Synthesis and Antiplatelet and Anticoagulant Activity of Thietane-Containing 2-(5-Bromo-2,4-Dihydro-3-Oxo-1,2,4-Triazolyl-4)Acetate Salts

Sulfone was synthesized via oxidation of ethyl 2-[5-bromo-2,4-dihydro-3-oxo-2-(thietanyl-3)-1,2,4-triazolyl- 4]acetate () by HO. Hydrolysis of esters and synthesized 2-[5-bromo-2,4-dihydro- 3-oxo-2-(thietanyl-3)-1,2,4-triazolyl-4]- and 2-[5-bromo-2,4-dihydro-3-oxo-2-(1,1-dioxothietanyl-3)-1,2,4- triazolyl-4]acetic acids and , respectively.Water-soluble salts and were prepared by reacting acids and with alkali-metal hydroxides and amines. The structures of the synthesized compounds were confirmed IR and NMR spectroscopic data. The antiplatelet and anticoagulant activity of the synthesized compounds was studied based on predictions of the PASS computer program. Compounds and , which showed the absence of predicted toxic risks and were superior to the reference drug in the collagen-induced aggregation test, had the most pronounced antiplatelet activity (comparable to that of acetylsalicylic acid) in the ADP-induced aggregation test. The anticoagulant activity of the compounds was significantly inferior to that of heparin sodium. All synthesized compounds satisfied Lipinski's rule-of-5.