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

Optimization studies aimed at improving the potency and selectivity profiles of a recently discovered series of acetyl-CoA carboxylase (ACC) inhibitors are described. The incorporation of 2-position phenyl ring substituents resulted in dramatic and general ACC2 selectivity enhancements (>3000-fold) within the lead series.