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 α,β-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 GTPγS binding studies selected compounds were shown to be antagonists or inverse agonists.

3-Benzylcoumarin derivatives synthesized from substituted salicylaldehydes and α,β-unsaturated aldehydes by an umpoled domino reaction were identified as new lead structures for the development of cannabinoid receptor antagonists/inverse agonists.Figure optionsDownload as PowerPoint slide