Development of CoMFA and CoMSIA models of affinity and selectivity for indole ligands of cannabinoid CB1 and CB2 receptors

This paper describes CoMFA and CoMSIA studies for affinity and selectivity of a series of indole ligands to cannabinoid CB1 and CB2 receptors. The developed models have proven to be predictive, with average q2 of 0.675 and average r2 of 0.855, demonstrating a good statistical validation. The obtained results have helped us to understand the structural motifs that are responsible for the affinity and selectivity of some of these derivatives towards each subtype of cannabinoid receptor and have demonstrated that the exploited 3D-QSAR methods could be useful tools for the design of new safer analogues presenting better affinity and selectivity profiles.

Graphical abstractPredictive CoMFA and CoMSIA models for cannabinoid CB1 and CB2 receptors, with average q2 of 0.675 and r2 of 0.855, are described.Figure optionsDownload full-size imageDownload as PowerPoint slide