title: Synthesis and pharmacological evaluation of coumarin derivatives as cannabinoid receptor antagonists and inverse agonists.
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.
authors.affiliation: PharmaCenter Bonn, University of Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Behrenswerth
authors.forename: Nicole
authors.initials: N
authors.lastname: Volz
authors.forename: Jakob
authors.initials: J
authors.lastname: Toräng
authors.forename: Sonja
authors.initials: S
authors.lastname: Hinz
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
mesh_terms: 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
chemical_list: D003374:Coumarins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2