O²-acetoxymethyl 1-[N-(2-hydroxyethyl)-N-methylamino]diazen-1-ium-1,2-diolate | 742081-70-5

• 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: O²-acetoxymethyl 1-[N-(2-hydroxyethyl)-N-methylamino]diazen-1-ium-1,2-diolate
• 英文别名: (Z)-1-(acetoxymethoxy)-3-(2-hydroxyethyl)-3-methyltriaz-1-ene 2-oxide；(Z)-acetyloxymethoxyimino-[2-hydroxyethyl(methyl)amino]-oxidoazanium
• CAS: 742081-70-5
• 化学式: C₆H₁₃N₃O₅
• 分子量: 207.186
• InChiKey: SAVQNBAMJIYLAZ-CLFYSBASSA-N

物化性质

• 沸点：
  314.1±52.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  O²-acetoxymethyl 1-[N-(2-hydroxyethyl)-N-methylamino]diazen-1-ium-1,2-diolate 在 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 87.0h， 生成
  参考文献：
  名称：

  具有潜在的充血性心力衰竭治疗的具有diazen-1-ium-1,2-glycate一氧化氮供体部分的1,4-二氢吡啶钙通道调节剂的合成和生物学评估。

  摘要：

  一组具有一氧化氮供体O（2）-乙酰氧基甲基-1-（N-乙基-N-甲基氨基）或4的外消旋4-芳基（杂芳基）-1,4-二氢-2,6-二甲基-3-硝基吡啶-乙基哌嗪-1-基）重氮-1-1,2-二醇酸酯，通过偶联各自的4-芳基（杂芳基）-1,4-二氢-2,6-二甲基-3合成C-5酯取代基-硝基吡啶-5-羧酸与O（2）-乙酰氧基甲基-1- [N-（2-甲基磺酰氧基乙基）-N-甲基氨基]重氮-1-1,2-二醇酸酯或O（2）-乙酰氧基甲基-1- [4-（2-甲基磺酰氧基乙基）哌嗪-1-基]重氮-1-1,2-二醇盐。具有C-4 2-吡啶基，4-吡啶基，2-三氟甲基苯基或苯并呋喃山-4-基取代基的化合物显示出比在0.37-1.09 microM范围内更强的平滑肌钙通道拮抗剂活性（IC（50）在0.37-1.09 microM范围内）具有C-4 3-吡啶基取代基的相关类似物（IC（50）'s = 3.03-9。相对于参考药物硝苯地平为14

  DOI：

  10.1016/j.bmc.2004.05.008
• 作为产物：
  描述：

  (Z)-1-hydroxy-3-(2-hydroxyethyl)-3-methyltriaz-1-ene 2-oxide sodium salt 、 碘甲醇乙酸酯 以 乙腈 为溶剂， 反应 19.0h， 以15.54 g的产率得到O²-acetoxymethyl 1-[N-(2-hydroxyethyl)-N-methylamino]diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  具有潜在的充血性心力衰竭治疗的具有diazen-1-ium-1,2-glycate一氧化氮供体部分的1,4-二氢吡啶钙通道调节剂的合成和生物学评估。

  摘要：

  一组具有一氧化氮供体O（2）-乙酰氧基甲基-1-（N-乙基-N-甲基氨基）或4的外消旋4-芳基（杂芳基）-1,4-二氢-2,6-二甲基-3-硝基吡啶-乙基哌嗪-1-基）重氮-1-1,2-二醇酸酯，通过偶联各自的4-芳基（杂芳基）-1,4-二氢-2,6-二甲基-3合成C-5酯取代基-硝基吡啶-5-羧酸与O（2）-乙酰氧基甲基-1- [N-（2-甲基磺酰氧基乙基）-N-甲基氨基]重氮-1-1,2-二醇酸酯或O（2）-乙酰氧基甲基-1- [4-（2-甲基磺酰氧基乙基）哌嗪-1-基]重氮-1-1,2-二醇盐。具有C-4 2-吡啶基，4-吡啶基，2-三氟甲基苯基或苯并呋喃山-4-基取代基的化合物显示出比在0.37-1.09 microM范围内更强的平滑肌钙通道拮抗剂活性（IC（50）在0.37-1.09 microM范围内）具有C-4 3-吡啶基取代基的相关类似物（IC（50）'s = 3.03-9。相对于参考药物硝苯地平为14

  DOI：

  10.1016/j.bmc.2004.05.008

文献信息

• NO-RELEASING NONOATE(NITROGEN-BOUND)SULFONAMIDE-LINKED-COXIB ANTI-CANCER AGENTS
  申请人：Euclises Pharmaceuticals, Inc.

  公开号：US20140018544A1

  公开（公告）日：2014-01-16

  The present invention provides NO-releasing NONOate(nitrogen bound)sulfonamide-linked-coxib anti-cancer agents, having the structure of Formula (I): wherein R 1 , X, L, R 2 , R 3 , R 4 , and Z are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis or acne, using a compound of Formula (I).

