Cyclic urea derivatives as potent NK1 selective antagonists. Part II: Effects of fluoro and benzylic methyl substitutions.
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.
Shue
Ho-Jane
HJ
Chemical Research Department, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Chen
Xiao
X
Schwerdt
John H
JH
Paliwal
Sunil
S
Blythin
David J
DJ
Lin
Ling
L
Gu
Danlin
D
Wang
Cheng
C
Reichard
Gregory A
GA
Wang
Hongwu
H
Piwinski
John J
JJ
Duffy
Ruth A
RA
Lachowicz
Jean E
JE
Coffin
Vicki L
VL
Nomeir
Amin A
AA
Morgan
Cynthia A
CA
Varty
Geoffrey B
GB
Shih
Neng-Yang
NY
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*
D014151:Anti-Anxiety Agents; D001592:Benzyl Alcohols; D064729:Neurokinin-1 Receptor Antagonists; D005461:Fluorine; D014508:Urea