Discovery of a series of potent, orally active α,α-disubstituted piperidine NK(1) antagonists.
Modification of prototype NK(1) antagonist 2 resulted in the synthesis of a series of simple amides 6 and retroamides 9. These compounds were shown to be potent and orally active NK(1) antagonists.
Xiao
Dong
D
Chemical Research Department, Merck Research Laboratories, Kenilworth, NJ 07033, USA. dong.xiao@merck.com
Wang
Cheng
C
Palani
Anandan
A
Tsui
Hon-Chung
HC
Reichard
Gregory
G
Paliwal
Sunil
S
Shih
Neng-Yang
NY
Aslanian
Robert
R
Duffy
Ruth
R
Lachowicz
Jean
J
Varty
Geoffrey
G
Morgan
Cynthia
C
Liu
Fei
F
Nomeir
Amin
A
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005849:Gerbillinae; D006207:Half-Life; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines