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Thrombosis is responsible for thousands of deaths in a myriad of countries particularly the developed ones. Venous thrombosis incidents such as deep vein thrombosis and thromboembolism are the inevitable results of the contemporary lifestyle. In this article, we have designed a new family of tehtrahydro pyrido pyrimidines inspired by structures of antiplatelet agents reported in the literature. Furthermore, 13 derivatives of our lead compound  N '-benzylidene-7-(4-methoxyphenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carbohydrazide have been synthesized. The molecular docking study was conducted on COX-1 enzyme (pdb: 2oye), Compounds  8b  and  8d  had the most calculated binding energy with Δ G  values of −8.41 and −7.74 Kcal/mol, sequentially. The platelet aggregometry inhibition effects of the synthesized compounds have been measured on the voluntarily donated human platelets using BORN turbidimetry method. Furthermore, compound  8d  showed the most potency with the IC 50  value of 16.9 and 37.41 µM on the ADP and AA inducers, respectively. Generally, all the compounds with electron-withdrawing substituents showed plausible activity against the ADP-inducing platelet aggregation. Besides, electron-withdrawing compounds in para position showed an acceptable inhibitory effect on the AA platelet inducer.

polycyclic aromatic compounds

Design, Docking Study, Synthesis, and Platelet Aggregometry Assay of Novel  N '-Benzylidene-7-(4-Methoxyphenyl)-2,4-Dioxo-1,2,3,4-Tetrahydropyrido[2,3-d]Pyrimidine-5-Carbohydrazide Derivatives as Antiplatelet Agents