Discovery, synthesis, and biological evaluation of novel pyrrole derivatives as highly selective potassium-competitive acid blockers
Discovery, synthesis, and biological evaluation of novel pyrrole derivatives as highly selective potassium-competitive acid blockers
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DOI：
10.1016/j.bmc.2012.04.014
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发表时间：
2012-06-15
影响因子：
3.5
通讯作者：
Kajino, Masahiro
中科院分区：
文献类型：
--
作者：
Nishida, Haruyuki;Hasuoka, Atsushi;Kajino, Masahiro
为了发现比现有质子泵抑制剂更有效的胃抑制剂，合成了新型吡咯衍生物，并评价了它们的H+，K+-ATP酶抑制活性和对组胺刺激的大鼠胃酸分泌的抑制作用。在所合成的化合物中，化合物17 a通过可逆和K+竞争性离子结合表现出选择性和有效的H+，K+-ATP酶抑制活性;此外，化合物17 c表现出对组胺刺激的大鼠和Heidenhain pouch犬胃酸分泌的有效抑制作用。(C)2012爱思唯尔有限公司保留所有权利。
To discover a gastric antisecretory agent more potent than existing proton pump inhibitors, novel pyrrole derivatives were synthesized, and their H+, K+-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 17a exhibited selective and potent H+, K+-ATPase inhibitory activity through reversible and K+-competitive ionic binding; furthermore, compound 17c exhibited potent inhibitory action on histamine-stimulated gastric acid secretion in rats and Heidenhain pouch dogs. (C) 2012 Elsevier Ltd. All rights reserved.