Discovery of the imidazole-derived GPR40 agonist AM-3189

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• 作者：Zhihua Ma^a ; ; Daniel C.-H. Lin^b ; Rajiv Sharma^a ; Jinqian Liu^a ; Liusheng Zhu^a ; An-Rong Li^a ; Todd Kohn^a ; Yingcai Wang^a ; Jiwen (Jim) Liu^a ; Michael D. Bartberger^a ; Julio C. Medina^a ; Run Zhuang^b ; Frank Li^b ; Jane Zhang^b ; Jian Luo^b ; Simon Wong^c ; George R. Tonn^c ; Jonathan B. Houze^a
• 关键词：GPR40 ; FFAR1 ; GPCR ; Agonist ; Type II diabetes ; Insulin secretagogue ; AMG 837 ; AM-3189
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：26
• 期：1
• 页码：15-20
• 全文大小：1521 K

文摘

As a follow-up to the GPR40 agonist AMG 837, which was evaluated in clinical trials for the treatment of type II diabetes, further optimization led to the discovery of AM-3189 (13k). AM-3189 is representative of a new class of compounds with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837.