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DOI: 10.1055/s-0032-1307619
Identification of Hydrazone Derivatives as Cannabinoid Receptor Inverse Agonists
Cannabinoid receptors, CB1 and CB2, are G-protein linked receptors that are positively coupled to adenylyl cyclase. These discoveries have led to the development of selective CB1 and CB2 receptor ligands. Our strategy is to identify selective CB1 and CB2 receptor ligands from natural products or synthetic compounds for pain management, drug abuse, cancer and diabetes. Compounds HZ 1–10 were synthesized via the nucleophilic addition-elimination reaction of 3-cyclohexylpropionic acid hydrazide with various benzaldehydes and evaluated for their CB1 and CB2 receptor activities by specific receptor binding assays and [35S]-GTPãS membrane functional assay. Compounds 1, 5, 7, 8, 9 exhibited binding to CB1 and CB2 receptors, further [35S] GTPãS membrane functional assays show that compound HZ-9 produced CB1 and CB2 inverse agonist activities with an EC50 of 1.2 and 0.065µM on CB1 and CB2 receptors, respectively.