339094-27-8Relevant academic research and scientific papers
Structural modifications of the cannabinoid side chain towards C3-aryl and 1′,1′-cycloalkyl-1′-cyano cannabinoids
Papahatjis, Demetris P.,Nahmias, Victoria R.,Andreou, Thanos,Fan, Pusheng,Makriyannis, Alexandros
, p. 1616 - 1620 (2006)
The compounds reported in this study are Δ8-THC analogues in which the C3 five-carbon linear side chain of Δ8-THC was replaced with aryl and 1′,1′-cycloalkyl substituents. Of the compounds described here analogues 2d (CB1,
C1′-cycloalkyl side chain pharmacophore in tetrahydrocannabinols
Papahatjis, Demetris P.,Nahmias, Victoria R.,Nikas, Spyros P.,Andreou, Thanos,Alapafuja, Shakiru O.,Tsotinis, Andrew,Guo, Jianxin,Fan, Pusheng,Makriyannis, Alexandros
, p. 4048 - 4060 (2008/02/09)
In earlier work we have provided evidence for the presence of a subsite within the CB1 and CB2 cannabinoid receptor binding domains of classical cannabinoids. This putative subsite corresponds to substituents on the C1-position of the C3-alkyl side chain, a key pharmacophoric feature in this class of compounds. We have now refined this work through the synthesis of additional C1′-cycloalkyl compounds using newly developed approaches. Our findings indicate that the C1′-cyclopropyl and C1′-cyclopentyl groups are optimal pharmacophores for both receptors while the C1′-cyclobutyl group interacts optimally with CB1 but not with CB2. The C1′-cyclohexyl analogs have reduced affinities for both CB1 and CB2. However, these affinities are significantly improved with the introduction of a C2′-C3′ cis double bond that modifies the available conformational space within the side chain and allows for a better accommodation of a six-membered ring within the side chain subsite. Our SAR results are highlighted by molecular modeling of key analogs.
