Structure–activity relationships for a novel series of thiazolyl phenyl ether derivatives exhibiting potent and selective acetyl-CoA carboxylase 2 inhibitory activity

Structure–activity relationships for a recently discovered thiazolyl phenyl ether series of acetyl-CoA carboxylase (ACC) inhibitors were investigated. Preliminary efforts to optimize the series through modification of the distal aryl ether moiety of the lead scaffold resulted in the identification of compounds exhibiting low-nanomolar potency and isozyme-selective ACC2 activity.

Graphical abstractThe SAR for a novel series of acetyl-CoA carboxylase inhibitors are described. Optimization of distal aryl ring substitution in the lead scaffold resulted in the identification of compounds displaying low-nanomolar potency and high isozyme-selectivity for acetyl-CoA carboxylase 2.Figure optionsDownload full-size imageDownload as PowerPoint slide