2-((2-(nitrooxy)ethyl)disulfanyl)ethyl 2-acetoxybenzoate

• 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: 2-((2-(nitrooxy)ethyl)disulfanyl)ethyl 2-acetoxybenzoate
• 英文别名: P 1538；2-(2-Nitrooxyethyldisulfanyl)ethyl 2-acetyloxybenzoate
• 化学式: C₁₃H₁₅NO₇S₂
• 分子量: 361.397
• InChiKey: HNFUOASNELUHCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  158
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(2-bromoethyldisulfanyl)ethyl 2-acetyloxybenzoate 在 silver nitrate 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以50%的产率得到2-((2-(nitrooxy)ethyl)disulfanyl)ethyl 2-acetoxybenzoate
  参考文献：
  名称：

  Prodrugs containing novel bio-cleavable linkers

  摘要：

  本发明提供了公式(I)的化合物或其药用可接受的盐。本发明还提供了包含一个或多个公式I的化合物或其中间体以及一个或多个药用可接受的载体、车辆或稀释剂的药物组合物。本发明进一步提供了包括制备方法和使用方法在内的前药，包括释放一氧化氮的前药、双前药和相互前药，由公式I的化合物组成。

  公开号：

  US20060046967A1

文献信息

• NO-NSAIDs. Part 3: Nitric Oxide-Releasing Prodrugs of Non-steroidal Anti-inflammatory Drugs
  作者：Namdev Borhade、Asif Rahimkhan Pathan、Somnath Halder、Manoj Karwa、Mini Dhiman、Venu Pamidiboina、Machhindra Gund、Jagannath Janardhan Deshattiwar、Sunil Vasantrao Mali、Nitin Janardanrao Deshmukh、Subrayan Palanisamy Senthilkumar、Parikshit Gaikwad、Santhosh Goud Tipparam、Jayesh Mudgal、Milan Chandra Dutta、Aslam Usmangani Burhan、Gajanan Thakre、Ankur Sharma、Shubhada Deshpande、Dattatraya Chandrakant Desai、Nauzer Pervez Dubash、Arun Kumar Jain、Somesh Sharma、Kumar Venkata Subrahmanya Nemmani、Apparao Satyam

  DOI：10.1248/cpb.60.465

  日期：——

  "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30)

  为了继续努力发现可释放一氧化氮的新型非甾体抗炎药（NO-NSAID）作为潜在的“安全NSAID”，我们在此报告了21种常用NSAID的新NO-NSAID的设计，合成和评估。如阿司匹林，双氯芬酸，萘普生，氟比洛芬，酮洛芬，舒林酸，布洛芬和消炎痛。这些前药具有可通过诸如酯（化合物9-16），双酯（化合物17-24），酰亚胺（化合物25-30）或酰胺（化合物31）之类的键连接到母体NSAID上的释放NO的二硫键。 -33）。在这些NO-NSAID中，含酯的NO-阿司匹林（9），NO-双氯芬酸（10），NO-萘普生（11）和含酰亚胺的NO-阿司匹林（25），NO-氟比洛芬（27）和NO-酮洛芬（28）已显示出良好的口服吸收，抗炎活性和NO释放特性，并保护大鼠免受NSAID引起的胃损伤。NO-阿司匹林化合物25与等摩尔剂量的阿司匹林进一步共同评估，显示出与阿司匹林相当的剂量依赖性药代动力学，胃黏膜前
• PRODRUGS CONTAINING NOVEL BIO-CLEAVABLE LINKERS
  申请人：Satyam Apparao

  公开号：US20110269709A1

  公开（公告）日：2011-11-03

  The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

  该发明提供式（I）的化合物或其药学上可接受的盐。该发明还提供包含一个或多个式I化合物或其中间体以及一个或多个药学上可接受的载体、车载物或稀释剂的制药组合物。该发明还提供制备方法和使用方法，其中包括释放NO的前药、双前药和相互前药的前药，其中包括式I的化合物。
• Prodrugs Containing Novel Bio-Cleavable Linkers
  申请人：Piramal Life Sciences Limited

  公开号：EP2266625A2

  公开（公告）日：2010-12-29

  The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula 1.

  本发明提供了式 (I) 化合物或其药学上可接受的盐。本发明还提供了包含一种或多种式 I 化合物或其中间体以及一种或多种药学上可接受的载体、载体或稀释剂的药物组合物。本发明进一步提供了包括NO释放原药、双原药和包含式1化合物的互作原药在内的原药的制备方法和使用方法。
• NO-NSAIDs: Gastric-sparing nitric oxide-releasable prodrugs of non-steroidal anti-inflammatory drugs
  作者：Kumar V.S. Nemmani、Sunil V. Mali、Namdev Borhade、Asif R. Pathan、Manoj Karwa、Venu Pamidiboina、S.P. Senthilkumar、Machhindra Gund、Arun K. Jain、Naveen K. Mangu、Nauzer P. Dubash、Dattatraya C. Desai、Somesh Sharma、Apparao Satyam

  DOI：10.1016/j.bmcl.2009.07.142

  日期：2009.9

  Recently, a new class of nitric-oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) is being studied as 'Safe NSAIDs' because of their gastric-sparing properties. As an extension of our novel disulfide linker technology, we have designed, synthesized and evaluated novel NO-releasing NSAID prodrugs such as NO-Aspirin (1b-d) and NO-Diclofenac (2b-c). Although the amide-containing derivative 1d did not show any bioavailability, the remaining compounds have shown fair to excellent pharmacokinetic. anti-inflammatory and gastric-sparing properties. Among them, however, the NO-Diclofenac (2b) has shown the most promising pharmacokinetic, anti-inflammatory and NO-releasing properties and protected rats from NSAID-induced gastric damage which could be attributable to the beneficial effects of NO released from these prodrugs. (C) 2009 Elsevier Ltd. All rights reserved.
• US7932294B2
  申请人：——

  公开号：US7932294B2

  公开（公告）日：2011-04-26