(C5H8N2)4]NO3, was prepared by reaction of cadmium nitrate and 3,5-dimethyl­pyrazole in ethanol solution. The Cd atom adopts a distorted cis-CdO2N4 octa­hedral geometry involving four dimethylpyrazole molecules and one bidentate nitrate anion. The mol­ecular structure and packing are stabilized by N—H⋯O and C—H⋯O inter- and intra­molecular hydrogen-bonding inter­actions.

  9. 1-[3-(4-Chlorophenyl-5-(4-methoxyphenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2012-04-01

    Full Text Available In the title compound, C18H17ClN2O2, the benzene rings form dihedral angles of 6.69 (6 and 74.88 (5° with the 4,5-dihydro-1H-pyrazole ring. The benzene rings form a dihedral angle of 76.67 (5° with each other. In the crystal, molecules are linked via bifurcated (C,C–H...O hydrogen bonds into chains along [010]. The crystal structure is further consolidated by C—H...π interactions.

  10. Methyl N-[(4-chlorophenyl(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-ylidenemethyl]glycinate

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2009-08-01

    Full Text Available The title compound, C20H18ClN3O3, is in an enamine–keto form, stabilized by two strong intramolecular N—H...O hydrogen bonds. The pyrazole ring is oriented at dihedral angles of 4.13 (3 and 85.60 (3° with respect to the aromatic rings. The dihedral angle between the aromatic rings is 81.79 (3°. In the crystal structure, intermolecular C—H...O hydrogen bonds link the molecules into double chains, which are further linked by weak C—H...π interactions, forming a two-dimensional network.

  11. Microwave-assisted synthesis of novel 5-trichloromethyl-4,5-dihydro-1H-1-pyrazole methyl esters under solvent free conditions

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Marcos A.P.; Beck, Paulo; Machado, Pablo; Brondani, Sergio; Moura, Sidnei; Zanatta, Nilo; Bonacorso, Helio G.; Flores, Alex F.C. [Universidade Federal de Santa Maria, RS (Brazil). Dept. de Quimica. Nicleo de Quimica de Heterociclos (NUQUIMHE)]. E-mail: mmartins@base.ufsm.br

    2006-03-15

    Twelve novel 5-trichloromethyl-4,5-dihydro-1H-1-pyrazole ethyl esters have been synthesized in good yields (70-98%) by using environmentally benign microwave induced techniques. The compounds were synthesized from the cyclocondensation of 1,1,1-trichloro-4-alkoxy-3-alken-2-ones [CCl3{sub C}(O)C(R{sup 2})=C(R{sup 1} )OR, where R, R{sup 2} = H, alkyl; R{sup 1} = H, alkyl and aryl] with hydrazine methyl carboxylate. The advantages obtained by the using of microwave irradiation under solvent-free conditions, rather than a conventional method, were demonstrated. (author)

  12. Simple and Efficient One-Pot Synthesis, Spectroscopic Characterization and Crystal Structure of Methyl 5-(4-Chlorobenzoyloxy-1-phenyl-1H-pyrazole-3-carboxylate

    Directory of Open Access Journals (Sweden)

    Imtiaz Khan

    2012-07-01

    Full Text Available A facile one-pot synthesis of methyl 5-(4-chlorobenzoyloxy-1-phenyl-1H-pyrazole-3-carboxylate (4 is described. The title compound was efficiently synthesized by the reaction of phenyl hydrazine, dimethyl acetylenedicarboxylate and 4-chlorobenzoyl chloride in dichloromethane under reflux in good yield. The structure of the target compound was deduced by modern spectroscopic and analytical techniques and unequivocally confirmed by a single crystal X-ray diffraction analysis. The crystal of the title compound belongs to orthorhombic system, space group P 21 21 21 with cell parameters a = 6.6491(3 Å, b = 7.9627(6 Å, c = 30.621(5 Å, α = β = γ = 90° and Z = 4. The crystal packing of the compound (4 is stabilized by an offset π-stacking between the planar benzoyl-substituted diazole moieties.

  13. Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: identification of a lead for anti-inflammatory drug.

    Science.gov (United States)

    Shaveta; Singh, Amrinder; Kaur, Matinder; Sharma, Surbhi; Bhatti, Rajbir; Singh, Palwinder

    2014-04-22

    Conjugates of chromone-indole and chromone-pyrazole were screened for cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitory activities. Compounds 8 and 9 were identified as preferred inhibitors of COX-2 over the other two enzymes. Their IC50 for COX-2 was 29 nM and 20 nM, respectively and selectivity indices (SI) for COX-2 over COX-1 was 46 and 337. NMR, mass spectral studies and molecular modelling also indicated preferential interactions of compounds 8 and 9 with COX-2. Tested on albino mice against capsaicin induced algesia, compound 8 exhibited analgesic potential comparable to diclofenac. In addition to the biological profile, the desirable physico-chemical properties of these compounds make them promising leads for anti-inflammatory drugs.

  14. Crystal structure of trans-diaquabis(1H-pyrazole-3-carboxylato-κ2N,Ocopper(II dihydrate

    Directory of Open Access Journals (Sweden)

    Santiago Reinoso

    2015-12-01

    Full Text Available In the title compound, [Cu(C4H3N2O22(H2O2]·2H2O, the CuII ion is located on an inversion centre and exhibits an axially elongated octahedral coordination geometry. The equatorial plane is formed by two N,O-bidentate 1H-pyrazole-3-carboxylate ligands in a trans configuration. The axial positions are occupied by two water molecules. The mononuclear complex molecules are arranged in layers parallel to the ab plane. Each complex molecule is linked to four adjacent species through intermolecular O—H...O and N—H...O hydrogen bonds that are established between the coordinating water molecules and carboxylate O atoms or protonated N atoms of the organic ligands. These layers are further connected into a three-dimensional network by additional hydrogen bonds involving solvent water molecules and non-coordinating carboxylate O atoms.

  15. Bis{tris[3-(2-pyridyl-1H-pyrazole]manganese(II} dodecamolybdo(V,VIphosphate hexahydrate

    Directory of Open Access Journals (Sweden)

    Lujiang Hao

    2010-02-01

    Full Text Available The asymmetric unit of the title compound, [Mn(C8H7N33]2[PMo12O40]·6H2O, consists of a complex [Mn(C8H7N33]2+ cation, half of a mixed-valent MoV,VI α-Keggin-type [PMo12O40]4− heteropolyanion, and three uncoordinated water molecules. The Mn2+ cation is surrounded by six N atoms from three chelating 3-(2-pyridyl-1H-pyrazole ligands in a distorted octahedral coordination. In the heteropolyanion, two O atoms of the central PO4 group (overline{1} symmetry are equally disordered about an inversion centre. N—H...O and O—H...O hydrogen bonding between the cations, anions and the uncoordinated water molecules leads to a consolidation of the structure.

  16. (E-3,5-Dimethyl-1-p-tolyl-4-(p-tolyldiazenyl-1H-pyrazole

    Directory of Open Access Journals (Sweden)

    Carlos Bustos

    2012-02-01

    Full Text Available There are two independent molecules, A and B, in the asymmetric unit of the title compound, C19H20N4, in each of which the N=N double bond has an E conformation. The dihedral angles between the pyrazole ring and the p-tolyl rings in the 1- and 4-positions are 22.54 (8 and 35.73 (7°, respectively, in molecule A. The corresponding dihedral angles in molecule B are 28.13 (8 and 22.18 (8°. In the crystal, the A and B molecules are linked by weak C—H...π interactions, leading to inversion dimers in each case.

  17. Methyl 5-methyl-1-(1H-pyrazol-3-yl-1H-1,2,3-triazole-4-carboxylate

    Directory of Open Access Journals (Sweden)

    Xiao-Guang Bai

    2014-07-01

    Full Text Available The asymmetric unit of the title compound, C8H9N5O2, contains two independent molecules (A and B in which the dihedral angles between the triazole and pyrazole rings are 4.80 (14 and 8.45 (16°. In the crystal, molecules are linked by N—H...N hydrogen bonds into supramolecular independent A and B chains propagating along the b-axis direction. The crystal structure also features π–π stacking between the aromatic rings of adjacent chains, the centroid–centroid separations being 3.8001 (15, 3.8078 (17, 3.8190 (14 and 3.8421 (15 Å.

  18. New structural forms in molecular metal phosphonates: novel tri- and hexanuclear zinc(II) cages containing phosphonate and pyrazole ligands.

    Science.gov (United States)

    Chandrasekhar, Vadapalli; Kingsley, Savariraj; Rhatigan, Brian; Lam, Matthew K; Rheingold, Arnold L

    2002-03-11

    The reaction of ZnCl(2) with tert-butylphosphonic acid and 3,5-dimethylpyrazole in the presence of triethylamine as a hydrogen chloride scavenger affords a trinuclear molecular zinc phosphonate [Zn(3)Cl(2)(3,5-Me(2)Pz)(4)(t-BuPO(3))(2)]. The structure of this compound contains a planar trizinc assembly containing two bicapping mu(3) [t-BuPO(3)](2-) ligands and terminal pyrazole and chloride ligands. In contrast an analogous reaction of ZnCl(2) with phenylphosphonic acid and 3,5-dimethylpyrazole affords a hexanuclear zinc phosphonate [Zn(6)Cl(4)(3,5-Me(2)PzH)(8)(PhPO(3))(4)]. The six zinc centers are arranged in a chairlike conformation. The four phosphonates in this complex also act as bridging tripodal mu(3) [RPO(3)](2-) ligands.

  19. Synthesis and crystal structure studies of ethyl 5-methyl-1, 3-diphenyl-1H-pyrazole-4-carboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Chandra,; Babu, E. A. Jithesh; Mahendra, M., E-mail: mahendra@physics.uni-mysore.ac.in [Department of Studies in Physics, Manasagangotri, University of Mysore, Mysore-570006 (India); Srikantamurthy, N.; Umesha, K. B. [Department of Chemistry, Yuvaraja' s College, University of Mysore, Mysore-570005 (India)

    2014-04-24

    The title compound, C{sub 19}H{sub 18}N{sub 2}O{sub 2}, was investigated by single crystal X-ray diffraction method. It crystallizes in monoclinic class under the space group P2{sub 1}/c with cell parameters a= 8.4593(4) Å, b=15.6284(6) Å, c=12.4579(5) Å, α=90°, β=98.241(3)°, γ=90° and Z=2. The ethoxycarbonyl group is slightly twisted from the pyrazole ring, and adopts syn-periplanar conformation. The crystal structure is stabilized by intermolecular C-H….O hydrogen bonds, which help in stabilizing the crystal structure.

  20. Au(I)-Catalyzted Synthesis of 5-Bromodifluoromethyl Pyrazoles from Fluorinated Alkynyl Ketones and Hydrazine

    Institute of Scientific and Technical Information of China (English)

    李珊; 李正珂; 彭东杰; 李亚军; 祝江涛; 解海波; 袁雅芬; 陈资衔; 吴永明

    2011-01-01

    Fluorinated alkynyl ketones react with hydrazine to give fluorinated pyrazols in good to excellent yields with Au(I) as catalyst. All the reactions were carried out at room temperature with excellent regioselectivity.

  1. Pyrazole scaffold: a remarkable tool in the development of anticancer agents.

    Science.gov (United States)

    Kumar, Harish; Saini, Deepika; Jain, Sandeep; Jain, Neelam

    2013-01-01

    Pyrazole has been the topic of interest for thousands of researchers across the world because of its wide spectrum pharmacological activities. Various structural modifications of the pyrazole nucleus have been made to explore its characteristics and biological potential. The present work aims to review the use of molecular modeling in the designing of novel pyrazole analogs that may target various receptors such as protein kinase inhibitor, tyrosine kinase, Aurora-A kinase, tumor growth factor (TGF), cyclin dependent kinase (CDK) and fibroblast growth factor (FGF), which are significant for the management of cancer. An insight has been given in this article for the importance of pyrazoles in the treatment of cancer and the perspectives that they hold for future research.

  2. Synthesis and antimicrobial screening of novel 2-(5-(4-(allyloxy-3-methoxyphenyl-1H-pyrazol-3-ylphenols analogues of 2-(4-(allyloxy-3-methoxyphenyl-4H-chromen-4-ones

    Directory of Open Access Journals (Sweden)

    Asha V. Chate

    2012-01-01

    Full Text Available A series of novel 2-(5-(4-(allyloxy-3-methoxyphenyl-1H-pyrazol-3-ylphenols derivatives have been synthesized via the ring opening of 2-(4-(allyloxy-3-methoxyphenyl-4H-chromen-4-ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened for antibacterial and antifungal activity against bacteria Staphylococcus aureus (MRSA E710 and Escherichia coli (ATCC 25922 and fungi Candida albicans and Aspergillus fumigates respectively. Some of the tested compounds showed significant antimicrobial activity. 1H NMR, IR, Mass spectral data and elemental analysis elucidated the structures of the all newly synthesized compounds.

  3. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.

    Science.gov (United States)

    Abd El-Karim, Somaia S; Anwar, Manal M; Mohamed, Neama A; Nasr, Tamer; Elseginy, Samia A

    2015-12-01

    This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.

  4. Crystal structure of 1-(2,4-dinitrophenyl-3,5-diphenyl-1H-pyrazole

    Directory of Open Access Journals (Sweden)

    Shaaban K. Mohamed

    2015-12-01

    Full Text Available In the title molecule, C21H14N4O4, the phenyl rings make dihedral angles of 39.61 (8 and 9.4 (1°, respectively, with the central pyrazole ring. The dihedral angle between the pyrazole and dinitrophenyl rings is 46.95 (5°. In the crystal, molecules pack in helical stacks parallel to the a axis aided by weak C—H...O interactions.

  5. An unexpected tetranuclear Li2Cr2 trimethylsilylacetylide complex bridged by two μ3-pyrazolates

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; CAO Li; LIAO HongLin; JIANG Jun; JIA XiaoLu; GAO Qian; LI DongFeng

    2012-01-01

    A tetranuclear Li2Cr2 acetylide precursor complex,[Li(Tp)CrⅢ(C≡CSiMe3)2(μ3-pz)]2.(n-pentane)2(Tp =hydridotris(pyrazolyl)borate,pz =pyrazolate)(1)has been synthesized and characterized.The X-ray structure analysis shows that the complex contains a Li2Cr2 core bridged by twoμa-pyrazolates.The magnetic data exhibit the existenceof weak antiferromagnetic interaction in the cluster.

  6. An efficient synthesis of pyrazole chalcones under solvent free conditions at room temperature

    Institute of Scientific and Technical Information of China (English)

    Parvin Kumar; Sunil Kumar; Khalid Husain; Ashwani Kumar

    2011-01-01

    An easy,safe,solvent free and effective method for the synthesis of pyrazole-substituted chalcones has been achieved by grinding pyrazole aldehydes and acetophenones in the presence of activated barium hydroxide(C-200) in high yield within short span of time.All reactions were carried out just by grinding the two reactants in the presence of activated barium hydroxide(C-200).Results are also compared with sodium hydroxide and potassium hydroxide.

  7. Magnetocaloric effect in Mn2-pyrazole-[Nb(CN)8] molecular magnet by relaxation calorimetry

    Science.gov (United States)

    Pełka, R.; Gajewski, M.; Miyazaki, Y.; Yamashita, S.; Nakazawa, Y.; Fitta, M.; Pinkowicz, D.; Sieklucka, B.

    2016-12-01

    Magnetocaloric effect in {[Mn(pyrazole)4]2[Nb(CN)8]·4 H2O}n molecular magnet is reported. It crystallizes in tetragonal I41/a space group. The compound exhibits a phase transition to a long range magnetically ordered state at TN ≈ 22.8 K. Temperature dependences of the magnetic entropy change ΔSM as well as the adiabatic temperature change ΔTad due to applied field change μ0 ΔH in the range of 0.1-9 T have been inferred from the relaxation calorimetry measurements. A systematic approximate approach has been used to determine the lattice contribution to the heat capacity. The maximum value of ΔSM for μ0 ΔH = 5 T is 6.83 J mol-1 K-1 (6.65 J kg-1 K-1) at 24.3 K. The corresponding maximum value of ΔTad is 1.4 K at 23.8 K. The temperature dependence of the exponent n characterizing the field dependence of ΔSM has been estimated. It attains the value of 0.64 at the transition temperature, which is consistent with the 3D Heisenberg universality class. A hitherto unobserved two-peak structure has been revealed in the temperature dependence of ΔTad.

  8. Evaluation of anti-inflammatory, analgesic activities, and side effects of some pyrazole derivatives.

    Science.gov (United States)

    Domiati, Souraya; El-Mallah, Ahmed; Ghoneim, Asser; Bekhit, Adnan; El Razik, Heba Abd

    2016-08-01

    Non-steroidal anti-inflammatory drugs are associated with several side effects, such as gastrointestinal mucosal damage, renal toxicity, and cardiovascular side effects. Aiming to find a novel analgesic/anti-inflammatory drug with minimal side effects, the present study was designed to screen and evaluate some newly synthesized pyrazole derivatives. Anti-inflammatory activity using carrageenan-induced rat paw edema and cotton-pellet-induced granuloma, COX-1/COX-2 selectivity using thin layer chromatography, and analgesic using hot plate and tail flick tests as well as ulcerogenic and renal side effects of the ten compounds were assessed. The results of the carrageenan-induced rat paw edema showed that the carboxyphenylhydrazone derivative (N9) was more potent than the chlorophenyl counterpart (N8) with a relative activity compared to celecoxib of 1.08 and -0.13, respectively, after 1 h. Even though this is true, N9 caused significant increase in the ulcer index, creatinine, and Blood Urea Nitrogen levels. The cotton granuloma test showed that the carboxyphenylhydrazone derivative (N7) was also more potent than its chlorophenyl counterpart (N6) with a relative activity compared to celecoxib of 1.13 and 0.86, respectively. Moreover, adding an acetyl not only increased the anti-inflammatory activity from a relative activity compared to celecoxib of 0.57-1.17 for the compounds X4 and N5, respectively, in the granuloma test, but also increased the selectivity toward COX-2 from 0.197 to 47.979. As a conclusion, from the ten compounds analyzed, N5 and N7 showed promising results as anti-inflammatory/analgesic agents with low ulcerogenicity and nephrotoxicity and thus should be further analyzed to determine the ED50 and other side effects.

  9. Studies on film formation on cathodes using pyrazole derivatives as electrolyte additives in the Li-ion battery

    Energy Technology Data Exchange (ETDEWEB)

    Kam, Daewoong; Kim, Ketack; Kim, Hyun-Soo [Battery Research Group, Korea Electrotechnology Research Institute, Changwon 641-600 (Korea); Liu, Hua Kun [Energy Materials Research Program, Institute for Superconducting and Electronic Materials, ARC Centre for Electromaterials Science, University of Wollongong, NSW 2519 (Australia)

    2009-08-15

    Pyrazole derivatives are flame retardants and provide thermal protection on cathodes, as they help to form a thick protective film. A thicker film provides more protection and delays the thermal decomposition of the cathode. Among the tested pyrazoles, bis(trifluoromethyl)pyrazole (BFTMP) serves as the best flame retardant additive. Additionally, a cell with BFTMP shows better capacity retention than a cell with no additive in full-cell cycle life tests. (author)

  10. Effects of Micelle on Pyrazoles as Antioxidants in Radical-induced Oxidation of DNA

    Institute of Scientific and Technical Information of China (English)

    LI Yan-feng; LIU Zai-qun

    2013-01-01

    Effects of 4-(1,3-diphenyl-1H-pyrazol-5-yl)phenol(APP),4-(1,5-diphenyl-lH-pyrazol-3-yl)phenol(BPP) and 4-(3,5-diphenyl-1H-pyrazol-1-yl)phenol(CPP) on 2,2'-azobis-(2-amidinopropane hydrochloride)(AAPH)-induced oxidation of DNA were measured in the presence of various concentrations of Triton X-100,cetyltrimethylammonium bromide(CTAB),or sodium dodecyl sulfate(SDS) in order to clarify the influence of neutral,cationic and anionic microenvironments on antioxidant capacities of APP,BPP and CPP.Although these surfactants can protect DNA against AAPH-induced oxidation,the pyrazoles in the presence of these surfactants functioned as prooxidants when the concentrations of Triton X-100 and CTAB increased.However,CPP exhibited antioxidant property with the increase of the concentration of CTAB.On the contrary,APP,BPP and CPP were antioxidants in the presence of various concentrations of SDS.The added surfactants resulted in the complication of the microenvironments around DNA,pyrazoles and peroxyl radical(ROO*) derived from AAPH.The anionic charge of SDS was beneficial to enhancing the antioxidant effectiveness of these pyrazoles.It can be concluded that the charge property of surfactants markedly influenced the behavior of an antioxidant in AAPH-induced oxidation of DNA.

  11. The synthesis and characterization of the 'research chemical' N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer.

    Science.gov (United States)

    McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V; Power, John D; Twamley, Brendan; O'Brien, John; Talbot, Brian; Dowling, Geraldine; Brandt, Simon D

    2016-09-01

    This study presents the identification of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide that was termed 3,5-AB-CHMFUPPYCA. This compound was obtained from a UK-based Internet vendor, who erroneously advertised this 'research chemical' as AZ-037 and which would have been associated with (S)-N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide. The presence of the pyrazole core indicates a bioisosteric replacement of an indazole ring that is frequently associated with synthetic cannabinoids of the PINACA, FUBINACA, and CHMINACA series. The pyrazole ring system present in 3,5-AB-CHMFUPPYCA gives rise to the regioisomer N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide (named 5,3-AB-CHMFUPPYCA) and both isomers were synthesized using two specific routes which supported the correct identification of the 'research chemical' as 3,5-AB-CHMFUPPYCA. Both isomers could be conveniently differentiated. Interestingly, a route specific chlorine-containing by-product also was observed during the synthesis of 3,5-AB-CHMFUPPYCA and identified as N-(1-amino-3-methyl-1-oxobutan-2-yl)-4-chloro-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide. An extensive analytical characterization included chromatographic, spectroscopic, mass spectrometric platforms as well as crystal structure analysis. The syntheses and analytical characterizations of both AB-CHMFUPPYCA isomers are reported for the first time and serves as a reminder that the possibility of mislabeling of 'research chemicals' cannot be excluded. The pharmacological activities of both AB-CHMFUPPYCA isomers remain to be explored. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Crystal structure of (4Z-4-[(2E-1-hydroxy-3-(naphthalen-2-ylprop-2-en-1-ylidene]-3-methyl-1-phenyl-1H-pyrazol-5(4H-one

    Directory of Open Access Journals (Sweden)

    Muhammad Salim

    2015-06-01

    Full Text Available In the title compound, C23H18N2O2, the pyrazole ring subtends dihedral angles of 2.01 (13 and 1.55 (10° with the pendant benzene ring and the naphthalene ring system, respectively. The molecule is almost planar (r.m.s. deviation for the 27 non-H atoms = 0.025 Å and intramolecular O—H...O and C—H...O hydrogen bonds both close S(6 loops. In the crystal, very weak aromatic π–π stacking interactions between the benzene and the pyrazole rings, with centroid–centroid distances of 3.8913 (14 and 3.9285 (15 Å, are observed.

  13. Crystal structure of (4Z-4-[(2E-3-(2-chlorophenyl-1-hydroxyprop-2-en-1-ylidene]-3-methyl-1-phenyl-1H-pyrazol-5(4H-one

    Directory of Open Access Journals (Sweden)

    Muhammad Shahid

    2015-06-01

    Full Text Available In the title compound, C19H15ClN2O2, the pyrazole ring is almost planar (r.m.s. deviation = 0.002 Å and subtends dihedral angles of 5.31 (16 and 1.86 (16° with the phenyl and chlorobenzene rings, respectively. An intramolecular O—H...O hydrogen bond closes an S(6 ring and a short C—H...O contact is also observed. In the crystal, molecules are linked by weak C—H...O interactions to generate (001 sheets. Weak aromatic π–π interactions between the chlorobenzene and pyrazole rings, with a centroid–centroid distance of 3.7956 (17 Å are also observed.

  14. Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole-benzimidazole derivatives as potent Aurora A/B kinase inhibitors.

    Science.gov (United States)

    Zheng, Youguang; Zheng, Ming; Ling, Xin; Liu, Yi; Xue, Yunsheng; An, Lin; Gu, Ning; Ji, Min; Jin, Min

    2013-06-15

    Novel pyrazole-benzimidazole derivatives have been designed and synthesized. The entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro. The compounds 7a, 7b, 7i, 7k and 7l demonstrated significant cancer cell lines and Aurora A/B kinase inhibitory activities. Molecular modeling studies suggested the derivatives have bound in the active site of Aurora A kinase through the formation of four hydrogen bonds. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. The cellular activity of 7k was also tested by immunofluorescence.

  15. Synthesis of Novel β-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents

    Directory of Open Access Journals (Sweden)

    Smaail Radi

    2015-11-01

    Full Text Available Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241 human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO. Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls.

  16. Synthesis and Antibacterial Activities of N-[(1-Aryl-3-phenyl-pyrazol-4-yl)methylene]-2-(halo-o-hydroxyphenyl)hydrazide Derivatives

    Institute of Scientific and Technical Information of China (English)

    LIU Ya; LU Bo-wei; LU Jun-rui; XIN Chun-wei; LI Jian-fa; MU Jiang-bei; BAO Xiu-rong

    2013-01-01

    A series of novel N-[(1-aryl-3-phenyl-pyrazol-4-yl)methylene]-2-(halo-o-hydroxyphenyl)hydrazide derivatives was synthesized and the antibacterial activity of each of them was evaluated.The supposed reaction mechanism of acquiring compounds 3a—3d is that catalytic activity is enhanced by the electron-donating groups of the first phenyl ring while decreased by electron-withdrawing groups of that ring.The result of preliminary bioassay shows that the lowest minimal inhibitory concentration(MIC) of the title compounds against Escherichia coli is 2 μg/mL.MIC values against Monilia albican and Staphlococcus aureus are as low as 4 μg/mL.They will be a series of potential antibacterial compounds against fungi and gram-negative bacteria.

  17. 4-(1H-Pyrazol-1-yl Benzenesulfonamide Derivatives: Identifying New Active Antileishmanial Structures for Use against a Neglected Disease

    Directory of Open Access Journals (Sweden)

    Leonor L. Leon

    2012-11-01

    Full Text Available Leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. Despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. In this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1H-pyrazol-1-ylbenzenesulfonamides. Our experimental data showed an active profile for some compounds against Leishmania infantum and Leishmania amazonensis. The profile of two compounds against L. infantum was similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling evaluation indicated that changes in electronic regions, orientation as well as lipophilicity of the derivatives were areas to improve the interaction with the parasitic target. Overall the compounds represent feasible prototypes for designing new molecules against L. infantum and L. amazonensis.

  18. Novel fluorescent 1,8-naphthalimide derivatives containing thiophene and pyrazole moieties: Synthesis by direct C-H arylation and evaluation of photophysical and electrochemical properties

    Science.gov (United States)

    Jin, Zhengneng; Wu, Jiashou; Wang, Chuanfeng; Dai, Guoliang; Liu, Shiyong; Lu, Jianmei; Jiang, Huajiang

    2014-01-01

    A series of novel 1,8-naphthalimide derivatives containing thiophene and pyrazole moities were synthesized by direct Pd-catalyzed C-H arylation and then characterized by 1H NMR, 13C NMR, MALDI-HRMS, and elementary analysis. The photophysical and electrochemical properties of the derivatives were also investigated. All compounds have green emission both in diluted CH2Cl2 solution and solid film. The cyclic voltammetry (CV) measurements showed that the target compounds had a lowest unoccupied molecular orbital (LUMO) range from -3.49 eV to -3.29 eV and a highest occupied molecular orbital (HOMO) range from -6.04 eV to -5.81 eV. Quantum chemical calculations were performed to obtain the optimized ground-state geometry as well as the spatial distributions of the HOMO, LUMO levels of the compounds.

  19. Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes.

    Science.gov (United States)

    Vaarla, Krishnaiah; Kesharwani, Rajesh Kumar; Santosh, Karnewar; Vedula, Rajeswar Rao; Kotamraju, Srigiridhar; Toopurani, Murali Krishna

    2015-12-15

    A novel series of coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes (4a-o) were synthesized via an efficient, one-pot multicomponent approach involving 3-(2-bromoacetyl)coumarins (1a-g), thiosemicarbazide (2) and substituted acetophenones (3a-c) utilizing Vilsmeier-Haack reaction condition with good yields. The title compounds structure was elucidated by spectroscopic data (IR, NMR and Mass) and elemental analysis. All the synthesized compounds were screened for their in vitro cytotoxic activity against MCF-7, DU-145 and HeLa cell lines and studied detailed about molecular interaction of probable target protein human microsomal cytochrome CYP450 2A6 using docking simulation. These coumarin derivatives were exhibiting moderate to appreciable cytotoxic activities. The compounds 4m and 4n exhibited significant cytotoxic activity with IC50 values having 5.75 and 6.25μM against HeLa cell line. Similarly compound 4n also exhibiting good anti cancer property and antibacterial activity against DU-145 cell line and Gram negative bacterial strains.

  20. Ultrasound-promoted clean synthesis of 1-thiocarbamoyl-3-(2-hydroxyphenyl-5-aryl-4,5-dihydro-1H-pyrazoles

    Directory of Open Access Journals (Sweden)

    Israel Leite Bogarim Jr.

    2012-06-01

    Full Text Available of important biological and pharmaceutical activities. In recent years, we described the synthesis of many heterocycles by non-traditional conditions, such as microwaves and ultrasound. In particular, the beneficial effects of ultrasonic irradiation are playing an increasing role in process chemistry, especially in cases where classical methods require drastic conditions or prolonged reaction times. These observations and our interest in clean production of heterocyclic compounds prompted us to apply ultrasound in the preparation of 1-thiocarbamoyl-3-(2-hydroxyphenyl-5-aryl-4,5-dihydro-1H-pyrazoles. The best condition for preparing the target pyrazoles (5a-c was achieved when two equivalents of both KOH and thiosemicarbazide and 1 equivalent of the chalcones/flavanones (3,4a-c were sonicated for 30 minutes, affording the desired pure product in good yield (Scheme. In conclusion, we have developed a mild, convenient and environmentally friendly protocol for the preparation of target compounds under ultrasonic irradiation. Significant advantages of the method include the fact that: (i the reaction is simple to execute; (ii the products are isolated in good yields (61-76%; (iii the work-up is very simple and (iv the reaction time is short (30 min.

  1. Synthesis, characterization and in vitro inhibition of metal complexes of pyrazole based sulfonamide on human erythrocyte carbonic anhydrase isozymes I and II.

    Science.gov (United States)

    Büyükkıdan, Nurgün; Büyükkıdan, Bülent; Bülbül, Metin; Kasımoğulları, Rahmi; Mert, Samet

    2017-12-01

    Sulfonamides represent an important class of biologically active compounds. A sulfonamide possessing carbonic anhydrase (CA) inhibitory properties obtained from a pyrazole based sulfonamide, ethyl 1-(3-nitrophenyl)-5-phenyl-3-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)carbamoyl)-1H-pyrazole-4-carboxylate (1), and its metal complexes with the Ni(II) for (2), Cu(II) for (3) and Zn(II) for (4) have been synthesized. The structures of metal complexes (2-4) were established on the basis of their elemental analysis, (1)H NMR, IR, UV-Vis and MS spectral data. The inhibition of two human carbonic anhydrase (hCA, EC 4.2.1.1) isoenzymes I and II, with 1 and synthesized complexes (2-4) and acetazolamide (AAZ) as a control compound was investigated in vitro by using the hydratase and esterase assays. The complexes 2, 3 and 4 showed inhibition constant in the range 0.1460-0.3930 µM for hCA-I and 0.0740-0.0980 µM for hCA-II, and they had effective more inhibitory activity on hCA-I and hCA-II than corresponding free ligand 1 and than AAZ.

  2. Trans-dichlorotetrakis(1H-pyrazole-κN2)copper(II): Synthesis, crystal structure, hydrogen bonding graph-sets, vibrational and DFT studies

    Science.gov (United States)

    Direm, Amani; Tursun, Mahir; Parlak, Cemal; Benali-Cherif, Nourredine

    2015-08-01

    The copper complex [Cu(HPrz)4]Cl2 (HPrz = Pyrazole) was synthesized and its structure was characterized by FT-IR, Raman and single-crystal X-ray diffraction (XRD) techniques. The structural conformers, optimized geometric parameters, normal mode frequencies and corresponding vibrational assignments of the compound were examined by means of the density functional theory (DFT) method, the Becke-3-Lee-Yang-Parr (B3LYP) functional, the 6-311+G(3df,p) and lanl2dz basis sets. Reliable vibrational assignments were investigated by the potential energy distribution (PED) analysis. The compound crystallizes in the monoclinic space group C2/c with the unit cell parameters a = 13.5430 (10) Å, b = 9.1480 (10) Å, c = 14.6480 (10) Å and β = 116.7° (5). There is a good agreement between the theoretically predicted structural parameters and vibrational frequencies and those obtained experimentally. The findings of this work reveals further insight into molecular copper(II) pyrazole systems.

