Design, synthesis, binding and docking-based 3D-QSAR studies of 2-pyridylbenzimidazoles - A new family of high affinity CB1 cannabinoid ligands

Article abstract of DOI:10.3390/molecules18043972

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 (q² = 0.710, r² = 0.998, r²_pred = 0.823).