Sample records for benzothiadiazines

  1. A Palladium-Catalyzed Method for the Synthesis of 2-(α-Styryl)-2,3-dihydroquinazolin-4-ones and 3-(α-Styryl)-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide: Access to 2-(α-Styryl)quinazolin-4(3H)-ones and 3-(α-Styryl)-1,2,4-benzothiadiazine-1,1-dioxides. (United States)

    Kundu, Priyanka; Mondal, Amrita; Chowdhury, Chinmay


    An efficient synthesis of 2-(α-styryl)-2,3-dihydroquinazolin-4-ones and 3-(α-styryl)-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides has been achieved in 39-94% yield through palladium-catalyzed cyclocondensation of aryl/vinyl iodides with allenamides 13-15 and 22, respectively. Base treatment of the N-tosylated products provides an easy access to 2-(α-styryl)quinazolin-4(3H)-ones and 3-(α-styryl)-1,2,4-benzothiadiazine-1,1-dioxides, hitherto unknown heterocycles. The method has been tested with phenyl substituted allenamides, applied for bis-heteroannulation, and used in the preparation of analogues of the natural product Luotonin F. PMID:27454621

  2. Low-valent titanium induced reductive cyclization of nitro com pounds and aliphatic ketones: facile synthesis of 3, 4-dihydro ( 2 H ) - 1,2,4- benzothiadiazine- 1,1-dioxides

    Institute of Scientific and Technical Information of China (English)

    ZHONG, Wei-Hui; CHEN, Xiao-Yuan; ZHANG, Yong-Min


    The intermolecular reductivc cyclization of o-nitrobenzene sulfonamides with aliphafic ketones induced by TiCl4/Sm sys tem was studied and a series of 3,3-disubstituted-3,4-dihydro (2H)-1, 2, 4-benzothiadiazine-1, 1-dioxides were synthesized in moderate to high yields under mild and neutral conditions.

  3. Synthesis, pharmacological and structural characterization, and thermodynamic aspects of GluA2-positive allosteric modulators with a 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide scaffold

    DEFF Research Database (Denmark)

    Nørholm, Ann-Beth; Francotte, Pierre; Olsen, Lars;


    Positive allosteric modulators of ionotropic glutamate receptors are potential compounds for treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind within the dimer interface of the ligand-binding domain (LBD) and stabilize the agonist-bound conformation, thereby slowing...

  4. Complexes With Biologically Active Ligands. Part 4. Coordination Compounds of Chlorothiazide With Transition Metal Ions Behave as Strong Carbonic Anhydrase Inhibitors


    Supuran, Claudiu T.


    Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl- 1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of carbonic anhydrase (CA).

  5. Positive Allosteric Modulators of 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors Belonging to 4-Cyclopropyl-3,4-dihydro-2H-1,2,4-pyridothiadiazine Dioxides and Diversely Chloro-Substituted 4-Cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides

    DEFF Research Database (Denmark)

    Francotte, Pierre; Nørholm, Ann-Beth; Deva, Taru;


    Two 4-ethyl-substituted pyridothiadiazine dioxides belonging to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators were cocrystallized with the GluA2 ligand binding domain in order to decipher the impact of the position of the nitrogen atom on thei...

  6. [The inhibition of prostaglandin induced uterine contractions by diazoxide in vitro (author's transl)]. (United States)

    Schneider-Affeld, F; Rüttgers, H; Hter, J; Kubli, F


    The tocolytic efficiency of Diazoxide, a benzothiadiazine derivative with pronounced musculotropic action, was tested on the isolated uteri of non-gravid and gravid rats. Regular uterine contractions were induced by the prostaglandines E2 and F2 alpha. Their amplitude and frequency could be suppressed totally or subtotally. Contraction intervals lasted 4--22 min. The basal tone was reduced in most cases.

  7. Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2

    DEFF Research Database (Denmark)

    Krintel, Christian; Francotte, Pierre; Pickering, Darryl S;


    The 1,2,4-benzothiadiazine 1,1-dioxide type of positive allosteric modulators of the ionotropic glutamate receptor A2 (GluA2) are promising lead compounds for the treatment of cognitive disorders, e.g., Alzheimer’s disease. The modulators bind in a cleft formed by the interface of two neighboring...


