Discovery of cyclic amine-substituted benzoic acids as PPAR¦Á agonists

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• 作者：Masahiro Nomura ; ^{masahiro.nomura@mb.kyorin-pharm.co.jp} ; Kazuhiro Yumoto ; Takehiro Shinozaki ; Shigeki Isogai ; Yasuo Takano ; Koji Murakami
• 关键词：PPAR¦Á agonist ; Cyclic amine-substituted benzoic acid ; Structure&ndash ; activity relationship ; Triglyceride ; Total cholesterol
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 January, 2012
• 年：2012
• 卷：22
• 期：1
• 页码：334-338
• 全文大小：608 K

文摘

A series of novel cyclic amine-substituted benzoic acid derivatives were synthesized and evaluated for their PPAR¦Á 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 PPAR¦Á agonist. (S)-4f showed excellent PK profile and oral administration of (S)-4f to high-fat diet dogs effectively lowered triglycerides.