Synthesis and structure-activity relationships of 8-azabicyclo[3.2.1]octane benzylamine NK1 antagonists

Christopher G Thomson; Emma Carlson; Gary G Chicchi; Janusz J Kulagowski; Marc M Kurtz; Christopher J Swain; Kwei-Lan C Tsao; Alan Wheeldon

doi:10.1016/j.bmcl.2005.11.026

Synthesis and structure-activity relationships of 8-azabicyclo[3.2.1]octane benzylamine NK1 antagonists

Bioorg Med Chem Lett. 2006 Feb 15;16(4):811-4. doi: 10.1016/j.bmcl.2005.11.026. Epub 2005 Nov 22.

Authors

Christopher G Thomson¹, Emma Carlson, Gary G Chicchi, Janusz J Kulagowski, Marc M Kurtz, Christopher J Swain, Kwei-Lan C Tsao, Alan Wheeldon

Affiliation

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

PMID: 16307878
DOI: 10.1016/j.bmcl.2005.11.026

Abstract

A series of 8-azabicyclo[3.2.1]octane amine hNK1 antagonists has been investigated and structure-activity relationships of the benzylamine and 6-exo substituents described. Acidic substituents at C6 give a series of high affinity compounds for hNK1 with selectivity over the hERG channel.

MeSH terms

Aza Compounds / chemical synthesis*
Aza Compounds / chemistry
Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
Bridged Bicyclo Compounds, Heterocyclic / chemistry
Humans
Molecular Conformation
Neurokinin-1 Receptor Antagonists*
Stereoisomerism
Structure-Activity Relationship

Substances

8-azabicyclo(3.2.1)octane benzylamine
Aza Compounds
Bridged Bicyclo Compounds, Heterocyclic
Neurokinin-1 Receptor Antagonists