    To elucidate the binding mechanism of the herbicide bentazon (3-isopropyl-1H-2,1,3-benzothiadiazine-4(3H)-one 2,2-dioxide) with humic monomers in the presence of an oxidative enzyme, the reaction of bentazon with catechol, caffeic acid, protocatechuic...

  9. Interactions of acidic herbicides bentazon and dicamba with organoclays


    Carrizosa, M. J.; Koskinen, W. C.; Hermosín, M. C.


    We determined the sorption mechanism of the acidic herbicides bentazon [3-(1-methylethyl)-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide] and dicamba (3,6-dichloro-2-methoxybenzoic acid) on two organoclays, octadecylammonium (ODA)- and hexadecyltrimethylammonium (HDTMA)-exchanged Arizona montmorillonite (SAz-1), as part of a study to determine their potential use assorbent materials for ionizable organic pollutants. To determine the mechanisms involved in the sorption process, herbicide-organ...

  10. Use of organosmectites to reduce leaching losses of acidic herbicides


    Carrizosa, M. J.; Hermosín, M. C.; Koskinen, W. C.; Cornejo, J.


    The modification of smectitic clays with organic cations via cation-exchange reactions produces sorbents with an increased sorption capacity for organic compounds such as acidic herbicides. These organoclays (OCIs) could be used as carriers in controlled release formulations of herbicides to decrease their contamination potential. Various OCIs and two acidic herbicides (bentazone [3-isopropyl-1H-2,1,3-benzothiadiazin-4 (3H) one 2,2-dioxide] and dicamba [2-methoxy-3,6-dichlorobenzoic acid]) we...

  11. Polythiazide


    Thomas Gelbrich; Mairi F. Haddow; Griesser, Ulrich J.


    The crystal structure of the title compound, C11H13ClF3N3O4S3 (systematic name: 6-chloro-2-methyl-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; CRN: 346–18–9), exhibits a two-dimensional network of hydrogen-bonded molecules parallel to (overline{1}01). The NH and NH2 groups act as donor sites and the sulfonyl O atoms as acceptor sites in N—H...O hydrogen bonds, and a C—H...O interaction also ...

  12. 7-Chloro-5-(furan-3-yl)-3-methyl-4H-benzo[e][1,2,4]thiadiazine 1,1-Dioxide as Positive Allosteric Modulator of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor. The End of the Unsaturated-Inactive Paradigm? (United States)

    Citti, Cinzia; Battisti, Umberto M; Cannazza, Giuseppe; Jozwiak, Krzysztof; Stasiak, Natalia; Puja, Giulia; Ravazzini, Federica; Ciccarella, Giuseppe; Braghiroli, Daniela; Parenti, Carlo; Troisi, Luigino; Zoli, Michele


    5-Arylbenzothiadiazine type compounds acting as positive allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-PAMs) have received particular attention in the past decade for their nootropic activity and lack of the excitotoxic side effects of direct agonists. Recently, our research group has published the synthesis and biological activity of 7-chloro-5-(3-furanyl)-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (1), one of the most active benzothiadiazine-derived AMPA-PAMs in vitro to date. However, 1 exists as two stereolabile enantiomers, which rapidly racemize in physiological conditions, and only one isomer is responsible for the pharmacological activity. In the present work, experiments carried out with rat liver microsomes show that 1 is converted by hepatic cytochrome P450 to the corresponding unsaturated derivative 2 and to the corresponding pharmacologically inactive benzenesulfonamide 3. Surprisingly, patch-clamp experiments reveal that 2 displays an activity comparable to that of the parent compound. Molecular modeling studies were performed to rationalize these results. Furthermore, mice cerebral microdialysis studies suggest that 2 is able to cross the blood-brain barrier and increases acetylcholine and serotonin levels in the hippocampus. The experimental data disclose that the achiral hepatic metabolite 2 possesses the same pharmacological activity of its parent compound 1 but with an enhanced chemical and stereochemical stability, as well as an improved pharmacokinetic profile compared with 1. PMID:26580317

  13. Adsorption of pesticides onto quartz, calcite, kaolinite, and α-alumina

    DEFF Research Database (Denmark)

    Clausen, Liselotte; Fabricius, Ida Lykke; Madsen, L.


