Discovery of the imidazole-derived GPR40 agonist AM-3189
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.
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Acknowledgments
Zhihua Ma thanks Margaret Chu-Moyer, Paul Dransfield, Richard V. Connors and Larry McGee for their very helpful comments on the manuscript and numerous helpful discussions.
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