Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB(1)/CB(2) Receptor Interaction

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB(1) and/or CB(2) receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB(1) antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB(1) or CB(2) receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.