339094-26-7Relevant academic research and scientific papers
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 (2007)
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.
Novel Functionalized Cannabinoid Receptor Probes: Development of Exceptionally Potent Agonists
Jiang, Shan,Iliopoulos-Tsoutsouvas, Christos,Tong, Fei,Brust, Christina A.,Keenan, Catherine M.,Raghav, Jimit Girish,Hua, Tian,Wu, Simiao,Ho, Jo-Hao,Wu, Yiran,Grim, Travis W.,Zvonok, Nikolai,Thakur, Ganesh A.,Liu, Zhi-Jie,Sharkey, Keith A.,Bohn, Laura M.,Nikas, Spyros P.,Makriyannis, Alexandros
, p. 3870 - 3884 (2021/05/04)
We report the development of novel cannabinergic probes that can stabilize the cannabinoid receptors (CBRs) through tight binding interactions. Ligand design involves the introduction of select groups at a judiciously chosen position within the classical
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 (2007/10/03)
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,
Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1′
Papahatjis, Demetris P.,Nikas, Spyros P.,Kourouli, Therapia,Chari, Ravi,Xu, Wei,Pertwee, Roger G.,Makriyannis, Alexandros
, p. 3221 - 3229 (2007/10/03)
Earlier work from our laboratories has provided evidence for the existence of a subsite within the CB1 and CB2 cannabinoid receptor binding domain corresponding to substituents at the benzylic side chain position of classical cannabinoids. The existence a
