Discovery of the imidazole-derived GPR40 agonist AM-3189. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: Ma, Zhihua; Lin, Daniel C.-H.; Sharma, Rajiv; Liu, Jinqian; Zhu, Liusheng; Li, An-Rong; Kohn, Todd; Wang, Yingcai; Liu, Jiwen (Jim); Bartberger, Michael D.; Medina, Julio C.; Zhuang, Run; Li, Frank; Zhang, Jane; Luo, Jian; Wong, Simon; Tonn, George R.; Houze, Jonathan B.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 1(2016)
• Page Start: 15
• Page End: 20
• Publication Date: 2016-01-01
• Subjects: GPR40 -- FFAR1 -- GPCR -- Agonist -- Type II diabetes -- Insulin secretagogue -- AMG 837 -- AM-3189; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.050
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 comparable in vivo efficacy. Abstract: 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.