A Cannabinoid Derived Prototypical Analgesic

Article abstract of DOI:10.1021/jm00367a013

The synthesis and analgesic testing of 3-<4-(1,1-dimethylheptyl)-2-hydroxyphenyl>cyclohexanol (1) are described.Prior (SAR) studies led us to conclude that the pyran ring of 9-nor-9β-hydroxyhexahydrocannabinol (HHC) was not necessary for the expression of biological activity in this series of cannabinoids.Analysis of models and the use of molecular mechanics calculations suggested that a simpler compound, such as 1, would possess the biological activity of HHC.Compound 1 was prepared in nine steps from <3-(benzyloxy)phenyl>acetonitrile (2).Biological testing in five models of pain shows that compound 1 and morphine are equally potent as analgesics and demonstrates that the pyran ring of HHC is not necessary for biological activity.Further simplification of 1 was pursued by the synthesis of 4-<4-(1,1-dimethylheptyl)-2-hydroxyphenyl>-2-pentanol (17), but this derivative exhibits significantly reduced analgesic activity.