  3. Synthesis, anti-inflammatory, analgesic, COX1/2-inhibitory activity, and molecular docking studies of hybrid pyrazole analogues

    Directory of Open Access Journals (Sweden)

    Alam MJ

    2016-10-01

    Full Text Available Md Jahangir Alam,1 Ozair Alam,1 Suroor Ahmad Khan,1 Mohd Javed Naim,1 Mohammad Islamuddin,2 Girdhar Singh Deora3 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 2Parasite Immunology Laboratory, Department of Biotechnology, Faculty of Science, Jamia Hamdard, New Delhi, 3Institute of Life Sciences, University of Hyderabad, Hyderabad, India Abstract: This article reports on the design, synthesis, and pharmacological activity of a new series of hybrid pyrazole analogues: 5a–5u. Among the series 5a–5u, the compounds 5u and 5s exhibited potent anti-inflammatory activity of 80.63% and 78.09% and inhibition of 80.87% and 76.56% compared with the standard drug ibuprofen, which showed 81.32% and 79.23% inhibition after 3 and 4 hours, respectively. On the basis of in vivo studies, 12 compounds were selected for assessment of their in vitro inhibitory action against COX1/2 and TNFα. The compounds 5u and 5s showed high COX2-inhibitory activity, with half-maximal inhibitory concentrations of 1.79 and 2.51 µM and selectivity index values of 72.73 and 65.75, respectively, comparable to celecoxib (selectivity index =78.06. These selected compounds were also tested for TNFα, cytotoxicity, and ulcerogenicity. Docking studies were also carried out to determine possible interactions of the potent compounds (5u and 5s, which also showed high docking scores of -12.907 and -12.24 compared to celecoxib, with a -9.924 docking score. These selective COX2 inhibitors were docked into the active site of COX2, and showed the same orientation and binding mode to that of celecoxib (selective COX2 inhibitor. Docking studies also showed that the SO2NH2 of 5u and 5s is inserted deep inside the selective pocket of the COX2-active site and formed a hydrogen-bond interaction with His90, Arg513, Phe518, Ser353, Gln192, and Ile517, which was further validated by superimposed docked pose with celecoxib. Keywords: anti-inflammatory activity, analgesic activity

  4. Reaction of Ketene Dithioacetals with Pyrazolylcarbohydrazide:Synthesis and Biological Activities of Ethyl 5-Amino-1-(5'-methyl-1'-t-butyl-4'-pyrazolyl)carbonyl-3-methylthio-1H-pyrazole-4-carboxylate

    Institute of Scientific and Technical Information of China (English)

    LI Ming李明; WEN Li-Rong文丽荣; FU Wei-Jun付维军; ZHAO Gui-Long赵桂龙; HU Fang-Zhong胡方中; YANG Hua-Zheng杨华铮

    2004-01-01

    The title compound, C16-H23N5O3S, ethyl 5-amino-1-(5'-methyl-1'-t-butyl-4'-pyrazolyl)carbonyl-3-methylthio1H-pyrazole-4-carboxylate (5) has been synthesized by the treatment of ethyl 2-cyano-3,3-dimethylthioacrylate with 1-t-butyl-5-methyl-4-hydrazinocarbonylpyrazole (4) in refluxed ethanol. The possible mechanism of the above reaction was also discussed. The results of biological test show that the title compound has fungicidal and plant growth regulation activities.

  5. Thermodynamic characterization of pyrazole and azaindole derivatives binding to p38 mitogen-activated protein kinase using Biacore T100 technology and van't Hoff analysis.

    Science.gov (United States)

    Papalia, Giuseppe A; Giannetti, Anthony M; Arora, Nidhi; Myszka, David G

    2008-12-15

    Biacore T100 technology was used in conjunction with a van't Hoff analysis to characterize the thermodynamic binding parameters of 85 small-molecule inhibitors of adenosine triphosphate (ATP) binding to p38 mitogen-activated protein (MAP) kinase. The compounds were selected from a large panel of azaindole and pyrazole derivatives for which IC(50) data exist. We showed a strong relationship between the K(D) and IC(50) of a compound, but only a modest relationship between k(off) and IC(50) was detected and an apparent relationship between a compound's k(on) and its IC(50) could not be discerned. Similarly, a correlation between a compound's IC(50) and its thermodynamic parameters DeltaH degrees and DeltaS degrees could not be established. The lack of a predominant kinetic or thermodynamic signature associated with the inhibitory potential of these compounds demonstrates that there exists, even within a single well-defined system, a library of kinetic routes or, alternatively, a library of initial and final enthalpic and entropic states from which to effect inhibition. As a complement to these studies, selected double mutant thermodynamic cycles were performed to probe the energetic coupling, if any, between common sites of fluorination in both the azaindole and pyrazole classes and two different substituents. Although both cycles indicated negligible coupling free energies, both revealed significant coupling enthalpies, an observation made in other similarly dissected systems. The possible significance and caveats associated with these findings along with the advantages of using Biacore technology to derive thermodynamic parameters in drug discovery efforts are discussed.

  6. Synthesis and antimicrobial evaluation of some novel thiazole, pyridone, pyrazole, chromene, hydrazone derivatives bearing a biologically active sulfonamide moiety.

    Science.gov (United States)

    Darwish, Elham S; Fattah, Azza M Abdel; Attaby, Fawzy A; Al-Shayea, Oqba N

    2014-01-17

    This study aimed for the synthesis of new heterocyclic compounds incorporating sulfamoyl moiety suitable for use as antimicrobial agents via a versatile, readily accessible N-[4-(aminosulfonyl)phenyl]-2-cyanoacetamide (3). The 2-pyridone derivatives were obtained via reaction of cyanoacetamide with acetylacetone or arylidenes malononitrile. Cycloaddition reaction of cyanoacetamide with salicyaldehyde furnished chromene derivatives. Diazotization of 3 with the desired diazonium chloride gave the hydrazone derivatives 13a-e. Also, the reactivity of the hydrazone towards hydrazine hydrate to give Pyrazole derivatives was studied. In addition, treatment of 3 with elemental sulfur and phenyl isothiocyanate or malononitrile furnished thiazole and thiophene derivatives respectively. Reaction of 3 with phenyl isothiocyanate and KOH in DMF afforded the intermediate salt 17 which reacted in situ with 3-(2-bromoacetyl)-2H-chromen-2-one and methyl iodide afforded the thiazole and ketene N,S-acetal derivatives respectively. Finally, reaction of 3 with carbon disulfide and 1,3-dibromopropane afforded the N-[4-(aminosulfonyl) phenyl]-2-cyano-2-(1,3-dithian-2-ylidene)acetamide product 22. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. The compounds were evaluated for both their in vitro antibacterial and antifungal activities and showed promising results.

  7. Computational studies on energetic properties of trinitro-substituted imidazole-triazole and pyrazole-triazole derivatives.

    Science.gov (United States)

    Ghule, Vikas D

    2012-09-20

    Heats of formation (HOFs) for 24 designed compounds were obtained by using the density functional theory (DFT). Molecular structures were investigated at the B3PW91/6-31G(d,p) level, and isodesmic reactions were designed for calculating the gas phase heats of formation. The solid state heats of formation for designed compounds were calculated by the Politzer approach using heats of sublimation. All the designed compounds possess solid state heats of formation above 140 kJ/mol. The distance between nitro groups influences the steric and repulsive interactions. Detonation performances were evaluated by the Kamlet-Jacobs equations based on the predicted densities and solid state heats of formation, and susceptibility of decomposition was studied by the computations of bond dissociation energy (BDE). Further, the present study might provide useful information for the structure-property relationship, the laboratory synthesis of imidazole-triazole and pyrazole-triazole based nitro derivatives and the development of novel high energy materials (HEMs).

  8. Synthesis and Antimicrobial Evaluation of Some Novel Thiazole, Pyridone, Pyrazole, Chromene, Hydrazone Derivatives Bearing a Biologically Active Sulfonamide Moiety

    Directory of Open Access Journals (Sweden)

    Elham S. Darwish

    2014-01-01

    Full Text Available This study aimed for the synthesis of new heterocyclic compounds incorporating sulfamoyl moiety suitable for use as antimicrobial agents via a versatile, readily accessible N-[4-(aminosulfonylphenyl]-2-cyanoacetamide (3. The 2-pyridone derivatives were obtained via reaction of cyanoacetamide with acetylacetone or arylidenes malononitrile. Cycloaddition reaction of cyanoacetamide with salicyaldehyde furnished chromene derivatives. Diazotization of 3 with the desired diazonium chloride gave the hydrazone derivatives 13a–e. Also, the reactivity of the hydrazone towards hydrazine hydrate to give Pyrazole derivatives was studied. In addition, treatment of 3 with elemental sulfur and phenyl isothiocyanate or malononitrile furnished thiazole and thiophene derivatives respectively. Reaction of 3 with phenyl isothiocyanate and KOH in DMF afforded the intermediate salt 17 which reacted in situ with 3-(2-bromoacetyl-2H-chromen-2-one and methyl iodide afforded the thiazole and ketene N,S-acetal derivatives respectively. Finally, reaction of 3 with carbon disulfide and 1,3-dibromopropane afforded the N-[4-(aminosulfonyl phenyl]-2-cyano-2-(1,3-dithian-2-ylideneacetamide product 22. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis. The compounds were evaluated for both their in vitro antibacterial and antifungal activities and showed promising results.

  9. Biological activity of pyrazole and imidazole-dehydroepiandrosterone derivatives on the activity of 17β-hydroxysteroid dehydrogenase.

    Science.gov (United States)

    Cabeza, Marisa; Posada, Alejandro; Sánchez-Márquez, Araceli; Heuze, Yvonne; Moreno, Isabel; Soriano, Juan; Garrido, Mariana; Cortés, Francisco; Bratoeff, Eugene

    2016-01-01

    The enzyme type 5 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17β-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ(4)-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17β-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in castrated hamsters treated with T or 4-dione. Inhibition of 17β-HSD5 by these compounds could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia.

  10. Electronic Configuration of Five-Coordinate High-Spin Pyrazole-Ligated Iron(II) Porphyrinates

    Science.gov (United States)

    Hu, Chuanjiang; Noll, Bruce C.; Schulz, Charles E.; Scheidt, W. Robert

    2010-01-01

    Pyrazole, a neutral nitrogen ligand and an isomer of imidazole, has been used as a fifth ligand to prepare two new species, [Fe(TPP)(Hdmpz)] and [Fe(Tp-OCH3PP)(Hdmpz)] (Hdmpz = 3,5-dimethylpyrazole), the first structurally characterized examples of five-coordinate iron(II) porphyrinates with a nonimidazole neutral ligand. Both complexes are characterized by X-ray crystallography, and structures show common features for five-coordinate iron(II) species, such as an expanded porphinato core, large equatorial Fe–Np bond distances and a significant out-of-plane displacement of the iron(II) atom. The Fe–N(pyrazole) and Fe–Np bond distances are similar to those in imidazole-ligated species. These suggest that the coordination abilities to iron(II) for imidazole and pyrazole are very similar even though pyrazole is less basic than imidazole. Mössbauer studies reveal that [Fe(TPP)(Hdmpz)] has the same behavior as those of imidazole-ligated species, such as negative quadrupole splitting values and relative large asymmetry parameters. Both the structures and Mössbauer spectra suggest pyrazole-ligated five-coordinate iron(II) porphyrinates have the same electronic configuration as imidazole-ligated species. PMID:21047081

  11. Electronic configuration of five-coordinate high-spin pyrazole-ligated iron(II) porphyrinates.

    Science.gov (United States)

    Hu, Chuanjiang; Noll, Bruce C; Schulz, Charles E; Scheidt, W Robert

    2010-12-06

    Pyrazole, a neutral nitrogen ligand and an isomer of imidazole, has been used as a fifth ligand to prepare two new species, [Fe(TPP)(Hdmpz)] and [Fe(Tp-OCH(3)PP)(Hdmpz)] (Hdmpz = 3,5-dimethylpyrazole), the first structurally characterized examples of five-coordinate iron(II) porphyrinates with a nonimidazole neutral ligand. Both complexes are characterized by X-ray crystallography, and structures show common features for five-coordinate iron(II) species, such as an expanded porphyrinato core, large equatorial Fe-N(p) bond distances, and a significant out-of-plane displacement of the iron(II) atom. The Fe-N(pyrazole) and Fe-N(p) bond distances are similar to those in imidazole-ligated species. These suggest that the coordination abilities to iron(II) for imidazole and pyrazole are very similar even though pyrazole is less basic than imidazole. Mössbauer studies reveal that [Fe(TPP)(Hdmpz)] has the same behavior as those of imidazole-ligated species, such as negative quadrupole splitting values and relative large asymmetry parameters. Both the structures and the Mössbauer spectra suggest pyrazole-ligated five-coordinate iron(II) porphyrinates have the same electronic configuration as imidazole-ligated species.

  12. Synthesis, crystal structures and theoretical calculations of new 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles

    Science.gov (United States)

    Gökşen, Umut Salgın; Alpaslan, Yelda Bingöl; Kelekçi, Nesrin Gökhan; Işık, Şamil; Ekizoğlu, Melike

    2013-05-01

    1-[2-(5-Chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3-methoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5a), 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-phenyl-5-(3,4-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5b) and 1-[2-(5-chloro-2-benzoxazolinone-3-yl)acetyl]-3-(4-methylphenyl)-5-(2,3-dimethoxyphenyl)-4,5-dihydro-(1H)-pyrazole (5c) were synthesized. The crystal and molecular structures of the compounds 5a, 5b and 5c were determined by elemental analyses, IR, 1H NMR, ESI-MS and single-crystal X-ray diffraction. DFT method with 6-31G(d,p) basis set was used to calculate the optimized geometrical parameters, vibrational frequencies and chemical shift values. The calculated vibrational frequencies and chemical shift values were compared with experimental IR and 1H NMR values. The results represented that there was a good agreement between experimental and calculated values of the compounds 5a-5c. In addition, DFT calculations of the compounds, molecular electrostatic potentials (MEPs) and frontier molecular orbitals were performed at B3LYP/6-31G(d,p) level of theory. Furthermore, compounds were tested against three Gram-positive bacteria: Staphylococcus aureus ATCC 29213 (American Type Culture Collection), methicillin resistant S. aureus (MRSA) ATCC 43300 and Enterococcus faecalis ATCC 29212; two Gram negative bacteria: Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853; and three fungi: Candida albicans ATCC 90028, Candida krusei ATCC 6258 and Candida parapsilosis ATCC 90018. In general, all of the compounds were found to be slightly active against tested microorganisms.

  13. Highly efficient redox isomerisation of allylic alcohols catalysed by pyrazole-based ruthenium(IV) complexes in water: mechanisms of bifunctional catalysis in water.

    Science.gov (United States)

    Bellarosa, Luca; Díez, Josefina; Gimeno, José; Lledós, Agustí; Suárez, Francisco J; Ujaque, Gregori; Vicent, Cristian

    2012-06-18

    The catalytic activity of ruthenium(IV) ([Ru(η(3):η(3)-C(10)H(16))Cl(2)L]; C(10)H(16) = 2,7-dimethylocta-2,6-diene-1,8-diyl, L = pyrazole, 3-methylpyrazole, 3,5-dimethylpyrazole, 3-methyl-5-phenylpyrazole, 2-(1H-pyrazol-3-yl)phenol or indazole) and ruthenium(II) complexes ([Ru(η(6)-arene)Cl(2)(3,5-dimethylpyrazole)]; arene = C(6)H(6), p-cymene or C(6)Me(6)) in the redox isomerisation of allylic alcohols into carbonyl compounds in water is reported. The former show much higher catalytic activity than ruthenium(II) complexes. In particular, a variety of allylic alcohols have been quantitatively isomerised by using [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)] as a catalyst; the reactions proceeded faster in water than in THF, and in the absence of base. The isomerisations of monosubstituted alcohols take place rapidly (10-60 min, turn-over frequency = 750-3000 h(-1)) and, in some cases, at 35 °C in 60 min. The nature of the aqueous species formed in water by this complex has been analysed by ESI-MS. To analyse how an aqueous medium can influence the mechanism of the bifunctional catalytic process, DFT calculations (B3LYP) including one or two explicit water molecules and using the polarisable continuum model have been carried out and provide a valuable insight into the role of water on the activity of the bifunctional catalyst. Several mechanisms have been considered and imply the formation of aqua complexes and their deprotonated species generated from [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)]. Different competitive pathways based on outer-sphere mechanisms, which imply hydrogen-transfer processes, have been analysed. The overall isomerisation implies two hydrogen-transfer steps from the substrate to the catalyst and subsequent transfer back to the substrate. In addition to the conventional Noyori outer-sphere mechanism, which involves the pyrazolide ligand, a new mechanism with a hydroxopyrazole complex as the active species can be at work in water. The

  14. Inhibition of the mitochondrial permeability transition by cyclosporin A prevents pyrazole plus lipopolysaccharide-induced liver injury in mice.

    Science.gov (United States)

    Zhuge, Jian; Cederbaum, Arthur I

    2009-02-01

    Previous results showed that pyrazole potentiates lipopolysaccharide (LPS)-induced liver injury in mice. Mechanisms involved the overexpression of cytochrome P450 2E1 (CYP2E1), oxidative stress, and activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). The current study was carried out to test the hypothesis that the mitochondria permeability transition (MPT) plays a role in this pyrazole plus LPS toxicity. Mice were injected intraperitoneally with pyrazole for 2 days, followed by a challenge with LPS with or without treatment with cyclosporin A (CsA), an inhibitor of the MPT. Serum alanine aminotransferase and aspartate aminotransferase were increased by pyrazole plus LPS treatment, and CsA treatment could attenuate these increases. CsA also prevented pyrazole plus LPS-induced hepatocyte necrosis. Formation of 4-hydroxynonenal protein adducts and 3-nitrotyrosine protein adducts in liver tissue was increased by the pyrazole plus LPS treatment, and CsA treatment blunted these increases. Swelling, cytochrome c release from mitochondria to the cytosol, and lipid peroxidation were increased in mitochondria isolated from the pyrazole plus LPS-treated mice, and CsA treatment prevented these changes. CsA did not prevent the increased levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), pp38 MAPK, and p-JNK2. In conclusion, although CsA does not prevent elevations in upstream mediators of the pyrazole plus LPS toxicity (iNOS, TNF-alpha, CYP2E1, MAPK), it does protect mice from the pyrazole plus LPS-induced liver toxicity by preventing the MPT and release of cytochrome c and decreasing mitochondrial oxidative stress. These results indicate that mitochondria are the critical targets of pyrazole plus LPS in mediating liver injury.

  15. Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H-pyrazole niacinamide derivatives as BRAF inhibitors.

    Science.gov (United States)

    Li, Cui-Yun; Li, Qing-Shan; Yan, Li; Sun, Xiao-Guang; Wei, Ran; Gong, Hai-Bin; Zhu, Hai-Liang

    2012-06-15

    A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. Results of the bioassays against BRAF(V600E) and WM266.4 human melanoma cell line showed several compounds to be endowed potent activities with IC(50) and GI(50) value in low micromolar range, among which compound 27e, (5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3-yl methanone (IC(50)=0.20 μM, GI(50)=0.89 μM) was bearing the best bioactivity comparable with the positive control Sorafenib. Docking simulation was performed to determine the probable binding model and 3D-QSAR model was built to provide more pharmacophore understanding that could use to design new agents with more potent BRAF(V600E) inhibitory activity.

  16. Theoretical insights into the cycloaddition reaction mechanism between ketenimine and methyleneimine: An alternative approach to the formation of pyrazole and imidazole

    Indian Academy of Sciences (India)

    Nana Wang; Xiaojun Tan; Weihua Wang; Fangfang Wang; Ping Li

    2016-02-01

    The cycloaddition reaction mechanism between interstellar molecules, ketenimine and methyleneimine, has been systematically investigated employing the second-order Møller-Plesset perturbation theory (MP2) method in order to better understand the reactivity of nitrogenous cumulene ketenimine with the C=N double bond compound methyleneimine. Geometry optimizations and vibrational analyses have been performed for the stationary points on the potential energy surfaces of the system. Calculations show that five-membered cyclic carbene intermediates could be produced through pericyclic reaction processes between ketenimine and methyleneimine. Through the subsequent hydrogen transfer processes, carbene intermediates can be isomerized to the pyrazole and imidazole compounds, respectively. The present study is helpful to understand the formation of prebiotic species in interstellar space.

  17. Synthesis and Crystal Structure of Ethyl 5-Amino-1-[(5'-methyl-1'-t-butyl-4'-pyrazolyl)carbonyl]-3- methylthio-1H-pyrazole-4-carboxylate

    Institute of Scientific and Technical Information of China (English)

    李明; 文丽荣; 赵桂龙; 王啸; 杨华铮

    2005-01-01

    The title compound, ethyl 5-amino-1-[(5'-methyl-1'-t-butyl-4'-pyrazolyl)carbonyl] -3-methylthio-1H-pyrazole-4-carboxylate 5, has been synthesized by the treatment of 4 with ethyl 2-cyano-3,3-dimethylthioacrylate, and its crystal structure was determined by X-ray diffraction method. The crystal belongs to monoclinic, space group P21/c with a = 12.194(4), b = 12.909(4), c = 11.607(4) (A), β= 90.183(5)°, V = 1827.2(10) (A)3, Mr = 365.45, Z = 4, Dc = 1.328 g/cm3, μ = 0.203 mm-1, F(000) = 776, R = 0.0586 and wR = 0.1558. Preliminary bioassays indicated that the title compound shows fungicidal and plant growth regulation activities.

  18. Hydrogen bonding in the crystal structure of the molecular salt of pyrazole-pyrazolium picrate.

    Science.gov (United States)

    Su, Ping; Song, Xue-Gang; Sun, Ren-Qiang; Xu, Xing-Man

    2016-06-01

    The asymmetric unit of the title organic salt [systematic name: 1H-pyrazol-2-ium 2,4,6-tri-nitro-phenolate-1H-pyrazole (1/1)], H(C3H4N2)2 (+)·C6H2N3O7 (-), consists of one picrate anion and one hydrogen-bonded dimer of a pyrazolium monocation. The H atom involved in the dimer N-H⋯N hydrogen bond is disordered over both symmetry-unique pyrazole mol-ecules with occupancies of 0.52 (5) and 0.48 (5). In the crystal, the component ions are linked into chains along [100] by two different bifurcated N-H⋯(O,O) hydrogen bonds. In addition, weak C-H⋯O hydrogen bonds link inversion-related chains, forming columns along [100].

  19. (3-Acetyl-4-methyl-1H-pyrazol-1-ide-5-carboxylatobis(1,10-phenanthrolinenickel(II 3.5-hydrate

    Directory of Open Access Journals (Sweden)

    Sergey Malinkin

    2013-07-01

    Full Text Available The title compound, [Ni(C7H6N2O3(C12H8N22]·3.5H2O, crystallizes as a neutral mononuclear complex with 3.5 solvent water molecules. One of the water molecules lies on an inversion centre, so that its H atoms are disordered over two sites. The coordination environment of NiII has a slightly distorted octahedral geometry, which is formed by one O and five N atoms belonging to the N,O-chelating pyrazol-1-ide-5-carboxylate and two N,N′-chelating phenanthroline molecules. In the crystal, O—H...O, N—H...O and O—H...N hydrogen bonds involving the solvent water molecules and pyrazole-5-carboxylate ligands form layers parallel to the ab plane. These layers are linked further via weak π–π interactions between two adjacent phenanthroline molecules, with centroid-to-centroid distances in the range 3.886 (2–4.018 (1 Å, together with C—H...π contacts, forming a three-dimensional network.

  20. Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds.

    Science.gov (United States)

    Eurtivong, Chatchakorn; Reynisdóttir, Inga; Kuczma, Stephanie; Furkert, Daniel P; Brimble, Margaret A; Reynisson, Jóhannes

    2016-08-15

    Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI50 at 30nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI50=296nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various substituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found.

  1. Synthesis and Crystal Structure of Ethyl 1-(2-bromoethyl)-3-(4-meth-oxyphenyl)-1H-pyrazole-5-carboxylate

    Institute of Scientific and Technical Information of China (English)

    王毅; 邵华; 徐为人; 王建武

    2012-01-01

    The title compound ethyl 1-(2-bromoethyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate 1 has been synthesized and structurally characterized by single-crystal X-ray diffraction.The crystal is of monoclinic(C15H17BrN2O3,Mr = 353.22),space group C21 with a = 24.691(7),b = 6.7678(17),c = 17.884(5) ,β = 97.184(5)o,V = 2965.1(13) 3,Z = 8,Dc = 1.583 g.cm-3,F(000) = 1440,μ = 2.784 mm-1,the final R = 0.0260 and wR = 0.0596 for 2684 observed reflections with I 2σ(I).All the carbon atoms in the molecule are nearly coplanar except C(15),with a large conjugated system among the carbonyl group,pyrazole ring and the benzene ring.Three non-classical intermolecular hydrogen bonds help to stabilize the crystal lattice.The regioselectivity was rationalized based on the coordination of potassium ion with the N-anion and the carbonyl oxygen atom.

  2. Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Cascioferro, Stella; Plescia, Fabiana; Cancemi, Gabriella; Daidone, Giuseppe

    2015-06-05

    In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules.

  3. Regioselective Synthesis of Some Pyrazole Scaffolds Attached to Benzothiazole and Benzimidazole Moieties

    Directory of Open Access Journals (Sweden)

    Nabila A. Kheder

    2014-01-01

    Full Text Available Condensation of 2-(benzothiazol-2-ylacetonitrile (1 or 2-(1-methyl-1H-benzimidazol-2-ylacetonitrile (2 with thiophene-2-carbaldehyde afforded the corresponding acrylonitrile derivatives 3 or 4, respectively. The 1,3-dipolar cycloaddition reaction of the acrylonitrile 3 or 4 with nitrile-imine 6 gave novel pyrazole derivatives pendant to benzothiazole and benzimidazole. The pyrazoline derivative 7 was converted into the corresponding pyrazole derivative 11 via thermal elimination of hydrogen cyanide upon heating in sodium ethoxide solution. The structures of the synthesized products were confirmed by IR, 1H NMR, and mass spectral techniques.

  4. (Furan-2-yl(5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pyrazol-1-ylmethanone

    Directory of Open Access Journals (Sweden)

    Hadi Kargar

    2011-02-01

    Full Text Available In the title compound, C15H14N2O3, the furan ring is disordered over two positions with a refined site-occupancy ratio of 0.587 (11:0.413 (11. The mean plane of the approximately planar pyrazole ring [maximum deviation = 0.0469 (11 Å] makes dihedral angles of 86.13 (11 and 4.5 (5° with the phenyl and furan rings, respectively. The dihedral angle between the phenyl ring and the major component of the disordered furan ring is 81.8 (5°. The molecule shows chirality in one of the carbon atoms but the centrosymmetric space group means the compound is a racemic mixture. In the crystal, intermolecular O—H...O and C—H...O hydrogen bonds connect the molecules. The crystal structure is further stabilized by π–π stacking interactions with a centroid–centroid distance of 3.8646 (12 Å.

  5. Formation of a dinuclear copper(II) complex through the cleavage of CN bond of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole

    Energy Technology Data Exchange (ETDEWEB)

    Shardin, Rosidah; Pui, Law Kung; Yamin, Bohari M. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM 43600 Bangi, Selangor (Malaysia); Kassim, Mohammad B. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM 43600 Bangi, Selangor, Malaysia and Fuel Cell Institute, Universiti Kebangsaan Malaysia, UKM 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    A simple mononuclear octahedral copper(II) complex was attempted from the reaction of three moles of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole and one mole of copper(II) perchlorate hexahydrate in methanol. However, the product of the reaction was confirmed to be a dinuclear copper(II) complex with μ-(3-(pyridin-2-yl)-pyrazolato) and 3-(pyridin-2-yl)-1H-pyrazole ligands attached to each of the Cu(II) centre atom. The copper(II) ion assisted the cleavage of the C{sub benzoyl}N bond afforded a 3-(pyridin-2-yl)-1H-pyrazole molecule. Deprotonation of the 3-(pyridin-2-yl)-1H-pyrazole gave a 3-(pyridin-2-yl)-pyrazolato, which subsequently reacted with the Cu(II) ion to give the (3-(pyridin-2-yl)-pyrazolato)(3-(pyridin-2-yl)-1H-pyrazole)Cu(II) product moiety. The structure of the dinuclear complex was confirmed by x-ray crystallography. The complex crystallized in a monoclinic crystal system with P2(1)/n space group and cell dimensions of a = 12.2029(8) Å, b = 11.4010(7) Å, c = 14.4052(9) Å and β = 102.414(2)°. The compound was further characterized by mass spectrometry, CHN elemental analysis, infrared and UV-visible spectroscopy and the results concurred with the x-ray structure. The presence of d-d transition at 671 nm (ε = 116 dm{sup 3} mol{sup −1} cm{sup −1}) supports the presence of Cu(II) centres.

  6. Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents.

    Science.gov (United States)

    Reddy, T Srinivasa; Kulhari, Hitesh; Reddy, V Ganga; Bansal, Vipul; Kamal, Ahmed; Shukla, Ravi

    2015-08-28

    A series of forty different pyrazole containing benzimidazole hybrids (6-45) have been designed, synthesized and evaluated for their potential anti-proliferative activity against three human tumor cell lines - lung (A549), breast (MCF-7), and cervical (HeLa). Some of the compounds, specifically 9, 17, and 28, showed potent growth inhibition against all the cell lines tested, with IC50 values in the range of 0.83-1.81 μM. Breast cancer cells were used for further detailed studies to understand the mechanism of cell growth inhibition and apoptosis inducing effect of compounds. The morphology, cell migration and long term clonogenic survival of MCF-7 breast cancer cells were severely affected by treatment with these compounds. Flow-cytometry revealed the compounds arrested MCF-7 cells in the G1 phase of the cell cycle via down regulation of cyclin D2 and CDK2. Fluorescent staining and DNA fragmentation studies showed that cell proliferation was inhibited by induction of apoptosis. Moreover, the compounds led to collapse of mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted. The ease of synthesis and the remarkable biological activities make these compounds promising new frameworks for the development of cancer therapeutics.

  7. Combining silver- and organocatalysis: an enantioselective sequential catalytic approach towards pyrano-annulated pyrazoles.

    Science.gov (United States)

    Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Mizutani, Yusuke; Raabe, Gerhard; Enders, Dieter

    2015-02-11

    A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new series of chiral pyrano-annulated pyrazole derivatives in excellent yields (up to 95%) and high enantioselectivities (up to 97% ee).

  8. Non-covalent interactions at bis(pyrazole)silver(i) or -gold(i) cations.

    Science.gov (United States)

    García-Pacios, Vanesa; Arroyo, Marta; Antón, Noelia; Miguel, Daniel; Villafañe, Fernando

    2009-03-28

    The reaction of AgBF(4) with two equivalents of pzH (pyrazole) or dmpzH (3,5-dimethylpyrazole) leads to [Ag(pzH)(2)]BF(4) or [Ag(dmpzH)(2)]BF(4). The reaction of [AuCl(tht)] with an equimolar amount of dmpzH in refluxing hexane leads to [Au(dmpzH)(2)][AuCl(2)]. Similar complexes [Au(dmpzH)(2)]A (A = BF(4) or NO(3)) are obtained from [AuCl(tht)], two equivalents of dmpzH, and AgBF(4) or AgNO(3). The complexes [Ag(dmpzH)(2)]BF(4) and [Au(dmpzH)(2)]A (A = [AuCl(2)], BF(4) or NO(3)) crystallize as ionic pairs where the NH groups of the pyrazoles are involved in short cation-anion interactions. The nitrate complex crystallizes as a dimer, where both molecules are supported by pi-stacking interactions between the pyrazole rings. The crystal structure of [Ag(pzH)(2)]BF(4) reveals a three dimensional array of cations and anions. In solution, [Ag(pzH)(2)]BF(4) and [Ag(dmpzH)(2)]BF(4) undergo intermolecular processes involving pyrazole decoordination, and behave as 1/1 electrolytes; whereas dimethylpyrazole gold complexes do not display any dynamic behavior, and show cation-anion association also in solution.

