title: 1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor.
abstract: This communication reports SARs for the first orexin-1 receptor antagonist series of 1-aryl-3-quinolin-4-yl and 1-aryl-3-naphthyridin-4-yl ureas. One of these compounds, 31 (SB-334867), has excellent selectivity for the orexin-1 receptor, blood-brain barrier permeability and shows in vivo activity following ip dosing.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park North, Third Avenue, Harlow, CM19 5AW, Essex, UK. porter@sbphrd.com
authors.forename: R A
authors.initials: RA
authors.lastname: Porter
authors.forename: W N
authors.initials: WN
authors.lastname: Chan
authors.forename: S
authors.initials: S
authors.lastname: Coulton
authors.forename: A
authors.initials: A
authors.lastname: Johns
authors.forename: M S
authors.initials: MS
authors.lastname: Hadley
authors.forename: K
authors.initials: K
authors.lastname: Widdowson
authors.forename: J C
authors.initials: JC
authors.lastname: Jerman
authors.forename: S J
authors.initials: SJ
authors.lastname: Brough
authors.forename: M
authors.initials: M
authors.lastname: Coldwell
authors.forename: D
authors.initials: D
authors.lastname: Smart
authors.forename: F
authors.initials: F
authors.lastname: Jewitt
authors.forename: P
authors.initials: P
authors.lastname: Jeffrey
authors.forename: N
authors.initials: N
authors.lastname: Austin
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D016466:CHO Cells; D002490:Central Nervous System / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000737:chemistry; D007262:Infusions, Intravenous; D009287:Naphthyridines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D064446:Orexin Receptors; D010539:Permeability; D011804:Quinolines / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D007211:Indoles; D009287:Naphthyridines; D064446:Orexin Receptors; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C030374:indole; D014508:Urea; C037219:quinoline