| Literature DB >> 22512618 |
Yasuyoshi Arikawa1, Haruyuki Nishida, Osamu Kurasawa, Atsushi Hasuoka, Keizo Hirase, Nobuhiro Inatomi, Yasunobu Hori, Jun Matsukawa, Akio Imanishi, Mitsuyo Kondo, Naoki Tarui, Teruki Hamada, Terufumi Takagi, Toshiyuki Takeuchi, Masahiro Kajino.
Abstract
In our pursuit of developing a novel and potent potassium-competitive acid blocker (P-CAB), we synthesized pyrrole derivatives focusing on compounds with low log D and high ligand-lipophilicity efficiency (LLE) values. Among the compounds synthesized, the compound 13e exhibited potent H(+),K(+)-ATPase inhibitory activity and potent gastric acid secretion inhibitory action in vivo. Its maximum efficacy was more potent and its duration of action was much longer than those of proton pump inhibitors (PPIs). Therefore, compound 13e (1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate, TAK-438) was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases.Entities:
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Year: 2012 PMID： 22512618 DOI： 10.1021/jm300318t
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446