Novel compounds of hybrid structure pyridazinone–coumarin as potent inhibitors of platelet aggregation

The current limitations of antiplatelet therapy promote the search for new antithrombotic agents. Here we describe novel platelet aggregation inhibitors that combine pyridazinone and coumarin scaffolds in their structure. The target compounds were synthesized in good yield from maleic anhydride, fol...

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Bibliographic Details
Published in:Future medicinal chemistry 2019-08, Vol.11 (16), p.2051-2062
Main Authors: Costas-Lago, María C, Besada, Pedro, Cano, Ernesto, Terán, Carmen
Format: Article
Language:English
Subjects:
Antibodies
Binding sites
Blood clots
Blood platelets
Cardiovascular disease
Cardiovascular system
Coumarin
Glycoproteins
hybrid structures
Kinases
pharmacology
Phosphatase
Phosphorylation
Platelet aggregation
platelet aggregation inhibitors
Proteins
Pyridazinone
synthetic chemistry
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Summary:The current limitations of antiplatelet therapy promote the search for new antithrombotic agents. Here we describe novel platelet aggregation inhibitors that combine pyridazinone and coumarin scaffolds in their structure. The target compounds were synthesized in good yield from maleic anhydride, following a multistep strategy. The studies demonstrated significant antiplatelet activity in many of these compounds, with IC values in the low micromolar range, revealing that the activity was affected by the substitution pattern of the two selected cores. Additional studies point out their effect as inhibitors of glycoprotein (Gp) IIb/IIIa activation. This novel hybrid structure can be considered a good prototype for the development of potent platelet aggregation inhibitors. Potent platelet aggregation inhibitors were discovered by combining both pyridazinone and coumarin scaffolds. Compounds , and with IC values in the low micromolar range, against thrombin, seem to be the most promising.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2018-0373