title: N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists.
abstract: A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4-carbohydrazide core is described. In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properties.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. jason@elliottj25.fsnet.co.uk
authors.forename: Jason M
authors.initials: JM
authors.lastname: Elliott
authors.forename: Robert W
authors.initials: RW
authors.lastname: Carling
authors.forename: Mark
authors.initials: M
authors.lastname: Chambers
authors.forename: Gary G
authors.initials: GG
authors.lastname: Chicchi
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hutson
authors.forename: A Brian
authors.initials: AB
authors.lastname: Jones
authors.forename: Angus
authors.initials: A
authors.lastname: MacLeod
authors.forename: Rose
authors.initials: R
authors.lastname: Marwood
authors.forename: Georgina
authors.initials: G
authors.lastname: Meneses-Lorente
authors.forename: Elena
authors.initials: E
authors.lastname: Mezzogori
authors.forename: Fraser
authors.initials: F
authors.lastname: Murray
authors.forename: Michael
authors.initials: M
authors.lastname: Rigby
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Royo
authors.forename: Michael G N
authors.initials: MG
authors.lastname: Russell
authors.forename: Bindi
authors.initials: B
authors.lastname: Sohal
authors.forename: Kwei Lan
authors.initials: KL
authors.lastname: Tsao
authors.forename: Brian
authors.initials: B
authors.lastname: Williams
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D006834:Hydrazines; C515786:N-((methoxycarbonyl)(phenyl)amino)-3-methoxy-2-phenylquinoline-4-carboxamide; D018377:Neurotransmitter Agents; D011804:Quinolines; D018042:Receptors, Neurokinin-3; C019289:carbohydrazide