Recent Developments Cannabinoids in the Medicinal Chemistry of Cannabinoids

Abstract

Abstract: As a result of the recognition of a cannabinoid receptor, the isolation of the first endogenous cannabinoid and, more recently, the significant discovery of a cannabinoid antagonist, there has been a resurgence of interest in the medicinal chemistry of cannabinoids. This has included inter alia investigations into the effects of side chain substitution and overall molecular geometry on the biological activity of traditional cannabi­ noids, which are partially reduced dibenzopyrans, as well as the design and synthesis of a variety of non-traditional cannabinoids. These compounds include indole and pyrrole derivatives, which are agonists, a diarylpyrazole, which is the first cannabinoid antagonist, and various amides of arachidonic acid. The latter compounds are patterned on anandamide (arachidonic acid ethanolamide), the first endogenous cannabinoid isolated from mammalian brain tissue. Modeling studies of the cannabinoid receptor are beginning to provide some insight into the interaction of various agonists with the receptor. This article will review recent developments in the medicinal chemistry of cannabinoids with an emphasis on work reported since 1992.