title: 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.
abstract: A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.
authors.affiliation: Cardiovascular and Metabolism Research, Janssen Research and Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA. Electronic address: shyhyang99@yahoo.com.
authors.forename: Shyh-Ming
authors.initials: SM
authors.lastname: Yang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Tang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Huajun
authors.initials: H
authors.lastname: Lu
authors.forename: Gee-Hong
authors.initials: GH
authors.lastname: Kuo
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gaul
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Ho
authors.forename: James G
authors.initials: JG
authors.lastname: Conway
authors.forename: Yin
authors.initials: Y
authors.lastname: Liang
authors.forename: James M
authors.initials: JM
authors.lastname: Lenhard
authors.forename: Keith T
authors.initials: KT
authors.lastname: Demarest
authors.forename: William V
authors.initials: WV
authors.lastname: Murray
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010880:Piperidines; C032727:piperidine; D014508:Urea; D013230:Stearoyl-CoA Desaturase
keywords: Desaturation index; Obesity; SCD1 inhibitors; Stearoyl-CoA desaturase