  9. Role of Rydberg states in the photostability of heterocyclic dimers: the case of pyrazole dimer.

    Science.gov (United States)

    Zilberg, Shmuel; Haas, Yehuda

    2012-11-26

    A new route for the nonradiative decay of photoexcited, H-bonded, nitrogen-containing, heterocyclic dimers is offered and exemplified by a study of the pyrazole dimer. In some of these systems the N(3s) Rydberg state is the lowest excited singlet state. This state is formed by direct light absorption or by nonradiative transition from the allowed ππ* state. An isomer of this Rydberg state is formed by H atom transfer to the other component of the dimer. The newly formed H-bonded radical pair is composed of two radicals (a H-adduct of pyrazole, a heterocyclic analogue of the NH(4) radical) and the pyrazolium π-radical. It is calculated to have a shallow local minimum and is the lowest point on the PES of the H-pyrazole/pyrazolium radical pair. This species can cross back to the ground state of the original dimer through a relatively small energy gap and compete with the H-atom loss channel, known for the monomer. In both Rydberg dimers, an electron occupies a Rydberg orbital centered mostly on one of the two components of the dimer. This Rydberg Center Shift (RCS) mechanism, proposed earlier (Zilberg, S.; Kahan, A.; Haas, Y. Phys. Chem. Chem. Phys. 2012, 14, 8836), leads to deactivation of the electronically excited dimer while keeping it intact. It, thus, may explain the high photostability of the pyrazole dimer as well as other heterocyclic dimers.

  10. A Pyrazole to Furan Rearrangement. Thermolysis of 5-Azido-4-formylpyrazoles

    DEFF Research Database (Denmark)

    Svenstrup, Niels; Simonsen, Klaus B.; Thorup, Niels

    1999-01-01

    -phenylpyrazoles 3a-c. The formation of the 4-cyano-2-phenyl-3- phenylazofurans 2a-c is the first example in the pyrazole series of a nitrene rearrangement, in which the parent heterocyclic system of the product differs from that of the starting material. The isolation of equimolar amounts of the two products...

  11. N-Substituted pyrazole-3-carboxamides as inhibitors of human 15-lipoxygenase.

    Science.gov (United States)

    Pelcman, Benjamin; Sanin, Andrei; Nilsson, Peter; Schaal, Wesley; Olofsson, Kristofer; Krog-Jensen, Christian; Forsell, Pontus; Hallberg, Anders; Larhed, Mats; Boesen, Thomas; Kromann, Hasse; Claesson, Hans-Erik

    2015-08-01

    High-throughput screening was used to find selective inhibitors of human 15-lipoxygenase-1 (15-LOX-1). One hit, a 1-benzoyl substituted pyrazole-3-carboxanilide (1a), was used as a starting point in a program to develop potent and selective 15-LOX-1 inhibitors.

  12. Synthesis and Crystal Structure of a Novel Ethyl 5-(4-(2-Phenylacetamido)phenyl)-lH-pyrazole- 3-carboxylate as an Acrosin Inhibitor%Synthesis and Crystal Structure of a Novel Ethyl 5-(4-(2-Phenylacetamido)phenyl)-lH-pyrazole- 3-carboxylate as an Acrosin Inhibitor

    Institute of Scientific and Technical Information of China (English)

    QI Jing-Jing; ZHOU You-Jun; LIU Xue-Fei; DING Li-Li; ZHENG Can-Hui; SHENG Chun-Quan; LV Jia-Guo; ZHU Ju

    2011-01-01

    The title compound (ethyl5-(4-(2-phenylacetamido)phenyl)-lH-pyrazole-3-carboxylate, C20H19N3O3) was synthesized by the reaction of Claisen condensation, cyclization, reduction and acylation. The structure was characterized by X-ray diffraction, MS, NMR and IR. It belongs to the monoclinic system, space group C2/c with a = 22.723(9), b = 9.324(4), c = 18.890(8) A, β = 114.259(6)°, V = 3649(3) A^3, Dc = 1.272 Mg·m^3, Z = 8, Mr = 349.38, p = 0.087 mm^-1, F(000) = 1472, the final R = 0.0615 and wR = 0.1643. The biological test shows that the title compound has a moderate acrosin inhibition activity.

  13. Crystal structure of 5-butylamino-3-methyl-1-(pyridin-2-yl-1H-pyrazole-4-carbaldehyde obtained from a microwave-assisted reaction using caesium carbonate as catalyst

    Directory of Open Access Journals (Sweden)

    Mario A. Macías

    2016-11-01

    Full Text Available The title compound, C14H18N4O, synthesized from an unconventional microwave-assisted method using caesium carbonate as catalyst, has an approximately planar conformation with the pyridyl and pyrazole rings inclined by a dihedral angle of 7.94 (3°, allowing the formation of an intramolecular N—H...N hydrogen bond. The supramolecular assembly has a three-dimensional arrangement controlled mainly by weak C—H...O and C—H...π interactions.

  14. A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives.

    Science.gov (United States)

    Lazzari, Paolo; Distinto, Rita; Manca, Ilaria; Baillie, Gemma; Murineddu, Gabriele; Pira, Marilena; Falzoi, Matteo; Sani, Monica; Morales, Paula; Ross, Ruth; Zanda, Matteo; Jagerovic, Nadine; Pinna, Gérard Aimè

    2016-10-04

    8-Chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 9a was discovered as potent and selective CB1 antagonist by part of our group few years ago. In particular it was reported to have an affinity towards the CB1 cannabinoid receptor (CB1R), expressed as Ki, of 0.00035 nM. Nevertheless significantly divergent data were reported for the same compound from other laboratories. To unequivocally define the receptor profile of 9a, we have critically reviewed both its synthesis approach and binding data. Here we report that, in contrast to our previously reported data, 9a showed a Ki value for CB1R in the order of nanomolar rather than of fentomolar range. The new determined receptor profile of 9a was also ascertained for analogue derivatives 9b-i, as well as for 12. Moreover, the structural features of the synthesized compounds necessary for CB1R were investigated. Amongst the novel series, effects on CB1R intrinsic activity was highlighted due to the substituents at the position 3 of the pyrazole ring of the 1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole scaffold. Although the cannabinoid receptor profile of 9a was reviewed in this work, the relevance of this compound in CB1R antagonist based drug discovery is confirmed.

  15. 5-Methyl-1-[(4-methyl-phen-yl)sulfon-yl]-1H-pyrazol-3-yl 4-methyl-benzene-sulfonate.

    Science.gov (United States)

    Murtaza, Shahzad; Kausar, Naghmana; Tahir, M Nawaz; Tariq, Javaria; Bibi, Samaira

    2012-07-01

    In the title compound, C(18)H(18)N(2)O(5)S(2), the tolyl rings are oriented at a dihedral angle of 16.15 (11)° with respect to one another. The 5-methyl-1H-pyrazol-3-ol ring is roughly planar (r.m.s. deviation = 0.0231 Å) and subtends angles of 73.82 (8) and 89.85 (8)° with the tolyl rings. In the crystal, very weak π-π inter-actions between tolyl groups, with centroid-centroid distances of 4.1364 (19) and 4.0630 (16) Å, together with a C-H⋯π contact generate a three-dimensional network.

  16. Synthesis, Crystal Structure and Thermal Stability of 1D Linear Silver(I Coordination Polymers with 1,1,2,2-Tetra(pyrazol-1-ylethane

    Directory of Open Access Journals (Sweden)

    Evgeny Semitut

    2016-10-01

    Full Text Available Two new linear silver(I nitrate coordination polymers with bitopic ligand 1,1,2,2-tetra(pyrazol-1-ylethane were synthesized. Synthesized compounds were characterized by IR spectroscopy, elemental analysis, powder X-ray diffraction and thermal analysis. Silver coordination polymers demonstrated a yellow emission near 500 nm upon excitation at 360 nm. Crystal structures of coordination polymers were determined and structural peculiarities are discussed. In both of the structures, silver ions are connected via bridging ligand molecules to form polymeric chains with a five-atomic environment. The coordination environment of the central atom corresponds to a distorted trigonal bipyramid with two N atoms of different ligands in apical positions. The Ag–N bond distances vary in a wide range of 2.31–2.62 Å, giving strongly distorted metallacycles. Thermolysis of coordination polymers in reductive atmosphere (H2/He leads to the formation of silver nanoparticles with a narrow size distribution.

  17. Tris(ethyl­enediamine)­nickel(II) 1H-pyrazole-3,5-dicarboxyl­ate 1.67-hydrate

    Science.gov (United States)

    Demirtaş, Güneş; Dege, Necmi; Yeşilel, Okan Zafer; Erer, Hakan; Büyükgüngör, Orhan

    2010-01-01

    The asymmetric unit of the title compound, [Ni(C2H8N2)3](C5H2N2O4)·1.67H2O, consists of three [Ni(en)3]2+ dications (en is ethyl­enediamine), three [(pzdc)3]2− dianions (pzdc is pyrazole-3,5-dicarboxyl­ate) and five water mol­ecules. In each complex dication, the NiII atom is coordinated by six N atoms from three en ligands forming a distorted octa­hedral coordination geometry. In the crystal, the ions and water mol­ecules are linked into a three-dimensional framework by a large number of N—H⋯O and O—H⋯O hydrogen bonds. PMID:21588159

  18. Crystal structure of ethyl N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylcarbamate

    Directory of Open Access Journals (Sweden)

    Muhammad Danish

    2015-04-01

    Full Text Available In the title compound, C14H17N3O3, the dihedral angle between the benzene ring and the five-membered dihydropyrazole ring is 52.26 (9°. The ethyl ester group is approximately planar (r.m.s. deviation 0.0568 Å and subtends an angle 67.73 (8° to the pyrazole ring. In the crystal, molecules are linked by pairs of N—H...O hydrogen bonds, forming inversion dimers with an R22(10 ring motif. Weaker C—H...O contacts link these dimers into a three-dimensional network of molecules stacked along the a-axis direction. Offset π–π stacking interactions between the benzene rings [centroid-to-centroid distance = 3.8832 (12 Å] further stabilize the crystal packing.

  19. Vibrational and theoretical analysis of pentyl-4-benzoyl-1-[2,4-dinitrophenyl]-5-phenyl-1H-pyrazole-3-carboxylate

    Science.gov (United States)

    Arı, Hatice; Büyükmumcu, Zeki; Özpozan, Talat; İlhan, İlhan Özer; Bahadır, Özlem

    2013-06-01

    Infrared spectrum of the compound, pentyl-4-benzoyl-1-[2,4-dinitrophenyl]-5-phenyl-1H-pyrazole-3-carboxylate (PBDPPC) has been measured. Conformational search through relaxed scan has been carried out to find the most stable conformational isomer. After the full geometry optimization for the most stable conformer using B3LYP and BLYP hybrid functionals of Density Functional Theory (DFT), vibrational normal modes have been calculated at the same theoretical levels. Potential Energy Distribution (PED) of each normal mode has been calculated by means of VEDA4 to obtain contributions of internal coordinates to the normal modes. Natural Bond Orbital (NBO) analysis has been performed to get insights into the possible hydrogen bonding sites for all the conformational isomers.

  20. Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study.

    Science.gov (United States)

    Bhatt, Jaimin D; Chudasama, Chaitanya J; Patel, Kanuprasad D

    2015-12-15

    A series of novel pyrazole linked triazolo-pyrimidine hybrids were synthesized and evaluated for their anti-tuberculosis activity against M.tb H37Rv strain. Some of the screened entities rendered promising anti-tb activity (MIC: 0.39μg/mL) and were found non toxic against Vero cells (IC50: ⩾20μg/mL). Further, the docking study against wild type InhA enzyme of Mycobacterium tuberculosis using Glide reproduced the most active inhibitors (J21 and J27) with lowest binding energies and highest Glide XP scores demonstrating efficient binding to the active pocket. Additionally, the enzyme inhibition assay and ADME prediction of the active proved to be an attest to the possibility of developing compound J27 as a potent anti-tubercular lead.

  1. Crystal structure of ethyl (2Z-2-cyano-3-[(3-methyl-1-phenyl-1H-pyrazol-5-ylamino]prop-2-enoate

    Directory of Open Access Journals (Sweden)

    Joel T. Mague

    2014-11-01

    Full Text Available The title compound, C16H16N4O2, crystallizes with two molecules in the asymmetric unit, one of which shows disorder of the acetate group over two sets of sites in a 0.799 (2:0.201 (2 ratio. The phenyl group has a similar but opposite sense of twist relative to the pyrazole ring in the two molecules, as indicated by the syn N—N—Car—Car (ar = aromatic torsion angles of 39.7 (2 and −36.9 (2°. Each molecule features an intramolecular N—H...O hydrogen bond, which closes an S(6 ring. In the crystal, C—H...O and C—H...N interactions direct the packing into a layered structure parallel to (110.

  2. Access to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group.

    Science.gov (United States)

    Mistico, Laetitia; Querolle, Olivier; Meerpoel, Lieven; Angibaud, Patrick; Durandetti, Muriel; Maddaluno, Jacques

    2016-07-04

    A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chemistry is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chemistry, the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd-catalyzed activation of a non-activated C(sp(3) )-H bond alpha to a silicon atom. The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation-deprotonation (CMD) mechanism.

  3. Secondary metabolites from the sponge Tedania anhelans: Isolation and characterization of two novel pyrazole acids and other metabolites

    Digital Repository Service at National Institute of Oceanography (India)

    Parameswaran, P.S.; Naik, C.G.; Hegde, V.R.

    Chemical investigation of the methanol extract of the sponge Tedania anhelans yielded the two unusual heteroaromatic acids, pyrazole-3(5)-carboxylic acid (2) and 4-methylpyrazole-3(5)-carboxylic acid (3), which are reported for the first time...

  4. Modification, biological evaluation and 3D QSAR studies of novel 2-(1,3-diaryl- 4,5-dihydro-1H-pyrazol-5-ylphenol derivatives as inhibitors of B-Raf kinase.

    Directory of Open Access Journals (Sweden)

    Yu-Shun Yang

    Full Text Available A series of novel 2-(1,3-diaryl- 4,5-dihydro-1H-pyrazol-5-ylphenol derivatives (C1-C24 have been synthesized. The B-Raf inhibitory activity and anti-proliferation activity of these compounds have been tested. Compound C6 displayed the most potent biological activity against B-RafV600E (IC50 = 0.15 µM and WM266.4 human melanoma cell line (GI50 = 1.75 µM, being comparable with the positive control (Vemurafenib and Erlotinib and more potent than our previous best compounds. The docking simulation was performed to analyze the probable binding models and poses while the QSAR model was built to check the previous work as well as to introduce new directions. This work aimed at seeking more potent inhibitors as well as discussing some previous findings. As a result, the introduction of ortho-hydroxyl group on 4,5-dihydro-1H-pyrazole skeleton did reinforce the anti-tumor activity while enlarging the group on N-1 of pyrazoline was also helpful.

  5. The synthesis of novel pyrazole-3,4-dicarboxamides bearing 5-amino-1,3,4-thiadiazole-2-sulfonamide moiety with effective inhibitory activity against the isoforms of human cytosolic carbonic anhydrase I and II.

    Science.gov (United States)

    Mert, Samet; Alım, Zuhal; İşgör, Mehmet Mustafa; Beydemir, Şükrü; Kasımoğulları, Rahmi

    2016-10-01

    A series of 1-(3-substituted-phenyl)-5-phenyl-N(3),N(4)-bis(5-sulfamoyl-1,3,4-thiadiazol-2-yl)-1H-pyrazole-3,4-dicarboxamides (4-15) were synthesized. The structures of these pyrazole-sulfonamides were confirmed by FT-IR, (1)H NMR, (13)C NMR and elemental analysis methods. Human cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes (hCA I and II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of newly synthesized derivatives (4-15) were investigated in vitro on esterase activities of these isozymes. The Ki values were determined as 0.119-3.999μM for hCA I and 0.084-0.878μM for hCA II. The results showed that the compound 6 for hCA I and the compound 11 for hCA II had the highest inhibitory effect. Beside that, the compound 8 had the lowest inhibition effect on both isozymes.

  6. Tailored design of ruthenium molecular catalysts with 2,2'-bypyridine-6,6'-dicarboxylate and pyrazole based ligands for water oxidation.

    Science.gov (United States)

    Daniel, Quentin; Wang, Lei; Duan, Lele; Li, Fusheng; Sun, Licheng

    2016-10-07

    With the incorporation of pyrazole and DMSO as axial ligands, a series of tailor-designed Ru water oxidation catalysts [Ru(bda)(DMSO)(L)] (H2bda = 2,2'-bypyridine-6,6'-dicarboxylic acid; DMSO = dimethyl sulfoxide; L = pyrazole, A-1; 4-Br-3-methyl pyrazole, B-1) and [Ru(bda)(L)2] (L = pyrazole, A-2; 4-Br-3-methyl pyrazole, B-2) have been generated in situ from their corresponding precursors [Ru(κ3(O,N,N)-bda)(DMSO)x(L)3-x] which are in a zwitterionic form with an extra pyrazole based ligand in the equatorial position. Formation of the active catalyst has been investigated under pH 1.0 conditions. Electrochemistry and water oxidation activity of these catalysts were investigated. By fine tuning of the catalyst structure, the turnover frequency was increased up to 500 s(-1) and the stability over 6000 turnovers.

  7. Anti-Candida, Anti-Enzyme Activity and Cytotoxicity of 3,5-Diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides

    Directory of Open Access Journals (Sweden)

    Simone Oliveira

    2014-05-01

    Full Text Available Because of the need for more effective and less harmful antifungal therapies, and interest in the synthesis of new carboximidamides, the goal of this study was to determine the antifungal and anti-enzyme activities of some new pyrazole carboximidamides and their cytotoxicity. For this purpose, tests were performed to evaluate: minimum inhibitory concentration (MIC and minimum fungicidal concentration (MFC; production of proteinases and phospholipase, and cytotoxicity of the extracts. Data were analyzed by ANOVA and Tukey Tests (α = 5%. The results were: MIC and MFC ≥ 62.5 μg/mL (C. albicans, C. parapsilosis, C. famata, C. glabrata, and Rhodotorula mucillaginosa and MIC and MFC ≥ 15.6 μg/mL (C. lipolytica. The values of proteinase and phospholipase (Pz of C. albicans before and after exposure to the compounds were: 0.6 (±0.024 and 0.2 (±0.022 and 0.9 (±0.074 and 0.3 (±0.04, respectively. These proteinase results were not significant (p = 0.69, but those of phospholipase were (p = 0.01, and 15.6 μg/mL was the most effective concentration. The cytotoxicity means were similar among the tests (p = 0.32. These compounds could be useful as templates for further development through modification or derivatization to design more potent antifungal agents. Data from this study provide evidence that these new pyrazole formulations could be an alternative source for the treatment of fungal infections caused by Candida. However, a specific study on the safety and efficacy of these in vivo and clinical trials is still needed, in order to evaluate the practical relevance of the in vitro results.

  8. (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety as potential immunosuppressive agents: Design, synthesis, molecular docking and biological evaluation.

    Science.gov (United States)

    Lv, Xian-Hai; Li, Qing-Shan; Ren, Zi-Li; Chu, Ming-Jie; Sun, Jian; Zhang, Xin; Xing, Man; Zhu, Hai-Liang; Cao, Hai-Qun

    2016-01-27

    A series of novel (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety were firstly synthesized and their immunosuppressive activities were evaluated. Among all the compounds, 4n exhibited the most potent inhibitory activity (IC50 = 1.18 μM for lymph node cells and IC50 = 0.28 μM for PI3Kγ), which was comparable to that of positive control. Moreover, selected compounds were tested for their inhibitory activities against IL-6 released in ConA-simulated mouse lymph node cells, 4n exhibited the most potent inhibitory ability. Furthermore, in order to study the preliminary mechanism of the compounds with potent inhibitory activity, the RT-PCR experiment was performed to assay the effect of selected compounds on mRNA expression of IL-6. Among them, compound 4n strongly inhibited the expression of IL-6 mRNA.

  9. Crystal structure and DFT calculations of 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic acid

    Science.gov (United States)

    Alaşalvar, Can; Soylu, Mustafa Serkan; Ünver, Hüseyin; Ocak İskeleli, Nazan; Yildiz, Mustafa; Çiftçi, Murat; Banoğlu, Erden

    2014-11-01

    The title compound, 5-(4-Chlorophenyl)-1-(6-methoxypyridazin-3-yl)-1H-pyrazole-3-carboxylic acid, has been characterized by using elemental analysis, MS, FT-IR, 1H NMR and 13C NMR spectroscopic, and crystallographic techniques. The title compound crystallizes in the triclinic space group P-1 with a = 9.612(1), b = 9.894(1), c = 17.380(1) Å, α = 90.213(5)°, β = 104.99(1)°, γ = 111.072(5)°, V = 1481.3(2) Å3 and Dx = 1.483 g cm-3 respectively. The structure of the compound has also been examined by using quantum chemical methods. The molecular geometry and vibrational frequencies of monomeric and dimeric form of the title compound in the ground state have been calculated by using the B3LYP/6-31G(d,p) level of the theory. The calculated results show that the optimized geometry and the theoretical vibration frequencies of the dimeric form are good agreement with experimental data. In addition, HOMO-LUMO energy gap, molecular electrostatic potential map, thermodynamic properties of the title compound were performed at B3LYP/6-31G(d,p) level of theory.

  10. Synthesis and antibacterial and cytotoxic activities of new N-3 substituted thiazolidine-2,4-dione derivatives bearing the pyrazole moiety.

    Science.gov (United States)

    Desai, Nisheeth C; Satodiya, Hitesh M; Kotadiya, Ghanshyam M; Vaghani, Hasit V

    2014-07-01

    Two new series of N-3 substituted thiazolidine-2,4-dione derivatives bearing the pyrazole moiety (5a-j and 7a-j) were synthesized and assessed in vitro for their efficacy as antibacterial agents against gram-positive and gram-negative bacterial strains. Among the tested compounds, 7b, 7c, 7i, and 7j were found to be active against gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) with minimum inhibitory concentration (MIC) values in the range of 6.25-25 µg/mL, and some compounds were also tested against methicillin-resistant S. aureus (MRSA). Compounds 7c and 7j inhibited the growth of MRSA at MIC values of 6.25 and 12.5 µg/mL, respectively. The influence of the lipophilicity (C log P) on the biological profile (MIC) of the prepared products was also discussed. From the standpoint of structure-activity relationship studies, it was observed that the lipophilic profiles of the compounds were crucial for their antibacterial activities. Further, the results of the MTT cytotoxicity studies on a human cervical cancer cell line (HeLa) and a mouse embryonic fibroblast cell line (NIH 3T3) suggested that compounds 7b, 7c, 7i, and 7j were endowed with low levels of cytotoxicity.

  11. Bis{tris[3-(2-pyridyl-1H-pyrazole]iron(II} dodecamolybdo(V,VIphosphate hexahydrate

    Directory of Open Access Journals (Sweden)

    Xiaofei Zhang

    2010-03-01

    Full Text Available Crystals of the title compound, [Fe(C8H7N33]2[PMo12O40]·6H2O, prepared under hydrothermal conditions, are isotypic with the Mn2+ and Cd2+ analogues. The Fe2+ cation is in a distorted octahedral coordination by six N atoms from three chelating 3-(2-pyridyl-1H-pyrazole ligands. The heteropolyanion [PMo12O40]4− is a one-electron reduced species in which two O atoms of the central PO4 group (overline{1} symmetry are equally disordered about an inversion centre. N—H...O and O—H...O hydrogen bonds make a contribution to the crystal packing. The Fe—N bond lengths [2.085 (19—2.15 (2 Å] are somewhat shorter than the Mn—N and Cd—N bond lengths [2.224 (6–2.283 (5 and 2.316 (7–2.334 (6 Å, respectively]. All other bond lengths and angles and the hydrogen-bonding motifs are very similar in the isotypic structures.

  12. Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress.

    Science.gov (United States)

    Lu, Yongke; Leung, Tung Ming; Ward, Stephen C; Nieto, Natalia

    2012-02-01

    Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the L-citrulline/nitric oxide (NO·) salvage pathway to continually supply L-arginine from L-citrulline for sustained NO· generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO· synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO· generation and formation of 3-nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/- mice (Ass+/+ mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFα. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/- mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/- compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFα, apoptosis, and neutrophil infiltration.

  13. Thermodynamic functions of Ni(II) complexes with 5-(2-hydroxyphenyl)-pyrazole derivatives. A potentiometric study

    Science.gov (United States)

    Deosarkar, S. D.; Narwade, M. L.; Thakre, V. J.

    2013-10-01

    Proton-ligand dissociation constants of five biologically important pyrazole derivatives, viz. [5-(2-hydroxyphenyl)-3-(pyridin-3-yl)-4-benzoyl]-pyrazol (HPPBP), [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(3-pyridinoyl)]-pyrazol (HPNPPP), [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-benzoyl]-pyrazol (HPNPBP), [5-(2-hydroxyphenyl)-3-phenyl-4-(3-pyridinoyl)]-pyrazol (HPPPP), and [5-(2-hydroxyphenyl)-3-(3-nitrophenyl)-4-(2-furoyl) pyrazol (HPNPFP) and metal ligand stability constants of their Ni(II) complexes in 70% (v/v) dioxane-water and 0.1 M KNO3 were determined at 298.15, 303.15, and 308.15 K by potentiometric method. Thermodynamic functions, such as, free energy change (Δ G ○), enthalpy change (Δ H ○) and entropy (Δ S ○) change for dissociation and complex formation have been estimated form temperature dependence of proton-ligand and metal-ligand stability constants and interpreted in terms of feasibility of these processes.

  14. Preparation of 5-acyl- and 5-aryl-substituted 1-(benzyloxy)pyrazoles via directed ortho-lithiation/transmetalation and palladium catalyzed cross- coupling

    DEFF Research Database (Denmark)

    Kristensen, Jesper Langgaard; Begtrup, M.; Vedsø, P.

    1998-01-01

    Palladium(0) catalyzed cross-coupling of 1-(benzyloxy)pyrazol-5-ylzinc halides 3a,b, prepared by transmetalation of 1-(benzyloxy)-5-lithiopyrazole (2), with acyl chlorides produced 5 acyl-1-(benzyloxy)pyrazoles 4a-d in high yields. Similar coupling of the pyrazol-5-ylzinc halide with amino-, hydr......-, hydroxy- , methoxy-, fluoro-, nitro-, or formyl-substituted iodobenzene gave the corresponding 5-aryl-1-(benzyloxy)pyrazoles 5a-f, while coupling with iodothiophene, iodopyrazole or bromopyridine provided the corresponding 1- (benzyloxy)-5-heteroarylpyrazoles 6a-c....

  15. Preparation of 5-acyl- and 5-aryl-substituted 1-(benzyloxy)pyrazoles via directed ortho-lithiation/transmetalation and palladium catalyzed cross- coupling

    DEFF Research Database (Denmark)

    Kristensen, Jesper Langgaard; Begtrup, M.; Vedsø, P.

    1998-01-01

    Palladium(0) catalyzed cross-coupling of 1-(benzyloxy)pyrazol-5-ylzinc halides 3a,b, prepared by transmetalation of 1-(benzyloxy)-5-lithiopyrazole (2), with acyl chlorides produced 5 acyl-1-(benzyloxy)pyrazoles 4a-d in high yields. Similar coupling of the pyrazol-5-ylzinc halide with amino......-, hydroxy- , methoxy-, fluoro-, nitro-, or formyl-substituted iodobenzene gave the corresponding 5-aryl-1-(benzyloxy)pyrazoles 5a-f, while coupling with iodothiophene, iodopyrazole or bromopyridine provided the corresponding 1- (benzyloxy)-5-heteroarylpyrazoles 6a-c....

  16. Microwave Assisted Synthesis of 1-[5-(Substituted Aryl-1H-Pyrazol-3-yl]-3,5-Diphenyl-1H-1,2,4-Triazole as Antinociceptive and Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Shantaram Gajanan Khanage

    2014-05-01

    Full Text Available Purpose: An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. Methods: The desired compounds (S1-S10 were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. Results: The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy’s hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 μg/ml and compound S6 was exhibited antifungal potential at 15.62 μg/mL on both fungal strains. Conclusion: Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics.

  17. X-Ray Supramolecular Structure, NMR Spectroscopy and Synthesis of 3-Methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-ones Formed by the Unexpected Cyclization of 3-[1-(Phenyl-hydrazonoethyl]-chromen-2-ones

    Directory of Open Access Journals (Sweden)

    Efren V. García-Baez

    2011-01-01

    Full Text Available The molecular structures of nine 3-methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one isomers, obtained by the oxidative cyclization of the corresponding 1-phenylhydrazono chromen-2-ones with copper acetate as catalyst, are reported. The molecular and supramolecular structures of the 8-chloro, 8-bromo- and 8-nitro isomers 2b-d, were established by X-ray diffraction. The halogenated isomers 2b and 2c are isomorphs, they crystallize as a triclinic system, space group P-1 with two molecules in the asymmetric unit. Compound 2d crystallizes as a monoclinic system, space group P21/m with two molecules in the unit cell. The 1-phenyl ring [Cg(4] is almost perpendicularly positioned to the chromene-pyrazole ring system. This conformation is in agreement with the anisotropic NMR shielding effect exerted by the phenyl ring over H-9 in solution. The supramolecular architecture is almost controlled by C―H···A (A = O, p and face to face p-stacking interactions. The observed p-stacking trend between chromene and pyrazole rings is given by the overlapping between the best donor and acceptor rings in each compound.

  18. Synthesis, characterization and cholinesterase enzymes inhibitory activity of 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

    Science.gov (United States)

    Mehdi, Sayed Hasan; Ghalib, Raza Murad; Hashim, Rokiah; da Silva, M. Fátima C. Guedes; Sulaiman, Othman; Murugaiyah, Vikneswaran; Marimuthu, Mani Maran; Naqvi, Mehnaz

    2013-10-01

    The crystal structure of the title compound, 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone has been determined by single crystal X-ray diffraction. It crystallizes in the orthorhombic space group P212121. The FTIR as well as the 1H and 13C NMR spectra of the compound were also recorded and briefly discussed. Compound 1 demonstrated good inhibitory activity against butyrylcholinesterase (BChE; IC50 = 46.42 μM) comparable to physostigmine. However it showed moderate inhibitory activity against acetylcholinesterase (AChE; IC50 = 157.31 μM). It showed moderate inhibitory activity against acetylcholinesterase and selective inhibitory activity towards butyrylcholinesterase enzyme.

  19. Synthesis and activity evaluation of 2-(1-naphtho[2,1- b ]furan-2-yl-carbonyl-3,5-disubstituted-2,3-dihydro-1H-pyrazoles

    Directory of Open Access Journals (Sweden)

    Kumaraswamy M

    2008-01-01

    Full Text Available Ethyl naphtho[2,1- b ]furan-2-carboxylate (2 on reaction with hydrazine hydrate in presence of acid catalyst in ethanol medium affords naphtho[2,1-b]furan-2-carbohydrazide (3. The reaction of substituted acetophenones (4a-c with aromatic aldehydes (5a-e produces chalcones (6a-o via the Claisen condensation. The reaction of naphtho[2,1- b ]furan-2-carbohydrazide (3 with chalcones (6a-6o in presence of acetic acid as catalyst in dioxane produces 1-(naphtho[2,1- b ]furan-2-yl-carbonyl-3,5-disubstituted-2,3-dihydro-1H-pyrazoles (7a-o. The structures of newly synthesized compounds have been established by elemental analysis and spectral studies. The compounds 7a-o have been evaluated for their antimicrobial activity and some selected compounds evaluated for antiinflammatory, analgesic, anthelmintic, diuretic and antipyretic activities.

  20. Synthesis of benzofuran based 1,3,5-substituted pyrazole derivatives: as a new class of potent antioxidants and antimicrobials--a novel accost to amend biocompatibility.

    Science.gov (United States)

    Rangaswamy, Javarappa; Kumar, Honnaiah Vijay; Harini, Salakatte Thammaiah; Naik, Nagaraja

    2012-07-15

    In search for a new antioxidant and antimicrobial agent with improved potency, we synthesized a series of benzofuran based 1,3,5-substituted pyrazole analogues (5a-l) in five step reaction. Initially, o-alkyl derivative of salicyaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, on treatment with 1,8-diaza bicyclo[5.4.0]undec-7-ene (DBU) in the presence of molecular sieves. Further, aldol condensation with vanillin, Claisen-Schmidt condensation reaction with hydrazine hydrate followed by coupling of substituted anilines afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, mass, elemental analysis and further screened for their antioxidant and antimicrobial activities. Among the tested compounds 5d and 5f exhibited good antioxidant property with 50% inhibitory concentration higher than that of reference while compounds 5h and 5l exhibited good antimicrobial activity at concentration 1.0 and 0.5 mg/mL compared with standard, streptomycin and fluconazole respectively.

  1. Water mediated construction of trisubstituted pyrazoles/isoxazoles library using ketene dithioacetals.

    Science.gov (United States)

    Savant, Mahesh M; Pansuriya, Akshay M; Bhuva, Chirag V; Kapuriya, Naval; Patel, Anil S; Audichya, Vipul B; Pipaliya, Piyush V; Naliapara, Yogesh T

    2010-01-01

    A small molecule library of alkyl, sulfone, and carboxamide functionalized pyrazoles and isoxazoles has been developed via a rapid sequential condensation of various alpha-acylketene dithioacetals (1a-o) with hydrazine hydrate or hydroxylamine hydrochloride, followed by oxidation of sulfide to sulfone using water as the reaction medium. An efficient and safe oxidation of sulfides (4/5a-o) to the corresponding sulfones (6/7a-o) using sodium per borate system in aqueous medium is reported. The concise and two step synthesis of trisubstituted pyrazoles and isoxazoles was investigated under variety of reaction condition. The newly developed methodology has the advantage of excellent yield and chemical purity with short reaction time using water as a solvent.

