Synthesis of Phenoxyacetic Acid Derivatives as Highly Potent Antagonists of Gastrin/Cholecystokinin-B Receptors. II

Yasuyuki TAKEDA; Keiichi KAWAGOE; Aki YOKOMIZO; Yoshihiro YOKOMIZO; Toru HOSOKAMI; Yoshimasa SHIMOTO; Yoshiaki TABUCHI; Yoshiyasu OGIHARA; Rira OTSUBO; Yuko HONDA; Shuichi YOKOHAMA

doi:10.1248/cpb.46.951

Yasuyuki TAKEDA, Keiichi KAWAGOE, Aki YOKOMIZO, Yoshihiro YOKOMIZO, Toru HOSOKAMI, Yoshimasa SHIMOTO, Yoshiaki TABUCHI, Yoshiyasu OGIHARA, Rira OTSUBO, Yuko HONDA, Shuichi YOKOHAMA

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Keywords: phenoxyacetic acid, gastrin/cholecystokinin-B receptor antagonist, DA-3934, structure-activity relationship, gastric acid secretion, ureido-phenylacetic acid

JOURNAL FREE ACCESS

1998 Volume 46 Issue 6 Pages 951-961

DOI https://doi.org/10.1248/cpb.46.951

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Abstract

A series of phenoxyacetanilide derivatives was synthesized and their antagonist activities for human gastrin/cholecystokinin (CCK)-B and CCK-A receptors were evaluated. Among the compounds synthesized, 2-[3-[3-[N-[2-(N-methyl-N-phenylcarbamoylmethoxy)phenyl]-N-(N-methyl-N-phenylcarbamoylmethyl)carbamoylmethyl]-ureido]phenyl]acetic acid (20i, DA-3934) exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A receptors. DA-3934 and its methyl ester derivative inhibited pentagastrin-induced gastric acid secretion in rats in a dose-dependent manner.

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