isosorbide-5-mononitrate-2-aspirinate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: isosorbide-5-mononitrate-2-aspirinate
• 英文别名: isosorbide mononitrate aspirinate；ISMNA；isosorbide-2-aspirinate-5-mononitrate；[(3S,3aR,6R,6aS)-6-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl] 2-acetyloxybenzoate
• 化学式: C₁₅H₁₅NO₉
• 分子量: 353.285
• InChiKey: WKOQXDYPKBXKJG-REWJHTLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  126
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  isosorbide-5-mononitrate-2-aspirinate 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 8.0h， 以7.4 g的产率得到isosorbide 2-aspirinate
  参考文献：
  名称：

  发现“真正的”阿司匹林前药。

  摘要：

  通过苯甲酸酯基团的衍生形成的阿司匹林前药非常难以获得，因为该肽原促进了邻近乙酰基团上血浆酯酶的水解速度，从而产生了水杨酸衍生物。通过追踪人血浆溶液中阿司匹林前药异山梨醇-2,5-二氢阿司匹林酸酯（ISDA）的水解模式，我们能够鉴定出代谢物异山梨醇-2-aspirinate-5-salicylate，该代谢物几乎完全转化为阿司匹林人血浆丁酰胆碱酯酶，使其成为迄今为止发现的最成功的阿司匹林前药。

  DOI：

  10.1021/jm801094c
• 作为产物：
  描述：

  5-单硝酸异山梨酯 、 邻乙酰水杨酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 isosorbide-5-mononitrate-2-aspirinate
  参考文献：
  名称：

  发现“真正的”阿司匹林前药。

  摘要：

  通过苯甲酸酯基团的衍生形成的阿司匹林前药非常难以获得，因为该肽原促进了邻近乙酰基团上血浆酯酶的水解速度，从而产生了水杨酸衍生物。通过追踪人血浆溶液中阿司匹林前药异山梨醇-2,5-二氢阿司匹林酸酯（ISDA）的水解模式，我们能够鉴定出代谢物异山梨醇-2-aspirinate-5-salicylate，该代谢物几乎完全转化为阿司匹林人血浆丁酰胆碱酯酶，使其成为迄今为止发现的最成功的阿司匹林前药。

  DOI：

  10.1021/jm801094c

文献信息

• [EN] EFFICIENT ASPIRIN PRODRUGS<br/>[FR] PROMÉDICAMENTS EFFICACES DE L'ASPIRINE
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2009080795A1

  公开（公告）日：2009-07-02

  Aspirin is one of the most widely used drugs in the treatment of inflammation, pain and fever. It has more recently found application in the prevention of heart attacks and stroke and is being studied as a cancer chemopreventative agent. Despite its value aspirin continues to be underutilized because it causes gastric bleeding. The technology under development potentially removes this problem. It is designed to reduce contact between the drug and the intestinal lining. An isosorbide aspirinate prodrug compound is thus provided. The compound has the general structure as shown in general formula (I) wherein Y is a C1 - C8 alkyl ester, a C1 - C8 alkoxy ester, a C3 - C10 cycloalkyl ester, an arylester, a C1 - C8 alkylaryl ester or -C(O)ORring, wherein Rring is a 5-membered aromatic or nonaromatic 5-member ring having at least one heteroatom substituted for a carbon of the ring system, which can be unsubstituted or substituted with at least one nitric oxide releasing group.

  阿司匹林是治疗炎症、疼痛和发热最广泛使用的药物之一。它最近在预防心脏病和中风方面找到了应用，并且正在作为抗癌化学预防剂进行研究。尽管阿司匹林具有价值，但由于它会导致胃出血，因此其使用仍然不足。正在开发中的技术可能解决了这个问题。该技术旨在减少药物与肠粘膜的接触。因此，提供了一种异山梨醇阿司匹林前药化合物。该化合物的通用结构如通用公式(I)所示，其中Y是C1 - C8烷基酯，C1 - C8烷氧基酯，C3 - C10环烷基酯，芳基酯，C1 - C8烷基芳基酯或-C(O)ORring，其中Rring是具有至少一个杂原子代替环系统中的碳的5元芳香或非芳香5元环，该环可以是未取代的或至少取代有一个释放一氧化氮的基团。
• Synthesis, hydrolysis kinetics and anti-platelet effects of isosorbide mononitrate derivatives of aspirin
  作者：John F Gilmer、Louise M Moriarty、Dermot F McCafferty、John M Clancy

  DOI：10.1016/s0928-0987(01)00183-x

  日期：2001.10

  Two isomeric aspirin derivatives of isosorbide-5-mononitrate (ISMN) were prepared and evaluated as potential mutual prodrugs of aspirin and nitric oxide. The hydrolysis of both compounds was studied in pH 7.4 phosphate buffer solution, buffered alpha -chymotrypsin solution and 10% buffered rabbit plasma. The benzodioxin-4-one derivative was hydrolysed to salicylic acid and ISMN acetate in buffer solution (t(1/2) 32. t h), 10% buffered rabbit plasma (t(1/2) 25.7 min) and alpha -chymotrypsin (t(1/2) 86.6 min). The carboxylic acid ester derivative ISMNA was hydrolysed via the salicylate ester in buffer solution (t(1/2) 48.5 h) but was rapidly and almost exclusively hydrolysed to aspirin and ISMN in plasma solution (t(1/2) 2.8 min). The hydrolysis appeared to be enzyme mediated as it was suppressed by co-incubation with eserine. ISMNA was evaluated for its ability to inhibit platelet aggregation in rabbit PRP in response to the following agonists: arachidonic acid (AA) (100 muM), ADP (1.2 muM) phorbol ester (0.5 muM). platelet activating factor (PAF) (5 nM) and the thromboxane mimic U46619 (1.5 muM). ISMNA suppressed platelet response to AA at 1 muM whereas 10 muM aspirin showed no inhibitory effects. (C) 2001 Published by Elsevier Science B.V.