Discovery of the imidazole-derived GPR40 agonist AM-3189

  • Bioorg Med Chem Lett. 2016 Jan 1;26(1):15-20. doi: 10.1016/j.bmcl.2015.11.050.
Zhihua Ma  1 ,  Daniel C-H Lin  2 ,  Rajiv Sharma  1 ,  Jinqian Liu  1 ,  Liusheng Zhu  1 ,  An-Rong Li  1 ,  Todd Kohn  1 ,  Yingcai Wang  1 ,  Jiwen Jim Liu  1 ,  Michael D Bartberger  1 ,  Julio C Medina  1 ,  Run Zhuang  2 ,  Frank Li  2 ,  Jane Zhang  2 ,  Jian Luo  2 ,  Simon Wong  3 ,  George R Tonn  3 ,  Jonathan B Houze  1
Affiliations
  • 1. Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
  • 2. Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
  • 3. Department of Pharmacokinetics & Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
PMID: 26620255 DOI: 10.1016/j.bmcl.2015.11.050
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.

Keywords
AM-3189; AMG 837; Agonist; FFAR1; GPCR; GPR40; Insulin secretagogue; Type II diabetes.
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