Discovery of cyclic amine-substituted benzoic acids as PPARα agonists

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):334-8. doi: 10.1016/j.bmcl.2011.11.002.
Masahiro Nomura  1 ,  Kazuhiro Yumoto ,  Takehiro Shinozaki ,  Shigeki Isogai ,  Yasuo Takano ,  Koji Murakami
Affiliations
  • 1. Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. [email protected]
PMID: 22133631 DOI: 10.1016/j.bmcl.2011.11.002
Abstract

A series of novel cyclic amine-substituted benzoic acid derivatives were synthesized and evaluated for their PPARα Agonist activity. Strucure-activity relationship studies led to the identification of (S)-3-[3-[2-(4-chlorophenyl)-4-methylthyazole-5-carboxamido]piperidin-1-yl]benzoic acid (S)-4f (KRP-105) as a potent and high subtype-selective human PPARα Agonist. (S)-4f showed excellent PK profile and oral administration of (S)-4f to high-fat diet dogs effectively lowered triglycerides.

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