Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.

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.

SUBMITTER: Du X 

PROVIDER: S-EPMC4027632 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature