title: Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors.
abstract: A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.
authors.affiliation: Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Road, Abbott Park, IL 60064, USA. zhili.xin@biogenidec.com
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Serby
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Szczepankiewicz
authors.forename: Lissa T J
authors.initials: LT
authors.lastname: Nelson
authors.forename: Harriet T
authors.initials: HT
authors.lastname: Smith
authors.forename: Tom S
authors.initials: TS
authors.lastname: Suhar
authors.forename: Rich S
authors.initials: RS
authors.lastname: Janis
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Camp
authors.forename: Christine A
authors.initials: CA
authors.lastname: Collins
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Surowy
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C530575:4-(2-chlorophenoxy)-N-(3-(methyl carbamoyl)phenyl)piperidine-1-carboxamide; D004791:Enzyme Inhibitors; D010880:Piperidines; D014508:Urea; D013230:Stearoyl-CoA Desaturase