Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists

Karin Worm; Damian G Weaver; Rosalyn C Green; Christopher T Saeui; Doreen-Marie S Dulay; William M Barker; Joel A Cassel; Gabriel J Stabley; Robert N DeHaven; Christopher J LaBuda; Michael Koblish; Bernice L Brogdon; Steven A Smith; Roland E Dolle

doi:10.1016/j.bmcl.2009.07.057

Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5004-8. doi: 10.1016/j.bmcl.2009.07.057. Epub 2009 Jul 12.

Authors

Karin Worm¹, Damian G Weaver, Rosalyn C Green, Christopher T Saeui, Doreen-Marie S Dulay, William M Barker, Joel A Cassel, Gabriel J Stabley, Robert N DeHaven, Christopher J LaBuda, Michael Koblish, Bernice L Brogdon, Steven A Smith, Roland E Dolle

Affiliation

¹ Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. [email protected]

PMID: 19646869
DOI: 10.1016/j.bmcl.2009.07.057

Abstract

Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB(2) agonists. Selective CB(2) agonist 31 (K(i)=2.7; CB(1)/CB(2)=190) displayed robust activity in a rodent model of postoperative pain.

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacology
Benzamides / chemical synthesis
Benzamides / chemistry*
Benzamides / pharmacology
CHO Cells
Cell Line
Cricetinae
Cricetulus
Drug Discovery
Humans
Pain, Postoperative / drug therapy
Rats
Receptor, Cannabinoid, CB2 / agonists*
Receptor, Cannabinoid, CB2 / metabolism
Stereoisomerism
Structure-Activity Relationship
Transfection

Substances

Anti-Inflammatory Agents
Benzamides
Receptor, Cannabinoid, CB2