Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors. III. Synthesis and gastric antisecretory activity of 2-[(2- and 4-aminobenzyl, and alpha-methylbenzyl)sulfinyl]-N-(4-pyridinyl) -3-pyridinecarboxamides.
A new series of 2-[(2-aminobenzyl, 4-aminobenzyl, and alpha-methylbenzyl) sulfinyl]-N-(4-pyridinyl)-3-pyridinecarboxamides. was synthesized and evaluated for gastric antisecretory activities. Several of the compounds synthesized exhibited potent inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration. In particular, the more polar diastereoisomer of 2-[(4-methoxy-alpha-methylbenzyl)sulfinyl] -N-(4-pyridinyl)-3-pyridinecarboxamide (13b) showed in vivo inhibitory activity equivalent or superior to that of omeprazole and was a more selective (H+/K+)-ATPase inhibitor than omeprazole.
Terauchi
H
H
Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Tanitame
A
A
Tada
K
K
Nakamura
K
K
Seto
Y
Y
Nishikawa
Y
Y
D000818:Animals; D000863:Antacids / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D013329:Structure-Activity Relationship
D000863:Antacids; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D011725:Pyridines; D009536:Niacinamide