O²-(methylthiomethyl)-1-(N-isopropylamino)diazen-1-ium-1,2-diolate | 1334486-37-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫基化合物
• 英文名称: O²-(methylthiomethyl)-1-(N-isopropylamino)diazen-1-ium-1,2-diolate
• 英文别名: O2-(methylthiomethyl) 1-(isopropylamino)diazen-1-ium-1,2-diolate；O2-(methylthiomethyl)-1-(N-isopropylamino)diazen-1-ium-1,2-diolate；(Methylsulfanylmethoxyamino)-oxido-propan-2-yliminoazanium；(methylsulfanylmethoxyamino)-oxido-propan-2-yliminoazanium
• CAS: 1334486-37-1
• 化学式: C₅H₁₃N₃O₂S
• 分子量: 179.243
• InChiKey: OXLHRPRMVOMAFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  87.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O²-(methylthiomethyl)-1-(N-isopropylamino)diazen-1-ium-1,2-diolate 在 磺酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 O²-(chloromethyl)-1-(N-isopropylamino)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS OF DIAZENIUMDIOLATE-BASED PRODRUGS FOR TREATING CANCER
  [FR] COMPOSITIONS DE PROMÉDICAMENTS À BASE DE DIAZÉNIUMDIOLATE POUR LE TRAITEMENT DU CANCER ET PROCÉDÉS

  摘要：

  本公开提供了一种利用基于偶氮双酸盐的前药治疗癌症的方法，通过各种机制和程序。本公开还提供了包含基于偶氮双酸盐的前药的试剂盒。尽管在抗癌技术方面取得了重大进展，如放射治疗、化学治疗和激素治疗，但癌症在美国仍然是继心脏病之后的第二大死因。通常，癌症使用高活性药物进行化疗。

  公开号：

  WO2016073835A1
• 作为产物：
  描述：

  氯甲基甲硫醚 、 isopropylammonium 1-(isopropylamino)diazen-1-ium-1,2-diolate 在 sodium carbonate 、 potassium iodide 作用下， 以 甲醇 为溶剂， 反应 17.0h， 以10%的产率得到O²-(methylthiomethyl)-1-(N-isopropylamino)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  O²-Sulfonylethyl Protected Isopropylamine Diazen-1-ium-1,2-diolates as Nitroxyl (HNO) Donors: Synthesis, β-Elimination Fragmentation, HNO Release, Positive Inotropic Properties, and Blood Pressure Lowering Studies

  摘要：

  New types of nonexplosive O-2-sulfonylethyl protected (-CH2CH2SO2R; R = OMe, NHOMe, NHOBn, Me) derivatives of isopropylamine diazen-1-ium-1,2-diolate (IPA/NO) (2-5) were developed that are designed to act as novel HNO donors. These compounds, with suitable half lives (6.6-17.1 h) at pH 7.4, undergo a base induced beta-elimination reaction that releases a methyl vinyl sulfone product and the, parent IPA/NO anion which subsequently preferentially releases HNO (46-61% range). Importantly, the O-2-methylsulfonylethyl compound 5 exhibited a significant in vitro inotropic effect up to 283% of the baseline value and increased the rates of contraction and relaxation but did not induce a chronotropic effect. Furthermore; compound 5 (22.5 mg/kg po dose). provided a significant reduction in blood pressure up to 6 h after drug administration. All these data suggest that O-2-sulfonylethyl protected derivatives of IPA/NO, which are efficient HNO donors, could have potential applications to treat cardiovascular disease(s) such as congestive heart failure.

  DOI：

  10.1021/jm301303p

文献信息

• [EN] NITROXYL (HNO) RELEASING COMPOUNDS AND USES THEREOF IN TREATING DISEASES<br/>[FR] COMPOSÉS LIBÉRANT DU NITROXYLE (HNO) ET LEURS UTILISATIONS DANS LE TRAITEMENT DE MALADIES
  申请人：US HEALTH

  公开号：WO2011116336A1

  公开（公告）日：2011-09-22

  Disclosed is a compound of the formula (I) or a pharmaceutically acceptable salt thereof:(I) in which R1, R2, R3, and R4 are defined herein and pharmaceutical compositions thereof. Further provided is a method of treating various disorders, such as a disorder selected from the group consisting of a cardiovascular disorder, cancer, chronic pain, alcohol dependence, and inflammation in a patient comprising administering an effective amount of a compound or pharmaceutically acceptable salt of formula (I).

