Enantiomeric cannabidiol derivatives: synthesis and binding to cannabinoid receptors.
(-)-Cannabidiol (CBD) is a major, non psychotropic constituent of cannabis. It has been shown to cause numerous physiological effects of therapeutic importance. We have reported that CBD derivatives in both enantiomeric series are of pharmaceutical interest. Here we describe the syntheses of the major CBD metabolites, (-)-7-hydroxy-CBD and (-)-CBD-7-oic acid and their dimethylheptyl (DMH) homologs, as well as of the corresponding compounds in the enantiomeric (+)-CBD series. The starting materials were the respective CBD enantiomers and their DMH homologs. The binding of these compounds to the CB(1) and CB(2) cannabinoid receptors are compared. Surprisingly, contrary to the compounds in the (-) series, which do not bind to the receptors, most of the derivatives in the (+) series bind to the CB(1) receptor in the low nanomole range. Some of these compounds also bind weakly to the CB(2) receptor.
Hanus
Lumír O
LO
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Medical Faculty, The Hebrew University of Jerusalem, Ein Kerem 91120, Jerusalem, Israel. lumir@cc.huji.ac.il
Tchilibon
Susanna
S
Ponde
Datta E
DE
Breuer
Aviva
A
Fride
Ester
E
Mechoulam
Raphael
R
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002185:Cannabidiol / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
C469526:Cnr2 protein, rat; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D002185:Cannabidiol