2-aryl indole NK1 antagonists: Optimisation of the amide substituent

Authors
Shaw, D Chicchi, GG Elliott, JM Kurtz, M Morrison, D Ridgill, MP Szeto, N Watt, AP Williams, AR Swain, CJ
Citation
D. Shaw et al., 2-aryl indole NK1 antagonists: Optimisation of the amide substituent, BIOORG MED, 11(23), 2001, pp. 3031-3034
Citations number
7
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
23
Year of publication
2001
Pages
3031 - 3034
Database
ISI
SICI code
0960-894X(200112)11:23<3031:2INAOO>2.0.ZU;2-Y
Abstract
The in vivo properties of a series of 2-arylindole NK1 antagonists have bee n improved, by modification of the amide substituent. The 1-(2-methoxypheny l)piperazine amide was identified as a major area of metabolism in the lead compound 1. Replacement of this amine moiety by a 4-benzyl-4-hydroxypiperi dine resulted in a compound IS with reduced clearance and improved central duration of action. (C) 2001 Published by Elsevier Science Ltd.