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 α-methylbenzyl)sulfinyl]-N-(4-pyridinyl)-3-pyridinecarboxamides

Abstract

A new series of 2-[(2-aminobenzyl, 4-aminobenzyl, and α-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. Inparticular, the more polar diastereoisomer of 2-[(4-methoxy-α-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.