  2. DOCKING OF 1-PHENYLSULFONAMIDE-3-TRIFLUOROMETHYL-5-PARABROMOPHENYL-PYRAZOLE TO CYCLOOXYGENASE-2 USING PLANTS

    Directory of Open Access Journals (Sweden)

    Stefanus Layli Prasojo

    2010-12-01

    Full Text Available The docking protocols to virtually screen selective cyclooxygenase-2 (COX-2 ligands using PLANTS docking software were developed and validated. The crystal structure of 1-phenylsulfonamide-3-trifluoromethyl-5-parabromophenyl-pyrazole (S58 binds to cyclooxygenase-2 (COX-2 was used as the reference structure. The developed protocols could predict the binding pose of S58 to COX-2 accurately (RMSD is 1.2 Ǻ.

  3. DOCKING OF 1-PHENYLSULFONAMIDE-3-TRIFLUOROMETHYL-5-PARABROMOPHENYL-PYRAZOLE TO CYCLOOXYGENASE-2 USING PLANTS

    OpenAIRE

    Stefanus Layli Prasojo; Fajar Agung Dwi Hartanto; Nunung Yuniarti; Zullies Ikawati; Enade Perdana Istyastono

    2010-01-01

    The docking protocols to virtually screen selective cyclooxygenase-2 (COX-2) ligands using PLANTS docking software were developed and validated. The crystal structure of 1-phenylsulfonamide-3-trifluoromethyl-5-parabromophenyl-pyrazole (S58) binds to cyclooxygenase-2 (COX-2) was used as the reference structure. The developed protocols could predict the binding pose of S58 to COX-2 accurately (RMSD is 1.2 Ǻ).

  4. Fluoroalkyl-Substituted Diazomethanes and Their Application in a General Synthesis of Pyrazoles and Pyrazolines.

    Science.gov (United States)

    Mertens, Lucas; Hock, Katharina J; Koenigs, Rene M

    2016-07-01

    A novel continuous-flow approach for the synthesis of fluoroalkyl-substituted diazomethanes has been developed. Utilizing a cheap, self-made microreactor fluoroalkyl-substituted amines were transformed into the corresponding diazomethanes using tert-butyl nitrite and acetic acid as catalyst. These diazomethanes were employed in [2+3] cycloaddition reactions with olefins and alkynes, yielding valuable pyrazolines and pyrazoles in good to excellent yields.

  5. Crystal Structure of N,N-bis-(3-Carbomethoxy-5-methyl-pyrazol-1-ylmethylaniline

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    Taibi Ben-Hadda

    2002-09-01

    Full Text Available The tripodal ligand N,N-bis-(3-carbomethoxy-5-methylpyrazol-1-ylmethyl aniline (2 has been prepared by the condensation of aniline with two equivalents of N-hydroxymethyl[3-carbomethoxy-5-methyl]pyrazole. The molecule consists of two structurally analogous 3-carbomethoxy-5-methylpyrazol-1-ylmethyl moieties, which adopt a transoidal conformation via a central aniline ring, suggesting that this tripodal ligand is highly flexible and could accommodate many metals by coordination.

  6. Synthesis and Antibacterial Evaluation of Novel Heterocyclic Compounds Containing a Sulfonamido Moiety

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    Eman A. El-Bordany

    2013-01-01

    Full Text Available Aiming for the synthesis of new heterocyclic compounds containing a sulfonamido moiety suitable for use as antibacterial agents, the precursor ethyl {[4-N-(4,6-dimethylpyrimidin-2-ylsulfamoyl]phenylazo}cyanoacetate was reacted with a variety of active methylene compounds producing pyran, pyridine and pyridazine derivatives. Also, the reactivity of the precursor hydrazone towards hydrazine derivatives to give pyrazole and oxazole derivatives was studied. On the other hand, treatment of the same precursor with urea, thiourea and/or guanidine hydrochloride furnished pyrimidine and thiazine derivatives, respectively. The newly synthesized compounds were tested for antibacterial activity, whereby eight compounds were found to have high activities.

  7. Efficient catalytic phosphate ester cleavage by binuclear zinc(II) pyrazolate complexes as functional models of metallophosphatases.

    Science.gov (United States)

    Penkova, Larysa V; Maciag, Anna; Rybak-Akimova, Elena V; Haukka, Matti; Pavlenko, Vadim A; Iskenderov, Turganbay S; Kozłowski, Henryk; Meyer, Franc; Fritsky, Igor O

    2009-07-20

    A series of dizinc(II) complexes based on the pyrazolate ligands 3-[(1E)-N-hydroxyethanimidoyl]-4-methyl-1H-pyrazole-5-carboxylic acid (H(3)L(1)), (1E,1'E)-1,1'-(4-methyl-1H-pyrazole-3,5-diyl)diethanone dihydrazone (HL(2)), (E,E)-(4-methyl-1H-pyrazole-3,5-diyl)bis(methylmethanone) dioxime (H(3)L(3)), (E,E)-(4-phenyl-1H-pyrazole-3,5-diyl)bis(phenylmethanone) dioxime (H(3)L(4)), and 1H-pyrazole-3,5-dicarboxylic acid (H(3)L(5)) have been synthesized and investigated as functional models of phosphoesterases, focusing on correlations between the hydrolytic activity and molecular parameters of the bimetallic core. Speciation of the various dizinc complexes in solution has been determined potentiometrically, and the structures in the solid state have been established by X-ray crystallography. The hydrolysis of two phosphoesters, an RNA model 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP) and the pesticide paraoxon-ethyl (POE), promoted by the dinuclear phosphoesterase model complexes has been investigated in DMSO/buffered water (1:1) at 50 degrees C as a function of complex concentration, substrate concentration, and pH. Drastic differences in the hydrolytic activities of [Zn(2)(HL(1))(2)](0), [Zn(2)(L(2))(2)](2+), [Zn(2)(H(2)L(3))(2)](2+), and [Zn(2)(HL(5))(2)](2-) are observed and can be attributed to molecular peculiarities. Pyrazolate-bridged dinuclear zinc(II) complexes seem to provide a sufficient number of coordination sites for both activating the substrate and generating the nucleophile, where the phosphate esters are preferentially bound in a bidentate bridging fashion (in the case of HPNP) and in a monodentate fashion (in the case of POE).

  8. Pd/C-mediated synthesis of α-pyrone fused with a five-membered nitrogen heteroaryl ring: A new route to pyrano[4,3-c]pyrazol-4(1H-ones

    Directory of Open Access Journals (Sweden)

    Dhilli Rao Gorja

    2009-11-01

    Full Text Available Pd/C-mediated alkynylation of 5-iodo-pyrazole-4-carboxylic acid, involving the first regioselective construction of α-pyrone ring on a pyrazol moiety via tandem coupling–cyclization process, has been developed to afford pyrano[4,3-c]pyrazol-4(1H-one in a single pot.

  9. Infrared, Raman and NMR spectra, conformational stability, normal coordinate analysis and B3LYP calculations of 5-Amino-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde

    Science.gov (United States)

    Bahgat, Khaled; EL-Emary, Talaat

    2013-02-01

    FT Raman and IR spectra of the crystallized biologically active molecule, 5-Amino-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (5-APHC, C11H11N3O) have been recorded and analyzed. The equilibrium geometry, bonding features and harmonic vibrational frequencies of 5-APHC have been investigated with the help of B3LYP density functional theory (DFT) method with 6-31G(d) and 6-311+G(d,p) as basis set. The calculated molecular geometry has been compared with the experimental data. The assignments of the vibrational spectra have been carried out with the help of normal coordinate analysis (NCA) following the scaled quantum mechanical force field (SQM) technique. The optimized geometry shows the co-planarity of the aldehyde group with pyrazole ring. Potential energy surface (PES) scan studies has also been carried out by ab initio calculations with B3LYP/6-311+G(d,p) basis set. The red shifting of NH2 stretching wavenumber indicates the formation of N-H⋯O hydrogen bonding. 1H and 13C NMR spectra were recorded and 1H and 13C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. UV-Vis spectrum of the compound was recorded in the region 200-400 nm and the electronic properties HOMO and LUMO energies were calculated by time-dependent TD-DFT approach. Mulliken charges of the 5-APHC molecule was also calculated and interpreted.

  10. Microwave assisted synthesis and antimicrobial activity of novel 1-[1/2-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-naphthalen-2/1-yl]-3-(1-phenyl-3-aryl-1H-pyrazol-4-yl-propenones

    Directory of Open Access Journals (Sweden)

    Dongamanti Ashok

    2015-06-01

    Full Text Available A series of novel 1-[1/2-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-naphthalen-2/1-yl]-3-(1-phenyl-3-aryl-1H-pyrazol-4-yl-propenones were design and synthesized by Click reaction followed by Claisen-Schmidt condensation under microwave irradiation and conventional heating methods. The structures of newly synthesized compounds have been established on the basis of elemental analysis, IR, 1H & 13C NMR and mass spectral data. All the compounds were screened for their antimicrobial activity.

  11. A novel pyrazole-containing indolizine derivative suppresses NF-κB activation and protects against TNBS-induced colitis via a PPAR-γ-dependent pathway.

    Science.gov (United States)

    Fu, Yong; Ma, Junting; Shi, Xiafei; Song, Xiang-Yun; Yang, Yaping; Xiao, Shuke; Li, Jiahuang; Gu, Wei-Jin; Huang, Zhen; Zhang, Junfeng; Chen, Jiangning

    2017-07-01

    The nuclear factor-κB (NF-κB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn's disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-κB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-γ and inhibit the NF-κB pathway in colonic macrophages holds great promise for the treatment of CD. In this study, five novel pyrazole-containing indolizine derivatives (B1, B2, B3, B4 and B5) were successfully synthesized and characterized, and their anti-inflammatory activities for CD treatment were also investigated. Among the five compounds, compound B4 effectively decreased the NF-κB-mediated production of the pro-inflammatory cytokine TNF-α in LPS-stimulated peritoneal macrophages. Moreover, compound B4 significantly ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis symptoms, including body weight loss, colonic pathological damage and inflammatory cell infiltration. The results of western blotting and luciferase reporter assays indicated that compound B4 activated PPAR-γ and subsequently suppressed NF-κB activation. Conversely, the addition of the PPAR-γ antagonist GW9662 abrogated the anti-inflammatory effects of compound B4 both in vitro and in vivo. In summary, compound B4 activated the PPAR-γ pathway to inhibit downstream NF-κB signaling, which alleviated experimental colitis. Thus, this compound may serve as a potential therapeutic agent for patients with CD. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. An unusually stable octanuclear sigma-mesityl-bridged mu4-oxo-copper(I) complex encapsulated by a pyrazolate-based compartmental ligand scaffold.

    Science.gov (United States)

    Stollenz, Michael; Grosse, Christian; Meyer, Franc

    2008-04-21

    A new compartmental pyrazole-derived chelating ligand, four equivalents of mesitylcopper and stoichiometric amounts of dioxygen lead to the formation of a remarkably stable organometallic framework that can be described as a heteroleptic O-centered cuprate anion [(MesCu(I))(4)(mu(4)-O)](2-) linked via sigma-mesityl-bridges to two surrounding binuclear Cu(I)-pyrazolate clamps.

  13. Copper-catalyzed aerobic C(sp2)-H functionalization for C-N bond formation: synthesis of pyrazoles and indazoles.

    Science.gov (United States)

    Li, Xianwei; He, Li; Chen, Huoji; Wu, Wanqing; Jiang, Huanfeng

    2013-04-19

    A simple, practical, and highly efficient synthesis of pyrazoles and indazoles via copper-catalyzed direct aerobic oxidative C(sp(2))-H amination has been reported herein. This process tolerated a variety of functional groups under mild conditions. Further diversification of pyrazoles was also investigated, which provided its potential for drug discovery.

  14. Synthesis of 1H-indazoles and 1H-pyrazoles via FeBr3/O2 mediated intramolecular C-H amination.

    Science.gov (United States)

    Zhang, Tianshui; Bao, Weiliang

    2013-02-01

    A new synthesis of substituted 1H-indazoles and 1H-pyrazoles from arylhydrazones via FeBr(3)/O(2) mediated C-H activation/C-N bond formation reactions is reported. The corresponding 1,3-diaryl-substituted indazoles and trisubstituted pyrazoles were obtained in moderate to excellent yields under mild conditions.

  15. Un-catalyzed tandem Knoevenagel-Michael reaction for the synthesis of 4,4'-(arylmethylene)bis(7H-pyrazol-5-ols) in aqueous medium

    Institute of Scientific and Technical Information of China (English)

    Nilesh P. Tale; Girdharilal B. Tiwari; Nandkishor N. Karade

    2011-01-01

    An environmentally benign un-catalyzed one-pot synthesis of 4,4'-(arylmethylene)bis(7H-pyrazol-5-ols) has been reported via tandem Knoevenagel-Michael reaction of aldehydes with two equivalents of 3-methyl-l-phenyl-lH-pyrazol-5(4H)-one in aqueous medium.

  16. Synthesis of 1H-Indol-3-ylpyrazole Derivatives from 1,3,5-Triketones and Arylhydrazines: One-Pot Construction of Pyrazole and Indole Rings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hwan; Kim, Se Hee; Kim, Ko Hoon; Kim, Jae Nyoung [Chonnam National Univ., Gwangju (Korea, Republic of); Lee, Sang Ku [Immune Modulator Research Center, Daejeon (Korea, Republic of)

    2013-11-15

    The reaction of 1,3,5-triketones and arylhydrazines provided indolylpyrazole derivatives in a one-pot reaction in good to moderate yields. Both the pyrazole and indole rings were constructed simultaneously with phenylhydrazine, RCOCH{sub 2}CO- moiety for the pyrazole and the remaining -CH{sub 2}COR part for the indole ring.

  17. Synthesis of Heteroaromatic Compounds by Oxidative Aromatization Using an Activated Carbon/Molecular Oxygen System

    Directory of Open Access Journals (Sweden)

    Masahiko Hayashi

    2009-08-01

    Full Text Available A variety of heteroaromatic compounds, such as substituted pyridines, pyrazoles, indoles, 2-substituted imidazoles, 2-substituted imidazoles, 2-arylbenzazoles and pyrimidin-2(1H-ones are synthesized by oxidative aromatization using the activated carbon and molecular oxygen system. Mechanistic study focused on the role of activated carbon in the synthesis of 2-arylbenzazoles is also discussed. In the final section, we will disclose the efficient synthesis of substituted 9,10-anthracenes via oxidative aromatization.

  18. Protic N-Heterocyclic Carbene Versus Pyrazole: Rigorous Comparison of Proton- and Electron-Donating Abilities in a Pincer-Type Framework.

    Science.gov (United States)

    Toda, Tatsuro; Yoshinari, Akihiro; Ikariya, Takao; Kuwata, Shigeki

    2016-11-07

    Evaluation of the acidity of proton-responsive ligands such as protic N-heterocyclic carbenes (NHCs) bearing an NH-wingtip provides a key to understanding the metal-ligand cooperation in enzymatic and artificial catalysis. Here, we design a CNN pincer-type ruthenium complex 2 bearing protic NHC and isoelectronic pyrazole units in a symmetrical skeleton, to compare their acidities and electron-donating abilities. The synthesis is achieved by direct C-H metalation of 2-(imidazol-1-yl)-6-(pyrazol-3-yl)pyridine with [RuCl2 (PPh3 )3 ]. (15) N-Labeling experiments confirm that deprotonation of 2 occurs first at the pyrazole side, indicating clearly that the protic pyrazole is more acidic than the NHC group. The electrochemical measurements as well as derivatization to carbonyl complexes demonstrate that the protic NHC is more electron-donating than pyrazole in both protonated and deprotonated forms.

  19. Mixed-valence copper(I,II) complexes with 4-(1H-pyrazol-1-yl)-6-R-pyrimidines: from ionic structures to coordination polymers.

    Science.gov (United States)

    Vinogradova, Katerina A; Krivopalov, Viktor P; Nikolaenkova, Elena B; Pervukhina, Natalia V; Naumov, Dmitrii Yu; Boguslavsky, Evgenii G; Bushuev, Mark B

    2016-01-14

    Two pyrimidine-based ligands, 4-(3,5-diphenyl-1H-pyrazol-1-yl)-6-(morpholino)pyrimidine () and 4-(3,5-diphenyl-1H-pyrazol-1-yl)-6-phenoxypyrimidine (), and a series of mixed-valence copper(i,ii) halide complexes, [Cu(L(2))2Br]2[Cu2Br4] (), [Cu(L(2))2Cl][CuCl2] (), and [Cu2L(3)Br3]n (), have been synthesized. The complex [Cu(L(2))2Br]2[Cu2Br4] was prepared by the reaction of with CuBr2 in a 1 : 1 molar ratio in MeCN. Its chlorido-analogue, the complex [Cu(L(2))2Cl][CuCl2], was synthesized by the reaction between , CuCl2 and CuCl in a 2 : 1 : 1 molar ratio in MeCN. The ligand acts as a chelating one. In the structures of the complexes [Cu(L(2))2Br]2[Cu2Br4] and [Cu(L(2))2Cl][CuCl2] the Cu(2+) ion is in the cationic part of the complex whereas the Cu(+) ion is located in the anionic part. The best way to synthesize the mixed-valence 1D coordination polymer [Cu2L(3)Br3]n is to react CuBr2 with in a 2 : 1 molar ratio in the MeCN/CHCl3 mixture on heating. In the structure of [Cu2L(3)Br3]n the ligand shows chelating/bridging tridentate coordination. This is the first example of the tridentate coordination of 4-(1H-pyrazol-1-yl)-6-R-pyrimidines. The striking difference between the coordination behavior of and (chelating bidentate vs. chelating/bridging coordination) is related with the possibility of rotation of the 6-phenoxy group around the C-O bond which makes the N(1) pyrimidine atom less sterically hindered, enabling it to participate in metal ion binding. Importantly, all copper ions in [Cu2L(3)Br3]n show similar tetrahedral environments, CuNBr3 and CuN2Br2, which is extremely rare for mixed-valence copper(i,ii) compounds. The ligands and show blue emission which is quenched upon their coordination to copper ions. The 1D coordination polymer [Cu2L(3)Br3]n shows high thermal stability and unusual solvent-occlusion properties. The role of the substituents favoring the formation of the mixed-valence copper(i,ii) complexes with 4-(1H-pyrazol-1-yl)-6-R

  20. 1H and 13C NMR study of perdeuterated pyrazoles

    OpenAIRE

    Jimeno, María Luisa; Jagerovic, Nadine; Elguero, José; Junk, Thomas; Catallo, W. James

    1997-01-01

    The 1H and 13C chemical shifts as well as the 1H–2H and 2H–13C coupling constants of perdeuterated 3,5-dimethylpyrazole and 3,5-diphenylpyrazole have been measured and the values compared with those of the unlabelled compounds.

  1. Pyrazole induced oxidative liver injury independent of CYP2E1/2A5 induction due to Nrf2 deficiency.

    Science.gov (United States)

    Lu, Yongke; Gong, Pengfei; Cederbaum, Arthur I

    2008-10-30

    Pyrazole can induce CYP2E1 and 2A5, which produce reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates important antioxidant enzymes to remove ROS. In this study, we applied Nrf2 knockout mice to test the hypothesis that pyrazole will cause hepatotoxicity and elevate oxidative stress to a greater extent in Nrf2 knockout mice compared to wild type mice. Pyrazole induced severe oxidative liver damage in Nrf2 knockout mice but not in wild type mice. Activities and levels of CYP2E1 and 2A5 were elevated by pyrazole in the wild type mice but not in the Nrf2 knockout mice. However, expression or activity of Nrf2-regulated antioxidant enzymes, such as gamma-glutamylcysteine synthetase (GCS), heme oxygenase-1 (HO-1) and glutathione-S-transferase (GST), were upregulated in the pyrazole-treated wild type mice, but to a lesser extent or not at all in the pyrazole-treated Nrf2 knockout mice. Treatment with antioxidants such as vitamin C or S-adenosyl-l-methionine (SAM) or an inhibitor of iNOS prevented the pyrazole-induced oxidative liver damage, thus validating the role of oxidative/nitrosative stress in the pyrazole induced liver injury to the Nrf2 knockout mice. In summary, even though ROS-producing CYP2E1/2A5 were not elevated by pyrazole, impaired antioxidant capacity resulting from Nrf2 deficiency appear to be sufficient to promote pyrazole-induced oxidative liver injury.

  2. Corrosion inhibition properties of pyrazolylindolenine compounds on copper surface in acidic media

    Directory of Open Access Journals (Sweden)

    Ebadi Mehdi

    2012-12-01

    Full Text Available Abstract Background The corrosion inhibition performance of pyrazolylindolenine compounds, namely 4-(3,3-dimethyl-3H-indol-2-yl-pyrazole-1-carbothioamide (InPzTAm, 4-(3,3-dimethyl-3H-indol-2-yl-1H-pyrazole-1-carbothiohydrazide (InPzTH and 3,3-dimethyl-2-(1-phenyl-1H-pyrazol-4-yl-3H-indole (InPzPh, on copper in 1M HCl solution is investigated by electrochemical impedance spectroscopy (EIS, open circuit potential (OCP and linear scan voltammetry (LSV techniques. Results The results show that the corrosion rate of copper is diminished by the compounds with the inhibition strength in the order of: InPzTAm> InPzTH > InPzPh. The corrosion inhibition efficiencies for the three inhibitors are 94.0, 91.4 and 79.3, for InPzTAm, InPzTH and InPzPh respectively with the same inhibitor concentration (2 mM. Conclusion From the EIS, OCP and LSV results it was concluded that pyrazolylindolenine compounds with S-atom (with an amine group have illustrated better corrosion inhibition performance compared to hydrazine and phenyl group.

  3. Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

    2016-09-01

    4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif.

  4. Bis(4,4′′-difluoro-1,1′:3′,1′′-terphenyl-2′-carboxylato-κObis(3,5-dimethyl-1H-pyrazole-κN2manganese(II

    Directory of Open Access Journals (Sweden)

    Yeojin Jeon

    2012-05-01

    Full Text Available In the title compound, [Mn(C19H11F2O22(C5H8N22], the Mn2+ cation is coordinated by the N atoms of two 3,5-dimethylpyrazole ligands and carboxylate O atoms from two 4,4′′-difluoro-1,1′:3′,1′′-terphenyl-2′-carboxylato ligands, forming an MnN2O2 polyhedron with a slightly distorted tetrahedral coordination geometry. Two intramolecular hydrogen bonds are observed between the carboxylate and pyrazole ligands. The combined influence of the sterically hindered carboxylate ligands and the intramolecular hydrogen-bonding interactions stabilizes the title compound with a low coordination number of four. In the crystal, weak C—H...F and C—H...O hydrogen bonds are observed.

  5. Synthesis and antimicrobial studies of novel derivatives of 4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid as potent anti-Acinetobacter baumannii agents.

    Science.gov (United States)

    Allison, Devin; Delancey, Evan; Ramey, Hunter; Williams, Conrad; Alsharif, Zakeyah Ali; Al-Khattabi, Hessa; Ontko, Allyn; Gilmore, David; Alam, Mohammad A

    2017-02-01

    Microbial resistance to antibiotics is a global concern. The World Health Organization (WHO) has identified antimicrobial resistance as one the three greatest threats for human beings in the 21st century. Without urgent and coordinated action, the world is moving toward a post-antibiotic era, in which normal infections or minor injuries may become fatal. In an effort to find new agents, we report the synthesis and antimicrobial activities of 40 novel 1,3-diphenyl pyrazole derivatives. These compounds have shown zones of growth inhibition up to 85mm against Acinetobacter baumannii. We tested the active compounds against this Gram-negative bacterium in minimum inhibitory concentration (MIC) tests and found activity with concentration as low as 4μg/mL. Published by Elsevier Ltd.

  6. SOCl2 catalyzed cyclization of chalcones: Synthesis and spectral studies of some bio-potent 1H pyrazoles

    Directory of Open Access Journals (Sweden)

    K. Ranganathan

    2014-05-01

    Full Text Available Some aryl-aryl 1H pyrazoles have been synthesised by cyclization of aryl chalcones and hydrazine hydrate in the presence of SOCl2. The yields of the pyrazoles are more than 85%. These pyrazoles are characterized by their physical constants and spectral data. The infrared, NMR spectral group frequencies of these pyrazolines have been correlated with Hammett substituent constants, F and R parameters. From the results of statistical analyses the effects of substituent on the spectral frequencies have been studied. The antimicrobial activities of all synthesised pyrazolines have been studied using Bauer-Kirby method. DOI: http://dx.doi.org/10.4314/bcse.v28i2.11

  7. Efficient synthesis of trisubstituted pyrazoles and isoxazoles using a traceless "catch and release" solid-phase strategy.

    Science.gov (United States)

    Ma, Wenli; Peterson, Brian; Kelson, Andrew; Laborde, Edgardo

    2009-01-01

    An efficient three-component, two-step "catch and release" solid-phase synthesis of 3,4,5-trisubstituted pyrazoles and isoxazoles has been developed. The first step involves a base-promoted condensation of a 2-sulfonyl- or a 2-carbonyl-acetonitrile derivative (1 or 7) with an isothiocyanate 2 and in situ immobilization of the resulting thiolate anion on Merrifield resin. Reaction of the resin-bound sulfonyl intermediate 4 with hydrazine or hydroxylamine, followed by release from the resin and intramolecular cyclization, affords 3,5-diamino-4-(arylsulfonyl)-1H-pyrazoles 5 or isoxazoles 6, respectively. Reaction of the resin-bound carbonyl intermediate 9 with hydrazine, on the other hand, leads to 3-(arylamino)-5-aryl-1H-pyrazole-4-carbonitriles 10.

  8. Determination of Six Pyrazole Fungicides in Grape Wine by Solid-Phase Extraction and Gas Chromatography-Tandem Mass Spectrometry.

    Science.gov (United States)

    Shen, Yan; Li, Zhou; Ma, Qiang; Wang, Chuanxian; Chen, Xiangzhun; Miao, Qian; Han, Chao

    2016-05-18

    A gas chromatography-tandem mass spectrometry (GC-MS/MS) method was developed for the first simultaneous identification and quantification of six pyrazole fungicides (furametpyr, rabenzazole, fluxapyroxad, penflufen, bixafen, and isopyrazam) in grape wine samples. The grape wine samples were first diluted with water, then purified by solid-phase extraction, and finally examined by GC-MS/MS in multiple reaction monitoring (MRM) mode. Matrix-matched calibration curves were used to correct the matrix effects. The limits of quantification (LOQs), calculated as 10 times the standard deviation, were 0.2-0.8 μg kg(-1) for the six pyrazole fungicides. The average recoveries were in the range of 74.3-94.5%, with relative standard deviations (RSDs) below 5.8%, measured at three concentration levels. The proposed method is suitable for the simultaneous determination of six pyrazole fungicides in grape wine samples.

  9. Molecular structure of 4-methoxy-2,3-dimethyl-2,4-dihydro[1,2]benzoxaphosphinino-[4,3- c]pyrazole-4-oxide and its carboxylic analogues

    Science.gov (United States)

    Małecka, Magdalena; Massa, Werner; Harms, Klaus; Budzisz, Elżbieta

    2005-03-01

    The crystal structures of 5a 4-methoxy-2,3-dimethyl-2,4-dihydro[1,2]benzoxaphosphinino-[4,3- c]pyrazole-4-oxide and 5b 2,3-dimethyl[1]benzopyrano[4,3- c]pyrazol-4-one have been determined by 31P and 1H NMR study and single-crystal X-ray diffraction. The progress of conversion of chromone 1a was monitored by 31P NMR. After 24 h two additional signals of 4a and 5a could be seen in NMR spectrum. Both compounds crystallise in monoclinic system in space group P2 1/c . The crystal data are: 5aa=10.306(1), b=11.875(1), c=11.221(1) Å, β=112.992(7)°, Z=4; 5ba=7.386(1), b=17.094(2), c=8.557(1) Å, β=114.208(9)°, Z=4. The structure of 5a contains methanol disordered over a centre of symmetry. The crystal of 5b was twinned.

  10. Proton Transfer Isomerization of Pyrazole in the Ground State:σν sπ Mechanism and Water Assisting Effect

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The proton transfer isomerization of pyrazole and the water assisting effect by looping 1 to 4 water molecules on the singlet state potential energy surface have been investigated by using hybrid density functional theory method (B3PW91) with a 6-311++G** basis set. Two mechanisms were proposed to explain the mono- and multi-water assisting effects, respectively. The reactants and products of all groups have been characterized on their potential energy surfaces. For the isomerization of monomolecule pyrazole, the isomerization energy barrier is 46.4 kcal·mol-1. For the monohydration assisting mechanism, the reactant complex is connected to the product complex via two saddle points. The corresponding isomerization barriers are 46.7and 23.0 kcal(mol-1, respectively. As to the multihydration assisting mechanism, the isomerization barriers are 12.0, 10.9 and 13.14 kcal(mol-1 accordingly, when the number of water molecules is 2, 3 and 4, respectively. The multihydration assisting isomerization can occur in water-dominated environments, for example, in the organism, and thereby is crucial to energy transference. The deproton and dehydrogen energies of monomolecule pyrazole and various hydrated pyrazoles were calculated and then found much bigger than the isomerization barriers of their relative complexes, suggesting the impossibility of deprotonation or dehydrogenation. The isomerization of pyrazole is a proton-coupling-electron-migration process, but two different mechanisms are noticed, viz.σ- and π-type mechanisms. The π-bond of pyrazole participates in isomerization in the π-type mechanism, whereas only σelectron takes part in isomerization in the σ-type mechanism.

  11. Synthesis and spectroscopy studies of the inclusion complex of 3-amino-5-methyl pyrazole with beta-cyclodextrin

    Science.gov (United States)

    Louiz, S.; Labiadh, H.; Abderrahim, R.

    2015-01-01

    Amino pyrazole belongs to anti-inflammatory class, and is characterized by a low solubility in water. (In order to increase its solubility in water, inclusion complex of amino pyrazole with β-CD was obtained.) The inclusion complex obtained between AMP and β-cyclodextrin, was characterized by FT-IR, 1H NMR, 1H-1H NOESY, 13C NMR, DEPT, XHCOR, spectra, through TG analysis, DTA, DSC and Scanning Electron Microscopy (SEM). The stoichiometry of inclusion complex is 1:1 (guest-host) and K stability is 1.1 × 104 M-1.

  12. Pyrazolylamidino ligands from coupling of acetonitrile and pyrazoles: a systematic study.

    Science.gov (United States)

    Gómez-Iglesias, Patricia; Arroyo, Marta; Bajo, Sonia; Strohmann, Carsten; Miguel, Daniel; Villafañe, Fernando

    2014-12-01

    Mixed pyrazole-acetonitrile complexes, both neutral fac-[ReBr(CO)3(NCMe)(pz*H)] (pz*H = pzH, pyrazole; dmpzH, 3,5-dimethylpyrazole; or indzH, indazole) and cationic fac-[Re(CO)3(NCMe)(pz*H)2]A (A = BF4, ClO4, or OTf), are described. Their role as the only starting products to obtain final pyrazolylamidino complexes fac-[ReBr(CO)3(NH═C(Me)pz*-κ(2)N,N)] and fac-[Re(CO)3(pz*H)(NH═C(Me)pz*-κ(2)N,N)]A, respectively, is examined. Other products involved in the processes, such as fac-[ReBr(CO)3(pz*H)2], fac-[Re(CO)3(NCMe)(NH═C(Me)pz*-κ(2)N,N)]A, and fac-[Re(CO)3(pz*H)2(OTf)] are also described. Warming CD3CN solutions of fac-[Re(CO)3(NCMe)(pz*H)2]A at 40 °C gives cleanly the pyrazolylamidino complexes [Re(CO)3(pz*H)(NH═C(Me)pz*-κ(2)N,N)]A as the only products, pointing to an intramolecular process. This is confirmed by carrying out reactions in the presence of one equivalent of a pyrazole different from that coordinated, which affords complexes where the pyrazolylamidino ligand contains only the pyrazole previously coordinated. When the reactions lead to an equilibrium mixture of the final and starting products, the reverse reaction gives the same equilibrium mixture, which indicates that the coupling reaction of pyrazoles and nitriles to obtain pyrazolylamidino ligands is a reversible intramolecular process. A systematic study of the possible factors which may affect the reaction gives the following results: (a) the yields of the direct reactions are higher for lower temperatures; (b) the tendency of the pyrazoles to give pyrazolylamidino complexes follows the sequence indzH > pzH > dmpzH; and (c) the reaction rates do not depend on the nature of the anion even when a large excess is added. The presence of a small amount of aqueous solution of NaOH catalyzes the reaction. Thus, addition of 0.5-1% of NaOH (aq) to solutions of fac-[ReBr(CO)3(NCMe)(pz*H)] (in CD3CN) or fac-[Re(CO)3(NCMe)(pz*H)2]A (in CD3CN, CD3NO2 or (CD3)2CO) allowed the syntheses of the

  13. Theoretical studies on proton transfer reaction of 3(5)-substituted pyrazoles

    Indian Academy of Sciences (India)

    Alireza Najafi Chermahini; Abbas Teimouri

    2014-01-01

    The inter and intra molecular proton transfer reactions of a series of pyrazole derivatives have been studied by using density functional theory (DFT) andMP2 methods implementing 6-311++G(d,p) atomic basis set. The substituents have been selected to cover a wide range of electronic effects. Proton transfer process was studied for mechanisms including single proton transfer, double proton transfer and proton transfer assisted by a water or ammonia molecule. The results showed single proton transfer reactions for interconversion pyrazole derivatives need highest activation energies in the range of 45.7−51.59 and 49.4−53.96 kcal/mol at B3LYP and MP2 levels, respectively. It was found that for the 3-substituted pyrazoles, electron withdrawing groups form stronger dimers but in the 5-substituted tautomers electron donating groups form stronger hydrogen bond. The double proton transfer reactions between dimers were studied and transition states calculated. The ranges of activation energies were found to be 17.51−19.36 and 17.02−17.80 kcal/mol for the C → E and D → D reactions respectively. In addition, the activation energies for the proton transfer reaction assisted by water or ammonia molecules were found to be in the range of 26.62−31.78 and 17.25−22.46 kcal/mol, respectively, calculated at MP2/6-311++G(d,p) level of theory.

