339094-29-0Relevant academic research and scientific papers
A New Ring-Forming Methodology for the Synthesis of Conformationally Constrained Bioactive Molecules
Papahatjis, Demetris P.,Nikas, Spyros,Tsotinis, Andrew,Vlachou, Margarita,Makriyannis, Alexandros
, p. 192 - 193 (2001)
A new, general, one pot method for introducing carboxylic rings alpha to a nitrile moiety is described. Treatment of readily available arylacetonitriles with potassium bis(trimethylsilyl)amide and subsequent alkylation with α,ω-dibromo or dichloroalkanes
Improved cyclobutyl nabilone analogs as potent CB1 receptor agonists
Papanastasiou, Ioannis P.,Georgiadis, Markos-Orestis,Iliopoulos-Tsoutsouvas, Christos,Paronis, Carol A.,Brust, Christina A.,Tran, Ngan K.,Ji, Lipin,Ma, Xiaoyu,Wood, JodiAnne T.,Zvonok, Nikolai,Tong, Fei,Bohn, Laura M.,Nikas, Spyros P.,Makriyannis, Alexandros
supporting information, (2022/01/20)
In earlier work, we explored the SAR for the C3 side chain pharmacophore in the hexahydrocannabinol template represented by the drug nabilone, which resulted in the development of AM2389. In an effort for further optimization, we have merged features of n
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.
