piperidines and 1-2-4-triazole-3-carboxamide

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.

Topics: Animals; Binding Sites; Cyclohexanols; Male; Mice; Piperidines; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant; Structure-Activity Relationship; Triazoles; Vas Deferens