title: 1-Benzhydryl-3-phenylurea and 1-benzhydryl-3-phenylthiourea derivatives: new templates among the CB1 cannabinoid receptor inverse agonists.
abstract: New 1-benzhydryl-3-phenylurea derivatives and their 1-benzhydryl-3-phenylthiourea isosteres were synthesized and evaluated for their human CB1 and CB2 cannabinoid receptor affinity. These compounds proved to be selective CB1 cannabinoid receptor ligands, acting as inverse agonists in a [35S]-GTPgammaS assay. The affinity of 3,5,5'-triphenylimidazolidine-2,4-dione and 3,5,5'-triphenyl-2-thioxoimidazolidin-4-one derivatives, possessing the 1-benzhydryl-3-phenylurea and 1-benzhydryl-3-phenylthiourea moiety, respectively, was also evaluated. In conclusion, the 1-benzhydryl-3-phenylurea scaffold seems to be a new interesting template of CB1 cannabinoid receptor inverse agonists.
authors.affiliation: Unité de Chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Faculté de Médecine, Université catholique de Louvain, Avenue E. Mounier 73, UCL-CMFA 7340, B-1200 Bruxelles, Belgium.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: Johan
authors.initials: J
authors.lastname: Wouters
authors.forename: Gerhard K E
authors.initials: GK
authors.lastname: Scriba
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poppitz
authors.forename: Jacques H
authors.initials: JH
authors.lastname: Poupaert
authors.forename: Didier M
authors.initials: DM
authors.lastname: Lambert
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists; D013329:Structure-Activity Relationship
chemical_list: D001559:Benzhydryl Compounds; D010671:Phenylurea Compounds; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D010670:Phenylthiourea