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A new class of anti-thrombosis hexahydropyrazino-[1 ′,2 ′: 1,6]pyrido-[3,4-b]-indole-1,4-dions: Design, synthesis, log K determination, and QSAR analysis
Liu, Jiawang1; Wu, Guofeng1; Cui, Guohui1; Wang, Wei-Xuan1; Zhao, Ming1; Wang, Chao1; Zhangc, Ziding1; Peng, Shiqi1
关键词Anti-thrombotic Agent Hexahydropyrazino[1 &Prime 2 &Prime Intramolecular Cyclization : 1 Tetrahydro-beta-carboline-3-carboxylic Acid 6]-pyrido[3 4-b]Indole-1 4-dions
刊名BIOORGANIC & MEDICINAL CHEMISTRY
2007-09-01
DOI10.1016/j.bmc.2007.06.012
15期:17页:5672-5693
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
研究领域[WOS]Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
关键词[WOS]PERFORMANCE LIQUID-CHROMATOGRAPHY ; PRO-ALA-LYS ; MYOCARDIAL-INFARCTION ; PLATELET ACTIVATION ; NITRONYL NITROXIDE ; COEFFICIENTS ; ANALOGS ; FUMITREMORGIN ; METABOLITES ; INHIBITION
英文摘要

Based on the fact that the cyclization of N-[(3S)1-1,2,3,4-tetrahydro-beta-carboline-3-carboxyl]-L-lysine in both of acetic acid aqueous (5%) and rat plasma gave the same product and the hypothesis that the cyclization product is antithrombotic active, we report the synthesis, in vitro anti-aggregation, and in vivo anti-thrombosis activity of 20 hexahydropyrazino[1′,2′:1,6]pyrido[3,4-blindole-1,4-dions (5a-t) as potential anti-thrombosis agents in this study. Two intermediates (tetrahydro-beta-carboline-3-carboxy-L-amino acid benzylesters, 2-aminoacyltetrahydro-beta-carboline-3-carboxylic acid benzylesters) were prepared and used for the cyclization to form 5a-t. Coupling hydrochloric acid salt of tetrahydro-beta p-carboline-3-carboxylic acid esters and Boc-amino acids in the reported literature usually generates very low yield products accompanied by racernization. However, in our case, the free base of tetrahydro-beta-carboline-3-carboxylic acid benzylester produced the desired products in high yields and without racemization. The anti-thrombosis results from both in vitro and in vivo studies revealed that 5a-t may be a new class of anti-thrombosis agents with potent effective concentration at 0.5 mu mol/kg with oral administration. Moreover, a QSAR analysis was performed on these 20 compounds by using molecular descriptors generated by e-dragon server. Although the activities of these compounds are weakly correlated with the log P values, the current QSAR analysis revealed that the anti-thrombotic activity of these compounds can be explained by their steric and electrostatic effects. (c) 2007 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000248779000003
引用统计
被引频次:25[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50416
专题北京大学药学院
作者单位1.Capital Med Univ, Coll Pharmaceut Sci, Beijing 100069, Peoples R China
2.Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China
3.China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China
推荐引用方式
GB/T 7714
Liu, Jiawang,Wu, Guofeng,Cui, Guohui,et al. A new class of anti-thrombosis hexahydropyrazino-[1 ′,2 ′: 1,6]pyrido-[3,4-b]-indole-1,4-dions: Design, synthesis, log K determination, and QSAR analysis[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2007,15(17):5672-5693.
APA Liu, Jiawang.,Wu, Guofeng.,Cui, Guohui.,Wang, Wei-Xuan.,Zhao, Ming.,...&Peng, Shiqi.(2007).A new class of anti-thrombosis hexahydropyrazino-[1 ′,2 ′: 1,6]pyrido-[3,4-b]-indole-1,4-dions: Design, synthesis, log K determination, and QSAR analysis.BIOORGANIC & MEDICINAL CHEMISTRY,15(17),5672-5693.
MLA Liu, Jiawang,et al."A new class of anti-thrombosis hexahydropyrazino-[1 ′,2 ′: 1,6]pyrido-[3,4-b]-indole-1,4-dions: Design, synthesis, log K determination, and QSAR analysis".BIOORGANIC & MEDICINAL CHEMISTRY 15.17(2007):5672-5693.
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