Natural cannabinoids: templates for drug discovery.
Recent studies have elucidated the biosynthetic pathway of cannabinoids and have highlighted the preference for a C-3 n-pentyl side chain in the most prominently represented cannabinoids from Cannabis sativa and their medicinally important decarboxylation products. The corresponding C-3 n-propyl side chain containing cannabinoids are also found, although in lesser quantities. Structure-activity relationship (SAR) studies performed on Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the key psychoactive ingredient of Cannabis, and its synthetic analogues have identified the C-3 side chain as the key pharmacophore for ligand affinity and selectivity for the known cannabinoid receptors and for pharmacological potency. Interestingly, the terminal n-pentyl saturated hydrocarbon side chain of endocannabinoids also plays a corresponding crucial role in conferring similar properties. This review briefly summarizes the biosynthesis of cannabinoids and endocannabinoids and focuses on their side chain SAR.
Thakur
Ganesh A
GA
Center for Drug Discovery, Northeastern University, 360 Huntington Avenue, 116 Mugar Life Sciences Building, Boston, MA 02115, USA.
Duclos
Richard I
RI
Makriyannis
Alexandros
A
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D002186:Cannabinoids / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D010600:Pharmacology; D013329:Structure-Activity Relationship
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids