New platelet aggregation inhibitors based on pyridazinone moiety

被引：24

作者：

Costas, Tamara ^{[1
,2
]}

Carmen Costas-Lago, Maria ^{[1
,2
]}

Vila, Noemi ^{[1
,2
]}

Besada, Pedro ^{[1
,2
]}

Cano, Ernesto ^{[3
]}

Teran, Carmen ^{[1
,2
]}

机构：

[1] Univ Vigo, Dept Quim Organ, Vigo 36310, Spain

[2] Univ Vigo, Inst Invest Biomed IBI, Vigo 36310, Spain

[3] Univ Santiago Compostela, Dept Farmacol, Santiago De Compostela 15782, Spain

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 94卷

关键词：

Pyridazinone; 3-Alkylfuran; Singlet oxygen; Butenolide; Bicyclic lactone; Platelet aggregation inhibitors; RECEPTOR GLYCOPROTEIN VI; COLLAGEN RECEPTOR; PHOSPHODIESTERASE INHIBITORS; GAMMA-HYDROXYBUTENOLIDES; CARDIOTONIC AGENTS; DERIVATIVES; DESIGN; VASORELAXANT; ASSOCIATION; AFFINITY;

D O I：

10.1016/j.ejmech.2015.02.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New series of pyridazinone derivatives (4, 5 and 6) were synthesized in good yields following a synthetic strategy based on singlet oxygen oxidation of alkyl furans, in which a suitable beta(alpha)-substituted gamma-hydroxybutenolide (10 or 11) or a bicyclic lactone (12 or 13) was the key intermediate. The synthesized compounds were tested in vitro as antiplatelet agents and some of them (compounds 4b, 4d and 5b) exhibited potent inhibitory effects on collagen-induced platelet aggregation with IC50 values in the low mu M range. Studies performed with the most active compound of these series (4b) demonstrated its lack of activity as inhibitor of platelet aggregation induced by other agonists as thrombin, ionomycin or U-46619 suggesting a selective action on the biochemical mechanisms triggered by collagen in the platelets. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：113 / 122

页数：10

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