Discovery of a series of potent, orally active α,α-disubstituted piperidine NK(1) antagonists

Dong Xiao; Cheng Wang; Anandan Palani; Hon-Chung Tsui; Gregory Reichard; Sunil Paliwal; Neng-Yang Shih; Robert Aslanian; Ruth Duffy; Jean Lachowicz; Geoffrey Varty; Cynthia Morgan; Fei Liu; Amin Nomeir

doi:10.1016/j.bmcl.2010.08.059

Discovery of a series of potent, orally active α,α-disubstituted piperidine NK(1) antagonists

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6313-5. doi: 10.1016/j.bmcl.2010.08.059. Epub 2010 Aug 15.

Authors

Dong Xiao¹, Cheng Wang, Anandan Palani, Hon-Chung Tsui, Gregory Reichard, Sunil Paliwal, Neng-Yang Shih, Robert Aslanian, Ruth Duffy, Jean Lachowicz, Geoffrey Varty, Cynthia Morgan, Fei Liu, Amin Nomeir

Affiliation

¹ Chemical Research Department, Merck Research Laboratories, Kenilworth, NJ 07033, USA. dong.xiao@merck.com

PMID: 20846861
DOI: 10.1016/j.bmcl.2010.08.059

Abstract

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.

MeSH terms

Animals
Area Under Curve
Chromatography, High Pressure Liquid
Gerbillinae
Half-Life
Neurokinin-1 Receptor Antagonists*
Piperidines / chemical synthesis*
Piperidines / pharmacokinetics
Piperidines / pharmacology*
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

Neurokinin-1 Receptor Antagonists
Piperidines