Identification of a novel 1'-[5-((3,5-dichlorobenzoyl)methylamino)-3-(3,4-dichlorophenyl)-4-(methoxyimino)pentyl]-2-oxo-(1,4'-bipiperidine) as a dual NK(1)/NK(2) antagonist.
A novel series of dual NK(1)/NK(2) receptor antagonists, based on the 2-oxo-(1,4'-bipiperidine) template, has been prepared. Compound 10R is a potent dual NK(1)/NK(2) antagonist and demonstrates excellent in vivo activity and good oral plasma levels in the dog.
Ting
Pauline C
PC
The Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. pauline.ting@spcorp.com
Lee
Joe F
JF
Shih
Neng Yang
NY
Piwinski
John J
JJ
Anthes
John C
JC
Chapman
Richard W
RW
Rizzo
Charles A
CA
Hey
John A
JA
Ng
Kwokei
K
Nomeir
Amin A
AA
D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018041:Receptors, Neurokinin-2