3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 2: Optimization of the side chains to improve in vitro and in vivo potencies

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• 作者：Masaki Asada ; Maki Iwahashi ; Tetsuo Obitsu ; Atsushi Kinoshita ; Yoshihiko Nakai ; Takahiro Onoda ; Toshihiko Nagase ; Motoyuki Tanaka ; Yoshiyuki Yamaura ; Hiroya Takizawa ; Ken Yoshikawa ; Kazutoyo Sato ; Mas
• 关键词：EP3 receptor ; Antagonist ; Uterine contraction
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 February 2010
• 年：2010
• 卷：18
• 期：4
• 页码：1641-1658
• 全文大小：492 K

文摘

A series of 3-[2-{[(3-methyl-1-phenylbutyl)amino]carbonyl}-4-(phenoxymethyl)phenyl]propanoic acid analogs were synthesized and evaluated for their in vitro potency. In most cases, introduction of one or two substituents into the two phenyl moieties resulted in the tendency of an increase or retention of in vitro activities. Several compounds, which showed excellent subtype selectivity, were evaluated for their inhibitory effect against PGE₂-induced uterine contraction in pregnant rats, which is thought to be mediated by the EP3 receptor subtype. The structure–activity relationships (SARs) are also discussed.