  14. DFT and QSAR study of corrosion inhibition on 3,5-di-substituted pyrazole derivatives with heteroatom on position one

    Directory of Open Access Journals (Sweden)

    Mariam Olayemi Abdulazeez

    2016-12-01

    Full Text Available Abdulazeez, M.O., Oyabamiji, A.K. and Semire, B. 2016. DFT and QSAR study of corrosion inhibition on 3,5-di-substituted pyrazole derivatives with heteroatom on position one. Lebanese Science Journal, 17(2: 217-232. A class of organic corrosion inhibitors namely; 2,5-bis(4-dimethylaminophenyl-1,3,4-thiadiazole (DAPT, 2,5-bis(4-dimethylaminophenyl-1,3,4-oxadiazole (DAPO, 3,5-diphenyl-4H-1,2,4-triazole (DHT, 3,5-di(4-pyridyl-4H-1,2,4-triazole (PHT, 2,5-bis(4-aminophenyl-1,3,4-oxadiazole (PAOX, 3,5-di(4-methylthiophenyl-4H-1,2,4-triazole (4-MTHT were investigated at density functional theory (DFT B3LYP/6-31G** (d,p level. The calculated molecular descriptors such as the HOMO, LUMO, the dipole moment, chemical potential (μ, chemical hardness (ղ, softness (s, global nucleophilicity (N and average Mulliken charges on nitrogen atoms are discussed in relation to the observed inhibitory efficiency for the compounds. The developed qualitative structural activity relationship (QSAR models relate the calculated molecular descriptors to the corrosion efficiency; thus QSAR model predicted the experimental corrosion efficiencies. The possible sites for nucleophilic and electrophilic attacks on the compounds were analyzed through the Fukui functions.

  15. The synthesis of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol using sodium impregnated on activated chicken eggshells catalyst

    Science.gov (United States)

    Mardiana, L.; Bakri, R.; Septiarti, A.; Ardiansah, B.

    2017-04-01

    The novel compound of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol as a pyrazoline derivative has been synthesized by two-steps reaction using sodium impregnated on activated chicken eggshells (Na-ACE) catalyst. Na-ACE was primarily prepared by a simple wet impregnation of NaOH solution on activated chicken eggshells solid support. The Na-ACE catalyst produced was characterized using FTIR spectrophotometer, XRD and SEM then applied in pyrazoline synthesis. First, chalcone was prepared from the reaction of 2-hydroxyacetophenone and 3-methoxybenzaldehyde by base-catalyzed aldol condensation. This product was subsequently reacted with hydrazine hydrate to give corresponding pyrazoline. The structure elucidation of the compound using FTIR, UV-Vis, LC-ESI-MS and 1H-NMR indicated the desired product has been successfully synthesized. Furthermore, the potential antioxidant activities of chalcone and pyrazoline have also been studied in-vitro using DPPH radical scavenging method. The results revealed that pyrazoline has a greater antioxidant activity than chalcone.

  16. 5-Acetamido-1H-pyrazole-4-carboxamide monohydrate

    Directory of Open Access Journals (Sweden)

    Lhoussaine El Ghayati

    2016-06-01

    Full Text Available There are two independent molecules of the title carboxamide compound, C6H8N4O2·H2O, as well as two independent water molecules in the asymmetric unit. The two independent carboxamide molecules differ primarily in the relative orientations of the peripheral methyl and amino groups. Intramolecular N—H...O hydrogen bonds assist in determining the orientations of the acetamido substituents. The three-dimensional crystal packing is directed by a large network of O—H...O, N—H...O, C—H...O and C—H...N hydrogen bonds.

  17. Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles.

    Science.gov (United States)

    Antilla, Jon C; Baskin, Jeremy M; Barder, Timothy E; Buchwald, Stephen L

    2004-08-20

    This paper details the copper-catalyzed N-arylation of pi-excessive nitrogen heterocycles. The coupling of either aryl iodides or aryl bromides with common nitrogen heterocycles (pyrroles, pyrazoles, indazoles, imidazoles, and triazoles) was successfully performed in good yield with catalysts derived from diamine ligands and CuI. General conditions were found that tolerate functional groups such as aldehydes, ketones, alcohols, primary amines, and nitriles on the aryl halide or heterocycle. Hindered aryl halides or heterocycles were also found to be suitable substrates using the conditions reported herein. Copyright 2004 American Chemical Society

  18. Cascade multicomponent synthesis of indoles, pyrazoles, and pyridazinones by functionalization of alkenes.

    Science.gov (United States)

    Matcha, Kiran; Antonchick, Andrey P

    2014-10-27

    The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Dibromidobis(3,5-dimethyl-1H-pyrazole-κN)cobalt(II).

    Science.gov (United States)

    Tomyn, Stefania; Pavlenko, Vadim A; Gumienna-Kontecka, Elżbieta; Penkova, Larysa; Kotova, Natalia V

    2011-11-01

    In the mononuclear title complex, [CoBr(2)(C(5)H(8)N(2))(2)], the Co(II) atom is coordinated by two N atoms from two monodentate 3,5-dimethyl-pyrazole ligands and two Br atoms in a highly distorted tetra-hedral geometry. In the crystal, the complex mol-ecules are linked by inter-molecular N-H⋯Br hydrogen bonds into chains along [101]. An intra-molecular N-H⋯Br hydrogen bond is also present.

  20. Dibromidobis(3,5-dimethyl-1H-pyrazole-κN 2)cobalt(II)

    Science.gov (United States)

    Tomyn, Stefania; Pavlenko, Vadim A.; Gumienna-Kontecka, Elżbieta; Penkova, Larysa; Kotova, Natalia V.

    2011-01-01

    In the mononuclear title complex, [CoBr2(C5H8N2)2], the CoII atom is coordinated by two N atoms from two monodentate 3,5-dimethyl­pyrazole ligands and two Br atoms in a highly distorted tetra­hedral geometry. In the crystal, the complex mol­ecules are linked by inter­molecular N—H⋯Br hydrogen bonds into chains along [101]. An intra­molecular N—H⋯Br hydrogen bond is also present. PMID:22219744

  1. Coordination versus coupling of dicyanamide in molybdenum and manganese pyrazole complexes.

    Science.gov (United States)

    Arroyo, Marta; Gómez-Iglesias, Patricia; Martín-Alvarez, Jose Miguel; Alvarez, Celedonio M; Miguel, Daniel; Villafañe, Fernando

    2012-06-04

    The reactions of cis-[MoCl(η(3)-methallyl)(CO)(2)(NCMe)(2)] (methallyl = CH(2)C(CH(3))CH(2)) with Na(NCNCN) and pz*H (pzH, pyrazole, or dmpzH, 3,5-dimethylpyrazole) lead to cis-[Mo(η(3)-methallyl)(CO)(2)(pz*H)(μ-NCNCN-κ(2)N,N)](2) (pzH, 1a; dmpzH, 1b), where dicyanamide is coordinated as bridging ligand. Similar reactions with fac-[MnBr(CO)(3)(NCMe)(2)] lead to the pyrazolylamidino complexes fac-[Mn(pz*H)(CO)(3)(NH═C(pz*)NCN-κ(2)N,N)] (pzH, 2a; dmpzH, 2b), resulting from the coupling of pyrazol with one of the CN bonds of dicyanamide. The second CN bond of dicyanamide in 2a undergoes a second coupling with pyrazole after addition of 1 equiv of fac-[MnBr(CO)(3)(pzH)(2)], yielding the dinuclear doubly coupled complex [{fac-Mn(pzH)(CO)(3)}(2)(μ-NH═C(pz)NC(pz)=NH-κ(4)N,N,N,N)]Br (3). The crystal structure of 3 reveals the presence of two isomers, cis or trans, depending on whether the terminal pyrazoles are coordinated at the same or at different sides of the approximate plane defined by the bridging bis-amidine ligand. Only the cis isomer is detected in the crystal structure of the perchlorate salt of the same bimetallic cation (4), obtained by metathesis with AgClO(4). All the N-bound hydrogen atoms of the cations in 3 or 4 are involved in hydrogen bonds. Some of the C-N bonds of the pyrazolylamidino ligand have a character intermediate between single and double, and theoretical studies were carried out on 2a and 3 to confirm its electronic origin and discard packing effects. Calculations also show the essential role of bromide in the planarity of the tetradentate ligand in the bimetallic complex 3.

  2. Organocatalyzed enantioselective synthesis of 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles

    Science.gov (United States)

    Gogoi, Sanjib; Zhao, Cong-Gui

    2009-01-01

    The first enantioselective synthesis of biologically active 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles has been achieved through a cinchona alkaloid-catalyzed tandem Michael addition and Thorpe-Ziegler type reaction between 2-pyrazolin-5-ones and benzylidenemalononitriles. The reaction may also be carried out in a three-component or a four-component fashion via the in situ formation of these two components from simple and readily available starting materials. The desired products were obtained in excellent yields with mediocre to excellent enantioselectivities (up to >99% ee). PMID:19915654

  3. Synthesis and characterization of two new types of oxovanadium complexes with pyrazole as ligand

    Institute of Scientific and Technical Information of China (English)

    XING Yongheng; ZHANG Yuanhong; XU Yongting; ZHANG Baoli; NIU Shuyun; BAI Fengying

    2006-01-01

    At room temperature, two new different oxovanadium complexes with simple pyrazole (C3H4N2) as ligand were synthesized. VO(pz)4(SO4).H2O (1) (pz: pyrazole) is a mono-nuclear oxovanadium complex with pyrazole as terminal ligands. V2O2(μ-pz)(μ-OOSO2)(μ-OCH3)(pz)4 (2) is bi-nuclear oxovanadium complex containing three different bridges, which are pyrazolate, sulphate and methoxy, respectively. The two complexes were characterized by IR, elemental analyses, thermal analyses and X-ray diffraction. The crystal structural data of the complexes 1 and 2 are given as follows: Complex 1, orthorhombic, Pna21, a = 14.547(2)(°A), b =10.895(2)(°A), c =11.835(2)(°A); α=β=γ=90°, V=1875.8(5)(°A)3, Z = 4, R1 = 0.0485, WR2 = 0.1092. Complex 2, triclinic, , a =8.377(2)(°A), b =9.928(2)(°A), c = 16.527(3)(°A), α= 85.54(3)°, β = 80.92(3)°, γ= 87.92(3)°, R1 = 0.1461, WR2 = 0.4444. The study of non-thermal kinetic decomposition shows that, for complex 1, the possible reaction mechanisms of the two steps are nucleation and growth n=1/3, and three-dimensional pervasion n=2, respectively, and the kinetic equations may be expressed as dα/dT = (A/β)exp(-E/RT){1/3(1-α) [-In(1-α)]-2} and dα/dT = (A/β)exp(-E/RT){3/2(1-α)2/3 [1–(1-α)1/3]-1}, respectively; for complex 2, the possible reaction mechanisms of the two steps are chemical reaction, and three-dimensional pervasion n=2, respectively; the kinetic equations may be expressed as dα/dT = (A/β)exp(-E/RT)[(1-α)2], and dα/dT = (A/β)exp(-E/RT){3/2(1-α)2/3[1-(1-α)1/3]-1}, respectively.

  4. XRD, IR and XAFS studies of cobalt complexes having amino pyrazole dicarboxylate (APD) as ligand

    Science.gov (United States)

    Mishra, Ashutosh; Jain, Garima; Patil, H.

    2014-09-01

    X-ray absorption fine structure spectroscopic (XAFS) studies have been done on two cobalt complexes using APD (diethyl 4-amino-1-phenyl-1H-pyrazole-3,5 dicarboxylate) as ligand. The X-ray absorption spectra of the complexes have been recorded on beam line of synchrotron at Raja Ramanna Centre for Advanced Technology (RRCAT), Indore (India). The X-ray diffraction of the samples has also been carried out. FTIR studies of two samples were also reported in the present communication.

  5. Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements

    Energy Technology Data Exchange (ETDEWEB)

    Ameriks, Michael K.; Axe, Frank U.; Bembenek, Scott D.; Edwards, James P.; Gu, Yin; Karlsson, Lars; Randal, Mike; Sun, Siquan; Thurmond, Robin L.; Zhu, Jian; (J& J-PRD); (Sunesis)

    2010-01-12

    A crystal structure of 1 bound to a Cys25Ser mutant of cathepsin S helped to elucidate the binding mode of a previously disclosed series of pyrazole-based CatS inhibitors and facilitated the design of a new class of arylalkyne analogs. Optimization of the alkyne and tetrahydropyridine portions of the pharmacophore provided potent CatS inhibitors (IC{sub 50} = 40-300 nM), and an X-ray structure of 32 revealed that the arylalkyne moiety binds in the S1 pocket of the enzyme.

  6. Two tautomers in the same crystal: 3-(4-fluoro-phen-yl)-1H-pyrazole and 5-(4-fluoro-phen-yl)-1H-pyrazole.

    Science.gov (United States)

    Yamuna, Thammarse S; Kaur, Manpreet; Jasinski, Jerry P; Anderson, Brian J; Yathirajan, H S

    2014-09-01

    The title co-crystal, 3-(4-fluoro-phen-yl)-1H-pyrazole-5-(4-fluoro-phen-yl)-1H-pyrazole (1/1), C9H7FN2, crystallizes with four independent mol-ecules (A, B, C and D) in the asymmetric unit exhibiting two tautomeric forms (A and D; B and C) due to N-H proton exchange between the two N atoms of the pyrazole ring. The dihedral angles between the mean planes of the pyrazole and benzene rings are 15.6 (1), 19.8 (9), 14.0 (1) and 10.7 (7)° in mol-ecules A, B, C and D, respectively. In the crystal, N-H⋯N hydrogen bonds link the four mol-ecules in the asymmetric unit into a ring with an R 4 (4)(12) motif. Furthermore, weak C-H⋯F inter-actions link the mol-ecules into a three-dimensional network.

  7. The Influence of the 1-(3-Trifluoromethyl-Benzyl)-1H-Pyrazole-4-yl Moiety on the Adenosine Receptors Affinity Profile of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives.

    Science.gov (United States)

    Federico, Stephanie; Redenti, Sara; Sturlese, Mattia; Ciancetta, Antonella; Kachler, Sonja; Klotz, Karl-Norbert; Cacciari, Barbara; Moro, Stefano; Spalluto, Giampiero

    2015-01-01

    A new series of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine (PTP) derivatives has been developed in order to explore their affinity and selectivity profile at the four adenosine receptor subtypes. In particular, the PTP scaffold was conjugated at the C2 position with the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole, a group believed to confer potency and selectivity toward the human (h) A2B adenosine receptor (AR) to the xanthine ligand 8-(1-(3-(trifluoromethyl)benzyl)-1H-pyrazol-4-yl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (CVT 6975). Interestingly, the synthesized compounds turned out to be inactive at the hA2B AR but they displayed affinity at the hA3 AR in the nanomolar range. The best compound of the series (6) shows both high affinity (hA3 AR Ki = 11 nM) and selectivity (A1/A3 and A2A/A3 > 9090; A2B/A3 > 909) at the hA3 AR. To better rationalize these results, a molecular docking study on the four AR subtypes was performed for all the synthesized compounds. In addition, CTV 6975 and two close analogues have been subjected to the same molecular docking protocol to investigate the role of the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole on the binding at the four ARs.

  8. Poly(4-vinylpyridine efficiently catalyzed one-pot four-component synthesis of pyrano[2,3-c]pyrazoles

    Directory of Open Access Journals (Sweden)

    Jalal Albadi

    2014-10-01

    Full Text Available An efficient one-pot synthesis of pyrano[2,3-c]pyrazoles via four-component reaction of phenyl hydrazine, ethyl acetoacetate, malononitrile and aromatic aldehydes, catalyzed by poly(4-vinylpyridine is reported. This method provides many advantages such as, atom-economy, easy work up, clean procedure, short reaction times and high yields of products.

  9. A general and efficient synthesis of pyrazoles catalyzed by Sc(OTf)3 under solvent-free conditions

    OpenAIRE

    Xiong, Wei; Chen,Jiu-Xi; Liu,Miao-Chang; Ding,Jin-Chang; Wu,Hua-Yue; Su,Wei-Ke

    2009-01-01

    Pyrazoles were prepared in excellent yields via solventless condensation of various 1,3-diketones (R¹COCHXCOCH3, R¹ = Me, Ph; X = H, Me, Cl) and hydrazines, acylhydrazines or sulfonyl hydrazines in the presence of a catalytic amount of Sc(OTf)3 at room temperature. Additionally, the catalyst could be recovered easily after the reactions and reused without evident loss in activity.

  10. A mild and efficient method for the preparation of 3-(2'-Aminoaryl)pyrazoles from 4-chloroquinolines

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Julio C.; Oliveira, Cesar D. de; Pinheiro, Luiz C. da Silva; Marra, Roberta K.F.; Bernardino, Alice M.R. [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. de Quimica]. E-mail: alicerolim@globo.com; Khan, Misbahul Ain [The Islamia University of Bahawalpur, Bahawalpur (Pakistan). Chemistry Dept.; Wardell, James L. [University of Aberdeen, Old Aberdeen, Scotland (United Kingdom). Chemistry Dept.; Wardell, Solange M.S.V. [Fundacao Inst. Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto de Tecnologia em Farmacos - Farmanguinhos

    2007-07-01

    We describe a mild and efficient method for the formation of 3-(2'-aminoaryl)pyrazoles in excellent yields from reactions of 4-chloroquinolines with hydrazine. These heterocyclic ring opening reactions occur under much milder conditions then previously described. (author)

  11. A general and efficient synthesis of pyrazoles catalyzed by Sc(OTf)3 under solvent-free conditions

    OpenAIRE

    Xiong, Wei; Chen,Jiu-Xi; Liu,Miao-Chang; Ding,Jin-Chang; Wu,Hua-Yue; Su,Wei-Ke

    2009-01-01

    Pyrazoles were prepared in excellent yields via solventless condensation of various 1,3-diketones (R¹COCHXCOCH3, R¹ = Me, Ph; X = H, Me, Cl) and hydrazines, acylhydrazines or sulfonyl hydrazines in the presence of a catalytic amount of Sc(OTf)3 at room temperature. Additionally, the catalyst could be recovered easily after the reactions and reused without evident loss in activity.

  12. Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors

    DEFF Research Database (Denmark)

    Conti, Paola; Grazioso, Giovanni; di Ventimiglia, Samuele Joppolo

    2005-01-01

    N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are conformationally constrained analogues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested for activity at ionotropic and metabotropic glutamate receptors...

  13. Synthesis and biological evaluation of dihydropyrano-[2,3-c]pyrazoles as a new class of PPARγ partial agonists

    DEFF Research Database (Denmark)

    Qvortrup, Katrine; Jensen, Jakob Feldthusen; Sørensen, Mikael S.

    2017-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a well-known target for thiazolidinedione antidiabetic drugs. In this paper, we present the synthesis and biological evaluation of a series of dihydropyrano[2,3-c]pyrazole derivatives as a novel family of PPARγ partial agonists. Two analogues...

  14. Inorganic pigments doped with tris(pyrazol-1-yl)borate lanthanide complexes: A photoluminescence study

    Energy Technology Data Exchange (ETDEWEB)

    Gheno, Giulia, E-mail: giulia.gheno@unive.it [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari di Venezia, Dorsoduro 2137, 30123 Venezia (Italy); Bortoluzzi, Marco; Ganzerla, Renzo [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari di Venezia, Dorsoduro 2137, 30123 Venezia (Italy); Enrichi, Francesco [CIVEN, Coordinamento Interuniversitario Veneto per le Nanotecnologie, Via delle Industrie 5, 30175 Marghera, Venezia (Italy)

    2014-01-15

    The inorganic pigments malachite, Egyptian blue, Ercolano blue and chrome yellow have been doped with the neutral homoleptic Ln(III) complex Ln(Tp){sub 3} (Ln=Eu, Tb; Tp=hydrotris(pyrazol-1-yl)borate) in the presence of arabic gum or acrylic emulsion as binders, in order to obtain photoluminescent materials of interest for cultural heritage restoration. The doped pigments have shown emissions associated to f–f transitions in the visible range upon excitation with UV light. Thermal and UV-light ageings have been carried out. In all the cases the photoluminescent behaviour is maintained, but in the cases of acrylic-based paints emission spectra and lifetimes are strongly influenced by thermal treatments. The choice of binder and pigments influences the photoluminescent behaviour of the corresponding film paints. -- Highlights: • Inorganic pigments doped with photoluminescent lanthanide complexes. • Hydrotris(pyrazol-1-yl)borate (Tp) as antenna-ligand for Eu(III) and Tb(III). • Emission associated to f–f transitions upon excitation with UV light. • Photoluminescence of paints influenced by the choice of binder and pigments. • Photoluminescence after ageing depending upon the type of binder.

  15. Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds

    Science.gov (United States)

    Niculescu-Duvaz, Dan; Niculescu-Duvaz, Ion; Suijkerbuijk, Bart M.J.M.; Ménard, Delphine; Zambon, Alfonso; Nourry, Arnaud; Davies, Lawrence; Manne, Helen A.; Friedlos, Frank; Ogilvie, Lesley; Hedley, Douglas; Takle, Andrew K.; Wilson, David M.; Pons, Jean-Francois; Coulter, Tom; Kirk, Ruth; Cantarino, Neus; Whittaker, Steven; Marais, Richard; Springer, Caroline J.

    2010-01-01

    V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin-4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-{2-[4-(4-methyl-piperazin-1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. PMID:20667740

  16. [The ultraviolet absorption spectra of pyrazoles and 1-carboxamidepyrazoles and their application].

    Science.gov (United States)

    Shi, Yun-Feng; Wu, Zhi-Jie; Chen, Li-Jun; Chen, Guang; Liu, Yao-Peng; Zhang, Li-Li

    2009-03-01

    The ultraviolet absorption spectra of pyrazoles and 1-carboxamidepyrazoles were studied. The results indicated that substitution in the 3 or the 5 position it leads to a bathochromic shift of the position of the maximum absorption by about 3-4 nm, whereas in the 4 position leads to a much larger bathochromic shift (> 10 nm). The introduction of carboxamide causes a bathochromic shift of the position of the maximum absorption by about 20-26 nm. Its also leads to an increase in molar extinction coefficient by about 2-3 times. So UV methods were established for determining the contents of pyrazoles and their derivations. Using these methods, the content of 3,4-dimethylpyrazole phosphate (DMPP) in stabilized urea was determined to be 1.15% of urea-N, the hydrolytic half lives of 1-carboxamide-3-methylpyrazole (CMP) in water solution at 20, 25 and 30 degrees C were 48, 30 and 18 h, respectively, and the extraction percentage of nitrification inhibitor 3-methylpyrazole phosphate (MPP) in 3 soils by 3 different extractants were ranged from 63.2% to 89.2%.

  17. 芳基吡唑氟尿嘧啶类化合物的设计、合成与杀虫活性研究%Design, Synthesis, Insecticidal Activity and Structure-Activity Relationship of Aryl Pyrazole 5-Fluorouracil Derivatives

    Institute of Scientific and Technical Information of China (English)

    傅晓东; 陈月; 杨阳; 贺书泽; 沈陈; 万嵘

    2014-01-01

    利用以γ-氨基丁酸(GABA)受体抑制剂芳基吡唑类杀虫剂的关键结构5-氨基-3-氰基-1-(取代苯基)吡唑为基本母核,设计、合成了26个创新结构芳基吡唑氟尿嘧啶化合物.目标化合物结构均采用1H NMR, FTIR和元素分析进行了结构确证,以小菜蛾和库蚊为靶标进行了杀虫活性测试.评价结果表明创制化合物具有优越的杀虫活性:在浓度为1000 mg•L-1时,化合物5a~5c,5e,5m及5u对库蚊具有100%的杀虫活性;在浓度为400 mg•L-1时,化合物5p对小菜蛾具有94.5%的杀虫活性.初步构效关系研究表明:苯环上取代基种类及位置等对化合物的生物活性有重要的影响.%On the basis of the key structure of γ-amino butyric acid (GABA) receptor inhibitor aryl pyrazole pesticides, a series of novel aryl pyrazole derivatives containing 5-fluorouracil were designed and synthesized via the key intermediate 5-amino-3-cyano-1-(substituted phenyl)pyrazole. The structures of target compounds were confirmed by 1H NMR, FTIR and elemental analysis, and their insecticidal activities were evaluated against diamondback moth (Plutella xylostella) and mos-quito (Culex pipiens). The results of bioassays indicated that aryl pyrazole 5-fluorouracil derivatives exhibited satisfactory insecticidal activities. The insecticidal activities of compounds 5a~5c, 5e, 5m and 5u against mosquito were all 100%at 1000 mg•L-1. Moreover, the compound 5p exhibited good lethal activity (94.45%) against P. xylostella at the concentration of 400 mg•L-1. The results also indicated that the type and position of substituent on the phenyl ring play crucial roles on the bio-logical activities of the compounds.

  18. Synthesis and antibacterial activity of a new series of 3-[3-(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives.

    Science.gov (United States)

    Aragade, Prashant; Maddi, Veeresh; Khode, Suresh; Palkar, Mahesh; Ronad, Pradeepkumar; Mamledesai, Shivalingarao; Satyanarayana, Darbhamulla

    2009-06-01

    A novel series of 3-[3-(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives 4a-k have been synthesized by the reaction of 3-[2,3-dibromo-3-(substituted phenyl) propanoyl]-2H-chromen-2-one 3a-k and isonicotinic acid hydrazide in the presence of triethylamine in absolute ethanol, characterized by spectral data and screened for their in-vitro antibacterial activity against Gram-positive and Gram-negative bacteria. Among the series, compounds 4e, 4i, and 4k displayed an encouraging antibacterial activity profile as compared to the reference drug ampicillin against tested bacterial strains.

  19. Crystal structure of an organic-inorganic supra-molecular salt based on a 4,4'-methyl-enebis(3,5-dimethyl-1H-pyrazol-2-ium) cation and a β-octa-molybdate anion.

    Science.gov (United States)

    Amarante, Tatiana R; Gonçalves, Isabel S; Almeida Paz, Filipe A

    2016-02-01

    The asymmetric unit of the title compound, bis-[4,4'-methyl-enebis(3,5-dimethyl-1H-pyrazol-2-ium)] β-octa-molybdate, (C11H18N4)2[Mo8O26] or (H4mbdpz)2[Mo8O26], is composed of an H4mbdpz(2+) cation and half of the β-octa-molybdate anion which is completed by inversion symmetry. The organic mol-ecular units are engaged in a series of N-H⋯O hydrogen bonds with neighbouring anions, with N⋯O distances and N-H⋯O angles in the ranges 2.730 (2)-2.941 (2) Å and 122-166°, respectively. These inter-actions lead to the formation of a supra-molecular two-dimensional network parallel to the (010) plane.

  20. Bis(4-benzoyl-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-olato-κ2O,O′(methanol-κOdioxidouranium(VI methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Ouarda Dehbi

    2012-04-01

    Full Text Available In the title compound, [U(C17H13N2O22O2(CH3OH]·CH3OH, the UVI ion is coordinated by seven O atoms in a distorted pentagonal–bipyramidal geometry with two 3-methyl-1-phenyl-4-benzoyl-4,5-dihydro-1H-pyrazol-5-olate groups with two O atoms in a bidentate chelating coordination mode and by three O atoms, one of which is from a methanol ligand. The crystal packing can be described by alternating layers of complex molecules along the a axis. The structure is stabilized by O—H...N and O—H...O hydrogen bonding and van der Waals interactions.

  1. Crystal structure of (E)-N-{[3-methyl-1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazol-4-yl]methyl-idene}hydroxyl-amine.

    Science.gov (United States)

    Mague, Joel T; Mohamed, Shaaban K; Akkurt, Mehmet; El-Emary, Talaat I; Albayati, Mustafa R

    2014-11-01

    The title compound, C15H14N4O, crystallizes with two mol-ecules in the asymmetric unit with similar conformations (r.m.s. overlay fit for the 20 non-H atoms = 0.175 Å). In the first mol-ecule, the dihedral angles between the planes of the central pyrazole ring and the pendant phenyl and pyrrole rings are 42.69 (8) and 51.88 (6)°, respectively, with corresponding angles of 54.49 (7) and 49.61 (9)°, respectively, in the second mol-ecule. In the crystal, the two mol-ecules, together with their inversion-symmetry counterparts, are linked into tetra-mers by O-H⋯N hydrogen bonds. The tetra-mers form layers parallel to (211) through pairwise C-H⋯π inter-actions.

  2. Vibrational (FT-IR, FT-Raman) and UV-Visible spectroscopic studies, HOMO-LUMO, NBO, NLO and MEP analysis of Benzyl (imino (1H-pyrazol-1-yl) methyl) carbamate using DFT calculaions

    Science.gov (United States)

    Shankar Rao, Y. B.; Prasad, M. V. S.; Udaya Sri, N.; Veeraiah, V.

    2016-03-01

    This paper contains a combined experimental and theoretical study of vibrational and electronic properties of Benzyl(imino(1H-pyrazol-1-yl)methyl)carbamate (BPMC) molecule. The FT-IR and FT-Raman spectra of the title molecule in solid phase were recorded in the region 4000-400 cm-1 and 4000-50 cm-1, respectively. The UV absorption spectrum of the studied compound dissolved in ethanol was recorded in the range of 180-400 nm. The molecular geometries calculated using density functional theory (DFT) was compared with available experimental data. The vibrational spectra calculated at the B3LYP/6-31G(d,p) level were compared with the experimental spectra and assignment to each vibrational frequency was assigned on the basis of potential energy distribution (PED). The calculated electronic and nonlinear optical properties of the title molecule were reported. Furthermore, the thermodynamic properties of the molecule were discussed.

  3. Vibrational spectroscopic studies, NMR, HOMO-LUMO, NLO and NBO analysis of 1-(2-nitrobenzoyl)-3,5-diphenyl-4,5-dihydro-1H-pyrazole with use X-ray diffractions and DFT calculations

    Science.gov (United States)

    Demir, Sibel; Tinmaz, Feyza; Dege, Necmi; Ilhan, Ilhan Ozer

    2016-03-01

    The crystal and molecular structure of the title compound, 1-(2-nitrobenzoyl)-3,5-diphenyl-4,5-dihydro-1H-pyrazole, was reported and confirmed by single crystal X-ray diffraction and spectroscopic data. The structure, geometry optimization, vibrational frequencies and nuclear magnetic resonance were also investigated. Stability of the molecule arising from hyperconjugative interactions and charge delocalisation was analysed using natural bond orbital analysis. The results show that charge in electron density (ED) in the σ∗ and π∗ antibonding orbitals and second-order delocalisation energies E(2) confirms the occurrence of intramolecular charge transfer within the molecule. Satisfactory theoretical aspects were made for the stable conformer of the molecule using density functional theory DFT-B3LYP methods with the 6-311G++(d,p) basis set.

