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 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.
Behrenswerth
Andrea
A
PharmaCenter Bonn, University of Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany.
Volz
Nicole
N
Toräng
Jakob
J
Hinz
Sonja
S
Bräse
Stefan
S
Müller
Christa E
CE
D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054314:Drug Inverse Agonism; D006801:Humans; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship
D003374:Coumarins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2