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Discovery of the imidazole-derived GPR40 agonist AM-3189.

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2015

Bioorg Med Chem Lett. 2015 Nov 17. pii: S0960-894X(15)30258-4. doi: 10.1016/j.bmcl.2015.11.050. [Epub ahead of print]

Discovery of the imidazole-derived GPR40 agonist AM-3189.

Z Ma;DC Lin;R Sharma;J Liu;L Zhu;AR Li;T Kohn;Y Wang;JJ Liu;MD Bartberger;JC Medina;R Zhuang;L Li;J Zhang;J Luo;S Wong;GR Tonn;JB Houze

Amgen Inc., South San Francisco, CA, USA.

Service type: Knock-in mice

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.

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