  4. Synthesis, structural and spectroscopic evaluations and nonlinear optical properties of 3,5-bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioic O-acid

    Science.gov (United States)

    Tamer, Ömer; Dege, Necmi; Avcı, Davut; Atalay, Yusuf; Özer İlhan, İlhan; Çadır, Mehmet

    2015-02-01

    In this study, we report a combined experimental and theoretical study on 3,5-bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioic O-acid (C18H18N2O3S) molecule. The compound crystallizes in the trigonal space group R-3 with a = b = 27.7151(12) Å, c = 12.4866(6) Å, α = β = 90.0°, γ = 120.0° and Z = 18. The crystal packing is stabilized by Osbnd H⋯O and Osbnd H⋯S intermolecular hydrogen bonds. These hydrogen bond interactions are also proved by NBO analysis. A detailed spectroscopic investigation is performed by the application of FT-IR and FT-NMR in addition to the theoretical approaches. Small energy gap between the frontier molecular orbitals is responsible for the nonlinear optical activity of the title molecule.

  5. Crystal Structure and Photochromism of a Novel Organic Compound Condensed by Pyrazolone with Thiosemicarbazide

    Institute of Scientific and Technical Information of China (English)

    LIU, Guang-Fei; LIU, Lang; JlA, Dian-Zeng; ZHANG, Li

    2006-01-01

    A new photochromic organic compound of thiosemicarbazone, 4-(p-bromo-α-methylaminothiocarbonyl hydrazonobenzal)-2,5-dihydro-3-methyl-5-oxo-l-phenyl pyrazole, was synthesized and characterized by elemental analyses, IR, 1H NMR spectra, and X-ray single-crystal diffraction analysis. The compound exhibited an interesting photochromism in the solid state when irradiated by ultraviolet light at 365 nm. The photochromic kinetics was studied by the time-dependent powder UV-Vis reflectance spectra. The intermolecular and intramolecular hydrogen-bonding interactions may be responsible for the photochromic phenomenon.

  6. Synthesis and evaluation of some bioactive compounds having oxygen and nitrogen heteroatom

    Indian Academy of Sciences (India)

    Poonam Yadav; Nalini V Purohit

    2013-01-01

    Some new 3,4-disubstituted isocoumarins were synthesized having bioactive pyrazole molecule at 3rd position of isocoumarin moiety (5a,b), from isocoumarin -3- carboxylic acid hydrazide (4a,b) followed by cyclization with acetyl acetone. A series of isocoumarin derivative having Schiff base as lateral side chain at 3rd position of isocoumarin moiety were also synthesized (7a,b), by condensing isocoumarin acid hydrazide and benzaldehyde derivative followed by dehydration. The chemical structures of all the compounds were determined by analytical and spectral method. The lead compounds were screened for antimicrobial and analgesic activities.

  7. catena-Poly[[[trans-diaqua­bis(pyridine-κN)cobalt(II)]-μ-(4-{N′-[1-(3-acetyl-4-methyl-1H-pyrazol-5-yl)ethyl­idene]hydrazino}benzoato-κ3 O:N,N′)-[bis­(pyridine-κN)cobalt(III)]-μ-(4-{N′-[1-(3-acetyl-4-methyl-1H-pyrazol-5-yl)ethyl­idene]hydrazino}benzoato-κ3 N,N′:O)]perchlorate 3.66-hydrate

    Science.gov (United States)

    Penkova, Larysa; Azarkh, Mikhail P.; Haukka, Matti; Meyer, Franc; Fritsky, Igor O.

    2008-01-01

    The title compound, {[Co2(C15H14N4O3)2(C5H5N)4(H2O)2]ClO4·3.66H2O}n, is a one-dimensional coordination polymer, with both CoII and CoIII centres in its structure. The ligand environment surrounding CoIII is formed by two N,N-chelating pyrazole-containing ligands and two pyridine mol­ecules in axial positions. The high-spin CoII ions, situated at crystallographic centres of inversion, exhibit a distorted octa­hedral coordination mode. The ClO4 − anion is linked to the polymer chain via hydrogen bonds. The chains are connected by hydrogen bonds to produce a three-dimensional structure. PMID:21201374

  8. catena-Poly[[[trans-diaqua-bis(pyridine-κN)cobalt(II)]-μ-(4-{N'-[1-(3-acetyl-4-methyl-1H-pyrazol-5-yl)ethyl-idene]hydrazino}benzoato-κO:N,N')-[bis-(pyridine-κN)cobalt(III)]-μ-(4-{N'-[1-(3-acetyl-4-methyl-1H-pyrazol-5-yl)ethyl-idene]hydrazino}benzoato-κN,N':O)]perchlorate 3.66-hydrate].

    Science.gov (United States)

    Penkova, Larysa; Azarkh, Mikhail P; Haukka, Matti; Meyer, Franc; Fritsky, Igor O

    2008-01-30

    The title compound, {[Co(2)(C(15)H(14)N(4)O(3))(2)(C(5)H(5)N)(4)(H(2)O)(2)]ClO(4)·3.66H(2)O}(n), is a one-dimensional coordination polymer, with both Co(II) and Co(III) centres in its structure. The ligand environment surrounding Co(III) is formed by two N,N-chelating pyrazole-containing ligands and two pyridine mol-ecules in axial positions. The high-spin Co(II) ions, situated at crystallographic centres of inversion, exhibit a distorted octa-hedral coordination mode. The ClO(4) (-) anion is linked to the polymer chain via hydrogen bonds. The chains are connected by hydrogen bonds to produce a three-dimensional structure.

  9. catena-Poly[[[trans-diaquabis(pyridine-κNcobalt(II]-μ-(4-{N′-[1-(3-acetyl-4-methyl-1H-pyrazol-5-ylethylidene]hydrazino}benzoato-κ3O:N,N′-[bis(pyridine-κNcobalt(III]-μ-(4-{N′-[1-(3-acetyl-4-methyl-1H-pyrazol-5-ylethylidene]hydrazino}benzoato-κ3N,N′:O]perchlorate 3.66-hydrate

    Directory of Open Access Journals (Sweden)

    Igor O. Fritsky

    2008-02-01

    Full Text Available The title compound, {[Co2(C15H14N4O32(C5H5N4(H2O2]ClO4·3.66H2O}n, is a one-dimensional coordination polymer, with both CoII and CoIII centres in its structure. The ligand environment surrounding CoIII is formed by two N,N-chelating pyrazole-containing ligands and two pyridine molecules in axial positions. The high-spin CoII ions, situated at crystallographic centres of inversion, exhibit a distorted octahedral coordination mode. The ClO4− anion is linked to the polymer chain via hydrogen bonds. The chains are connected by hydrogen bonds to produce a three-dimensional structure.

  10. Synthesis, characterization, antimicrobial screening and computational studies of 4-[3-(4-methoxy-phenyl)-allylideneamino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one

    Science.gov (United States)

    Obasi, L. N.; Kaior, G. U.; Rhyman, L.; Alswaidan, Ibrahim A.; Fun, Hoong-Kun; Ramasami, P.

    2016-09-01

    The Schiff base, 4-[3-(4-methoxy-phenyl)-allylideneamino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one (TPMC/AAP) was synthesized by the condensation of 4-aminoantipyrine (4-amino-1,5-dimethyl-2-phenylpyrazole-3-one) and trans-para-methoxycinnamaldehyde (trans-3,4-methoxyphenyl-2-propenal) in dry methanol at 75 °C. The compound was characterized using elemental microanalysis, IR, NMR, UV spectroscopies and single-crystal X-ray crystallography. The X-ray structure determination shows that the Schiff base, (TPMC/AAP) is orthorhombic with the Pbca space group. The anti-microbial screening of the compound was carried out with Escherichia coli, Bacillus subtillis, Staphylococcus aureus, Pseudemonas aeruginosa, Candida albicans and Aspergillus niger using agar well diffusion method. The Schiff base possesses significant antimicrobial activity. The minimum inhibitory concentration (MIC) of the compound was also determined and the activity was compared with that of conventional drugs ciprofloxacin and ketoconazole. The compound (TPMC/AAP) showed varying activity against the cultured bacteria and fungi used. To complement the experimental data, density functional theory (DFT) was used to have deeper understanding into the molecular parameters and infrared spectra of the compound.

  11. Synthesis and the interaction of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines with telomeric DNA as lung cancer inhibitors.

    Science.gov (United States)

    Liu, Jiachun; Chen, Mei; Wang, Yanli; Zhao, Xiaoyin; Wang, Sijia; Wu, Yanling; Zhang, Wen

    2017-06-16

    A novel series of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines were designed, synthesized and evaluated for their antitumor activity against lung adenocarcinoma by CCK-8 assay, electrophoretic mobility shift assay (EMSA), UV-melting study, wound healing assay and docking study. These compounds showed good inhibitory activities against lung adenocarcinoma. Especially compound 12c exhibited potential antiproliferative activity against A549 cell line with the half maximal inhibitory concentration (IC50) value of 1.48 μM, which was a more potent inhibitor than cisplatin (IC50 = 12.08 μM) and leading compound 2 (IC50 = 1.69 μM), and the maximum cell inhibitory rate being up to 98.40%. Moreover, further experiments demonstrated that compounds 12a-d can strongly interact with telomeric DNA to stabilize G-quadruplex DNA with increased ΔTm values from 12.44 to 20.54 °C at a ratio of DNA to compound 1:10. These results implied that growth inhibition of A549 cells mediated by these phenanthroline derivatives is possibly positively correlated to the fact their interaction with telomeric G-quadruplexs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. 1-(3,5-Dinitro-1H-pyrazol-4-yl)-3-nitro-1H-1,2,4-triazol-5-amine (HCPT) and its energetic salts: highly thermally stable energetic materials with high-performance.

    Science.gov (United States)

    Li, Chuan; Zhang, Man; Chen, Qishan; Li, Yingying; Gao, Huiqi; Fu, Wei; Zhou, Zhiming

    2016-11-28

    A novel energetic heat-resistant explosive, 1-(3,5-dinitro-1H-pyrazol-4-yl)-3-nitro-1H-1,2,4-triazol-5-amine (HCPT), has been synthesized along with its salts. An intensive characterization of the compounds is given, including (1)H and (13)C NMR spectroscopy, IR spectroscopy, and elemental analysis. The crystal structures of neutral HCPT (3), its triaminoguanidinium salt (10), 3,4,5-triamino-1,2,4-triazolium salt (12), and copper(ii) complex (16) were determined by single-crystal X-ray diffraction. The physicochemical properties of the compounds, such as density, thermal stability, and sensitivity towards impact and friction were evaluated; all energetic compounds exhibited excellent thermal stabilities with decomposition temperatures ranging from 215 °C to 340 °C, and high positive heats of formation between 622.8 kJ mol(-1) and 1211.7 kJ mol(-1). The detonation pressures and velocities for the energetic compounds were calculated using EXPLO5 (V6.01) based on experimental densities and calculated heats of formation, and the corresponding values were in the ranges of 26.5 GPa to 37.8 GPa and 8236 m s(-1) to 9167 m s(-1). Based on thermal stability values and energetic parameters, compounds 3 and 7 were superior to those of all of the commonly used heat-resistant explosives, which may find potential application as heat-resistant energetic materials.

  13. Polymerization of 1,3-butadiene catalyzed by pincer cobalt(II) complexes derived from 2-(1-arylimino)-6-(pyrazol-1-yl)pyridine ligands

    KAUST Repository

    Gong, Dirong

    2013-08-01

    A new class of air stable and structurally well-defined cobalt complexes with unsymmetrical pincer type ligands ([2-(ArNCMe)-6-(Py)C5H 3N]CoCl2) (Ar = C6H5, Py = pyrazol-1-yl, 5a; Ar = 2,4,6-Me3C6H2, Py = pyrazol-1-yl, 5b; Ar = 2,6-iPr2C6H3, Py = pyrazol-1-yl, 5c; Ar = C6H5, Py = 3,5-Me 2pyrazol-1-yl, 5d; Ar = 2,4,6-Me3C6H 2, Py = 3,5-Me2pyrazol-1-yl, 5e; Ar = 2,6- iPr2C6H3, Py = 3,5-Me 2pyrazol-1-yl, 5f; Ar = 2,6-iPr2C 6H3, Py = 3,5-iPr2pyrazol-1-yl, 5g and [2-(OCMe)-6-(3,5-diphenylpyrazol-1-yl)C5H3N]CoCl 2 5h) were prepared and the molecular structures of 5a, 5c and 5f were determined by single crystal X-ray crystallography. Upon activation by methylaluminoxane (MAO) in toluene at room temperature, all complexes initiate polymerization of 1,3-butadiene (polymer yields: 65-99%), affording polybutadiene with excellent cis-1,4 regularity (97.5-98.7%). The polymer yields and properties in terms of molecular weight and distribution are well controlled by the substituents on iminoaryl rings and pyrazole rings. Selectivity switch from cis-1,4 to syndio-1,2 was also achievable by adding phosphine as microstructure regulator. © 2013 Elsevier B.V. All rights reserved.

  14. Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a high affinity niacin receptor.

    Science.gov (United States)

    Kim, Hyeon Young; Jadhav, Vithal B; Jeong, Dae Young; Park, Woo Kyu; Song, Jong-Hwan; Lee, Sunkyung; Cho, Heeyeong

    2015-06-01

    Even though nicotinic acid (niacin) appears to have beneficial effects on human lipid profiles, niacin-induced cutaneous vasodilatation called flushing limits its remedy to patient. GPR109A is activated by niacin and mediates the anti-lipolytic effects. Based on the hypothesis that β-arrestin signaling mediates niacin-induced flushing, but not its anti-lipolytic effect, we tried to find GPR109A agonists which selectively elicit Gi-protein-biased signaling devoid of β-arrestin internalization using a β-lactamase assay. We identified a 4-(phenyl)thio-1H-pyrazole as a novel scaffold for GPR109A agonist in a high throughput screen, which has no carboxylic acid moiety known to be important for binding. While 1-nicotinoyl derivatives (5a-g, 6a-e) induced β-arrestin recruitment, 1-(pyrazin-2-oyl) derivatives were found to play as G-protein-biased agonists without GPR109A receptor internalization. The activity of compound 5a (EC50 = 45 nM) was similar to niacin (EC50 = 52 nM) and MK-6892 (EC50 = 74 nM) on calcium mobilization assay, but its activity at 10 μM on β-arrestin recruitment were around two and five times weaker than niacin and MK-6892, respectively. The development of G-protein biased GPR109A ligands over β-arrestin pathway is attainable and might be important in differentiation of pharmacological efficacy.

  15. Ethyl 6-amino-5-cyano-4-phenyl-2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylate dimethyl sulfoxide monosolvate

    Directory of Open Access Journals (Sweden)

    Naresh Sharma

    2014-07-01

    Full Text Available In the asymmetric unit of the title compound, C16H14N4O3·C2H6OS, there are two independent main molecules (A and B and two dimethyl sulfoxide solvent molecules. In molecule A, the pyran ring is in a flattened sofa conformation, with the sp3-hydridized C atom forming the flap. In molecule B, the pyran ring is in a flattened boat conformation, with the sp3-hydridized C atom and the O atom deviating by 0.073 (3 and 0.055 (3 Å, respectively, from the plane of the other four atoms. The mean planes the pyrazole and phenyl rings form dihedral angles of 84.4 (2 and 84.9 (2°, respectively, for molecules A and B. In the crystal, N—H...O and N—H...N hydrogen bonds link the components of the structure into chains along [010]. In both solvent molecules, the S atoms are disordered over two sites, with occupancy ratios of 0.679 (4:0.321 (4 and 0.546 (6:0.454 (6.

  16. Crystal structure of 5-chloro-N1-(5-phenyl-1H-pyrazol-3-ylbenzene-1,2-diamine

    Directory of Open Access Journals (Sweden)

    Yegor Yartsev

    2017-06-01

    Full Text Available The title compound, C15H13ClN4, crystallizes with two independent molecules (A and B in the asymmetric unit, which are far from planar as a result of steric repulsion between the rings. The benzene and phenyl rings are inclined to the central pyrazole ring by 46.64 (10 and 17.87 (10° in molecule A, and by 40.02 (10 and 14.18 (10° in molecule B. The aromatic rings are inclined to one another by 58.77 (9° in molecule A, and 36.95 (8° in molecule B. In the crystal, the A and B molecules are linked by two pairs of N—H...N hydrogen bonds forming A–B dimers. These are further linked by a fifth N—H...N hydrogen bond, forming tetramer-like units that stack along the a-axis direction, forming columns, which are in turn linked by C—H...π interactions, forming layers parallel to the ac plane.

  17. Bromidobis[3-(1H-pyrazol-1-yl-κN2propionamide-κO]copper(II bromide methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Thomas Wagner

    2012-10-01

    Full Text Available The title copper(II N-pyrazolylpropanamide (PPA complex, [CuBr(PPA2]Br, was obtained in 78% yield by treatment of CuBr2 with an excess of the ligand in methanol. Crystallization from the mother liquid afforded the title compound, i.e. the methanol solvate [CuBr(C6H9N3O2]Br·CH3OH or [CuBr(PPA2]Br·MeOH, as bright green crystals. In the solid state, the title salt comprises isolated [CuBr(PPA2]+ cations, separated bromide ions and methanol of crystallization. In the cation, the central CuII ion is coordinated by two N,O-chelating PPA ligands and one Br− ion. The coordination geometry around the CuII ion is distorted trigonal–bipyramidal with the bromide ligand and the amide O atoms occupying the equatorial positions [Cu—Br = 2.4443 (4 Å; Cu—O = 2.035 (2 and 2.179 (2 Å], while the pyrazole N atoms coordinate in the axial positions [Cu—N = 1.975 (2 and 1.976 (2 Å]. In the crystal, the three constituents are linked by N—H...Br, O—H...Br, and N—H...O hydrogen bonds, forming a three-dimensional network.

  18. Synthesis of quinoline derivatives containing pyrazole group and investigation of their crystal structure and spectroscopic properties in relation to acidity and alkalinity of mediums

    Science.gov (United States)

    Ren, Tiegang; Wang, Jie; Li, Guihui; Cheng, Hongbin; Li, Yongzhe

    2014-08-01

    Two series of quinoline derivatives containing pyrazole group were synthesized and characterized by means of 1H NMR, FT-IR, MS, elemental analysis and X-ray single crystal diffraction, and their UV-vis absorption behavior and fluorescence properties were also measured. Moreover, the effects of acetic acid and triethylamine on the spectroscopic properties of synthesized products were examined with compounds 3a and 5a as examples. It has been found that all synthesized quinoline derivatives show maximum absorption peak at 303 nm and emission peaks around 445 nm. Besides, both acetic acid and triethylamine can change the acidity of the medium, thereby influencing the UV-vis absorption spectra and fluorescence spectra of synthesized products. Moreover, theoretical investigations indicate that the integration of H+ and N atom of quinoline ring favors the formation of a new product in the presence of acetic acid, and the product obtained in this case shows a new UV-vis absorption peak at 400 nm.

  19. 78 FR 33744 - Sedaxane; Pesticide Tolerances

    Science.gov (United States)

    2013-06-05

    ... pyrazole carboxamide fungicides. Metabolic processes involving cleavage of the linkage between the pyrazole and phenyl rings of these compounds have the potential to produce common pyrazole-metabolites....

  20. Sensitization of visible and NIR emitting lanthanide(III) ions in noncentrosymmetric complexes of hexafluoroacetylacetone and unsubstituted monodentate pyrazole.

    Science.gov (United States)

    Ahmed, Zubair; Iftikhar, K

    2013-11-07

    A series of highly volatile eight-coordinate air and moisture stable lanthanide complexes of the type [Ln(hfaa)3(L)2] (Ln = Pr (1), Nd (2), Eu (3), Gd (4), Tb (5), Dy (6), Ho (7), Er (8), Tm (9), and Yb (10); hfaa = anion of hexafluoroacetylacetone and L = pyrazole) have been synthesized and characterized by elemental analysis, IR, ESI-MS(+), and NMR studies. Single-crystal X-ray structures have been determined for the Eu(III) and Dy(III) complexes. These complexes crystallize in the monoclinic space group P2(1)/c. The lanthanide ion in each of these complexes is eight-coordinate with six oxygen atoms from three hfaa and two N-atoms from two pyrazole units, forming a coordination polyhedron best describable as a distorted square antiprism. The NMR spectra reveal that both the pyrazole units remain attached to the metal in solution and the β-diketonate and pyrazole protons are shifted in opposite directions in the case of paramagnetic complexes. The lanthanide-induced chemical shifts are dipolar in nature. The hypersensitive transitions of Nd(III), Ho(III), and Er(III) are sensitive to the environment (solvent), which is reflected by the oscillator strength and band shape of these transitions. The band shape due to the hypersensitive transition of Nd(III) in noncoordinating chloroform and dichloromethane is similar to those of the typical eight-coordinate Nd(III) β-diketonate complexes. The quantum yield and lifetime of Pr(III), Eu(III), Tb(III), Dy(III), and Tm(III) in visible and Pr(III), Nd(III), Dy(III), Ho(III), Er(III) Tm(III), and Yb(III) in the NIR region are sizable. The environment around these metal ions is asymmetric, which leads to increased radiative rates and luminescence efficiencies. The quantum yield of the complexes reveal that ligand-to-metal energy transfer follows the order Eu(III) > Tb(III) ≫ Pr(III) > Dy(III) > Tm(III). Both ligands (hfaa and pyrazole) are good sensitizers for all the visible and NIR emitters effectively, except for Tb

  1. Crystal structure of tris(3-methyl-1H-pyrazol-1-ylmethane

    Directory of Open Access Journals (Sweden)

    Margaret A. Goodman

    2015-11-01

    Full Text Available The title molecule, C13H16N6, crystallizes from hexane as a molecular crystal with no strong intermolecular interactions (the shortest C—H...N contact is longer than 3.38 Å. A relatively short intramolecular contact (3.09 Å has a C—H...N angle of 118° which is quite small to be still considered a hydrogen bond. The three pyrazole rings form a propeller-like motif, with one methylpyrazole unit almost perpendicular to the mean plane of the three rings [82.20 (6°]. The other two methylpyrazole units, with nitrogen donor atoms oriented in opposite directions, are oriented at 67.26 (6 and 72.53 (6° to the mean plane.

  2. Diaqua(5-methyl-1H-pyrazole-3-carboxylato(4-nitrobenzoatocopper(II

    Directory of Open Access Journals (Sweden)

    Shan-shan Zhang

    2009-02-01

    Full Text Available In the title complex, [Cu(C7H4NO4(C5H5N2O2(H2O2], the CuII ion is coordinated in a slightly distorted square-pyramidal enviroment. The basal plane is formed by an N atom and an O atom from a 5-methyl-1H-pyrazole-3-carboxylate ligand and by two O atoms from two water ligands. The apical position is occupied by a carboxylate O atom from a 4-nitrobenzoate ligand. In the crystal structure, intermolecular O—H...O and N—H...O hydrogen bonds link complex moleclues, forming extended chains parallel to the a axis.

  3. Dimensionality Variation in Dinuclear Cu(II Complexes of a Heterotritopic Pyrazolate Ligand

    Directory of Open Access Journals (Sweden)

    Chris S. Hawes

    2014-02-01

    Full Text Available Two new Cu(II complexes of the ligand 3-carboxy-5-(2-pyridyl-1H-pyrazole, H2L1, have been prepared and structurally characterized and found to be comprised of a similar [M2L2] dimer motif. Subtle variation in the synthetic conditions allowed isolation of two metal complexes: [Cu2L12(MeOH2], 1, a discrete dimer linked by hydrogen bonding interactions in the solid state, and poly-[Cu2L12], 2, a polymeric material where the dimer motif is linked by carboxylate bridges to give an extended two-dimensional sheet. The selective isolation of each phase by careful synthetic control highlights the subtlety and importance of the underlying synthetic conditions.

  4. Reversible Redox Activity in Multicomponent Metal-Organic Frameworks Constructed from Trinuclear Copper Pyrazolate Building Blocks.

    Science.gov (United States)

    Tu, Binbin; Pang, Qingqing; Xu, Huoshu; Li, Xiaomin; Wang, Yulin; Ma, Zhen; Weng, Linhong; Li, Qiaowei

    2017-06-14

    Inorganic functionalization of metal-organic frameworks (MOFs), such as incorporation of multiple inorganic building blocks with distinct metals into one structure and further modulation of the metal charges, endows the porous materials with significant properties toward their applications in catalysis. In this work, by an exploration of the role of 4-pyrazolecarboxylic acid (H2PyC) in the formation of trinuclear copper pyrazolate as a metalloligand in situ, four new MOFs with multiple components in order were constructed through one-pot synthesis. This metalloligand strategy provides multicomponent MOFs with new topologies (tub for FDM-4 and tap for FDM-5) and is also compatible with a second organic linker for cooperative construction of complex MOFs (1,4-benzenedicarboxylic acid for FDM-6 and 2,6-naphthalenedicarboxylic acid for FDM-7). The component multiplicity of these MOFs originates from PyC's ability to separate Cu and Zn on the basis of their differentiated binding affinities toward pyrazolate and carboxylate. These MOFs feature reversible and facile redox transformations between Cu(I)3(PyC)3 and Cu(II)3(μ-OH)(PyC)3(OH)3 without altering the connecting geometries of the units, thus further contributing to the significant catalytic activities in the oxidation of CO and aromatic alcohols and the decomposition of H2O2. This study on programming multiple inorganic components into one framework and modulating their electronic structures is an example of functionalizing the inorganic units of MOFs with a high degree of control.

  5. The Intramolecular Spin-Spin Interactions in Ruthenium Complexes of Pyrazole Derivatives

    Institute of Scientific and Technical Information of China (English)

    Peter A.Aj ibade

    2016-01-01

    The spin-spin coupling can provide useful information for analysing the structure of a system and the extent of non-covalent bonds interactions.In this study,we present the isotropic NMR properties and spin-spin coupling involving ruthenium-ligand (Ru-L)bonds and other spin-spin interactions obtained from DFT calculations.The proton shift which in close proximity with the Ru and Cl (or O)atoms are characterised with lower and higher chemical shift respectively.Though Ru-Cl bond has longer bond length than all other Ru-L bonds,yet its spin-spin coupling is higher than others because of a very high contribution of PSO which is far higher than the contribution from FC terms.In all other Ru-L bonds,FC is the most significant Ramsey terms that define their spin-spin coupling.Both the isotropic and anisotropic shielding of the Hz of the pyrazole is lower than Hc of the cymene and the spin-spin coupling 3 J(Hz…Hz)of the pyrazole are less than half of the 3 J (Hc…Hc)of the cymene unit in the complexes.There is a little increase in both the 3 J(Hc…Hc)and 3 J(Hz…Hz)spin-spin coupling in the hydrolysed complexes compare to the non-hydrolysed complexes.The isotropic and anisotropic shielding tensor of Ru atoms increases in magnitude as the complexes get hydrolysed that could be ascribed to a more deshielding chemical environments.

  6. Unexpected formation and crystal structure of tetra-kis-(1H-pyrazole-κN (2))-palladium(II) dichloride.

    Science.gov (United States)

    Wagner, Thomas; Christiansen, Nena; Hrib, Cristian G; Kaufmann, Dieter E; Edelmann, Frank T

    2014-12-01

    The title salt, [Pd(C3H4N2)4]Cl2, was obtained unexpectedly by the reaction of palladium(II) dichloride with equimolar amounts of 1-chloro-1-nitro-2,2,2-tris-(pyrazol-yl)ethane in methanol solution. The Pd(2+) cation is located on an inversion centre and has a square-planar coordination sphere defined by four N atoms of four neutral pyrazole ligands. The average Pd-N distance is 2.000 (2) Å. The two chloride anions are not coordinating to Pd(2+). They are connected to the complex cations through N-H⋯Cl hydrogen bonds. In addition, C-H⋯Cl hydrogen bonds are observed, leading to a three-dimensional linkage of cations and anions.

  7. A novel pyrazole biscoumarin based chemosensors for the selective detection of Cu(2+) and Zn(2+) ions.

    Science.gov (United States)

    Kandasamy, Karthikeyan; Ganesabaskaran, Sivaprasad; Pachamuthu, Muthusamy Poomalai; Ramanathan, Anand

    2015-09-05

    A novel chemosensor based on pyrazole biscoumarin molecule "4-hydroxy-3-((4-hydroxy-2-oxo-2H-chromen-3-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methyl)-2H-chromen-2-one" (PBC) was synthesized by a simple method. The chemosensing properties of PBC towards transition metal ions like Cu(2+) and Zn(2+) by naked eye, UV-Visible and fluorescence spectroscopic methods were described. The PBC solution with Cu(2+) and Zn(2+) ion showed brown and blue colour respectively. The UV-Visible spectra of PBC with Cu(2+) and Zn(2+) ions exposed their corresponding absorption maxima. Further, the Job's plot method confirmed the 1:1 and 2:1 stoichiometry of the complex formation between the PBC with Cu(2+) and Zn(2+) ions respectively. The fluorescence enhancement of PBC on binding with Cu(2+) and Zn(2+) is due to the inhibition of photo induced electron transfer mechanism.

  8. Pyrazole bridged dinuclear Cu(II) and Zn(II) complexes as phosphatase models: Synthesis and activity

    Science.gov (United States)

    Naik, Krishna; Nevrekar, Anupama; Kokare, Dhoolesh Gangaram; Kotian, Avinash; Kamat, Vinayak; Revankar, Vidyanand K.

    2016-12-01

    Present work describes synthesis of dibridged dinuclear [Cu2L2(μ2-NN pyr)(NO3)2(H2O)2] and [Zn2L(μ-OH)(μ-NNpyr)(H2O)2] complexes derived from a pyrazole based ligand bis(2-hydroxy-3-methoxybenzylidene)-1H-pyrazole-3,5-dicarbohydrazide. The ligand shows dimeric chelate behaviour towards copper against monomeric for zinc counterpart. Spectroscopic evidences affirm octahedral environment around the metal ions in solution state and non-electrolytic nature of the complexes. Both the complexes are active catalysts towards phosphomonoester hydrolysis with first order kcat values in the range of 2 × 10-3s-1. Zinc complex exhibited promising catalytic efficiency for the hydrolysis. The dinuclear complexes hydrolyse via Lewis acid activation, whereby the phosphate esters are preferentially bound in a bidentate bridging fashion and subsequent nucleophilic attack to release phosphate group.

  9. A novel pyrazole biscoumarin based chemosensors for the selective detection of Cu2+ and Zn2+ ions

    Science.gov (United States)

    Kandasamy, Karthikeyan; Ganesabaskaran, Sivaprasad; Pachamuthu, Muthusamy Poomalai; Ramanathan, Anand

    2015-09-01

    A novel chemosensor based on pyrazole biscoumarin molecule "4-hydroxy-3-((4-hydroxy-2-oxo-2H-chromen-3-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methyl)-2H-chromen-2-one" (PBC) was synthesized by a simple method. The chemosensing properties of PBC towards transition metal ions like Cu2+ and Zn2+ by naked eye, UV-Visible and fluorescence spectroscopic methods were described. The PBC solution with Cu2+ and Zn2+ ion showed brown and blue colour respectively. The UV-Visible spectra of PBC with Cu2+ and Zn2+ ions exposed their corresponding absorption maxima. Further, the Job's plot method confirmed the 1:1 and 2:1 stoichiometry of the complex formation between the PBC with Cu2+ and Zn2+ ions respectively. The fluorescence enhancement of PBC on binding with Cu2+ and Zn2+ is due to the inhibition of photo induced electron transfer mechanism.

  10. Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin; implications for their antitumor and chemosensitizing activities.

    Science.gov (United States)

    Labbozzetta, Manuela; Baruchello, Riccardo; Marchetti, Paolo; Gueli, Maria C; Poma, Paola; Notarbartolo, Monica; Simoni, Daniele; D'Alessandro, Natale

    2009-09-14

    Curcumin (CUR) can be considered as a good lead compound for the design of new anticancer drugs. Further, structure-activity relationship studies may clarify the importance of the redox activities in the antitumor effects of the drug. We have elaborated the alpha,beta-unsaturated 1,3-diketone moiety of CUR into the isoxazole (ISO) and pyrazole (PYR) derivatives. These derivatives should be much less prone to nucleophilic addition than CUR and benzyl mercaptan addition analyses showed that indeed they do not form isolable conjugated products. When compared with CUR, ISO and PYR exhibited increased cell growth inhibitory and pro-apoptotic effects in liver cancer HA22T/VGH cells as well as in other tumor cell types; in contrast to CUR, the antitumor effects of ISO or PYR were not influenced by concomitant administration of N-acetylcysteine, as a source of -SH groups, or buthionine sulfoximine, as an inhibitor of glutathione synthesis. Further, treatment with CUR, but not with ISO or PYR, significantly decreased the content of reduced glutathione in the HA22T/VGH cells. Finally, ISO and PYR lacked the ability of the parent compound to sensitize the HA22T/VGH cells to cisplatin (CIS), an effect which appeared to occur through an interaction of CUR and CIS at the level of the -SH groups. Thus, the ability of interacting with cell thiols might not be requested for the more potent antitumor activities of new diketone modified CUR derivatives, which might rely on other mechanisms, though possibly devoid of chemosensitization capabilities.

  11. Cobalt complexes with pyrazole ligands as catalyst precursors for the peroxidative oxidation of cyclohexane: X-ray absorption spectroscopy studies and biological applications.

