181823-83-6Relevant articles and documents
Nicotinamide derivatives as a new class of gastric H+/K+-ATPase inhibitors. 1. Synthesis and structure-activity relationships of N- substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides
Terauchi, Hideo,Tanitame, Akihiko,Tada, Keiko,Nakamura, Keiji,Seto, Yasuhiro,Nishikawa, Yoshinori
, p. 313 - 321 (2007/10/03)
A new series of N-Substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides 7 and 8 were synthesized. Upon acid activation in the acidic environment of the parietal cell, these compounds are converted into their active forms, 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines 5, which inhibit gastric H+/K+-ATPase. Inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cAMP in isolated rabbit parietal cells in vitro and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration in vivo were evaluated, and the structure-activity relationships were examined. Among the compounds synthesized, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4- pyridyl)nicotinamide (8b) showed potent inhibitory activities in vitro and in vivo equivalent to those of omeprazole, a typical H+/K+-ATPase inhibitor. Moreover, 8b was much more stable at neutral and weakly acidic pH than omeprazole, lansoprazole, and pantoprazole. Compound 8b is considered to be a promising agent for treating acid-related gastrointestinal disorders.
