烟酰胺衍生物作为一类新型胃（H⁺/K⁺）-ATP酶抑制剂。III. 2-[(2-和4-氨基苄基以及α-甲基苄基)亚磺酰基]-N-(4-吡啶基)-3-吡啶甲酰胺的合成及胃抗分泌活性

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.

作者信息

Terauchi H, Tanitame A, Tada K, Nakamura K, Seto Y, Nishikawa Y

机构信息

Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1997 Jul;45(7):1177-82. doi: 10.1248/cpb.45.1177.

DOI:10.1248/cpb.45.1177

PMID:9246752

Abstract

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.

摘要

合成了一系列新的2-[(2-氨基苄基、4-氨基苄基和α-甲基苄基)亚磺酰基]-N-(4-吡啶基)-3-吡啶甲酰胺，并对其胃抗分泌活性进行了评估。所合成的几种化合物对离体兔壁细胞中由二丁酰环磷腺苷刺激的[14C]氨基比林蓄积以及幽门结扎大鼠经十二指肠给药组胺诱导的胃酸分泌表现出强效抑制活性。特别是，2-[(4-甲氧基-α-甲基苄基)亚磺酰基]-N-(4-吡啶基)-3-吡啶甲酰胺(13b)的极性更强的非对映异构体在体内显示出与奥美拉唑相当或优于奥美拉唑的抑制活性，并且是一种比奥美拉唑更具选择性的(H+/K+)-ATP酶抑制剂。