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Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands

A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used as a template for optimization. In the present series, 21 compounds displayed high affinities with K(i) values in the nanomolar range. JM...

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Detalles Bibliográficos
Autores principales: Mella-Raipán, Jaime A., Lagos, Carlos F., Recabarren-Gajardo, Gonzalo, Espinosa-Bustos, Christian, Romero-Parra, Javier, Pessoa-Mahana, Hernán, Iturriaga-Vásquez, Patricio, Pessoa-Mahana, Carlos David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270614/
https://www.ncbi.nlm.nih.gov/pubmed/23558540
http://dx.doi.org/10.3390/molecules18043972
Descripción
Sumario:A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used as a template for optimization. In the present series, 21 compounds displayed high affinities with K(i) values in the nanomolar range. JM-39 (compound 39) was the most active of the series (K(iCB1) = 0.53 nM), while compounds 31 and 44 exhibited similar affinities to WIN 55212-2. CoMFA analysis was performed based on the biological data obtained and resulted in a statistically significant CoMFA model with high predictive value (q(2) = 0.710, r(2) = 0.998, r(2)(pred) = 0.823).