Tricyclic Fused Pyrazoles with a ‘Click’ 1,2,3-Triazole Substituent in Position 3 Are Nanomolar CB1 Receptor Ligands

Abstract Structural modification of the potent conformationally constrained tricyclic pyrazole CB1 ligand NESS0327 was achieved by replacing: (1) the chlorine substituent on the tricycle with a 3-fluoropropyl chain, and (2) the pyrazole 3-{[(piperidino)amino]carbonyl} substituent with a 4-substituted 1,2,3-triazole group obtained by click chemistry from an alkynyl precursor. Among the resulting compounds, two are particularly promising candidates for [18F]radiolabelling and PET imaging studies of the CB1 receptor, as they displayed K i CB1 = 62.5 nM and 42.5 nM, respectively, in the same range as that displayed by rimonabant.