Synthesis and pharmacological evaluation of coumarin derivatives as cannabinoid receptor antagonists and inverse agonists

Andrea Behrenswerth; Nicole Volz; Jakob Toräng; Sonja Hinz; Stefan Bräse; Christa E Müller

doi:10.1016/j.bmc.2009.02.027

Synthesis and pharmacological evaluation of coumarin derivatives as cannabinoid receptor antagonists and inverse agonists

Bioorg Med Chem. 2009 Apr 1;17(7):2842-51. doi: 10.1016/j.bmc.2009.02.027. Epub 2009 Feb 21.

Authors

Andrea Behrenswerth¹, Nicole Volz, Jakob Toräng, Sonja Hinz, Stefan Bräse, Christa E Müller

Affiliation

¹ PharmaCenter Bonn, University of Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany.

PMID: 19278853
DOI: 10.1016/j.bmc.2009.02.027

Abstract

In the present study we synthesized 36 coumarin and 2H-chromene derivatives applying a recently developed umpoled domino reaction using substituted salicylaldehyde and alpha,beta-unsaturated aldehyde derivatives as starting compounds. In radioligand binding studies 5-substituted 3-benzylcoumarin derivatives showed affinity to cannabinoid CB(1) and CB(2) receptors and were identified as new lead structures. In further GTPgammaS binding studies selected compounds were shown to be antagonists or inverse agonists.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Coumarins / chemical synthesis*
Coumarins / chemistry
Coumarins / pharmacology*
Drug Inverse Agonism
Humans
Rats
Receptor, Cannabinoid, CB1 / agonists*
Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
Receptor, Cannabinoid, CB1 / metabolism
Receptor, Cannabinoid, CB2 / agonists*
Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
Receptor, Cannabinoid, CB2 / metabolism
Species Specificity
Structure-Activity Relationship

Substances

Coumarins
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2