J Med Chem. 1976 Apr; 19(4): 552-4.

Drugs derived from cannabinoids. 4. Effect of alkyl substitution in sulfur and carbocyclic analogs.

Razdan RK, Handrick GR, Dalzell HC, Howes JF, Winn M, Plotnikoff NP, Dodge PW, Dren AT.

Various CNS-active cannabinoids in which the alicyclic ring was thiopheno, cyclopenteno, or cyclohexeno with the alkyl substituent in various positions (structural types 1-6) were synthesized by procedures described previously. These compounds were compared in selected pharmacological tests in mice, rats, dogs, and cats. The results suggested that methyl substitution in the close proximity of the phenolic hydroxyl group strongly influenced the activity of some cannabinoids, particularly of those which had a planar five-membered alicyclic ring rather than a six-membered ring.