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3-Oxopyridazin-5-yl-Chalcone Hybrids: Potent Antiplatelet Agents That Prevent Glycoprotein IIb/IIIa Activation
Univ Santiago de Compostela, Ctr Singular Invest Quim Biol & Mat Mol CIQUS, Santiago De Compostela 15782, Spain..
Univ Santiago de Compostela, Fac Farm, Dept Farmacol, Santiago De Compostela 15782, Spain..
Univ Santiago de Compostela, Ctr Singular Invest Quim Biol & Mat Mol CIQUS, Santiago De Compostela 15782, Spain..
Univ Santiago de Compostela, Fac Farm, Dept Farmacol, Santiago De Compostela 15782, Spain..
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2017 (English)In: CHEMISTRYSELECT, ISSN 2365-6549, Vol. 2, no 17, 4920-4933 p.Article in journal (Refereed) Published
Abstract [en]

A novel family of potent and broad-spectrum antiplatelet agents has been discovered by exploration of a library of 3-oxopyridazin-5-yl-chalcone hybrids. The pharmacological evaluation of the collection established the most salient features of the SAR in this series and allowed the identification of lead compounds that exhibit antiplatelet activity that is substantially superior to drugs in clinical use and 3,4-methylenedioxy-β-nitrostyrene (MNS). The derivatives reported herein act on GPIIb/IIIa, but in a different manner to classical antagonists (e.g., tirofiban), by preventing GPIIb/IIIa activation. Given their mechanism of action, these compounds might avoid the adverse effects of antagonists (paradoxical GPIIb/IIIa activation) and constitute attractive pharmacological tools for the development of tailored agents for the treatment of platelet-dependent thrombosis.

Place, publisher, year, edition, pages
2017. Vol. 2, no 17, 4920-4933 p.
Keyword [en]
Chalcones, GPIIb, IIIa activation, Platelets, Platelet aggregation inhibitors, Pyridazinones
National Category
Materials Chemistry Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:uu:diva-329688DOI: 10.1002/slct.201700243ISI: 000403886100051OAI: oai:DiVA.org:uu-329688DiVA: diva2:1148335
Available from: 2017-10-10 Created: 2017-10-10 Last updated: 2017-10-10Bibliographically approved

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Gutiérrez de Terán, Hugo

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