Synthesis of a Novel Series of Amino Acid Prodrugs Based on Thienopyridine Scaffolds and Evaluation of Their Antiplatelet Activity

Abstract

The thienopyridines class of drugs used as P2Y12 receptor antagonists plays a vital role in antiplatelet therapy. To further optimized this compound class, we designed and synthesized a series of amino acid prodrugs of 2-hydroxytetrahydrothienopyridine. All compounds were then evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats and then ED50 and bleeding time of the most potent compounds were compared with commercial drugs. The results showed compound 5c could be a potent and safe candidate for further research.

An expedient synthesis of novel bis[thienopyridines] linked to arene or heteroarene core as novel hybrid molecules

“…13,14 Thienopyridines are considered as one of the important fused heterocyclic compounds for their usefulness therapeutic applications. 15,16 Moreover, several thienopyridine derivatives are known to possess antiviral, 17 anti-inflammatory, 18 antimicrobial, 19 antidiabetic, 20 antihypertensive 21 and osteogenic activities. 22 In particular, thieno [2,3-b]pyridines are reported to be useful as anticancer agents.…”

Synthesis, In Vitro Antiplatelet Activity of 4‐Ethoxy‐isophthalamides

“…of potassium permanganate in water to form 4-ethoxyisophthalic acid (3). React with thionyl chloride to form 4-ethoxyisophthaloyl chloride (4), which can be directly used in the next reaction without further purification. [19] The yields of the three reactions to prepare intermediates (2), (3) and 4…”

“…[1,2] The pathogenesis of many cardiovascular diseases is related to platelet aggregation and thrombosis. [3][4][5] Platelets store growth factors, cytokines, and vasoactive substances in granules, which can be released in a controlled manner after stimulation, and can also increase the expression of various adhesion molecules and receptors and the cell surface. The production of thromboxane A 2 (TXA 2 ) in turn activates other platelets and promotes vasoconstriction and local thrombosis.…”