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Molecules 2013, 18(4), 3972-4001; doi:10.3390/molecules18043972
Article

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

1, 2, 2, 2, 2, 3, 4 and 2,*
1 Departamento de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Casilla 5030, Avda. Gran Bretaña 1111, Playa Ancha, Valparaíso, Chile 2 Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, 22, Santiago, Chile 3 Departamento de Química Orgánica y Físicoquímica, Facultad de Química y Ciencias Farmacéuticas, Universidad de Chile, Casilla 233, Santiago, Chile 4 Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 233, Santiago, Chile
* Author to whom correspondence should be addressed.
Received: 26 February 2013 / Revised: 24 March 2013 / Accepted: 1 April 2013 / Published: 4 April 2013
(This article belongs to the Section Medicinal Chemistry)
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Abstract

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 Ki values in the nanomolar range. JM-39 (compound 39) was the most active of the series (KiCB1 = 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 (q2 = 0.710, r2 = 0.998, r2pred = 0.823).
Keywords: cannabinoid; CB1 receptor; binding; docking; 3D-QSAR cannabinoid; CB1 receptor; binding; docking; 3D-QSAR
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Mella-Raipán, J.A.; Lagos, C.F.; Recabarren-Gajardo, G.; Espinosa-Bustos, C.; Romero-Parra, J.; Pessoa-Mahana, H.; Iturriaga-Vásquez, P.; Pessoa-Mahana, C.D. Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands. Molecules 2013, 18, 3972-4001.

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