Synthesis and antiaggregative acti vity of αIIbβ3-receptor antagonist based on 2-(4-piperazine- 1-yl)-3H-quinazoline-4-one

TitleSynthesis and antiaggregative acti vity of αIIbβ3-receptor antagonist based on 2-(4-piperazine- 1-yl)-3H-quinazoline-4-one
Publication TypeJournal Article
Year of Publication2019
AuthorsAndronati, SA, Kornylov, AY, Polishchuk, PG, Krysko, AA, Krysko, OL, Kabanova, TA, Sambursky, SE
Abbreviated Key TitleDopov. Nac. akad. nauk Ukr.
Date Published09/2019

A new derivative of 2-(4-piperazin-1-yl)-quinazolin-4-one is synthesized, the compound has structure similar to small-molecule αIIbβ3-receptor antagonist based on 7-(piperazin-1-yl)-[1,3,4]thiadiazolo[3,2-a]pirimidin-5- one (RUC-2). To obtain the target compound, two alternative methods are used. The compound is an antagonist of the αIIbβ3-receptor, which binds to the closed form of the protein. The antiaggregative activity of the compound is studied on platelet-rich plasma (PRP) in an in vitro test. The molecular mechanism of antiplatelet action is measured as the inhibition of the fluorescein isothiocyanate-labeled fibrinogen (FITC-Fg) binding to activated human platelets by the tested compound. Docking studies of the synthesized compound revealed that ligand–protein interactions mainly correspond to the complex RUC-2–αIIbβ3. The target compound has high antiaggregative activity and can be recommended for the further study as a promising antithrombotic agent.

Keywords6-bromo-3H-quinazoline-4-one, C–C cross-coupling, fibrinogen receptor antagonist, palladium-catalysis, peptide bond formation, platelet aggregation, αIIbβ3

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