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

…, T Zhang, X Wang, R Wang, X Zhang, HS Camp…

Index: Clark, Richard F.; Zhang, Tianyuan; Wang, Xiaojun; Wang, Rongqi; Zhang, Xiaolin; Camp, Heidi S.; Beutel, Bruce A.; Sham, Hing L.; Gu, Yu Gui Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 7 p. 1961 - 1965

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Citation Number: 31

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∼ 9–20nM) were identified.