    Science.gov (United States)

    Silva, Telma F S; Martins, Luísa M D R S; Guedes da Silva, M Fátima C; Kuznetsov, Maxim L; Fernandes, Alexandra R; Silva, Ana; Pan, Chun-Jern; Lee, Jyh-Fu; Hwang, Bing-Joe; Pombeiro, Armando J L

    2014-04-01

    [CoCl(μ-Cl)(Hpz(Ph))3]2 (1) and [CoCl2(Hpz(Ph))4] (2) were obtained by reaction of CoCl2 with HC(pz(Ph))3 and Hpz(Ph), respectively (Hpz(Ph)=3-phenylpyrazole). The compounds were isolated as air-stable solids and fully characterized by IR and far-IR spectroscopy, MS(ESI+/-), elemental analysis, cyclic voltammetry (CV), controlled potential electrolysis, and single-crystal X-ray diffraction. Electrochemical studies showed that 1 and 2 undergo single-electron irreversible Co(II)→Co(III) oxidations and Co(II)→Co(I) reductions at potentials measured by CV, which also allowed, in the case of dinuclear complex 1, the detection of electronic communication between the Co centers through the chloride bridging ligands. The electrochemical behavior of models of 1 and 2 were also investigated by density functional theory (DFT) methods, which indicated that the vertical oxidation of 1 and 2 (that before structural relaxation) affects mostly the chloride and pyrazolyl ligands, whereas adiabatic oxidation (that after the geometry relaxation) and reduction are mostly metal centered. Compounds 1 and 2 and, for comparative purposes, other related scorpionate and pyrazole cobalt complexes, exhibit catalytic activity for the peroxidative oxidation of cyclohexane to cyclohexanol and cyclohexanone under mild conditions (room temperature, aqueous H2O2). In situ X-ray absorption spectroscopy studies indicated that the species derived from complexes 1 and 2 during the oxidation of cyclohexane (i.e., Ox-1 and Ox-2, respectively) are analogous and contain a Co(III) site. Complex 2 showed low in vitro cytotoxicity toward the HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma cell lines.

  12. A systematic investigation of cooperativity between two types of hydrogen bonding in the nonlinear clusters of an aromatic molecule: Pyrazole

    Science.gov (United States)

    Amini, Saeed K.

    2014-06-01

    Crystalline pyrazole consists of nonlinear chains of an aromatic molecule. It includes two independent molecules which in turn causes two different types of hydrogen bonds (HBs). These two types of HBs with slight differences in their Nsbnd H⋯N geometries can be considered as interesting ones in the recent studies of cooperativity between different HBs. These HBs are investigated in several pyrazole clusters by electronic structure calculations. Parameters such as structure, binding energy, charge transfer, chemical shielding and electric field gradient (EFG) parameters calculated at the second order Moller-Plesset perturbation (MP2) and density functional (DF) levels of theory. Both the basis set superposition error (BSSE) and zero point vibrational energy (ZPVE) corrections on the cooperativity enhancement were considered. Changes of different properties of clusters against crystal size were investigated by proposed diagrams fitted to a logarithmic function which renders their extrema in the crystal limit. In each cluster, pyrazole molecules for which their parameters are more affected by cooperativity enhancement were explored employing these fitted diagrams. Most calculated energetic and spectroscopic parameters were in good linear correlations with both the structural parameters and charge transfer along HB (q). These correlations in the cases of nuclear magnetic resonance (NMR) and nuclear quadrupolar resonance (NQR) parameters, were explained in the terms of natural charges of bonding (σ(N1sbnd H1)) and antibonding (σ*(N1sbnd H1)) orbitals. Organizing calculated data for mental clusters with similar molecules and HB types produced better regression values in all linear correlations. According to the experimental CQ of N(2) in solid state and zero charge transfer in the gas phase, the value of charge transfer in the crystalline pyrazole and gas phase value of CQ of N(2) were assessed, respectively. Diagrams of the structural parameters against either

  13. A Novel Photochemical Reaction of 4-Bromo-3-methyl-1-phenyl-4,5-dihydro-pyrazol-5-one

    Institute of Scientific and Technical Information of China (English)

    LI,Xiao-Liu(李小六); SONG,Zhi-Yi(宋志毅); MENG,Ji-Ben(孟继本)

    2004-01-01

    UV-Irradiation of 4-bromo-3-methyl-l-phenyl-4,5-dihydro-pyrazol-5-one (1) in the presence of various aromatic hydrocarbons gave different types of photoproducts depending on the nature of the hydrocarbons via an electron-transfer mechanism. In the presence of naphthalene or phenanthrene a photochemical homocoupling reaction of 1 occurred to form 2 or 2 and 3, respectively.

  14. (2,6-Bis{5-amino-3-tert-butyl-4-[(3-methyl-1,2,4-thiadiazol-5-yldiazenyl]-1H-pyrazol-1-yl}-4-oxo-1,4-dihydro-1,3,5-triazin-1-idomethanol(phenolsodium phenol tetrasolvate

    Directory of Open Access Journals (Sweden)

    Hiroki Shibata

    2010-04-01

    Full Text Available The title compound, [Na(C23H28N17OS2(CH3OH(C6H5OH]·4C6H5OH, is a five-coordinate NaI complex. The Na+ cation is bound to three N atoms of the triazinide ligand, two from each pyrazole ring and one from the central deprotonated triazine ring system. O atoms from a methanol and a phenol molecule complete the five-coordinate NaN3O2 coordination environment. The asymmetric unit also includes three complete and two half phenol molecules, four of which are hydrogen bonded to the N atoms of the thiadiazole ring. Two of the phenol solvent molecules are disordered over two discrete inversion centres. The triazinide ligand is essentially planar (mean deviation from the least-squares plane = 0.0524 Å, with the methyl groups of the tert-butyl substituents on the pyrazole rings located above and below the plane. The planarity of this system is further assisted by the formation of four intramolecular N—H...N hydrogen bonds between the N—H bonds of both amino groups on the pyrazole rings and the N atoms of the triazine ring and also from each of the adjacent diazene (–N=N– bonds. The highly polar molecules are stacked along the a axis through the central Na atom sandwiched by two kinds of alternating intermolecular hydrogen bonds: O(carbonyl...H—O(methanol/Na/O—H(phenol...O(carbonyl. These interactions form two polymer chains per molecule.

  15. Synthesis and Antimicrobial Activity of Some New Pyrazole, Fused Pyrazolo[3,4-d]-pyrimidine and Pyrazolo[4,3-e][1,2,4]- triazolo[1,5-c]pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Omar A. Miqdad

    2008-07-01

    Full Text Available Hydrazonyl bromides 2a,b reacted with active methylene compounds (dibenzoylmethane, acetylacetone, ethyl acetoacetate, phenacyl cyanide, acetoacetanilide, ethyl cyanoacetate, cyanoacetamide and malononitrile to afford the corresponding 1,3,4,5- tetrasubstituted pyrazole derivatives 5-12a,b. Reaction of 12a,b with formamide, formic acid and triethyl orthoformate give the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4- d]pyrimidin-4(3Hone and 5-ethoxymethylene-aminopyrazole-4-carbo-nitrile derivatives 13-15a,b, respectively. Compounds 15a,b reacted with benzhydrazide and hydrazine hydrate to afford pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine and [4-iminopyrazolo- [3,4-d]pyrimidin-5-yl]amine derivatives 16a,b and 17a,b. Reactions of compounds 17a,b with triethyl orthoformate and carbon disulfide give the corresponding pyrazolo[4,3-e]- [1,2,4]triazolo[1,5-c]pyrimidine derivatives 18a,b and 19a,b, respectively.

  16. Vibrational and structural observations and molecular docking study on 1-{3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazol-1-yl}-ethanone

    Science.gov (United States)

    Parveen S, Shana; Al-Alshaikh, Monirah A.; Panicker, C. Yohannan; El-Emam, Ali A.; Narayana, B.; Saliyan, Vinutha V.; Sarojini, B. K.; Van Alsenoy, C.

    2016-05-01

    A combined experimental and theoretical analysis of on molecular structure, vibrational spectra and HOMO-LUMO analysis of 1-{3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazol-1-yl}-ethanone is reported. The equilibrium geometry and vibrational wavenumbers have been computed using desnity functional B3LYP method with 6-311++G(d) (5D, 7F) as basis set. The nonlinear optical properties were evaluated by the determination of the first and second hyperpolarizabilities of the title compound. HOMO is localized over the whole molecule except the ring PhIII and the CH3 groups attached to the PhIII while the LUMO is located through out the whole molecule except the CH3 groups attached with the PhIII and this shows that an eventual charge transfer occurs within the molecule. From the molecular electrostatic potential study, the negative electrostatic potential regions are mainly localized over the carbonyl group, phenyl rings and are possible sites for electrophilic attack and the positive regions are localized over the nitrogen atoms as possible sites for nucleophilic attack. The docked ligand title compound forms a stable complex with kinesin spindle protein (KSP) and gives a binding affinity value of -6.7 kcal/mol the results suggest that the compound might exhibit inhibitory activity against KSP.

  17. Post-transcriptional regulation of coumarin 7-hydroxylase (P450coh) induction by xenobiotics in mouse liver: mRNA stabilization by pyrazole

    Energy Technology Data Exchange (ETDEWEB)

    Aida, K.; Negishi, M. (NIEHS/NIH, Research Triangle Park, NC (United States))

    1991-03-15

    The induction mechanism by pyrazole or phenobarbital of coumarin 7-hydroxylase was investigated in DBA/2J male mice. The P450coh mRNA in the pyrazole-induced mice was increased gradually to a 20-fold higher level within 48 hr, yet transcription of the P450coh gene was not affected. The half-life of P450coh mRNA, on the other hand, was at least 4-fold longer in the pyrazole-induced DBA2J than in control DBA/2J male mice. The stabilization of P450coh mRNA, therefore, is the primary mechanism for the induction by pyrazole of coumarin 7-hydroxylase. Phenobarbital, on the other hand, regulates the induction translationally or post-translationally. This drug affected neither the P450coh mRNA nor the P450coh gene's transcription levels in the DBA/2J male mice, although Western blots showed a 2- to 3-fold increase of the P450coh protein in the liver microsomes of the drug-treated mice. The results indicate, therefore, that both phenobarbital and pyrazole regulate the P450coh induction post-transcriptional efficiency of P450coh mRNA or alters the degradation rate of P450coh protein, while the latter stabilizes P450coh mRNA.

  18. Synthesis, Structure and Electrochemistry of Tetranuclear Oxygen-Centered Copper(II) Clusters with Acetylacetone and Benz-pyrazole Hydrolyzed Derivatives as Ligand.

    Science.gov (United States)

    Vafazadeh, Rasoul; Willis, Anthony C

    2016-01-01

    Two copper(II) clusters Cu(4)OCl(6)(pyrazole)4, 1, and Cu(4)OBr(6)(Br-pyrazole)4, 2, have been synthesized by reacting acetylacetone and benzohydrazide (1:1 ratio) with CuX(2) (X = Cl for 1 and X= Br for 2) in methanol solutions. The structures of both clusters have been established by X-ray crystallography. The clusters contain four Cu, one O, six μ(2)-X atoms, and four pyrazole ligands. The pyrazoles was prepared in situ by the reaction of acetylacetone with benzohydrazide in methanol under reflux. In 2, the methine hydrogens of the pyrazole ligands have been replaced by bromine atoms. The four copper atoms encapsulate the central O atom in a tetrahedral arrangement. All copper atoms are five-coordinate and have similar coordination environments with slightly distorted trigonal bipyramidal geometry. The cyclic voltammogram of the clusters 1 and 2 show a one-electron quasi-reversible reduction wave in the region 0.485 to 0.731 V, and a one-electron quasi-reversible oxidation wave in the region 0.767 to 0.898 V. In 1, one irreversible oxidative response is observed on the positive of side of the voltammogram at 1.512 V and this can be assigned to Cu(II) to Cu(III) oxidation.

  19. Magnetocaloric effect in {[Fe(pyrazole)_4]_2[Nb(CN)_8]·4H_2O}{sub n} molecular magnet

    Energy Technology Data Exchange (ETDEWEB)

    Pełka, R., E-mail: robert.pelka@ifj.edu.pl [The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Radzikowskiego 152, 31-342 Kraków (Poland); Konieczny, P.; Zieliński, P.M.; Wasiutyński, T. [The H. Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences, Radzikowskiego 152, 31-342 Kraków (Poland); Miyazaki, Y.; Inaba, A. [Research Center for Structural Thermodynamics, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Pinkowicz, D.; Sieklucka, B. [Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków (Poland)

    2014-03-15

    Magnetocaloric effect in {[Fe(pyrazole)_4]_2[Nb(Cn)_8]·4H_2O}{sub n} molecular magnet is reported. It crystallizes in tetragonal I4{sub 1}/a space group. The compound exhibits a phase transition to a long range magnetically ordered state at T{sub c}≈8.3K. The magnetic entropy change ΔS{sub M} as well as the adiabatic temperature change ΔT{sub ad} due to applied field change μ{sub 0}ΔH=0.1, 0.2, 0.5, 1, 2, 5, 9 T as a function of temperature have been determined by the relaxation calorimetry measurements. The maximum value of ΔS{sub M} for μ{sub 0}ΔH=5T is 4.9 J mol{sup −1} K{sup −1} (4.8 J kg{sup −1} K{sup −1}) at 10.3 K. The corresponding maximum value of ΔT{sub ad} is 2.0 K at 8.9 K. The temperature dependence of the exponent n characterizing the field dependence of ΔS{sub M} has been estimated. It attains the value of 0.64 at the transition temperature, which is consistent with the 3D Heisenberg universality class. - Highlights: • Using the technique of relaxation calorimetry the magnetocaloric effect of a novel molecular magnet is analyzed. • Temperature dependencies of isothermal magnetic entropy change and adiabatic temperature change are estimated. • Scaling behavior of the magnetocaloric effect is discussed.

  20. Preparation, Structure and Electrochemical Property of a Pyrazole-substituted Diiron Dithiolate Complex

    Institute of Scientific and Technical Information of China (English)

    FENG Ya-Nan; CHEN Rui-Ping; LI Zhi-Hua; DU Shao-Wu

    2012-01-01

    A pyrazole-substituted diiron dithiolate complex [Fez(p-pdt)(CO)5(3,5-Me2Pz)] (1, 3,5-MezPz = 3,5-dimethylpyrazole) was prepared as a biomimetic model for the active site of [FeFe]-hydrogenase by CO-substitution of aU-carbonyl complex [Fe2(μ-pdt)(CO)6] with 3,5-Me2Pz. The molecular structure was confirmed by MS, IR, 1H NMR, elemental analysis and single-crystal X-ray analysis. Complex 1 crystallizes in the triclinic system, space group PI with a = 9.108(7), b = 9.743(8), c = 11.192(9)A, a = 109.235(5), fl = 101.914(9), y = 96.605(6). In CH3CN solution, reversible transformation between 1 and the acetonitrile-substituted species [Fe2(p-pdt)- (CO)5(NCCH3)] was detected by both IR and cyclic voltammetry (CV). The electrochemical proton reduction catalyzed by 1 in the presence of acetic acid was also studied in CH2C12.

  1. A combined experimental and DFT investigation of disazo dye having pyrazole skeleton

    Science.gov (United States)

    Şener, Nesrin; Bayrakdar, Alpaslan; Kart, Hasan Hüseyin; Şener, İzzet

    2017-02-01

    Disazo dye containing pyrazole skeleton has been synthesized. The structure of the dye has been confirmed by using FT-IR, 1H NMR, 13C NMR, HRMS spectral technique and elemental analysis. The molecular geometry and infrared spectrum are also calculated by the Density Functional Theory (DFT) employing B3LYP level with 6-311G (d,p) basis set. The chemical shifts calculation for 1H NMR of the title molecule is done by using by Gauge-Invariant Atomic Orbital (GIAO) method by utilizing the same basis sets. The total density of state, the partial density of state and the overlap population density of state diagram analysis are done via Gauss Sum 3.0 program. Frontier molecular orbitals such as highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and molecular electrostatic potential surface on the title molecule are predicted for various intramolecular interactions that are responsible for the stabilization of the molecule. The experimental results and theoretical values have been compared.

  2. QTAIM investigation of bis(pyrazol-1-yl)methane derivative and its Zn(II) complexes (ZnLX2, X=Cl, Br or I)

    OpenAIRE

    Dehestani Maryam; Zeidabadinejad Leila

    2015-01-01

    Topological analyses of the electron density using the quantum theory of atoms in molecules (QTAIM) have been carried out at the B3PW91/6-31g (d) theoretical level, on bis(pyrazol-1-yl)methanes derivatives 9-(4-(di (1H-pyrazol-1-yl)-methyl)phenyl)-9H-carbazole (L) and its zinc(II) complexes: ZnLCl2 (1), ZnLBr2 (2) and ZnLI2 (3). The topological parameters derived from Bader theory were also analyzed; these are characteristics of Zn-bond critical points and ...

  3. A 1H, 13C and 15N NMR study in solution and in the solid state of six N-substituted pyrazoles and indazoles.

    Science.gov (United States)

    Claramunt, Rosa M; Santa María, M Dolores; Sanz, Dionisia; Alkorta, Ibon; Elguero, José

    2006-05-01

    Three N-substituted pyrazoles and three N-substituted indazoles [1-(4-nitrophenyl)-3,5-dimethylpyrazole (1), 1-(2,4-dinitrophenyl)-3,5-dimethylpyrazole (2), 1-tosyl-pyrazole (3), 1-p-chlorobenzoylindazole (4), 1-tosylinda-zole (5) and 2-(2-hydroxy-2-phenylethyl)-indazole (6)] have been studied by NMR spectroscopy in solution (1H, 13C, 15N) and in the solid state (13C, 15N). The chemical shifts have been compared with GIAO/DFT calculated absolute shieldings. Some discrepancies have been analyzed.

  4. Coordination of bis(pyrazol-1-ylamine to palladium(II: influence of the co-ligands and counter-ions on the molecular and crystal structures

    Directory of Open Access Journals (Sweden)

    María de los Angeles Mendoza

    2015-01-01

    Full Text Available The structures of a series of complexes with general formula n[Pd(pzaX]Y·mH2O (n = 1, 2; X = Cl, Br, I, N3, NCS; Y = NO3, I, N3, [Pd(SCN4]; m = 0, 0.5, 1 have been determined, where pza is the tridentate ligand bis[2-(3,5-dimethylpyrazol-1-ylethyl]amine, C14H23N5. In all complexes, {bis[2-(3,5-dimethylpyrazol-1-yl-κN2ethyl]amine-κN}chloridopalladium nitrate, [Pd(pzaCl]NO3, (1, {bis[2-(3,5-dimethylpyrazol-1-yl-κN2ethyl]amine-κN}bromidopalladium nitrate, [Pd(pzaBr]NO3, (2, {bis[2-(3,5-dimethylpyrazol-1-yl-κN2ethyl]amine-κN}iodidopalladium iodide hemihydrate, [Pd(pzaI]I·0.5H2O, (3, azido{bis[2-(3,5-dimethylpyrazol-1-yl-κN2ethyl]amine-κN}palladium azide monohydrate, [Pd(pzaN3]N3·H2O, (4, and bis[{bis[2-(3,5-dimethylpyrazol-1-yl-κN2ethyl]amine-κN}(thiocyanato-κNpalladium] tetrakis(thiocyanato-κSpalladate, [Pd(pzaNCS]2[Pd(SCN4], (5, the [Pd(pzaX]+ complex cation displays a square-planar coordination geometry, and the pza ligand is twisted, approximating twofold rotation symmetry. Although the pza ligand is found with the same conformation along the series, the dihedral angle between pyrazole rings depends on the co-ligand X. This angle span the range 79.0 (3–88.6 (1° for the studied complexes. In (3, two complex cations, two I− anions and one water molecule of crystallization are present in the asymmetric unit. In (5, the central amine group of pza is disordered over two positions [occupancy ratio 0.770 (18:0.230 (18]. The complex [Pd(SCN4]2− anion of this compound exhibits inversion symmetry and shows the Pd2+ transition metal cation likewise in a square-planar coordination environment. Compound (5 is also a rare occurrence of a non-polymeric compound in which the pseudohalide ligand NCS− behaves both as thiocyanate and isothiocyanate, i.e. is coordinating either through the N atom (in the cation or the S atom (in the anion.

  5. Stability Constants of Some Biologically Important Pyrazoles and Their Ni2+ Complexes in Different Dielectric Constant of Medium

    Directory of Open Access Journals (Sweden)

    S. D. Deosarkar

    2012-01-01

    Full Text Available The proton-ligand stability constants of some biologically important new pyrazoles and formation constants of their complexes with Ni(II were determined at 0.1 mol dm-3 ionic strength and at 303.15 K in different dielectric constant of dioxane-water mixture by potentiometric method. The Calvin-Bjerrum's pH-titration technique as used by Irving and Rossotti was used for determination of stability constants. The results enabled to study the electrostatic forces of attraction between metal ion and ligand with changes in dielectric constant of the medium.

  6. Comparative Study of Various Pyrazole-based Anions: A Promising Family of Ionic Derivatives as Insensitive Energetic Materials.

    Science.gov (United States)

    Yin, Ping; Mitchell, Lauren A; Parrish, Damon A; Shreeve, Jean'ne M

    2017-02-01

    In the design of advanced energetic materials, high-density explosophores play a pivotal role because of their remarkable enhancement of both density and molecular stability. Using diversified functionalization strategies, a comparative study involving various nitropyrazole anions shows that these are crucially important in determining performance and stability. A promising family of pyrazole-based energetic ionic derivatives were synthesized and characterized by NMR and IR spectroscopies, and elemental analysis. Among them, 7, 8, 11-13 exhibit favorable overall performance as energetic materials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Influence of pyrazole derivatives in I{sup -}/I{sub 3}{sup -} redox electrolyte solution on Ru(II)-dye-sensitized TiO{sub 2} solar cell performance

    Energy Technology Data Exchange (ETDEWEB)

    Kusama, Hitoshi; Arakawa, Hironori [Photoreaction Control Research Center (PCRC), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565 (Japan)

    2005-01-31

    The influence of pyrazole additives in an I{sup -}/I{sub 3}{sup -} redox electrolyte solution on the performance of a bis(tetrabutylammonium)cis-bis(thiocyanato)bis(2,2'-bipyridine-4-carboxylic acid, 4'-carboxylate)ruthenium(II) (N719) dye-sensitized TiO{sub 2} solar cell was studied. The current-voltage characteristics of the cell were measured using 18 different pyrazole derivatives. All of the pyrazole additives enhanced the open-circuit photovoltage (V{sub oc}) and the solar energy conversion efficiency ({eta}), but reduced the short-circuit photocurrent density (J{sub sc}). Most of the pyrazoles improved fill factor (ff). The physical and chemical properties of the pyrazoles were computationally calculated in order to elucidate the reasons for the additive effects on cell performance. The greater the partial charge of the nitrogen atom at position 2 in the pyrazole group, the larger the V{sub oc,} but the smaller the J{sub sc} values. As the dipole moment of the pyrazole derivatives increased, the V{sub oc} value increased, but the J{sub sc} value decreased. The V{sub oc} of the cell also increased as the ionization energy of the pyrazoles decreased. These results suggest that the electron donicity of the pyrazole additives affected the interaction with the nanocrystalline TiO{sub 2} photoelectrode, the I{sup -}/I{sub 3}{sup -} electrolyte, and the acetonitrile solvent, which changed the Ru(II)-dye-sensitized solar cell performance.

  8. X-ray diffraction, DFT, spectroscopic study and insecticidal activity of (3-cyano-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-((trifluoromethyl)sulfinyl)-1 H-pyrazol-5- yl)(2-(triethylammonio)acetyl)amide inner salt

    Science.gov (United States)

    Jiang, D. X.; Zheng, X. H.; Xu, H. H.; Wong, N. B.

    2014-12-01

    In the title compound, C20H19Cl2F6N5O2S, an inner salt derivative of fipronil was synthesized and characterized by X-ray diffraction, 1H NMR, 13C NMR, IR, ESI-MS, EI-HRMS. The crystal is monoclinic, space group P21/ n, with a = 15.1655(7) Å, b = 15.0465(7) Å, c = 21.0713(9) Å, V = 4754.7(4) Å3 and Z = 8 (at 173(2) K), and its phenyl pyrazole ring together with bond C-N-O form a big π bond while bonds C-N-C and N-C-H form an inner salt molecular. Crystal stacking scheme indicates the crystal consists of two different molecules. The two molecules are nonplanar with the torsion angles between the pyrazole rings and benzene rings of -99.7(7)° and 88.1(7)°, respectively, and linked by intermolecular C-H⋯O, C-H⋯F hydrogen bonds. By DFT calculations, molecular electrostatic potential clearly shows that the formation of hydrogen bonding interaction, which F5⋯H'42 and F6⋯H'41 are intermolecular hydrogen bonds, and F7⋯H44 is an intramolecular hydrogen bond in the crystal structure, is between the positive and negative regions. In addition, molecular geometry optimized by DFT methods is in good agreement with the experimental values. In the optimized structure, the O-S, S-C, C-F and C-Cl bonds are slightly longer in comparison with those in the crystal. The intermolecular interaction energy for the dimmer was calculated to be 4.96 kcal mol-1. The results reveal that the two monomers are slightly combined with each other through two weak F⋯H hydrogen bonds. The compound and fipronil exhibited high insecticidal activity against the third instar larvae of Asian Corn Borer ( Ostrinia furnacalis (Guenée)) at 48 h after treatment with LC50 values of 4.17 μg/mL ( r 2 = 0.9974) and 5.36 μg/mL ( r 2 = 0.9970), respectively.

  9. Bis[tris(1H-pyrazol-1-yl-κN2methane]nickel(II bis{[tris(1H-pyrazol-1-yl-κN2methane]tris(thiocyanato-κNnickelate(II} methanol disolvate

    Directory of Open Access Journals (Sweden)

    Ganna Lyubartseva

    2011-12-01

    Full Text Available Attempts to prepare the mononuclear [(tpmNiIIL3]−1 [tpm = tris(1H-pyrazol-1-ylmethane and L = thiocyanate] anion yielded the methanol-solvated salt, [(tpm2NiII][(tpmNiII(NCS3]2·2CH3OH or [Ni(C10H10N62][Ni(NCS3(C10H10N6]2·2CH3OH. The asymmetric unit consists of half a centrosymmetric bis[tris(1H-pyrazol-1-ylmethane]nickel(II cation and an octahedral nickelate(II anion bound to one tpm and three L ligands, and a methanol solvent molecule. One of the L ligands is disordered over two positions with occupancy factors of 0.650 (3 and 0.350 (3. There are O—H...S interactions between the methanol and the disordered thiocyanate anion, and a weak C—H...O hydrogen bond between the cation and the methanol O atom.

  10. Induction profiles of P450 in rat liver microsomes by pyrazole or methylpyrazole

    Energy Technology Data Exchange (ETDEWEB)

    Krikun, G.; Cederbaum, A.I.

    1986-05-01

    Rats were injected for 2-3 days with pyrazole (P) or 4-methylpyrazole (MP) potent inhibitors of alcohol dehydrogenase. While P treatment induced a P450 isozyme with MW 52,000 as seen on SDS gels, MP induced 2 or 3 P450s. One of the P450s induced by MP appeared to be similar to the one increased by P treatment. The increase of 2-3 bands by MP correlated with a two fold increased in total P450 content. Microsomes from the P treated rats displayed increased activity (per mg protein or per nmole P450) with aniline, p-nitroanisole, dimethylnitrosamine (low Km DMN) and ethanol as substrates, but not with aminopyrine, ethoxycoumarin or DMN (high Km). A stereochemical preference for + 2-butanol over the -isomer was also observed. Kinetic experiments indicated that P treatment increased the Vmax for ethanol, aniline and + 2-butanol. These properties are similar to those found after chronic ethanol treatment. MP treatment resulted in an increased in the oxidation of all the drugs and alcohols tested, primarily due to the increase in content of P450. In analogy to results with P, MP treatment also resulted in stereochemical preference for + vs -2-butanol, and increased turnover numbers with aniline and p-nitroanisole. However in contrast to P, no increase in turnover number with ethanol, + 2-butanol or DMN (low Km) was found after MP treatment. It is probable that these divergent effects are due to the induction of several isozymes, one of which has properties similar to that induced by P. Thus, P induces a P450 similar to that induced by ethanol whereas MP induces that isozyme in addition to others.

  11. Butterfly Deformation Modes in a Photoexcited Pyrazolate-Bridged Pt Complex Measured by Time-Resolved X-Ray Scattering in Solution

    DEFF Research Database (Denmark)

    Haldrup, Kristoffer; Dohn, Asmus Ougaard; Shelby, Megan L.

    2016-01-01

    Pyrazolate-bridged dinuclear Pt(II) complexes represent a series of molecules with tunable absorption and emission properties that can be directly modulated by structural factors, such as the Pt-Pt distance. However, direct experimental information regarding the structure of the emissive triplet ...

  12. A general and efficient approach to 2H-indazoles and 1H-pyrazoles through copper-catalyzed intramolecular N-N bond formation under mild conditions.

    Science.gov (United States)

    Hu, Jiantao; Cheng, Yongfeng; Yang, Yiqing; Rao, Yu

    2011-09-28

    A new efficient copper-catalyzed intramolecular amination reaction has been developed to readily synthesise a wide variety of multi-substituted 2H-indazole and 1H-pyrazole derivatives from easily accessible starting materials under mild conditions. A highly selective ligand for estrogen receptor β was prepared in three steps by employing this method.

  13. High-resolution solid-state {sup 13}C and {sup 15}N NMR spectroscopy of pyrazole and 3,5-dimethylpyrazole adsorbed on alumina and silica

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar-Parrilla, F.; Limbach, H.H. [Ciudad Universitaria, Madrid (Spain); Claramunt, R.M. [Instituto de Quimica Medica, Madrid (Spain)] [and others

    1994-09-01

    Using pyrazole and 3,5-dimethylpyrazole mixtures with alumina and silica, high-resolution solid state {sup 13}C and {sup 15}N CPMAS NMR was performed to compare the spectra. The NH-N proton tautomers resulting depend strongly on the environment. 70 refs., 8 figs., 4 tabs.

  14. Luminescent dinuclear copper(I) complexes bearing 1,4-bis(diphenylphosphino)butane and functionalized 3-(2'-pyridyl)pyrazole mixed ligands.

    Science.gov (United States)

    Chen, Jing-Lin; Guo, Zong-Hao; Yu, Hua-Guang; He, Li-Hua; Liu, Sui-Jun; Wen, He-Rui; Wang, Jin-Yun

    2016-01-14

    A family of new dinuclear Cu(i) complexes with 1,4-bis(diphenylphosphino)butane (dppb) and functionalized 3-(2'-pyridyl)pyrazole mixed ligands has been synthesized and characterized. It is revealed that all these Cu(i) complexes include a [Cu2(dppb)2](2+) framework with the two Cu(i) atoms doubly bridged by a pair of dppb to generate a fourteen-membered Cu2P4C8 ring, and functionalized 3-(2'-pyridyl)pyrazole adopts a neutral chelating coordination mode without the N-H bond cleavage of the pyrazolyl ring. All these dinuclear Cu(i) complexes display a relatively weak low-energy absorption in CH2Cl2 solution, which is closely related to the variation of the Cu-N and Cu-P bonds caused by the substituent on the pyrazolyl ring. These dinuclear Cu(i) complexes are all emissive in solution and solid states at ambient temperature, which can be well modulated through structural modification of 3-(2'-pyridyl)pyrazole. It is shown that introduction of the trifluoromethyl group into the pyrazolyl ring is helpful for enhancing the luminescence properties of Cu(i) pyrazole phosphine complexes.

  15. MICROWAVE-ASSISTED CYCLOCONDENSATION OF HYDRAZINE DERIVATIVES WITH ALKYL DIHALIDES OR DITOSYLATES IN AQUEOUS MEDIA: SYNTHESES OF PYRAZOLE, PYRAZOLIDINE AND PHTHALAZINE DERIVATIVES

    Science.gov (United States)

    Direct synthesis of 4,5-dihydro-pyrazole, pyrazolidine, and 1,2-dihydro-phthalazine derivatives via double alkylation of hydrazines by alkyl dihalides or ditosylates were accomplished in aqueous media under microwave irradiation conditions; the environmentally friendlier chemical...

  16. Elucidating the mechanism of cytochrome P450-mediated pyrimidine ring conversion to pyrazole metabolites with the BACE1 inhibitor GNE-892 in rats.

