4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists I

Jason M Elliott; Jose L Castro; Gary G Chicchi; Laura C Cooper; Kevin Dinnell; Gregory J Hollingworth; Mark P Ridgill; Wayne Rycroft; Marc M Kurtz; Duncan E Shaw; Christopher J Swain; Kwei-Lan Tsao; Lihu Yang

doi:10.1016/s0960-894x(02)00249-4

4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists I

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1755-8. doi: 10.1016/s0960-894x(02)00249-4.

Authors

Jason M Elliott¹, Jose L Castro, Gary G Chicchi, Laura C Cooper, Kevin Dinnell, Gregory J Hollingworth, Mark P Ridgill, Wayne Rycroft, Marc M Kurtz, Duncan E Shaw, Christopher J Swain, Kwei-Lan Tsao, Lihu Yang

Affiliation

¹ Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. jason_elliot@merck.com

PMID: 12067554
DOI: 10.1016/s0960-894x(02)00249-4

Abstract

A series of novel 4,4-disubstituted cyclohexylamine based NK(1) antagonists is described. The effect of changes to the C(1)-C(4) relative stereochemistry on the cyclohexane ring and replacements for the flexible linker are discussed, leading to the identification of compounds with high affinity and good in vivo duration of action.

MeSH terms

Animals
Binding Sites
CHO Cells
Central Nervous System / drug effects
Central Nervous System / metabolism
Cricetinae
Cyclohexylamines / chemical synthesis*
Cyclohexylamines / pharmacokinetics
Cyclohexylamines / pharmacology*
Gerbillinae
Inhibitory Concentration 50
Molecular Conformation
Neurokinin-1 Receptor Antagonists*
Radioligand Assay
Receptors, Neurokinin-1 / chemistry
Structure-Activity Relationship

Substances

Cyclohexylamines
Neurokinin-1 Receptor Antagonists
Receptors, Neurokinin-1