Bioorg Med Chem Lett. 2007 Apr 1;17(7):1961-5. Epub 2007 Jan 19.

Phenoxy thiazole derivatives as potent and selective acetyl-CoA carboxylase 2 inhibitors: Modulation of isozyme selectivity by incorporation of phenyl ring substituents.

Clark RF, Zhang T, Wang X, Wang R, Zhang X, Camp HS, Beutel BA, Sham HL, Gu YG.

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Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. rick.clark@abbott.com

Abstract

A phenyl ring substitution strategy was employed to optimize the ACC2 potency and selectivity profiles of a recently discovered phenoxy thiazolyl series of acetyl-CoA carboxylase inhibitors. Ring substituents were shown to dramatically affect isozyme selectivity. Modifications that generally impart high levels of ACC2 selectivity (>3000-fold) while maintaining excellent ACC2 potency (IC50s approximately 9-20 nM) were identified.

PMID:: 17267221; [PubMed - indexed for MEDLINE]

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