Adamantyl Cannabinoids: A Novel Class of Cannabinergic Ligands
| العنوان: | Adamantyl Cannabinoids: A Novel Class of Cannabinergic Ligands |
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| المؤلفون: | Clifford George, John Steed, Damon A. Parrish, Dai Lu, Dow P. Hurst, Zhaoxing Meng, Pusheng Fan, Cindy L. Tartal, Richard J Lamb, Torbjörn U. C. Järbe, Jeffrey R. Deschamps, Alexandros Makriyannis, Ganesh A. Thakur, Patricia H. Reggio |
| المصدر: | Journal of Medicinal Chemistry. 48:4576-4585 |
| بيانات النشر: | American Chemical Society (ACS), 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, Models, Molecular, Molecular model, Protein Conformation, Stereochemistry, medicine.medical_treatment, Molecular Conformation, Adamantane, In Vitro Techniques, Crystallography, X-Ray, Ligands, Discrimination Learning, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB2, Radioligand Assay, Structure-Activity Relationship, chemistry.chemical_compound, Receptor, Cannabinoid, CB1, mental disorders, Drug Discovery, Cannabinoid receptor type 2, Side chain, medicine, Animals, Computer Simulation, Dronabinol, Binding site, chemistry.chemical_classification, Chemistry, Brain, Rats, Molecular Medicine, lipids (amino acids, peptides, and proteins), Cannabinoid, Pharmacophore, Lead compound, Tricyclic |
| الوصف: | Structure-activity relationship studies have established that the aliphatic side chain plays a pivotal role in determining the cannabinergic potency of tricyclic classical cannabinoids. We have now synthesized a series of analogues in which a variety of adamantyl substituents were introduced at the C3 position of Delta(8)-THC. Our lead compound, (-)-3-(1-adamantyl)-Delta(8)-tetrahydrocannabinol (1a, AM411), was found to have robust affinity and selectivity for the CB1 receptor as well as high in vivo potency. The X-ray crystal structure of 1a was determined. Exploration of the side chain conformational space using molecular modeling approaches has allowed us to develop cannabinoid side chain pharmacophore models for the CB1 and CB2 receptors. Our results suggest that although a bulky group at the C3 position of classical cannabinoids could be tolerated by both CB1 and CB2 binding sites, the relative orientation of that group with respect to the tricyclic component can lead to receptor subtype selectivity. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a547809c524c85ea79ba9f7b62fb8233 https://doi.org/10.1021/jm058175c |
| رقم الأكسشن: | edsair.doi.dedup.....a547809c524c85ea79ba9f7b62fb8233 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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