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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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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
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author 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
author_facet 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
author_sort Mella-Raipán, Jaime A.
collection PubMed
description 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).
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spelling pubmed-62706142018-12-14 Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands 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 Molecules Article 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). MDPI 2013-04-04 /pmc/articles/PMC6270614/ /pubmed/23558540 http://dx.doi.org/10.3390/molecules18043972 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
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
Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
title Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
title_full Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
title_fullStr Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
title_full_unstemmed Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
title_short Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
title_sort design, synthesis, binding and docking-based 3d-qsar studies of 2-pyridylbenzimidazoles—a new family of high affinity cb1 cannabinoid ligands
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270614/
https://www.ncbi.nlm.nih.gov/pubmed/23558540
http://dx.doi.org/10.3390/molecules18043972
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