Synthesis, QSAR modeling, and molecular docking of novel fused 7-deazaxanthine derivatives as adenosine A2A receptor antagonists

Abstract

Predictive QSAR models for the search of new adenosine A_2A receptor antagonists were developed by using OCHEM platform. The predictive ability of the regression models has coefficient of determination q² = 0.65-0.71 with cross-validation and independent test set. The inhibition activities of novel fused 7-deazaxanthine compounds were predicted by the developed QSAR models. A preparative method for the synthesis of pyrimido[5',4':4,5]pyrrolo[1,2-a][1,4]diazepine derivatives was developed, and 11 new adenosine A_2A receptor antagonists were obtained. Preliminary investigations into the toxicology of fused 7-deazaxanthine compounds toward commonly used model organism to assess toxicity invertebrate cladoceran D. magna were also described.

Keywords: A2A antagonists; Fused 7-deazaxanthine; QSAR; machine learning; molecular docking.