    The fate of pesticides in aquifers is influenced by the small but not insignificant adsorption of pesticides to mineral surfaces. Batch experiments with five pesticides and four minerals were conducted to quantify the contributions to adsorption from different mineral surfaces and compare...... adsorption characteristics of selected pesticides. Investigated mineral phases included quartz, calcite, kaolinite, and alpha -alumina. Selected pesticides comprised atrazine (6-chloro-N-2-ethyl-N-4-isopropyl-1,3,5-triazine-2,4-diamine isoproturon [3-(4-isopropyl-phenyl)-1,1-dimethylurea)], mecoprop [(RS)-2......-(4-chloro-2-methyl phenoxy)propionic acid], 2,4-D (2,4-dichlorophenoxyacetic acid), and bentazone [3-isopropyl-1H-2,1,3-benzothiadiazin-4-(3H)-one 2,2-dioxide]. Specific surface area and mineral surface charge proved to be important for the adsorption of these pesticides. Detectable adsorption...

  14. Polythiazide

    Directory of Open Access Journals (Sweden)

    Thomas Gelbrich


    Full Text Available The crystal structure of the title compound, C11H13ClF3N3O4S3 (systematic name: 6-chloro-2-methyl-3-{[(2,2,2-trifluoroethylsulfanyl]methyl}-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; CRN: 346–18–9, exhibits a two-dimensional network of hydrogen-bonded molecules parallel to (overline{1}01. The NH and NH2 groups act as donor sites and the sulfonyl O atoms as acceptor sites in N—H...O hydrogen bonds, and a C—H...O interaction also occurs. The thiadiazine ring adopts an envelope conformation with the N atom bonded to sulfur at the tip of the flap, and the methyl substituent is in an axial position.

  15. Modeling the THz spectrum of the bentazon

    Institute of Scientific and Technical Information of China (English)

    Huali Wang; Qiang Wang


    Bentazon, with chemical name 3-isopropyl-lH-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide,is a colorless to slightly brown,odorless crystalline solid.Bentazon is one of the synthetic,contact,and post-emergence herbicide used for selective control of broadleaf weeds and sedges in numerous crop fields.%Terahertz (THz) spectra of bentazon are determined within the range of 0.3-2.4 THz at room temperar ture. Density functional methods are used to compute the THz spectra using three different programs: GaussianO3 for isolated-molecule form, DMol3 and CRYSTAL09 for solid-state forms. Among the three, the computed THz spectrum of CRYSTAL09 shows better bond length and angle agreements with X-ray experimental results, and corresponds with observed THz experiment spectral characteristics. The isolated-molecule vibrational mode values are less by half than those derived from solid-state calculations. The last five peak positions of the two solid-state computations coincide with each other. Moreover, all the experimental THz absorption peaks are assigned by utilizing CRYSTAL09.

  16. Degradation of Herbicides Atrazine and Bentazone Applied Alone and in Combination in Soils

    Institute of Scientific and Technical Information of China (English)

    LI Ke-Bin; CHENG Jing-Tao; WANG Xiao-Fang; ZHOU Ying; LIU Wei-Ping


    The application of a mixture of bentazone (3-isopropyl-lH-2,1,3-benzothiadiazin-4(3H)-one-2,2-dioxide) and atrazine (6-chloro-N2-ethyl-N4-isopropy1-1,3,5-triazine-2,4-diamine) is a practical approach to enhance the herbicidal effect.Labo-ratory incubation experiments were performed to study the degradation of bentazone and atrazine applied in combination and individually in maize rhizosphere and non-rhizosphere soils.After a lag phase,the degradation of each individual herbicide in the non-autoclaved soil could be adequately described using a first-order kinetic equation.During a 30-d in-cubation,in the autoclaved rhizosphere soil,bentazone and atrazine did not noticeably degrade,but in the non-autoclaved soil,they rapidly degraded in both non-rhizosphere and rhizosphere soils with half-lives of 19.9 and 20.2 d for bentazone and 29.1 and 25.7 d for atrazine,respectively.The rhizosphere effect significantly enhanced the degradation of atrazine,but had no significant effect on bentazone.These results indicated that biological degradation accounted for the degrada-tion of both herbicides in the soil.When compared with the degradation of the herbicide applied alone,the degradation rates of the herbicides applied in combination in the soils were lower and the lag phase increased.With the addition of a surfactant,Tween-20,a reduced lag phase of degradation was observed for both herbicides applied in combination.The degradation rate of bentazone accelerated,whereas that of atrazine remained nearly unchanged.Thus,when these two herbicides were used simultaneously,their persistence in the soil was generally prolonged,and the environmental contamination potential increased.

