2026-06-27T23:20:12Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/937482025-02-22T00:47:12Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Ragusa, Giulio author Gómez Cañas, María author Pazos Rodríguez, María Ruth author Fernández Ruiz, José Javier author García Arencibia, Moisés author Murineddu, Gabriele 2024-01-18T08:38:03Z 2024-01-18T08:38:03Z 2015 Ragusa G, Gómez-Cañas M, Morales P, Hurst DP, Deligia F, Pazos R, Pinna GA, Fernández-Ruiz J, Goya P, Reggio PH, Jagerovic N, García-Arencibia M, Murineddu G. Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB2 receptor antagonists. Eur J Med Chem. 2015 Aug 28;101:651-67. doi: 10.1016/j.ejmech.2015.06.057 0223-5234 10.1016/j.ejmech.2015.06.057 https://hdl.handle.net/20.500.14352/93748 https://doi.org/10.1016/j.ejmech.2015.06.057 During the last years, there has been a continuous interest in the development of cannabinoid receptor ligands that may serve as therapeutic agents and/or as experimental tools. This prompted us to design and synthesize analogues of the CB2 receptor antagonist N-fenchyl-5-(4-chloro-3-methyl-phenyl)-1-(4- methyl-benzyl)-1H-pyrazole-3-carboxamide (SR144528). The structural modifications involved the bioisosteric replacement of the pyrazole ring by a pyrrole ring and variations on the amine carbamoyl substituents. Two of these compounds, the fenchyl pyrrole analogue 6 and the myrtanyl derivative 10, showed high affinity (Ki in the low nM range) and selectivity for the CB2 receptor and both resulted to be antagonists/inverse agonists in [35S]-GTPgS binding analysis and in an in vitro CB2 receptor bioassay. Cannabinoid receptor binding data of the series allowed identifying steric constraints within the CB2 binding pocket using a study of Van der Waals' volume maps. Glide docking studies revealed that all docked compounds bind in the same region of the CB2 receptor inactive state model. eng Synthesis, pharmacological evaluation and docking studies of pyrrole structure-based CB 2 receptor antagonists journal article 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URL https://docta.ucm.es/bitstreams/2bc51716-14b7-4ffd-b55b-80596b47109e/download File MD5 477ff9c1dcbb33fc11e23d524db2e3fb 1995164 application/pdf Structure-based_CB2_receptor_antagonists.pdf