  本发明提供了一种NO释放的NONOate（氮结合）磺酰胺-联苯并咪唑类抗癌药物，具有以下结构式（I）：其中R1、X、L、R2、R3、R4和Z如详细说明中所定义；包括至少一种式（I）化合物的制药组合物；以及使用式（I）化合物有益于治疗伤口、预防和治疗癌症、或治疗光化性角化症、囊性纤维化或痤疮的方法。
• O2-Acetoxymethyl-protected diazeniumdiolate-based NSAIDs (NONO–NSAIDs): Synthesis, nitric oxide release, and biological evaluation studies
  作者：Carlos A. Velázquez、P.N. Praveen Rao、Michael L. Citro、Larry K. Keefer、Edward E. Knaus

  DOI：10.1016/j.bmc.2007.05.009

  日期：2007.7

  A novel group of O-2-acetoxymethyl-protected diazeniumdiolate-based non-steroidal anti-inflammatory prodrugs (NONO-NSAIDs) were synthesized by esterifying the carboxylate group of aspirin, ibuprofen, or indomethacin with O-2-acetoxymethyl 1-[N-(2-hydroxyethyl)-N-methylamino]diazeniumdiolate. The resulting nitric oxide ((NO)-N-center dot)-releasing prodrugs (7-9) did not exhibit in vitro cyclooxygenase (COX) inhibitory activity against the COX-1 and COX-2 isozymes (IC50S > 100 mu M), In contrast, prodrugs 7 and 8 significantly decreased carrageenan-induced rat paw edema showing enhanced in vivo anti-inflammatory activities (ID50's = 552 and 174 mu mol/kg, respectively) relative to those of the parent NSAIDs aspirin (ID50 = 714 mu mol/kg) and ibuprofen (ID50 = 326 mu mol/kg). The rate of porcine liver esterase-mediated (NO)-N-center dot release from prodrugs 7-9 (2 mol of (NO)-N-center dot/mol of test compound in 0.6-6.5 min) was substantially higher compared to that observed without enzymatic catalysis (about 1 mol of (NO)-N-center dot/mol of test compound in 40-48 h). These incubation studies suggest that both (NO)-N-center dot and the parent NSAID would be released upon in vivo activation (hydrolysis) by esterases. Data acquired in an in vivo ulcer index (UI) assay showed that NONO-aspirin (UI = 0.8), NONO-indomethacin (UI = 1.3), and particularly NONO-ibuprofen (UI = 0) were significantly less ulcerogenic compared to the parent drugs aspirin (UI = 57), ibuprofen (UI = 46) or indomethacin (UI = 34) at equimolar doses. The release of aspirin and (NO)-N-center dot from the NONO-aspirin (7) prodrug constitutes a potentially beneficial property for the prophylactic prevention of thrombus formation and adverse cardiovascular events such as stroke and myocardial infarction. Published by Elsevier Ltd.
• US8859781B2
  申请人：——

  公开号：US8859781B2

  公开（公告）日：2014-10-14
• Synthesis and biological evaluation of 1,4-dihydropyridine calcium channel modulators having a diazen-1-ium-1,2-diolate nitric oxide donor moiety for the potential treatment of congestive heart failure
  作者：Carlos Velázquez、Edward E Knaus

  DOI：10.1016/j.bmc.2004.05.008

  日期：2004.7

  potent smooth muscle calcium channel antagonist activity (IC(50)'s in the 0.37-1.09 microM range) than related analogs having a C-4 3-pyridyl substituent (IC(50)'s=3.03-9.14 microM range) relative to the reference drug nifedipine (IC(50)=9.13 nM). The point of attachment of C-4 isomeric pyridyl substituents was a determinant of smooth muscle calcium channel antagonist activity where the relative potency

  一组具有一氧化氮供体O（2）-乙酰氧基甲基-1-（N-乙基-N-甲基氨基）或4的外消旋4-芳基（杂芳基）-1,4-二氢-2,6-二甲基-3-硝基吡啶-乙基哌嗪-1-基）重氮-1-1,2-二醇酸酯，通过偶联各自的4-芳基（杂芳基）-1,4-二氢-2,6-二甲基-3合成C-5酯取代基-硝基吡啶-5-羧酸与O（2）-乙酰氧基甲基-1- [N-（2-甲基磺酰氧基乙基）-N-甲基氨基]重氮-1-1,2-二醇酸酯或O（2）-乙酰氧基甲基-1- [4-（2-甲基磺酰氧基乙基）哌嗪-1-基]重氮-1-1,2-二醇盐。具有C-4 2-吡啶基，4-吡啶基，2-三氟甲基苯基或苯并呋喃山-4-基取代基的化合物显示出比在0.37-1.09 microM范围内更强的平滑肌钙通道拮抗剂活性（IC（50）在0.37-1.09 microM范围内）具有C-4 3-吡啶基取代基的相关类似物（IC（50）'s = 3.03-9。相对于参考药物硝苯地平为14