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Acta Crystallographica. Section E,... Jun 2010The crystal structure of the title compound, C(11)H(13)ClF(3)N(3)O(4)S(3) (systematic name:...
The crystal structure of the title compound, C(11)H(13)ClF(3)N(3)O(4)S(3) (systematic name: 6-chloro-2-methyl-3-{[(2,2,2-trifluoro-eth-yl)sulfan-yl]meth-yl}-3,4-dihydro-2H-1,2,4-benzothia-diazine-7-sul-f-on-amide 1,1-diox-ide; CRN: 346-18-9), exhibits a two-dimensional network of hydrogen-bonded mol-ecules parallel to (01). The NH and NH(2) 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.
PubMed: 21587890
DOI: 10.1107/S1600536810022105 -
British Heart Journal Oct 1972
Topics: Adult; Black or African American; Blood Pressure; Bronchial Spasm; Drug Synergism; Female; Hallucinations; Humans; Hypertension; Male; Middle Aged; Polythiazide; Propranolol; Pulse; Racial Groups; Sleep Wake Disorders; Substance Withdrawal Syndrome; Vertigo
PubMed: 5086971
DOI: 10.1136/hrt.34.10.1042 -
Annals of the Rheumatic Diseases Nov 1966
Topics: Allopurinol; Clopamide; Enzyme Therapy; Gout; Hematologic Diseases; Humans; Hypertension; Kidney Failure, Chronic; Polythiazide; Uric Acid; Xanthine Oxidase
PubMed: 5958696
DOI: 10.1136/ard.25.Suppl_6.660 -
The AAPS Journal Apr 2013Target identification of the known bioactive compounds and novel synthetic analogs is a very important research field in medicinal chemistry, biochemistry, and... (Comparative Study)
Comparative Study
Target identification of the known bioactive compounds and novel synthetic analogs is a very important research field in medicinal chemistry, biochemistry, and pharmacology. It is also a challenging and costly step towards chemical biology and phenotypic screening. In silico identification of potential biological targets for chemical compounds offers an alternative avenue for the exploration of ligand-target interactions and biochemical mechanisms, as well as for investigation of drug repurposing. Computational target fishing mines biologically annotated chemical databases and then maps compound structures into chemogenomical space in order to predict the biological targets. We summarize the recent advances and applications in computational target fishing, such as chemical similarity searching, data mining/machine learning, panel docking, and the bioactivity spectral analysis for target identification. We then described in detail a new web-based target prediction tool, TargetHunter (http://www.cbligand.org/TargetHunter). This web portal implements a novel in silico target prediction algorithm, the Targets Associated with its MOst SImilar Counterparts, by exploring the largest chemogenomical databases, ChEMBL. Prediction accuracy reached 91.1% from the top 3 guesses on a subset of high-potency compounds from the ChEMBL database, which outperformed a published algorithm, multiple-category models. TargetHunter also features an embedded geography tool, BioassayGeoMap, developed to allow the user easily to search for potential collaborators that can experimentally validate the predicted biological target(s) or off target(s). TargetHunter therefore provides a promising alternative to bridge the knowledge gap between biology and chemistry, and significantly boost the productivity of chemogenomics researchers for in silico drug design and discovery.
Topics: Algorithms; Anti-HIV Agents; Antihypertensive Agents; Antineoplastic Agents; Artificial Intelligence; Benzofurans; Computer Graphics; Computer Simulation; Data Mining; Databases, Chemical; Drug Discovery; Drug Repositioning; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Muscarinic Antagonists; Polythiazide; Pyrrolidines; Reproducibility of Results; Software; Structure-Activity Relationship; User-Computer Interface
PubMed: 23292636
DOI: 10.1208/s12248-012-9449-z -
American Journal of Physiology. Renal... Jul 2000The thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC) is the major pathway for salt reabsorption in the apical membrane of the mammalian distal convoluted tubule. When...
The thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC) is the major pathway for salt reabsorption in the apical membrane of the mammalian distal convoluted tubule. When expressed in Xenopus laevis oocytes, rat TSC exhibits high affinity for both cotransported ions, with the Michaelis-Menten constant (K(m)) for Na(+) of 7.6 +/- 1.6 mM and for Cl(-) of 6.3 +/- 1.1 mM, and Hill coefficients for Na(+) and Cl(-) consistent with electroneutrality. The affinities of both Na(+) and Cl(-) were increased by increasing concentration of the counterion. The IC(50) values for thiazides were affected by both extracellular Na(+) and Cl(-). The higher the Na(+) or Cl(-) concentration, the lower the inhibitory effect of thiazides. Finally, rTSC function is affected by extracellular osmolarity. We propose a transport model featuring a random order of binding in which the binding of each ion facilitates the binding of the counterion. Both ion binding sites alter thiazide-mediated inhibition of transport, indicating that the thiazide-binding site is either shared or modified by both Na(+) and Cl(-).
