(Z)-1-(acetoxymethoxy)-3,3-diethyltriaz-1-ene-2-oxide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (Z)-1-(acetoxymethoxy)-3,3-diethyltriaz-1-ene-2-oxide
• 英文别名: Diethylamine NONOate/AM；(Z)-acetyloxymethoxyimino-(diethylamino)-oxidoazanium
• 化学式: C₇H₁₅N₃O₄
• 分子量: 205.214
• InChiKey: NZMFKFGVIPMXHU-NTMALXAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  79.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  溴甲基乙酸酯 、 sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate 以 乙腈 为溶剂， 反应 48.0h， 以35%的产率得到(Z)-1-(acetoxymethoxy)-3,3-diethyltriaz-1-ene-2-oxide
  参考文献：
  名称：

  [EN] NITRIC OXIDE DONORS
  [FR] DONNEURS D'OXYDE NITRIQUE

  摘要：

  本发明部分提供了一种新型的非诺酸盐化合物，这些化合物表现出释放一氧化氮的活动，以及它们的药用可接受盐、酯和前药。这些化合物在与血浆接触激活时释放一氧化氮。本发明还涉及使用所披露的化合物来递送一氧化氮，以治疗由一氧化氮失调引起的疾病。

  公开号：

  WO2017223182A1

文献信息

• [EN] NITRIC OXIDE DONORS<br/>[FR] DONNEURS D'OXYDE NITRIQUE
  申请人：MEDCHEM PARTNERS LLC

  公开号：WO2017223182A1

  公开（公告）日：2017-12-28

  The present invention provides, in part a novel class of nonoate compounds which exhibit nitric oxide releasing activity and their pharmaceutically acceptable salts, esters and prodrugs. The compounds release nitric oxide upon activation by contact with plasma. The present invention also relates to the use of the disclosed compounds to deliver nitric oxide to treat disorders arising from nitric oxide dysregulation.

  本发明部分提供了一种新型的非诺酸盐化合物，这些化合物表现出释放一氧化氮的活动，以及它们的药用可接受盐、酯和前药。这些化合物在与血浆接触激活时释放一氧化氮。本发明还涉及使用所披露的化合物来递送一氧化氮，以治疗由一氧化氮失调引起的疾病。
• Nitric oxide donors
  申请人：MedChem Partners, LLC

  公开号：US11148999B2

  公开（公告）日：2021-10-19

  The present invention provides, in part a novel class of nonoate compounds which exhibit nitric oxide releasing activity and their pharmaceutically acceptable salts, esters and prodrugs. The compounds release nitric oxide upon activation by contact with plasma. The present invention also relates to the use of the disclosed compounds to deliver nitric oxide to treat disorders arising from nitric oxide dysregulation.

  本发明部分提供了一类具有一氧化氮释放活性的新型壬酸盐化合物及其药学上可接受的盐、酯和原药。这些化合物与血浆接触活化后释放一氧化氮。本发明还涉及使用所公开的化合物释放一氧化氮，以治疗一氧化氮失调引起的疾病。
• NITRIC OXIDE DONORS
  申请人：MedChem Partners, LLC

  公开号：US20190345099A1

  公开（公告）日：2019-11-14

  The present invention provides, in part a novel class of nonoate compounds which exhibit nitric oxide releasing activity and their pharmaceutically acceptable salts, esters and prodrugs. The compounds release nitric oxide upon activation by contact with plasma. The present invention also relates to the use of the disclosed compounds to deliver nitric oxide to treat disorders arising from nitric oxide dysregulation.
• Esterase-Sensitive Nitric Oxide Donors of the Diazeniumdiolate Family:  In Vitro Antileukemic Activity
  作者：Joseph E. Saavedra、Paul J. Shami、Lai Yi Wang、Keith M. Davies、Melissa N. Booth、Michael L. Citro、Larry K. Keefer

  DOI：10.1021/jm9903850

  日期：2000.1.1

  We have designed a novel prodrug class that is stable in neutral aqueous media but releases bioactive nitric oxide (NO) on metabolism by esterase. Diazeniumdiolates of structure R2N-N(O)=N-OR', in which R' = Na, were reacted with BrCH2OAc to convert the spontaneously NO-releasing salts 1a (R2N = diethylamino) and 1b (R2N = pyrrolidino) to prodrugs 2a (AcOM-DEA/NO) and 2b (AcOM-PYRRO/NO), respectively, where R' = CH2OAc. In contrast to anions la and Ib (half-lives in pH 7.4 phosphate at 37 degrees C of 2 min and 3 s, respectively), 2a and 2b showed only minimal decomposition after 16 h under these conditions. Very rapid hydrolysis occurred in the presence of porcine liver esterase, however, with free anion 1a being observed as an intermediate in the esterase-induced generation of NO from 2a. The potential utility of this prodrug class is illustrated with a comparison of 1 and 2 as antiproliferative agents in NO-sensitive human leukemia cell lines HL-60 and U937. While the 72-h IC50's for 1a and 1b (which generate NO throughout the medium) in HL-60 cell cultures were >600 mu M, those of 2a and 2b were 8.3 and 6.4 mu M, respectively. This result is consistent with our hypothesis that 2 is selectively hydrolyzed to 1 and thence to NO intracellularly. For U937 cells, the 72-h IC50 for both 2a and 2b was 53 mu M. By contrast, relatively high antiproliferative IC50's (>100 mu M in U937 cells) were observed for analogues in which R' = CH2CH2SC(O)Me, from which acetyl and 2-mercaptoethyl groups must be successively cleaved to free the NO-releasing diazeniumdiolate function. Within 24 h at initial concentrations of 50 mu M, 2a and 2b induced apoptosis in 50% and 57% of the HL-60 cells, respectively (35% and 40% of the U937 cells, respectively). The data reveal significant in vitro antileukemic activity on the part of these novel compounds. Moreover, their substantial ease-of-handling advantages over the anionic diazeniumdiolates from which they are derived suggest their use as convenient agents for probing the biological roles of NO.