Pharmacokinetic optimisation of novel indole-2-carboxamide cannabinoid CB1 antagonists

Phillip M Cowley; James Baker; Kirsteen I Buchanan; Ian Carlyle; John K Clark; Thomas R Clarkson; Maureen Deehan; Darren Edwards; Yasuko Kiyoi; Iain Martin; Dawn Osbourn; Glenn Walker; Nick Ward; Grant Wishart

doi:10.1016/j.bmcl.2011.02.019

Pharmacokinetic optimisation of novel indole-2-carboxamide cannabinoid CB1 antagonists

Bioorg Med Chem Lett. 2011 Apr 1;21(7):2034-9. doi: 10.1016/j.bmcl.2011.02.019. Epub 2011 Feb 19.

Authors

Phillip M Cowley¹, James Baker, Kirsteen I Buchanan, Ian Carlyle, John K Clark, Thomas R Clarkson, Maureen Deehan, Darren Edwards, Yasuko Kiyoi, Iain Martin, Dawn Osbourn, Glenn Walker, Nick Ward, Grant Wishart

Affiliation

¹ Department of Chemistry, MSD, Newhouse, Lanarkshire ML1 5SH, UK. [email protected]

PMID: 21334892
DOI: 10.1016/j.bmcl.2011.02.019

Abstract

The pharmacokinetic based optimisation of a novel series of indole-2-carboxamide antagonists of the cannabinoid CB(1) receptor is disclosed. Compound 24 was found to be a highly potent and selective cannabinoid CB(1) antagonist with high predicted human oral bioavailability.

MeSH terms

Administration, Oral
Biological Availability
Humans
Indoles / administration & dosage
Indoles / chemistry
Indoles / pharmacokinetics*
Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Indoles
Receptor, Cannabinoid, CB1