title: Structural-activity relationship study on C-4 carbon atom of the CB1 antagonist SR141716: synthesis and pharmacological evaluation of 1,2,4-triazole-3-carboxamides.
abstract: A series of 1,2,4-triazole-3-carboxamides has been prepared from alkyl-1,2,4-triazole-3-carboxylates under mild conditions. The ability of these triazoles to displace [3H]-CP55940 from CB1 cannabinoid receptor was measured. However, they showed only poor to moderate binding affinities, indicating that substitution of the C-4 pyrazole atom of the CB1 reference compound SR141716 by a nitrogen atom results in loss of affinity. Further investigations for functionality indicated that the compound 6a exhibited significant cannabinoid antagonistic properties in the mouse vas deferens functional assay. This leads us to the conclusion that 6a binds at a different CB1 binding site or at a new cannabinoid receptor subtype.
authors.affiliation: Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain. nadine@iqm.csic.es
authors.forename: Nadine
authors.initials: N
authors.lastname: Jagerovic
authors.forename: Laura
authors.initials: L
authors.lastname: Hernandez-Folgado
authors.forename: Ibon
authors.initials: I
authors.lastname: Alkorta
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Martín
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Dannert
authors.forename: Angela
authors.initials: A
authors.lastname: Alsasua
authors.forename: Jordi
authors.initials: J
authors.lastname: Frigola
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Cuberes
authors.forename: Alberto
authors.initials: A
authors.lastname: Dordal
authors.forename: Jörg
authors.initials: J
authors.lastname: Holenz
mesh_terms: D000818:Animals; D001665:Binding Sites; D003511:Cyclohexanols / Q000494:pharmacology; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077285:Rimonabant; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D003511:Cyclohexanols; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014230:Triazoles; C017957:1,2,4-triazole-3-carboxamide; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant