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

被引：40

作者：

Wang, Xuliang ^{[2
]}

Li, Yang ^{[2
]}

Zhao, Qian ^{[1
]}

Min, Zhenli ^{[2
]}

Zhang, Chao ^{[1
]}

Lai, Yisheng ^{[2
]}

Ji, Hui ^{[1
]}

Peng, Sixun ^{[2
]}

Zhang, Yihua ^{[2
]}

机构：

[1] China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Peoples R China

[2] China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Peoples R China

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2011年 / 9卷 / 16期

关键词：

CEREBRAL-BLOOD-FLOW; BIOLOGICAL EVALUATION; PLATELET-AGGREGATION; THROMBUS FORMATION; ISCHEMIC-STROKE; DONOR DRUGS; ACID; 2-(1-HYDROXYPENTYL)-BENZOATE; MECHANISMS; INHIBITORS;

D O I：

10.1039/c1ob05478c

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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 vitro platelet 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.

引用

页码：5670 / 5681

页数：12

共 38 条

[1]

BENEDINI F, 2007, Patent No. 000641

[2]

BORN GVR, 1963, J PHYSIOL-LONDON, V168, P178, DOI 10.1113/jphysiol.1963.sp007185

[3] Carbonic anhydrase inhibitors: Water-soluble 4-sulfamoylphenylthioureas as topical intraocular pressure-lowering agents with long-lasting effects [J].

Casini, A ;

Scozzafava, A ;

Mincione, F ;

Menabuoni, L ;

Ilies, MA ;

Supuran, CT .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (25) :4884-4892

[4] Design, synthesis, and antihepatocellular carcinoma activity of nitric oxide releasing derivatives of oleanolic acid [J].

Chen, Li ;

Zhang, Yihua ;

Kong, Xiangwen ;

Lan, Edward ;

Huang, Zhangjian ;

Peng, Sixun ;

Kaufman, Daniel L. ;

Tian, Jide .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (15) :4834-4838

[5] Synthesis and biological evaluation of nitric oxide-releasing derivatives of oleanolic acid as inhibitors of HepG2 cell apoptosis [J].

Chen, Li ;

Zhang, Yihua ;

Kong, Xiangwen ;

Peng, Sixun ;

Tian, Jide .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (11) :2979-2982

[6] Pathobiology of ischaemic stroke: an integrated view [J].

Dirnagl, U ;

Iadecola, C ;

Moskowitz, MA .

TRENDS IN NEUROSCIENCES, 1999, 22 (09) :391-397

[7] Targeting eNOS for stroke protection [J].

Endres, M ;

Laufs, U ;

Liao, JK ;

Moskowitz, MA .

TRENDS IN NEUROSCIENCES, 2004, 27 (05) :283-289

[8] Antithrombotic and Fibrinolytic Activities of Methanolic Extract of Aged Sorghum Vinegar [J].

Fan, Junfeng ;

Zhang, Yanyan ;

Chang, Xiaojie ;

Zhang, Bolin ;

Jiang, Da ;

Saito, Masayoshi ;

Li, Zaigui .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2009, 57 (18) :8683-8687

[9] Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer drug candidates [J].

Fang, Lei ;

Appenroth, Dorothea ;

Decker, Michael ;

Kiehmopf, Michael ;

Roegler, Carolin ;

Deufel, Thomas ;

Fleck, Christian ;

Peng, Sixun ;

Zhang, Yihua ;

Lehmann, Jochen .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (04) :713-716

[10] The liver-selective nitric oxide donor O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate(V-PYRRO/NO) protects HepG2 cells against cytochrome P450 2E1-dependent toxicity [J].

Gong, PF ;

Cederbaum, AI ;

Nieto, N .

MOLECULAR PHARMACOLOGY, 2004, 65 (01) :130-138

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