78945-29-6Relevant articles and documents
Structure-activity relationships for 1′,1′-dimethylalkyl-Δ8-tetrahydrocannabinols
Huffman, John W.,Miller, John R. A.,Liddle, John,Yu, Shu,Thomas, Brian F.,Wiley, Jenny L.,Martin, Billy R.
, p. 1397 - 1410 (2007/10/03)
A series of 1′,1′-dimethylalkyl-Δ8-tetrahydrocannabinol analogues with C-3 side chains of 2-12 carbon atoms has been synthesized and their in vitro and in vivo pharmacology has been evaluated. The lowest member of the series, 1′,1′-dimethylethyl-Δ8-THC (8, n=0) has good affinity for the CB1 receptor, but is inactive in vivo. The dimethylpropyl (8, n=1) through dimethyldecyl (8, n=8) all have high affinity for the CB1 receptor and are full agonists in vivo. 1′,1′-Dimethylundecyl-Δ8-THC (8, n=9) has significant affinity for the receptor (Ki=25.8±5.8 nM), but has reduced potency in vivo. The dodecyl analogue (8, n=10) has little affinity for the CB1 receptor and is inactive in vivo. A quantitative structure-activity relationship study of the side chain region of these compounds is consistent with the concept that for optimum affinity and potency the side chain must be of a length which will permit its terminus to loop back in proximity to the phenolic ring of the cannabinoid.
