Discovery of a potent, selective, and orally efficacious pyrimidinooxazinyl bicyclooctaneacetic acid diacylglycerol acyltransferase-1 inhibitor

  • J Med Chem. 2009 Mar 26;52(6):1558-68. doi: 10.1021/jm801507v.
Alan M Birch  1 ,  Susan Birtles ,  Linda K Buckett ,  Paul D Kemmitt ,  Graham J Smith ,  Tim J D Smith ,  Andrew V Turnbull ,  Steven J Y Wang
Affiliations
  • 1. AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom. [email protected]
PMID: 19256504 DOI: 10.1021/jm801507v
Abstract

Inhibition of DGAT-1 is increasingly seen as an attractive mechanism with the potential for treatment of obesity and Other elements of the metabolic syndrome. We report here a bicyclooctaneacetic acid derivative in the pyrimidinooxazine structural class of DGAT-1 inhibitors that has good potency, selectivity, and pharmacokinetic characteristics across a variety of species. This compound is an effective inhibitor of DGAT-1 in both intestinal and adipose tissue, which results in a reduction in body weight or body weight gain following oral administration in both mouse and rat models of dietary-induced obesity.

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