Synthesis of 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines and their antiplatelet and vasodilatory activity

• DOI: 10.1093/jpp/rgab075
• Publication Date: 2021-04-30T12:03:39Z
• Authors: Samvel N Sirakanyan; Marcel Hrubša; Domenico Spinelli; Patrícia Dias; Victor Kartsev; Alejandro Carazo; Anush A Hovakimyan; Jana Pourová; Elmira K Hakobyan; Jana Karlíčková; Shamima Parvin; Jaka Fadraersada; Kateřina Macáková; Athina Geronikaki; Přemysl Mladěnka
• Keywords: Enamine

Both pyridine and pyrano derivatives have been previously shown to possess biologically relevant activity. In this study, we report the incorporation of these two scaffolds into one molecule.The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by acylation enamine under Stork conditions followed condensation formed β-diketones with 2-cyanoacetamide. The structures compounds confirmed using a wide spectrum physico-chemical methods. Their antiplatelet, anticoagulant vasodilatory activity together toxicity evaluated.A series 6-oxopyrano[3,4-c]pyridines 3a-j was obtained. Four reported for first time. None tested demonstrated effect but 8-methyl derivative (3a) potent antiplatelet compound IC50 numerically twice as low clinically used acetylsalicylic acid. A further mechanistic tests showed that 3a interferes calcium signaling. is also not toxic in addition possesses well.Compound promising inhibitor platelet aggregation, whose mechanism action should be studied detail.