1992/05/01 by William A. Devane, Aviva Breuer, Tzviel Sheskin +3 · 203 citations
Chemistry · Medicine · #Agonist #Analytical Methods in Pharmaceuticals #Biochemistry #Biological activity #Cannabinoid #Cannabinoid Receptor Agonists #Cannabinoid receptor #Cannabis and Cannabinoid Research #Chemical synthesis #Chemistry #Dronabinol #Drug Transport and Resistance Mechanisms #ED50 #Epimer #In vitro #Intrinsic activity #Ligand (biochemistry) #Potency #Receptor #Stereochemistry #Tetrahydrocannabinol
paper · open access · doi:10.1021/jm00089a018
published in Journal of Medicinal Chemistry 35(11), 2065-2069 (American Chemical Society)
openalex publication_date 1992/05/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/01
The 1,1-dimethylheptyl (DMH) homologue of 7-hydroxy-delta 6-tetrahydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5'-(1,1-dimethylheptyl)-7-hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (8), depending on the catalysts and conditions used. Compound 7 discriminates for delta 1-THC (2) in pigeons (ED50 = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (1), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor.