Effects of Osutidine (T-593) and its Enantiomers on Gastric Mucosal Hemodynamics and Mucosal Integrity in Anesthetized Rats

Abstract

T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol-induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats.

Development of CN Coupling Using Mechanochemistry: Catalytic Coupling of Arylsulfonamides and Carbodiimides

“…The product was separated by vacuum filtration and dried. Details of all experiments, 1 H, 13 C NMR spectroscopy, and MS, TGA/DSC, and FTIR-ATR data are given in the Supporting Information. CCDC 995641 (2 a), 995642 (3 b), 995643 (4 a), 995644 (5 b) contain the supplementary crystallographic data for this paper.…”

“…We now demonstrate mechanochemistry as the enabling element of a new one-step route to N-sulfonylguanidines, a family of molecules which have significant potential as herbicides and pharmaceuticals, [13][14][15] by catalytic coupling of sulfonamides and carbodiimides (Scheme 1 a). Such coupling is not normally observed because of poor sulfonamide nucleophilicity.…”

Development of CN Coupling Using Mechanochemistry: Catalytic Coupling of Arylsulfonamides and Carbodiimides

“…We now demonstrate mechanochemistry as the enabling element of a new one‐step route to N ‐sulfonylguanidines, a family of molecules which have significant potential as herbicides and pharmaceuticals,13–15 by catalytic coupling of sulfonamides and carbodiimides (Scheme ). Such coupling is not normally observed because of poor sulfonamide nucleophilicity.…”