Topics: Animals; Bendroflumethiazide; Binding Sites; Biological Transport; Carrier Proteins; Chlorides; Diuretics; Hydrochlorothiazide; Hydrogen-Ion Concentration; Inhibitory Concentration 50; Kinetics; Metolazone; Microinjections; Models, Biological; Oocytes; Osmolar Concentration; Polythiazide; Rats; Receptors, Drug; Sodium; Sodium Chloride Symporter Inhibitors; Sodium Chloride Symporters; Solute Carrier Family 12, Member 3; Symporters; Xenopus
PubMed: 10894798
DOI: 10.1152/ajprenal.2000.279.1.F161 -
British Medical Journal Oct 1977
Topics: Aged; Female; Humans; Hyponatremia; Polythiazide; Water-Electrolyte Balance
PubMed: 922422
DOI: 10.1136/bmj.2.6094.1063 -
British Medical Journal Jul 1968In 123 patients with arterial hypertension the haemoglobin values were determined before and during long-term antihypertensive drug treatment. The haemoglobin values...
In 123 patients with arterial hypertension the haemoglobin values were determined before and during long-term antihypertensive drug treatment. The haemoglobin values found before treatment did not differ from those found in the normal population. In both sexes the haemoglobin values showed a significant increase after prolonged treatment. In males the average values rose from 15.1 to 16.7 g./100 ml., and in females from 13.96 to 14.82 g./100 ml. The increase in the haemoglobin concentration does not seem to be clearly correlated to the duration of treatment or to the decrease produced in mean blood pressure. On the other hand, the increase in haemoglobin depended to some extent on the nature of treatment. Diuretics alone resulted in a moderate increase only, whereas diuretics in combination with other antihypertensive drugs produced a more pronounced increase in haemoglobin values.
Topics: Adult; Aged; Antihypertensive Agents; Creatinine; Diuretics; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Hemoglobinometry; Humans; Hydrochlorothiazide; Male; Methyldopa; Middle Aged; Polycythemia; Polythiazide; Pyelonephritis; Renal Artery Obstruction; Triamterene
PubMed: 5668194
DOI: 10.1136/bmj.3.5611.163 -
American Journal of Physiology. Renal... Oct 2002To test the role of epithelial Na channels in the day-to-day regulation of renal Na excretion, rats were infused via osmotic minipumps with the Na channel blocker...
To test the role of epithelial Na channels in the day-to-day regulation of renal Na excretion, rats were infused via osmotic minipumps with the Na channel blocker amiloride at rates that achieved drug concentrations of 2-5 microM in the lumen of the distal nephron. Daily Na excretion rates were unchanged, although amiloride-treated animals tended to excrete more Na in the afternoon and less in the late evening than controls. When the rats were given a low-Na diet, Na excretion rates were elevated in the amiloride-treated group within 4 h and remained higher than controls for at least 48 h. Adrenalectomized animals responded similarly to the low-Na diet. In contrast, rats infused with polythiazide at rates designed to inhibit NaCl transport in the distal tubule were able to conserve Na as well as did the controls. Injection of aldosterone (2 microg/100 g body wt) decreased Na excretion in control animals after a 1-h delay. This effect was largely abolished in amiloride-treated rats. On the basis of quantitative analysis of the results, we conclude that activation of amiloride-sensitive channels by mineralocorticoids accounts for 50-80% of the immediate natriuretic response of the kidney to a reduction in Na intake. Furthermore, the channels are necessary to achieve minimal rates of Na excretion during more chronic Na deprivation.
Topics: Aldosterone; Amiloride; Animals; Chromatography, High Pressure Liquid; Circadian Rhythm; Diet, Sodium-Restricted; Diuretics; Electrolytes; Epithelial Cells; Female; Kidney; Kidney Tubules, Collecting; Kinetics; Polythiazide; Rats; Rats, Sprague-Dawley; Sodium; Sodium Channel Blockers; Sodium Channels; Sodium Chloride Symporter Inhibitors
PubMed: 12217863
DOI: 10.1152/ajprenal.00379.2001