  披露了一种公式(I)的化合物或其药物可接受的盐：(I)其中R1、R2、R3和R4按本说明书定义，以及其药物组合物。进一步提供了一种治疗各种疾病的方法，例如从心血管疾病、癌症、慢性疼痛、酒精依赖和炎症中选择的一种疾病，包括向患者施用公式(I)的化合物或药物可接受的盐的有效量。
• Synthesis and Chemical and Biological Comparison of Nitroxyl- and Nitric Oxide-Releasing Diazeniumdiolate-Based Aspirin Derivatives
  作者：Debashree Basudhar、Gaurav Bharadwaj、Robert Y. Cheng、Sarthak Jain、Sa Shi、Julie L. Heinecke、Ryan J. Holland、Lisa A. Ridnour、Viviane M. Caceres、Regina C. Spadari-Bratfisch、Nazareno Paolocci、Carlos A. Velázquez-Martínez、David A. Wink、Katrina M. Miranda

  DOI：10.1021/jm400196q

  日期：2013.10.24

  Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.
• [EN] COMPOSITIONS AND METHODS OF DIAZENIUMDIOLATE-BASED PRODRUGS FOR TREATING CANCER<br/>[FR] COMPOSITIONS DE PROMÉDICAMENTS À BASE DE DIAZÉNIUMDIOLATE POUR LE TRAITEMENT DU CANCER ET PROCÉDÉS
  申请人：UNIV ARIZONA STATE

  公开号：WO2016073835A1

  公开（公告）日：2016-05-12

  The present disclosure provides methods utilizing the diazeniumdiolate-based prodrugs for the treatment of cancer via various mechanisms and procedures. The disclosure also provides kits comprising the diazeniumdiolate-based prodrugs. Despite the fact that there have been significant developments in anti-cancer technology, such as radiotherapy, chemotherapy and hormone therapy, cancer still remains the second leading cause of death following heart disease in the United States. Most often, cancer is treated with chemotherapy utilizing highly potent drugs.

  本公开提供了一种利用基于偶氮双酸盐的前药治疗癌症的方法，通过各种机制和程序。本公开还提供了包含基于偶氮双酸盐的前药的试剂盒。尽管在抗癌技术方面取得了重大进展，如放射治疗、化学治疗和激素治疗，但癌症在美国仍然是继心脏病之后的第二大死因。通常，癌症使用高活性药物进行化疗。
• <i>O</i>²-Sulfonylethyl Protected Isopropylamine Diazen-1-ium-1,2-diolates as Nitroxyl (HNO) Donors: Synthesis, β-Elimination Fragmentation, HNO Release, Positive Inotropic Properties, and Blood Pressure Lowering Studies
  作者：Zhangjian Huang、Jatinder Kaur、Atul Bhardwaj、Nasser Alsaleh、Julie A. Reisz、Jenna F. DuMond、S. Bruce King、John M. Seubert、Yihua Zhang、Edward E. Knaus

  DOI：10.1021/jm301303p

  日期：2012.11.26

  New types of nonexplosive O-2-sulfonylethyl protected (-CH2CH2SO2R; R = OMe, NHOMe, NHOBn, Me) derivatives of isopropylamine diazen-1-ium-1,2-diolate (IPA/NO) (2-5) were developed that are designed to act as novel HNO donors. These compounds, with suitable half lives (6.6-17.1 h) at pH 7.4, undergo a base induced beta-elimination reaction that releases a methyl vinyl sulfone product and the, parent IPA/NO anion which subsequently preferentially releases HNO (46-61% range). Importantly, the O-2-methylsulfonylethyl compound 5 exhibited a significant in vitro inotropic effect up to 283% of the baseline value and increased the rates of contraction and relaxation but did not induce a chronotropic effect. Furthermore; compound 5 (22.5 mg/kg po dose). provided a significant reduction in blood pressure up to 6 h after drug administration. All these data suggest that O-2-sulfonylethyl protected derivatives of IPA/NO, which are efficient HNO donors, could have potential applications to treat cardiovascular disease(s) such as congestive heart failure.