title: Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions.
abstract: A series of novel five-membered urea derivatives as potent NK1 receptor antagonists is described. The effects of substitution of a 4-fluoro group at the phenyl ring and the introduction of an alpha-methyl group at the benzylic position to improve potency and duration of in vivo activity are discussed. Several compounds with high affinity and sustained in vivo activity were identified.
authors.affiliation: Chemical Research Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
authors.forename: Ho-Jane
authors.initials: HJ
authors.lastname: Shue
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: John H
authors.initials: JH
authors.lastname: Schwerdt
authors.forename: Sunil
authors.initials: S
authors.lastname: Paliwal
authors.forename: David J
authors.initials: DJ
authors.lastname: Blythin
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Danlin
authors.initials: D
authors.lastname: Gu
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Reichard
authors.forename: Hongwu
authors.initials: H
authors.lastname: Wang
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Duffy
authors.forename: Jean E
authors.initials: JE
authors.lastname: Lachowicz
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Coffin
authors.forename: Amin A
authors.initials: AA
authors.lastname: Nomeir
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Morgan
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: Varty
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000737:chemistry; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D005461:Fluorine / Q000737:chemistry; D005849:Gerbillinae; D008958:Models, Molecular; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D001592:Benzyl Alcohols; D064729:Neurokinin-1 Receptor Antagonists; D005461:Fluorine; D014508:Urea