Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Abstract

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 CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 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 CB1 or CB2 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.

Structure–Activity Relationship Studies on Highly Functionalized Pyrazole Hydrazones and Amides as Antiproliferative and Antioxidant Agents

“…Melting points were measured on a Fisher-Johns apparatus and are uncorrected. 1 H NMR and 13 C NMR spectra were collected on a JEOL JNM-ECZR (Tokyo, Japan) instrument (Figures S1-S44); chemical shifts were reported in δ (ppm) units, and the splitting patterns were described as follows: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), and m (multiplet). The first-order values reported for coupling constants J were given in Hz.The elemental composition of synthesized compounds was collected by an EA1110.…”

“…Pyrazole scaffold is a pharmaceutically relevant moiety [1][2][3][4][5][6], and pyrazole-containing compounds show antiviral [7], antibacterial [8,9], antimalarial [10], anti-inflammatory [11], antidiabetic [12], antiglaucoma [13,14], and anticancer [15][16][17][18][19][20][21] properties. Furthermore, pyrazole scaffolds are shared by several protein kinase inhibitors, including FDA-approved drugs Avapritinib, Asciminib, Crizotinib, Encorafenib, Erdafitinib, Pralsetinib, Pirtobrutinib, and Ruxolitinib (Figure 1) [22,23].…”

Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO2-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines

“…Due to the discovery of a number of practical applications, there is increasing interest in the chemistry of pyrazole-based compounds, and fluorinated analogues are of special significance in medicine, crop protection, as well as material sciences [ 1 , 2 , 3 , 4 ]. The title heterocycle constitutes a key structural element of pharmaceuticals and agrochemicals; they exhibit a variety of biological activities such as being anti-inflammatory (e.g., Celecoxib, Lonazolac), antibacterial, anticancer (e.g., Crizotinib), anti-obesity (e.g., Rimonabant), antidepressant (e.g., Fezolamine), antiviral (e.g., Lenacapavir), and antifungal (e.g., Penthiopyrad), and have been widely applied as pesticides ( Figure 1 ) [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. In addition, some pyrazoles have been successfully applied in polymer chemistry, as well as for the preparation of advanced liquid crystalline materials [ 14 , 15 ].…”