Design And Synthesis Of Novel 8-azapurine Nucleoside Derivatives Derived Based On Structure-activity Relationships

In this paper,by using SOMFA,CoMFA and CoMSIA three 3D-QSAR analysis methods,the structure-antiplatelet aggregation activity ralationships of a series of 6-alkylamino-2-alkylthio-purine nucleosides were studied.It were concluded that propylthio group was used C-2 position and amine compounds with strong electron-withdrawing groups such as F,Cl was used in the C-6 position of the purine ring;The use of strong hydrogen bonding donor groups such as-COOH in C-5' position of the sugar ring could further improve the activity of these drugs.These results provide theoretical guidance for the design of novel compounds.Two series of novel compounds were designed based on 3D-QSAR analysis,and the latter compounds were successfully synthesized in this paper.The isotopic configuration of the 8-azapurine nucleoside derivatives was identified,and the best closing cycle reaction conditions were explored.Eighteen novel 8-azapurine nucleoside derivatives were synthesized,these compounds were characterized by 1H NMR,13C NMR and HRMS.