1-Phenyl-8-azabicyclo[3.2.1]octane ethers: a novel series of neurokinin (NK1) antagonists

Ian T Huscroft; Emma J Carlson; Gary G Chicchi; Marc M Kurtz; Clare London; Piotr Raubo; Alan Wheeldon; Janusz J Kulagowski

doi:10.1016/j.bmcl.2005.12.069

1-Phenyl-8-azabicyclo[3.2.1]octane ethers: a novel series of neurokinin (NK1) antagonists

Bioorg Med Chem Lett. 2006 Apr 1;16(7):2008-12. doi: 10.1016/j.bmcl.2005.12.069. Epub 2006 Jan 18.

Authors

Ian T Huscroft¹, Emma J Carlson, Gary G Chicchi, Marc M Kurtz, Clare London, Piotr Raubo, Alan Wheeldon, Janusz J Kulagowski

Affiliation

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

PMID: 16413782
DOI: 10.1016/j.bmcl.2005.12.069

Abstract

1-Phenyl-8-azabicyclo[3.2.1]octane ethers are NK(1) receptor antagonists. Substitution at the 6-exo-position led to high affinity NK(1) antagonists with a prolonged duration of action in vivo. Incorporation of an alpha-methyl substituent in the pendent benzyl ether side chain gave compounds with increased selectivity over the hERG channel.

MeSH terms

Animals
Aza Compounds / pharmacology*
Bridged Bicyclo Compounds / pharmacology*
CHO Cells
Cricetinae
Cyclization
Ether-A-Go-Go Potassium Channels / drug effects
Humans
Neurokinin-1 Receptor Antagonists*

Substances

Aza Compounds
Bridged Bicyclo Compounds
Ether-A-Go-Go Potassium Channels
KCNH6 protein, human
Neurokinin-1 Receptor Antagonists