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Bioorg Med Chem Lett. 2011 Jun 1;21(11):3390-4. doi: 10.1016/j.bmcl.2011.03.114. Epub 2011 Apr 8.

3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists.

Author information

1
Merck Research Laboratories, Merck & Co., Inc., 126 E. Lincoln Ave., PO Box 2000, Rahway, NJ 07065-0900, USA. shawn_walsh@merck.com

Abstract

The design, synthesis, and structure-activity relationship (SAR) for a series of β-substituted 3-(4-aryloxyaryl)propanoic acid GPR40 agonists is described. Systematic replacement of the pendant aryloxy group led to identification of potent GPR40 agonists. In order to identify candidates suitable for in vivo validation of the target, serum shifted potency and pharmacokinetic properties were determined for several compounds. Finally, further profiling of compound 7 is presented, including demonstration of enhanced glucose tolerance in an in vivo mouse model.

PMID:
21514824
DOI:
10.1016/j.bmcl.2011.03.114
[Indexed for MEDLINE]

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