Synthesis of 6-Alkylamino-2-alkylthio(alkoxy) Purine Derivatives: Antiplatelet Aggregation Activity Evaluation and 3D-QSAR Analysis

Globally, cardio-cerebrovascular diseases caused by platelet aggregation pose a grave threat to human health, and hence, research on anti-platelet aggregation is of paramount importance. It has been demonstrated that purine derivatives are essential molecules for antiplatelet aggregation activity. Therefore, it would be of great value to investigate the correlation between the structure of purine derivatives and the antiplatelet aggregation function, which could be of great assistance in the search for novel drugs. In this paper, we investigate the structural modification of molecules with purine structure as backbone, 46 designed 6-alkylamino-alkylthio(alkoxy) purine derivatives were synthesized via a modification procedure and evaluate their antiplatelet aggregation activity, these compounds were analyzed by 3D-QSAR based on self-organized field analysis (SOMFA). The model with significant results was obtained (SOMFA r2 = 0.855, r2cv = 0.843, F = 247.316, SEE = 0.334), and the prediction ability of the model was verified by the test set. The results indicated that judicious modification of substituents would be beneficial in the development of more effective antiplatelet drugs.