Synthesis of 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines and their antiplatelet and vasodilatory activity
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články
Grantová podpora
CZ.02.1.01/0.0/0.0/16_019/0000841
EFSA-CDN project
SVV 260 549
ERDF
Charles University
PubMed
34106261
DOI
10.1093/jpp/rgab075
PII: 6295440
Knihovny.cz E-zdroje
- Klíčová slova
- anticoagulant, antiplatelet activity, cytotoxicity, pyranopyridine, vasodilatory, β-diketones,
- MeSH
- agregace trombocytů * MeSH
- antikoagulancia farmakologie MeSH
- inhibitory agregace trombocytů * chemie farmakologie MeSH
- pyridiny farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antikoagulancia MeSH
- inhibitory agregace trombocytů * MeSH
- pyridiny MeSH
OBJECTIVES: 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. METHODS: The designed 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines were synthesized by the acylation of enamine under Stork conditions followed by condensation of formed β-diketones with 2-cyanoacetamide. The structures of these compounds were confirmed by using a wide spectrum of physico-chemical methods. Their antiplatelet, anticoagulant and vasodilatory activity together with toxicity were evaluated. KEY FINDINGS: A series of 6-oxopyrano[3,4-c]pyridines 3a-j was obtained. Four of these compounds were reported for the first time. None of the tested compounds demonstrated anticoagulant effect but 8-methyl derivative (3a) was a potent antiplatelet compound with IC50 numerically twice as low as the clinically used acetylsalicylic acid. A series of further mechanistic tests showed that 3a interferes with calcium signaling. The compound is also not toxic and in addition possesses vasodilatory activity as well. CONCLUSIONS: Compound 3a is a promising inhibitor of platelet aggregation, whose mechanism of action should be studied in detail.
Department of Pharmacognosy Faculty of Pharmacy Charles University Hradec Králové Czech Republic
Dipartimento di Chimica G Ciamician Alma Mater Studiorum Università di BolognaBologna Italy
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