Synthesis of 3,3-dimethyl-6-oxopyrano[3,4-c]pyridines and their antiplatelet and vasodilatory activity
Language English Country Great Britain, England Media print
Document type Journal Article
Grant support
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-resources
- Keywords
- anticoagulant, antiplatelet activity, cytotoxicity, pyranopyridine, vasodilatory, β-diketones,
- MeSH
- Platelet Aggregation * MeSH
- Anticoagulants pharmacology MeSH
- Platelet Aggregation Inhibitors * chemistry pharmacology MeSH
- Pyridines pharmacology MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anticoagulants MeSH
- Platelet Aggregation Inhibitors * MeSH
- Pyridines 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
References provided by Crossref.org
