Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands
oleh: Patricio Iturriaga-Vásquez, Carlos David Pessoa-Mahana, Hernán Pessoa-Mahana, Javier Romero-Parra, Christian Espinosa-Bustos, Carlos F. Lagos, Gonzalo Recabarren-Gajardo, Jaime A. Mella-Raipán
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2013-04-01 |
Deskripsi
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).