title: Structure-activity relationships for a novel series of thiazolyl phenyl ether derivatives exhibiting potent and selective acetyl-CoA carboxylase 2 inhibitory activity.
abstract: 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.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. rick.clark@abbott.com <rick.clark@abbott.com>
authors.forename: Richard F
authors.initials: RF
authors.lastname: Clark
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: T Matthew
authors.initials: TM
authors.lastname: Hansen
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.forename: Rongqi
authors.initials: R
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.forename: Ernst U
authors.initials: EU
authors.lastname: Frevert
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Camp
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Beutel
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Yu Gui
authors.initials: YG
authors.lastname: Gu
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010647:Phenyl Ethers; C031538:phenyl ether; D000103:Acetyl-CoA Carboxylase