Abstract

Cannabinoid 1 Receptors (CB1) are neuronal terminals, responsible for synaptic communication between nerves. They are essential for binding of ligands to form biologically active complexes and monitor G-protein functions. CB1 agonists are already being used clinically for therapeutic uses such as multiple sclerosis, inflammatory disorder, and cancer. Naturally occurring cannabinoids show high affinity for CB1 receptors, with the presence of an indole ring increasing binding affinity. Substitutions and their various positions on an indole ring system plays a crucial role in the binding to CB1 receptors. The synthesis of various substituted indoles by the Hemetsberger-Knittel method from a variety of substituted aldehydes is underway. 3,4,5 Trimethoxybenzaldehyde provided the best yield of vinyl azide 67% prior to thermolysis. The formation of ethyl azidoacetate using water and acetone as co-solvents, produced ethyl azidoacetate in greater yield than previously reported by literature and previous group members. Knoevenagel process and xylene mediated thermolysis under nitrogenous conditions produced vinyl azide and indole ester, respectively. Previous research suggests the presence of the carboxamide functionality at the 2 position of the indole is crucial for increased affinity to the CB1 receptors. Reduction of the indole ester to an indole acid will allow for a variety of indole-2-carboxamides to be synthesized using BOP reagent, triethylamine and N,N-dimethylformamide.

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