Triazoloquinazolines as Human A3 Adenosine Receptor Antagonists: A QSAR Study

Multiple linear regression analysis was performed on the quantitative structureactivity relationships (QSAR) of the triazoloquinazoline adenosine antagonists for human A3 receptors. The data set used for the QSAR analysis encompassed the activities of 33 triazoloquinazoline derivatives and 72 physicochemical descriptors. A template molecule was derived using the known molecular structure for one of the compounds when bound to the human A2B receptor, in which the amide bond was in a cis-conformation. All the test compounds were aligned to the template molecule. In order to identify a reasonable QSAR equation to describe the data set, we developed a multiple linear regression program that examined every possible combination of descriptors. The QSAR equation derived from this analysis indicates that the spatial and electronic effects is greater than that of hydrophobic effects in binding of the antagonists to the human A3 receptor. It also predicts that a large sterimol length parameter is advantageous to activity, whereas large sterimol width parameters and fractional positive partial surface areas are nonadvatageous.