2D-QSAR of non-benzodiazepines to benzodiazepines receptor (BZR)

Abstract

Several non-benzodiazepine compounds such as beta-carbolines, imidazo[1,2-alpha]-pyrimidines, and disubstituted purines bind with the benzodiazepine receptor site ( BZR) with a high affinity. Thus, all compounds that bind to the BZR should have certain common characteristics that allow for recognition by the receptor regardless of the type of ( in vivo) activity. Quantitative structure-activity relationships ( QSAR) analyses of four series of non-benzodiazepines were carried out using different physicochemical descriptors. The molecular design and calculations were done by using ACD Lab software. For each set, 2048 regression models were generated and the best-fit model of each series was identified by using values of the coefficients q(2) and r(2). In the case of the best-fit model of series A (r(CV)(2) = 0.82 r(2) = 0.86) and series C (r(CV)(2) = 0.91, r(2) = 0.97) the steric bulk interaction was dominant, whereas in the cases of series B (r(CV)(2) = 0.87, r(2) = 0.96) and series D (r(CV)(2) = 0.63, r(2) = 0.82) the electrostatic interaction was dominant.