    Science.gov (United States)

    Takahashi, Ryan; Ma, Shuguang; Deese, Alan; Yue, Qin; Kim-Kang, Heasook; Yi, Yijun; Siu, Michael; Hunt, Kevin W; Kallan, Nicholas C; Hop, Cornelis E C A; Liu, Xingrong; Khojasteh, S Cyrus

    2014-05-01

    We investigated an uncommon biotransformation of pyrimidine during the metabolism of GNE-892 ((R)-2-amino-1,3',3'-trimethyl-7'-(pyrimidin-5-yl)-3',4'-dihydro-2'H-spiro[imidazole-4,1'-naphthalen]-5(1H)-one), a β-secretase 1 inhibitor. Three novel metabolites, formed by conversion of pyrimidine to pyrazole, were observed in the (14)C-radiolabeled mass balance study in rats. Their structures were characterized by high-resolution mass spectrometry and nuclear magnetic resonance. Although these metabolites accounted for pyrazole-containing metabolites were formed in vitro with rat hepatocytes and liver microsomes, which supported that they were formed during hepatic metabolism. Further, their generation was inhibited by 1-aminobenzotriazole, indicating involvement of cytochrome P450s. Studies with rat recombinant enzymes identified that CYP2D2 generated the N-hydroxypyrazole metabolite from GNE-892. This biotransformation proceeded through multiple steps from the likely precursor, pyrimidine N-oxide. On the basis of these data, we propose a mechanism in which the pyrimidine is activated via N-oxidation, followed by a second oxidative process that opens the pyrimidine ring to form a formamide intermediate. After hydrolysis of the formamide, a carbon is lost as formic acid, together with ring closure to form the pyrazole ring. This article highlights a mechanistic approach for determining the biotransformation of the pyrimidine to a pyrazole for GNE-892.

  17. Vicarious nucleophilic substitution of hydrogen vs. ANRORC-type ring transformation in reactions of 1,2,4-triazines with alpha-halocarbanions. Novel route to functionalized pyrazoles

    NARCIS (Netherlands)

    Rykowski, A.; Wolinska, E.; Branowska, D.; Plas, van der H.C.

    2004-01-01

    A novel route to pyrazole derivatives bearing sulfonyl, aminosulfonyl, alkoxy- and aryloxysulfonyl groups at C-3 by ring transformation of 3-chloro-6-aryl-1,2,4-triazines 1a-c with alpha-halocarbanions 2a-h is described.

  18. Mononuclear thiocyanate containing nickel(II) and binuclear azido bridged nickel(II) complexes of N4-coordinate pyrazole based ligand: Syntheses, structures and magnetic properties

    Science.gov (United States)

    Solanki, Ankita; Monfort, Montserrat; Kumar, Sujit Baran

    2013-10-01

    Two mononuclear nickel(II) complexes [NiL1(NCS)2] (1) and [NiL2(NCS)2] (2) and two azido bridged binuclear nickel(II) complexes [Ni(()2()2] (3) and [Ni(()2()2] (4), where L1, L2, L1‧ and L2‧ are N,N-diethyl-N‧,N‧-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)ethane-1,2-diamine (L1), N,N-bis((1H-pyrazol-1-yl)methyl)-N‧,N‧-diethylethane-1,2-diamine (L2), N,N-diethyl-N‧-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)ethane-1,2-diamine (L1‧) and N-((1H-pyrazol-1-yl)methyl)-N‧,N‧-diethylethane-1,2-diamine (L2‧) have been synthesized and characterized by microanalyses and physico-chemical methods. Single crystal X-ray diffraction analyses revealed that complexes 1 and 2 are mononuclear NCS- containing Ni(II) complex with octahedral geometry and complexes 3 and 4 are end-on (μ-1,1) azido bridged binuclear Ni(II) complexes with distorted octahedral geometry. Variable temperature magnetic studies of the complexes 3 and 4 display ferromagnetic interaction with J values 19 and 32 cm-1, respectively.

  19. The new Schiff base 4-[(4-Hydroxy-3-fluoro-5-methoxy-benzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one: Experimental, DFT calculational studies and in vitro antimicrobial activity

    Science.gov (United States)

    İskeleli, Nazan Ocak; Alpaslan, Yelda Bingöl; Direkel, Şahin; Ertürk, Aliye Gediz; Süleymanoğlu, Nevin; Ustabaş, Reşat

    2015-03-01

    The synthesized Schiff base, 4-[(4-Hydroxy-3-fluoro-5-methoxy-benzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one (I), has been characterized by 13C NMR, 1H NMR, 2D NMR (1H-1H COSY and 13C APT), FT-IR, UV-vis and X-ray single-crystal techniques. Molecular geometry of the compound I in the ground state, vibrational frequencies and chemical shift values have been calculated by using the density functional method (DFT) with 6-311++G(d,p) basis set. The obtained results indicate that optimized geometry can well reflect the crystal structural parameters. The differences between experimental and calculated results of FT-IR and NMR have supported the existence of intermolecular (O-H⋯O type) and intramolecular (C-H⋯O type) hydrogen bonds in the crystal structure. Molecular electrostatic potential (MEP), frontier molecular orbital analysis (HOMO-LUMO) and electronic absorption spectra were carried out at B3LYP/6-311G++(d,p). HOMO-LUMO electronic transition of 3.92 eV is due to contribution of the bands the n → π∗. The antimicrobial activity of the compound I was determined against the selected 11 bacteria and 8 fungi by microdilution broth assay with Alamar Blue. In vitro studies showed that the compound I has no antifungal effect for selected fungal isolates. However, the compound I shows remarkable antibacterial effect for the bacteria; Streptococcus pneumoniae, Haemophilus influenzae and Enterococcus faecalis.

  20. The photochemistry of M{sub 3}(CO){sub 12}(M = Ru, Os) with pyrazole and its substituted derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Leadbeater, N.E.; Lewis, J.; Raithby, P.R.; Ward, G.P. [Centre for Inorganic Photochemistry, Cambridge (United Kingdom). Dept. of Chemistry

    1998-10-01

    The photochemistry of M{sub 3}(CO){sub 12} [M = Ru (1a), Os (1b)] with pyrazole, 3,5-dimethylpyrazole, and 3,5-diphenylpyrazole is documented. With 1a, photolysis with pyrazole leads to the substitution product HRu{sub 3}(CO){sub 10}(C{sub 3}H{sub 3}N{sub 2}) (2a). In the case of 1b, the initial product is the ortho-metallated species HOs{sub 3}(CO){sub 10}(C{sub 3}H{sub 3}N{sub 2}), (3b), heating of which yields HOs{sub 3}(CO){sub 10}(C{sub 3}H{sub 3}N{sub 2}) (2b). Photolysis of 1a and 1b with 3,5-dimethylpyrazole yields HRu{sub 3}(CO){sub 10}({sub 3}HMe{sub 2}N{sub 2}) (4a) and HOs{sub 3}(CO){sub 10}(C{sub 3}HMe{sub 2}N{sub 2}) (4b), respectively. The molecular structure of 4b has been determined by X-ray crystallography. There is no reaction on photolysis of 1a and 1b with 3,5-diphenylpyrazole. (orig.)

  1. Synthesis of fatty trichloromethyl-{beta}-diketones and new 1H-Pyrazoles as unusual FAMEs and FAEEs

    Energy Technology Data Exchange (ETDEWEB)

    Flores, Alex F.C.; Souto, Alynne A.; Malavolta, Juliana L.; Flores, Darlene C., E-mail: alex.fcf@ufsm.br [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Departamento de Quimica; Blanco, Rogerio F. [Uniao de Ensino do Sudoeste do Parana (UNISEP), Dois Vizinhos, PR (Brazil). Faculdade de Farmacia

    2013-12-01

    The efficient synthesis of new fatty 1,1,1-trichloro-4-methoxy-3-alken-2-ones [Cl{sub 3}CC(O)C(R{sup 2})=C(R{sup 1})OMe, where R{sup 1} = n-hexyl, heptyl, nonyl, undecyl, tridecyl and R{sup 2} = H] and 1,1,1-trichloro-2,4-alkanediones [Cl{sub 3}CC(O)CHR{sup 2}C(O)R{sup 1}, where R{sup 1} = n-pentyl and R{sup 2} = Me, R{sup 1} = Et and R{sup 2} = n-butyl, R{sup 1} = n-butyl and R{sup 2} = n-propyl] in good yields (85-95%) from acetal acylation with trichloroacetyl chloride is reported. The fatty 1,1,1-trichloro-4-methoxy-3-alken-2-ones and 1,1,1-trichloro-2,4-alkanediones were reacted with hydrazine hydrochloride, leading to respective {sup 1}H-pyrazole-5-carboxylates, unusual class of fatty acid methyl (FAMEs) and ethyl (FAEEs) esters. Their structures were confirmed by elemental analysis and {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR). The fatty 1,1,1-trichloro-4-methoxy-3-alken-2-ones and {sup 1}H-pyrazole derivatives are new oleochemicals with potentially interesting and differential properties. (author)

  2. Polybenzimidazole compounds

    Science.gov (United States)

    Klaehn, John R.; Peterson, Eric S.; Wertsching, Alan K.; Orme, Christopher J.; Luther, Thomas A.; Jones, Michael G.

    2010-08-10

    A PBI compound that includes imidazole nitrogens, at least a portion of which are substituted with an organic-inorganic hybrid moiety. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2--, where R is selected from among methyl, phenyl, vinyl, and allyl. The PBI compound may exhibit similar thermal properties in comparison to the unsubstituted PBI. The PBI compound may exhibit a solubility in an organic solvent greater than the solubility of the unsubstituted PBI. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may occur at about room temperature and/or at about atmospheric pressure. Substituting may use at least five equivalents in relation to the imidazole nitrogens to be substituted or, preferably, about fifteen equivalents.

  3. Synthesis a nd Antifu nga l Activity of N-(1,4-Substitued-pyrazole-yl)-heterocyclic Carboxamide Derivatives%N-(1,4-二取代吡唑基)-杂环酰胺类化合物的合成及抗植病真菌生物活性

    Institute of Scientific and Technical Information of China (English)

    吴志兵; 何雪峰; 蔡桦; 邝继清; 薛伟

    2013-01-01

    [目的]吡唑类化合物是一类具有广泛生物活性的化合物,为了寻找到高活性的杂环酰胺类化合物,对此类化合物做迸一步研究.[方法]设计合成了12个N-(1,4-取代吡唑基)-吡啶酰胺类化合物;采用生长速率法,测试了化合物对小麦赤霉病菌(Gibberella zeae)、辣椒枯萎病菌(Fusarium oxysporum)和苹果腐烂病菌(Cytospora mandshurica)的抑制活性.[结果]初步生物活性表明:目标化合物在50 mg/L质量浓度下对小麦赤霉病菌、辣椒枯萎病菌和苹果腐烂病菌有一定的抑制作用,其中化合物9j对小麦赤霉病菌的抑制率达71.0%,化合物91对苹果腐烂病菌的抑制率达55.7%,具有进一步研究的价值.%[Aims] Pyrazole derivates was a kind of compounds with high and broad-spectrum activity. In order to find heterocyclic carboxamide derivatives with high activity, and this kind of compounds were further studied. [Methods] A series of JV-(l,4-disubstituted pyrazole-yl)-heterocyclic carboxamide derivatives were synthesized. All target compounds were bioassayed in vitro against three kinds of phytopathogenic fungi(G/bbere//a zeae, Fusarium oxysporum, Cytospora mandshurica). [Results] The preliminary results indicated most of the synthesized compounds possessed some antifungal activity against these three tested fungus at 50 mg/L, among which compounds 9j displayed 71.0% inhibition activities against G. zeae at 50 mg/L, and compounds 91 displayed 55.7% inhibition activities against C. mandshurica at 50 mg/L. The molecule structures of the target compounds could be optimized based on the designed compounds.

  4. Synthesis of New Pyrazolo[1,5-a]pyrimidine, Triazolo[4,3-a]pyrimidine Derivatives, and Thieno[2,3-b]pyridine Derivatives from Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl-3-oxoprop-1-en-1-olate

    Directory of Open Access Journals (Sweden)

    Abdou O. Abdelhamid

    2013-01-01

    Full Text Available Condensation of sodium 3-oxo-3-(1-phenyl-1H-pyrazol-4-ylprop-1-en-1-olate (2 with several heterocyclic amines, cyanoacetamide, cyanothioacetamide, and 2-cyanoacetohydrazide gives pyrazolo[1,5-a]pyrimidines (5a–d, pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9, benzo[4,5]imidazo[1,2-a]pyrimidine (10, [1,2,4]triazolo[1,5-a]pyrimidine (11, and pyridine derivatives (12–14. Also, thieno[2,3-b]pyridines (15–18 were synthesized via pyridinethione (13 with α-halo ketones and α-halo ester. Structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, alternative synthetic routes, and chemical transformation whenever possible.

  5. Crystal structure of poly[{μ3-(E-3-[3-(carboxylatomethoxyphenyl]acrylato-κ3O,O′:O′′:O′′′}[μ2-3-(pyridin-4-yl-1H-pyrazole-κ2N:N′]cobalt(II

    Directory of Open Access Journals (Sweden)

    Can Zhao

    2016-10-01

    Full Text Available The title compound, [Co(C11H8O5(C8H7N3]n, which is based on (E-3-[3-(carboxymethoxyphenyl]acrylic acid (H2L and 3-(pyridin-4-ylpyrazole (pp ligands, has been synthesized under solvothermal conditions. The dihedral angle between pyrazole and pyridine rings in the pp ligands is 23.1 (2°. In the crystal, helical chains formed by pp and L ligands connected to the CoII atom propagate parallel to the c axis. CoII atoms of adjacent chains are bridged by the acrylic acid groups of L ligands into corrugated polymeric sheets in the ac plane.

  6. Crystal structure of 6-amino-4-(3-bromo-4-meth-oxy-phen-yl)-3-methyl-2,4-di-hydro-pyrano[2,3-c]pyrazole-5-carbo-nitrile dimethyl sulfoxide monosolvate.

    Science.gov (United States)

    Yousuf, Sammer; Bano, Huma; Muhammad, Munira Taj; Khan, Khalid Mohammed

    2015-07-01

    In the pyrazole mol-ecule of the title solvate, C15H13BrN4O2·C2H6OS, the dihedral angle between the benzene ring and the mean plane of the di-hydro-pyrano[2,3-c]pyrazole ring system [r.m.s deviation = 0.031 (2) Å] is 86.71 (14)°. In the crystal, the pyrazole mol-ecules are linked by N-H⋯N hydrogen bonds, forming a layer parallel to (10-1). The pyrazole and dimethyl sulfoxide mol-ecules are connected by an N-H⋯O hydrogen bond.

  7. Assignment of the electronic states of pyrazole by ab initio multi-reference configuration interaction calculations

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, Michael H.; Guest, Martyn F

    2003-07-01

    The gas-phase VUV absorption spectrum of pyrazole, which we reported recently, has been further assigned in the light of multi-reference multi-root CI calculations, using basis sets of varying size up to quadruple zeta quality, and containing both valence and Rydberg type functions. A very intense VUV band centred near 7.8 eV appears to arise from the summation of three calculated bands of {pi}{pi}* character, of which the first and third are the most intense. The window resonance near the band maximum is ascribed to mutual annihilation of a Rydberg state and valence state, and a probable assignment is discussed. The electron energy loss (EEL) spectrum also obtained previously, showed low-lying triplet states at about 3.9 and 5.1 eV, respectively; the present computations suggest that two triplet ({sup 3}{pi}{pi}*) states lie within the 3.9 eV band, and identifies the species involved. The assignment of the UV-photoelectron spectrum has been reconsidered, but the identity of the first three IPs as {pi}{sub 3}<{pi}{sub 2}

  8. Orthogonal non-covalent binding forces in solid state supramolecular herringbone-shaped "interlocked dimers". Pseudopolymorphism in [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) complex.

    Science.gov (United States)

    Pérez, José; Espinosa, Arturo; Galiana, J Miguel; Pérez, Eduardo; Serrano, J Luis; Aranda, Miguel A G; Insausti, Maite

    2009-11-21

    The crystal structures of [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) (1) and two different solvatomorphs of it, [(ppy)Pd(mu-pz)](2) x 1/2 CH(2)Cl(2) (2) and [(ppy)Pd(mu-pz)](2) x 1/2 CHCl(3) (3) have been elucidated by powder (1 and 2) and single crystal (3) X-ray diffraction. In all of them two molecules fit together following a very similar pattern forming a "dimer". All neutral dinuclear square-planar complexes having mu-pz or related bridges and planar aromatic ligands completing the coordination spheres found in the CSD show a similar arrangement to those observed in compounds 1-3, consisting of "interlocked dimers" following a herringbone-like pattern. A DFT study reveals the simultaneous action of pi,pi- and T-stacking interactions occurring as two sets of orthogonally oriented binding forces, as well as anagostic bonds overlapped with the latter.

  9. Construction of Polynuclear Lanthanide (Ln = Dy(III), Tb(III), and Nd(III)) Cage Complexes Using Pyridine-Pyrazole-Based Ligands: Versatile Molecular Topologies and SMM Behavior.

    Science.gov (United States)

    Bala, Sukhen; Sen Bishwas, Mousumi; Pramanik, Bhaskar; Khanra, Sumit; Fromm, Katharina M; Poddar, Pankaj; Mondal, Raju

    2015-09-08

    Employment of two different pyridyl-pyrazolyl-based ligands afforded three octanuclear lanthanide(III) (Ln = Dy, Tb) cage compounds and one hexanuclear neodymium(III) coordination cage, exhibiting versatile molecular architectures including a butterfly core. Relatively less common semirigid pyridyl-pyrazolyl-based asymmetric ligand systems show an interesting trend of forming polynuclear lanthanide cage complexes with different coordination environments around the metal centers. It is noteworthy here that construction of lanthanide complex itself is a challenging task in a ligand system as soft N-donor rich as pyridyl-pyrazol. We report herein some lanthanide complexes using ligand containing only one or two O-donors compare to five N-coordinating sites. The resultant multinuclear lanthanide complexes show interesting magnetic and spectroscopic features originating from different spatial arrangements of the metal ions. Alternating current (ac) susceptibility measurements of the two dysprosium complexes display frequency- and temperature-dependent out-of-phase signals in zero and 0.5 T direct current field, a typical characteristic feature of single-molecule magnet (SMM) behavior, indicating different energy reversal barriers due to different molecular topologies. Another aspect of this work is the occurrence of the not-so-common SMM behavior of the terbium complex, further confirmed by ac susceptibility measurement.

  10. Synthesis, spectral characterization and biological evaluation of Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes with thiosemicarbazone ending by pyrazole and pyridyl rings

    Science.gov (United States)

    Yousef, T. A.; Abu El-Reash, G. M.; Al-Jahdali, M.; El-Rakhawy, El-Bastawesy R.

    2014-08-01

    Here we present the synthesis of the new Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes with chelating ligand (Z)-(2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene) hydrazinyl)(pyridin-2-ylamino)methanethiol. All the complexes were characterized by elemental analysis, IR, 1H NMR, UV-vis, magnetic susceptibility measurements and EPR spectral studies. IR spectra of complexes showed that the ligand behaves as NN neutral bidentate, NSN mononegative tridentate and NSNN mononegative tetradentate. The electronic spectra and the magnetic measurements suggested the octahedral geometry for all complexes as well as the EPR confirmed the tetragonal distorted octahedral for Cu(II) complex. Cd(II) complex showed the highest inhibitory antioxidant activity either using ABTS method. The SOD-like activity exhibited those Cd(II) and Zn(II) complexes have strong antioxidative properties. We tested the synthesized compounds for antitumor activity and showed that the ability to kill liver (HePG2) and breast (MCF-7) cancer cells definitely.

  11. Multipurpose Compound

    Science.gov (United States)

    1983-01-01

    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  12. Flowing atmospheric pressure afterglow combined with laser ablation for direct analysis of compounds separated by thin-layer chromatography.

    Science.gov (United States)

    Cegłowski, Michał; Smoluch, Marek; Reszke, Edward; Silberring, Jerzy; Schroeder, Grzegorz

    2016-01-01

    A thin-layer chromatography-mass spectrometry (TLC-MS) setup for characterization of low molecular weight compounds separated on standard TLC plates has been constructed. This new approach successfully combines TLC separation, laser ablation, and ionization using flowing atmospheric pressure afterglow (FAPA) source. For the laser ablation, a low-priced 445-nm continuous-wave diode laser pointer, with a power of 1 W, was used. The combination of the simple, low-budget laser pointer and the FAPA ion source has made this experimental arrangement broadly available, also for small laboratories. The approach was successfully applied for the characterization of low molecular weight compounds separated on TLC plates, such as a mixture of pyrazole derivatives, alkaloids (nicotine and sparteine), and an extract from a drug tablet consisting of paracetamol, propyphenazone, and caffeine. The laser pointer used was capable of ablating organic compounds without the need of application of any additional substances (matrices, staining, etc.) on the TLC spots. The detection limit of the proposed method was estimated to be 35 ng/cm(2) of a pyrazole derivative.

  13. Expression of CYP2A3 mRNA and its regulation by 3-methylcholanthrene, pyrazole, and ß-ionone in rat tissues

    Directory of Open Access Journals (Sweden)

    A.B. Robottom-Ferreira

    2003-07-01

    Full Text Available Cytochrome P450 (CYP 2A enzymes are involved in the metabolism of numerous drugs and hormones and activate different carcinogens. Human CYP2A6, mouse CYP2A5 and rat CYP2A3 are orthologous enzymes that present high similarity in their amino acid sequence and share substrate specificities. However, different from the human and mouse enzyme, CYP2A3 is not expressed in the rat liver. There are limited data about expression of CYP2A3 in extrahepatic tissues and its regulation by typical CYP inducers. Therefore, the objective of the present study was to analyze CYP2A3 mRNA expression in different rat tissues by RT-PCR, and to study the influence of 3-methylcholanthrene, pyrazole and ß-ionone treatment on its expression. Male Wistar rats were divided into four groups of 5 rats each, and were treated ip for 4 days with 3-methylcholanthrene (25 mg/kg body weight, pyrazole (150 mg/kg body weight, ß-ionone (1 g/kg body weight, or vehicle. Total RNA was extracted from tissues and CYP2A3 mRNA levels were analyzed by semiquantitative RT-PCR. CYP2A3 mRNA was constitutively expressed in the esophagus, lung and nasal epithelium, but not along the intestine, liver, or kidney. CYP2A3 mRNA levels were increased in the esophagus by treatment with 3-methylcholanthrene and pyrazole (17- and 7-fold, respectively, in lung by pyrazole and ß-ionone (3- and 4-fold, respectively, although not statistically significant, in the distal part of the intestine and kidney by 3-methylcholanthrene and pyrazole, and in the proximal part of the intestine by pyrazole. CYP2A3 mRNA was not induced in nasal epithelium, liver or in the middle part of the intestine. These data show that, in the rat, CYP2A3 is constitutively expressed in several extrahepatic tissues and its regulation occurs through a complex mechanism that is essentially tissue specific.

  14. 新型含吡啶环取代的吡唑肟醚类化合物的合成及生物活性研究%Synthesis and Biological Activities of Novel Pyrazole Oxime Ether Derivatives Containing Pyridyl Ring

    Institute of Scientific and Technical Information of China (English)

    戴红; 刘建兵; 苗文科; 吴珊珊; 秦雪; 张欣; 王婷婷; 方建新

    2011-01-01

    为了寻找新型高效低毒的农药先导化合物,通过N-吡啶基吡唑肟与2-氯-5-氯甲基吡啶的缩合反应,合成了一系列含吡啶环取代的吡唑肟醚类化合物.目标化合物的结构均经1H NMR,13C NMR和元素分析确证.初步生物活性试验结果表明,部分化合物具有一定的杀菌、杀虫和植物生长调节活性.如化合物5e在浓度为50 μtg/mL时对番茄早疫的抑制率为61.4%;化合物5j在浓度为50 μg/mL时对花生褐斑的抑制率为60.2%;化合物5i在浓度为500 μg/mL时对蚜虫表现出50.3%的杀死率;化合物5f在浓度为10 μg/mL时对黄瓜子叶生根表现出71.0%的促进生长作用.%In search of new low toxicity and potent pesticide lead compounds, a series of novel pyrazole oxime ether derivatives containing a pyridyl ring were synthesized by the condensation of iV-pyridyl pyrazole oximes with 2-chloro-5-chloromethyl pyridine. Their structures were determined by 1H NMR, 13C NMR spectra and elemental analysis. Preliminary bioassay showed that some of the target compounds displayed fungicidal, insecticidal, and plant growth regulatory activities to some extent. For example, compound 5c exhibited 61.4% inhibition rate against Alternaria solani at the concentration of 50 ug/mL, compound 5j showed 60.2% inhibition rate against Cercospora arachidicola at the concentration of 50 ug/mL, the mortality rate of compound 5i was 50.3% against Aphis craccivora at the concentration of 500 ug/mL, and compound 5f displayed 71.0% promotion effect on the radicle growth of cucumber cotyledons at the concentration of 10 ug/mL.

  15. Synthesis, structure characterization and antimicrobial evaluation of 4-(substituted phenylazo)-3,5-diacetamido-1H-pyrazoles.

    Science.gov (United States)

    Kinali-Demirci, Selin; Demirci, Serkan; Kurt, Mustafa

    2013-04-01

    The present article deals with the synthesis, spectral characterization and antimicrobial activity of phenylazo dyes. All of the synthesized phenylazo dyes were characterized using ATR-FTIR, FT-Raman, (1)H NMR, (13)C NMR, elemental analysis and mass spectroscopic techniques. Solvent effects on the UV-Vis absorption spectra of these phenylazo dyes were studied. Acid and base effects on the visible absorption maxima of the phenylazo dyes were also reported. The structural and spectroscopic analysis of the molecules were carried out using Density Functional Theory (DFT) employing the standard 6-31G(d) basis set, and the optimized geometries and calculated vibrational frequencies were evaluated via comparison with experimental values. The antimicrobial activity of 4-(substituted phenylazo)-3,5-diacetamido-1H-pyrazoles was reported against bacteria, including B. cereus (RSKK 863), S. aureus (ATCC 259231), M. luteus (NRRL B-4375), E. coli (ATCC 11230) and the yeast C. albicans (ATCC 10239).

  16. Diaqua-(5-methyl-1H-pyrazole-3-carboxyl-ato)(4-nitro-benzoato)copper(II).

    Science.gov (United States)

    Hu, Fei-Long; Yin, Xian-Hong; Feng, Yu; Mi, Yan; Zhang, Shan-Shan

    2009-01-23

    In the title complex, [Cu(C(7)H(4)NO(4))(C(5)H(5)N(2)O(2))(H(2)O)(2)], the Cu(II) ion is coordinated in a slightly distorted square-pyramidal enviroment. The basal plane is formed by an N atom and an O atom from a 5-methyl-1H-pyrazole-3-carboxyl-ate ligand and by two O atoms from two water ligands. The apical position is occupied by a carboxylate O atom from a 4-nitro-benzoate ligand. In the crystal structure, inter-molecular O-H⋯O and N-H⋯O hydrogen bonds link complex moleclues, forming extended chains parallel to the a axis.

  17. Synthesis and biological evaluation of dihydropyrano-[2,3-c]pyrazoles as a new class of PPARγ partial agonists.

    Science.gov (United States)

    Qvortrup, Katrine; Jensen, Jakob F; Sørensen, Mikael S; Kouskoumvekaki, Irene; Petersen, Rasmus K; Taboureau, Olivier; Kristiansen, Karsten; Nielsen, Thomas E

    2017-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a well-known target for thiazolidinedione antidiabetic drugs. In this paper, we present the synthesis and biological evaluation of a series of dihydropyrano[2,3-c]pyrazole derivatives as a novel family of PPARγ partial agonists. Two analogues were found to display high affinity for PPARγ with potencies in the micro molar range. Both of these hits were selective against PPARγ, since no activity was measured when tested against PPARα, PPARδ and RXRα. In addition, a novel modelling approach based on multiple individual flexible alignments was developed for the identification of ligand binding interactions in PPARγ. In combination with cell-based transactivation experiments, the flexible alignment model provides an excellent analytical tool to evaluate and visualize the effect of ligand chemical structure with respect to receptor binding mode and biological activity.

  18. Synthesis and Characterization of a New Conjugated Polymer Bearing Pyrazole and Thiophene Moieties as Potent NLO Material

    Science.gov (United States)

    Vishnumurthy, K. A.; Adhikari, A. Vasudeva; Sunitha, M. S.; Philip, Reji

    2011-10-01

    In this communication we describe the design and synthesis of a new conjugated polymer (P) carrying 3,4-dialkoxythiophene, 1,3,4 oxadiazole and pyrazole units, from its monomers through condensation polymerization method. The structure of newly synthesized polymer was established by FT-IR, 1H NMR, elemental analysis and gel permeation chromatographic techniques. Further, its electrochemical, linear and nonlinear optical properties of the polymer have been investigated. The optical and electrochemical band gap was found to be 2.39 eV. Z-scan results reveal that the polymer exhibits strong optical limiting behavior due to effective three-photon absorption (3PA). The value of 3PA coefficient was found to be 1.1×10-20 m3/W2, which is comparable to that of good optical limiting materials. The fluorescence quantum yield of the polymer in solution was determined using quinine sulfate as standard and it was found to be 42%.

  19. Organically modified silica with pyrazole-3-carbaldehyde as a new sorbent for solid-liquid extraction of heavy metals.

    Science.gov (United States)

    Radi, Smaail; Tighadouini, Said; Bacquet, Maryse; Degoutin, Stéphanie; Cazier, Francine; Zaghrioui, Mustapha; Mabkhot, Yahia N

    2013-12-24

    A new chelating matrix, SiNP, has been prepared by immobilizing 1.5-dimethyl-1H-pyrazole-3-carbaldehyde on silica gel modified with 3-aminopropyl-trimethoxysilane. This new chelating material was well characterized by elemental analysis, FT-IR spectroscopy, cross polarization magic angle spinning solid state 13C-NMR, nitrogen adsorption-desorption isotherm, BET surface area, BJH pore size, and scanning electron microscopy (SEM). The new product exhibits good chemical and thermal stability as determined by thermogravimetry curves (TGA). The new prepared material was used as an adsorbent for the solid-phase extraction (SPE) of Pb(II), Cd(II), Cu(II) and Zn(II) from aqueous solutions using a batch method, prior to their determination by flame atomic adsorption spectrometry. The adsorption capacity was investigated using kinetics and pH effects. Common coexisting ions did not interfere with separation and determination.

  20. Stereoselective formation and catalytic activity of hydrido(acylphosphane)(chlorido)(pyrazole)rhodium(III) complexes. Experimental and DFT studies.

    Science.gov (United States)

    San Nacianceno, Virginia; Azpeitia, Susan; Ibarlucea, Lourdes; Mendicute-Fierro, Claudio; Rodríguez-Diéguez, Antonio; Seco, José M; San Sebastian, Eider; Garralda, María A

    2015-08-07

    The reaction of [{RhCl(COD)}2] (COD = 1,5-cyclooctadiene) with L = pyrazole (Hpz), 3(5)-methylpyrazole (Hmpz) or 3,5-dimethylpyrazole (Hdmpz) and PPh2(o-C6H4CHO) (Rh : L : P = 1 : 2 : 1) gives hydridoacyl complexes [RhHCl{PPh2(o-C6H4CO)}(L)2] (). Stereoselective formation of and with pyrazoles trans to hydrido and phosphorus and hydrogen bond formation with O-acyl and chlorido occur. is a mixture of two linkage isomers in a 9 : 1 ratio, with two 5-methylpyrazole ligands or with one 3- and one 5-methylpyrazole ligand, respectively. Fluxional undergoes metallotropic tautomerization and is a mixture of equal amounts of and , with hydrido trans to pyrazole or chlorido, respectively. Complexes readily exchange hydrido by chlorido to afford [RhCl2{PPh2(o-C6H4CO)}(L)2] (, and ) as single isomers with cis chloridos and two N-HCl hydrogen bonds. The reaction of with PPh3 or PPh2OH affords static [RhHCl{PPh2(o-C6H4CO)}(PPh3)L] () or [RhHCl{PPh2(o-C6H4CO)}(PPh2OH)L] () respectively with trans P-atoms and pyrazoles forming N-HCl hydrogen bonds. and contain single species with hydrido cis to chlorido, while is a mixture of equal amounts of and . Complexes , with an additional O-HO hydrogen bond, selectively contain only the cis-H,Cl species with all the three ligands. The reaction of [{RhCl(COD)}2] with L and PPh2(o-C6H4CHO) (Rh : L : P = 1 : 1 : 2) led to complexes with trans P-atoms, [RhHCl{PPh2(o-C6H4CO)}{PPh2(o-C6H4CHO)-κP}L] (, and ), at room temperature, and to [RhCl{PPh2(o-C6H4CO)}{PPh2(o-C6H4CHOH)}(Hmpz)] () or [RhCl{PPh2(o-C6H4CO)}2L] () with hydrogen evolution in refluxing benzene. DFT calculations were used to predict the correct isomers, their ratios and the particular intramolecular hydrogen bonds in these complexes. Single crystal X-ray diffraction analysis was performed on , and . Complexes are efficient homogeneous catalysts (0.5 mol% loading) in the hydrolysis of amine- or ammonia-borane (AB) to generate up to 3 equivalents