Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents†,10.1039/C1OB05478C

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Lactoyl-CoA 全氟丁基戊烷白叶藤碱全氟己基辛烷新白叶藤碱壳寡糖特色专题-生物多肽

Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents†

Xuliang Wang,Yang Li,Qian Zhao,Zhenli Min,Chao Zhang,Yisheng Lai,Hui Ji,Sixun Peng,Yihua Zhang

Organic & Biomolecular Chemistry Pub Date : 04/12/2011 00:00:00 , DOI:10.1039/C1OB05478C

Abstract

Novel nitric oxide (NO) releasing derivatives (7a–7l) of 3-n-butylphthalide (NBP) were designed and synthesized. Compound 7e inhibited the adenosine diphosphate (ADP), thrombin (TH) and arachidonic acid (AA)-induced in vitroplatelet aggregation, superior to NBP and aspirin, released moderate levels of NO, and improved aqueous solubility relative to NBP. Furthermore, 7e exhibited greater antithrombotic activity than NBP and aspirin in rats, and protected against collagen and adrenaline-induced thrombosis in mice. Therefore, NO-releasing NBP derivatives possessed potent antiplatelet aggregation and antithrombotic activity. Our findings may aid in the design of new therapeutic agents for the treatment of thrombosis-related ischemic stroke.