Synthesis and structure-activity relationships of N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1- methylprop-2-ynyl}carboxy derivatives as selective acetyl-...
Basic Information
ID: ALA1138057
Journal: J Med Chem
Title: Synthesis and structure-activity relationships of N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1- methylprop-2-ynyl}carboxy derivatives as selective acetyl-CoA carboxylase 2 inhibitors.
Authors: Gu YG, Weitzberg M, Clark RF, Xu X, Li Q, Zhang T, Hansen TM, Liu G, Xin Z, Wang X, Wang R, McNally T, Zinker BA, Frevert EU, Camp HS, Beutel BA, Sham HL.
Abstract: A structurally novel acetyl-CoA carboxylase (ACC) inhibitor is identified from high-throughput screening. A preliminary structure-activity relationship study led to the discovery of potent dual ACC1/ACC2 and ACC2 selective inhibitors against human recombinant ACC1 and ACC2. Selective ACC2 inhibitors exhibited IC50<20 nM and >1000-fold selectivity against ACC1. (S)-Enantiomer 9p exhibited high ACC2 activity and lowered muscle malonyl-CoA dose-dependently in acute rodent studies, whereas (R)-enantiomer 9o was weak and had no effect on the malonyl-CoA level.
CiteXplore: 16789734
DOI: 10.1021/jm060484v
Patent ID: ┄