• anti-obesity agents;
  • bioactive ligands;
  • cannabinoid receptors;
  • CB1;
  • CoMFA;
  • hologram QSAR

Two-dimensional and 3D quantitative structure–activity relationships studies were performed on a series of diarylpyridines that acts as cannabinoid receptor ligands by means of hologram quantitative structure–activity relationships and comparative molecular field analysis methods. The quantitative structure–activity relationships models were built using a data set of 52 CB1 ligands that can be used as anti-obesity agents. Significant correlation coefficients (hologram quantitative structure–activity relationships: r 2 = 0.91, q 2 = 0.78; comparative molecular field analysis: r 2 = 0.98, q 2 = 0.77) were obtained, indicating the potential of these 2D and 3D models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted (calculated) values are in good agreement with the experimental results. The final quantitative structure–activity relationships models, along with the information obtained from 2D contribution maps and 3D contour maps, obtained in this study are useful tools for the design of novel CB1 ligands with improved anti-obesity potency.