title: Discovery of cyclic amine-substituted benzoic acids as PPARα agonists.
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.
authors: Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. masahiro.nomura@mb.kyorin-pharm.co.jp
authors: Masahiro
authors: M
authors: Nomura
authors: Kazuhiro
authors: K
authors: Yumoto
authors: Takehiro
authors: T
authors: Shinozaki
authors: Shigeki
authors: S
authors: Isogai
authors: Yasuo
authors: Y
authors: Takano
authors: Koji
authors: K
authors: Murakami
mesh_terms: D000284:Administration, Oral; D000588:Amines / Q000737:chemistry; D000818:Animals; D019817:Benzoic Acid / Q000737:chemistry; D016466:CHO Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D059305:Diet, High-Fat; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014280:Triglycerides / Q000737:chemistry
chemical_list: D000588:Amines; D047493:PPAR alpha; D014280:Triglycerides; D019817:Benzoic Acid; D002784:Cholesterol