  17. "Heart-cut" bidimensional achiral-chiral liquid chromatography applied to the evaluation of stereoselective metabolism, in vivo biological activity and brain response to chiral drug candidates targeting the central nervous system. (United States)

    Battisti, Umberto M; Citti, Cinzia; Larini, Martina; Ciccarella, Giuseppe; Stasiak, Natalia; Troisi, Luigino; Braghiroli, Daniela; Parenti, Carlo; Zoli, Michele; Cannazza, Giuseppe


    A "heart-cut" two-dimensional achiral-chiral liquid chromatography triple-quadrupole mass spectrometry method (LC-LC-MS/MS) was developed and coupled to in vivo cerebral microdialysis to evaluate the brain response to the chiral compound (±)-7-chloro-5-(3-furanyl)-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxide ((±)-1), a potent positive allosteric modulator (PAM) of AMPA receptor. The method was successfully employed to evaluate also its stereoselective metabolism and in vitro biological activity. In particular, the LC achiral method developed, employs a pentafluorinated silica based column (Discovery HS-F5) to separate dopamine, acetylcholine, serotonin, (±)-1 and its two hepatic metabolites. In the "heart-cut" two-dimension achiral-chiral configuration, (±)-1 and (±)-1-d4 eluted from the achiral column (1st dimension), were transferred to a polysaccharide-based chiral column (2nd dimension, Chiralcel OD-RH) by using an automatic six-port valve. Single enantiomers of (±)-1 were separated and detected using electrospray positive ionization mode and quantified in selected reaction monitoring mode. The method was validated and showed good performance in terms of linearity, accuracy and precision. The new method employed showed several possible applications in the evaluation of: (a) brain response to neuroactive compounds by measuring variations in the brain extracellular levels of selected neurotransmitters and other biomarkers; (b) blood brain barrier penetration of drug candidates by measuring the free concentration of the drug in selected brain areas; (c) the presence of drug metabolites in the brain extracellular fluid that could prove very useful during drug discovery; (d) a possible stereoselective metabolization or blood brain barrier stereoselective crossing of chiral drugs. Finally, compared to the methods reported in the literature, this technique avoids the necessity of euthanizing an animal at each time point to measure drug

  18. Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2. (United States)

    Krintel, Christian; Francotte, Pierre; Pickering, Darryl S; Juknaitė, Lina; Pøhlsgaard, Jacob; Olsen, Lars; Frydenvang, Karla; Goffin, Eric; Pirotte, Bernard; Kastrup, Jette S


    The 1,2,4-benzothiadiazine 1,1-dioxide type of positive allosteric modulators of the ionotropic glutamate receptor A2 (GluA2) are promising lead compounds for the treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind in a cleft formed by the interface of two neighboring ligand binding domains and act by stabilizing the agonist-bound open-channel conformation. The driving forces behind the binding of these modulators can be significantly altered with only minor substitutions to the parent molecules. In this study, we show that changing the 7-fluorine substituent of modulators BPAM97 (2) and BPAM344 (3) into a hydroxyl group (BPAM557 (4) and BPAM521 (5), respectively), leads to a more favorable binding enthalpy (ΔH, kcal/mol) from -4.9 (2) and -7.5 (3) to -6.2 (4) and -14.5 (5), but also a less favorable binding entropy (-TΔS, kcal/mol) from -2.3 (2) and -1.3 (3) to -0.5 (4) and 4.8 (5). Thus, the dissociation constants (Kd, μM) of 4 (11.2) and 5 (0.16) are similar to those of 2 (5.6) and 3 (0.35). Functionally, 4 and 5 potentiated responses of 10 μM L-glutamate at homomeric rat GluA2(Q)i receptors with EC50 values of 67.3 and 2.45 μM, respectively. The binding mode of 5 was examined with x-ray crystallography, showing that the only change compared to that of earlier compounds was the orientation of Ser-497 pointing toward the hydroxyl group of 5. The favorable enthalpy can be explained by the formation of a hydrogen bond from the side-chain hydroxyl group of Ser-497 to the hydroxyl group of 5, whereas the unfavorable entropy might be due to desolvation effects combined with a conformational restriction of Ser-497 and 5. In summary, this study shows a remarkable example of enthalpy-entropy compensation in drug development accompanied with a likely explanation of the underlying structural mechanism.