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Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists. | LitMetric

Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.

ACS Med Chem Lett

Departments of Therapeutic Discovery, Metabolic Disorders, Pharmaceutics, and Pharmacokinetic and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.

Published: April 2014

AI Article Synopsis

Article Abstract

We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027632PMC
http://dx.doi.org/10.1021/ml4005123DOI Listing

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