3D-QSAR studies of 4-quinolone derivatives as high-affinity ligands at the benzodiazepine site of brain GABAA receptors

Three dimensional quantitative structure activity relationship approach using CoMFA and CoMSIA was applied to a series of 4-quinolone derivatives as high-affinity ligands at the benzodiazepine site of brain GABAA receptors. For the purpose, 27 compounds were used to develop models. 3D-QSAR models with high-squared correlation coefficient of up to 0.979 for CoMFA and 0.931 for CoMSIA were established. The robustness of the model was confirmed with the help of leave one out cross-validation method with rcv2 values of up to 0.526 and 0.546 for CoMFA and CoMSIA, respectively. Developed models highlighted the importance of shape of the molecules, i.e., steric descriptors for GABAA receptor binding.