Comparative molecular field analysis (CoMFA) of a series of selective adenosine receptor A(2A) antagonists

Selective and potent antagonists for the A2A adenosine receptors have been described recently. The most potent compds. have a triazolo-​pyrimidine structure, whereas 8-​styryl-​xanthines usually possess lower affinity at the A2A receptor. We have examd. the quant. structure activity relationships of 34 triazolo-​pyrimidines using the Comparative Mol. Field Anal. (CoMFA)​. The model developed accounts in a satisfactory manner for the structure-​activity relationships within this series of A2A receptor antagonists (q2 = 0.840, r2 = 0.970) and, consequently, it can be used as a guide in the design of novel analogs with optimized antagonistic activity. The overall predictivity of this model was tested on the published data of a set of external mols. giving acceptable results. The validity of the CoMFA approach as an effective tool for studying the 3D-​QSAR of series of biol. active compds. is confirmed, even if addnl. efforts clearly are needed for trying to extend the models to structurally more varied series of derivs