Synthesis, anti‐platelet aggregation activity evaluation and structure–activity relationships of a series of novel purine derivatives

Abstract

This article described how further extensive variation of the substituents on the purine scaffold of adenosine triphosphate (ATP), and the human anti‐platelet aggregation activities were modified in order to find exploitation of the structure–activity relationships (SAR). A series of novel designed 6‐alkylamino‐2‐alkylthio‐9‐hydroxyalkyl(carbalkoxy) purine derivatives were synthesized via a modification procedure, and the human anti‐platelet aggregation activities were evaluated. The SAR of these compounds were analyzed in detail, and the results of the structural requirements of the substituents to improve potency may provide a basis for the development of potent P2Y12 antagonists.

Synthesis of novel purine derivatives: Antiplatelet aggregation activity evaluation and 3D‐QSAR analysis

“…The data set consists of 75 purine derivative molecules with the molecular structures shown in Table 1, of which 13 molecules data were obtained from our research paper [ 26 ] and the other 62 molecules data were synthesized and tested in this study. PAR values are the percentage of platelet aggregation and the data were processed using the equation lg(PAR) = lg([1/PAR]/c) (concentration c for compounds 1–36 was 100 × 10 −6 mol/L and c for compounds 37–75 was 10 × 10 −6 mol/L) for subsequent calculations.…”

“…b The compounds data are from our research article. [26] indicating that the model has better predictive ability, and the activity data lg (PAR) values for all compounds in the training and test sets were predicted using this model (the SOMFA model calculated predicted values are shown in Table 1). The combination coefficient c 1 of the model was 0.454, indicating that the steric field contribution has more influence on the activity.…”