Essential Structural Profile of Novel Adenosine Derivatives as Antiplatelet Aggregation Inhibitors based on 3D-QSAR Analysis

Aims: In this research, 3D-QSAR evaluation on a set of fresh purinoid compounds that we produced was conducted. This analysis aims to illustrate the correlation between the structure of purine and its ability to prevent platelet aggregation. Our findings could pave the way to discovering novel antithrombotic medications. background: Cardiovascular disease caused by platelet aggregation is a serious threat to human health. Purine derivatives are important molecules with antiplatelet aggregation activity. Background: The incidence of cardiovascular disease triggered by the clumping of platelets poses a significant danger to human health. Purine derivatives are important molecules with antiplatelet aggregation activity. Objective: The objectives of this research are to establish the correlation between the structure of purine and its ability to prevent platelet aggregation. Such a correlation could aid in the development of innovative antithrombotic medications. method: In this study, 3D-QSAR analysis was performed on a series of novel purine derivatives synthesized by us based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Methods: In this study, 3D-QSAR investigation on a collection of 75 new purine derivatives, which we synthesized, was conducted, utilizing Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). result: Significant correlation coefficients (CoMFA, q2=0.843, r2=0.930, F value=266.755, SEE=0.165; CoMSIA, q2=0.869, r2=0.918, F value=222.571, SEE=0.179) were obtained, and the model prediction ability was validated using the test set. Results: Significant correlation coefficients (CoMFA, q2= 0.843, r2= 0.930, F value= 266.755, SEE= 0.165; CoMSIA, q2= 0.869, r2= 0.918, F value= 222.571, SEE= 0.179) were obtained, and assessed the model's predictive capabilities by validating it with the test set. conclusion: The results suggest that it is beneficial to introduce a group of appropriate size at position C-2 of the purine ring, and that an excessively large group is disadvantageous; a bulky substituent group cannot be directly attached at the C-6 position of the purine ring, and the attachment of a group with low electron cloud density increases the activity, and the attachment of a bulky group at the C-5' of the sugar ring is beneficial, and the presence of hydrogen bond receptors in this region also increases the activity. Conclusion: Our findings indicate that the introduction of an appropriately sized structure at position 2 of the compound yields significant benefits. Conversely, the attachment of an excessively large group is detrimental. Direct attachment of a bulky substituent at C-6 of the compound is not feasible, and its activity increases when the structure with low electron cloud density is added. Moreover, the presence of a voluminous functional group at the 5' position of the compound is advantageous, and its activity will be further increased by the presence of hydrogen bond receptors in this region. These discoveries furnish significant comprehension for the formation of innovative structures with heightened efficacy.