2. Academic Validation
  3. 3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 3: Synthesis, metabolic stability, and biological evaluation of optically active analogs

3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 3: Synthesis, metabolic stability, and biological evaluation of optically active analogs

  • Bioorg Med Chem. 2010 May 1;18(9):3212-23. doi: 10.1016/j.bmc.2010.03.028.
Masaki Asada 1,  Tetsuo Obitsu,  Atsushi Kinoshita,  Toshihiko Nagase,  Tadahiro Yoshida,  Yoshiyuki Yamaura,  Hiroya Takizawa,  Ken Yoshikawa,  Kazutoyo Sato,  Masami Narita,  Hisao Nakai,  Masaaki Toda,  Yoshito Tobe
Affiliations

Affiliation

  • 1 Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. [email protected]
PMID: 20385498 DOI: 10.1016/j.bmc.2010.03.028
Abstract

A series of 3-(2-aminocarbonylphenyl)propanoic acid analogs possessing the (1R)-1-(3,5-dimethylphenyl)-3-methylbutylamine moiety on the carboxyamide side chain were synthesized and evaluated for their binding affinity for the EP1-4 receptors and their antagonist activity for the EP3 receptor. Rational drug design based on the structure of the metabolites in human liver microsomes led us to the discovery of another series of analogs. Several compounds were further evaluated for their in vivo efficacy in rats after oral administration and also for their pharmacokinetic profiles including in vitro stability in the liver microsomes.

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