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

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 CB1 and CB2 receptors and were identified as new lead structures. In further GTP gamma S binding studies selected compounds were shown to be antagonists or inverse agonists. (c) 2009 Elsevier Ltd. All rights reserved.