N-methyl-2-ethanolamine O-nitrate | 145459-15-0

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 英文名称: N-methyl-2-ethanolamine O-nitrate
• 英文别名: nitric acid-(2-methylamino-ethyl ester)；Salpetersaeure-(2-methylamino-aethylester)；Methyl-(2-nitryloxy-aethyl)-amin；2-(Methylamino)ethyl nitrate
• CAS: 145459-15-0
• 化学式: C₃H₈N₂O₃
• 分子量: 120.108
• InChiKey: VABPECJHZLXAFO-UHFFFAOYSA-N

物化性质

• 沸点：
  160.5±23.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  67.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-5-(4-phenoxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione 、 N-methyl-2-ethanolamine O-nitrate 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以32.3%的产率得到5-(4-phenoxyphenyl)-5-(methyl-(2-nitrooxy-ethyl)-amino)-pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  Design of Barbiturate–Nitrate Hybrids that Inhibit MMP-9 Activity and Secretion

  摘要：

  We describe a new type of barbiturate-based matrix metalloproteinase (MMP) inhibitor incorporating a nitric oxide (NO) donor/mimetic group (series 1). The compounds were designed to inhibit MMP at enzyme level and to attenuate MMP-9 secretion arising from inflammatory signaling. To detect effects related to the nitrate, we prepared and studied an analogous series of barbiturate C5-alkyl alcohols that were unable to release NO (series 2). Both series inhibited recombinant human MMP-2/9 activity with nanomolar potency. Series 1 consistently inhibited the secretion of MMP-9 from TNF alpha/IL1 beta stimulated Caco-2 cells at 10 mu M, which could be attributed to NO related effects because the non-nitrate panel did not affect enzyme levels. Several compounds from series 1 (10 mu M) inhibited tumor cell invasion but none from the non-nitrate panel did. The work shows that MMP-inhibitory barbiturates are suitable scaffolds for hybrid design, targeting additional facets of MMP pathophysiology, with potential to improve risk-benefit ratios.

  DOI：

  10.1021/jm201352k
• 作为产物：
  描述：

  N-甲基-2-羟基乙胺 在 硝酸 、 乙酸酐 作用下， 以 二氯甲烷 为溶剂， 生成 N-methyl-2-ethanolamine O-nitrate
  参考文献：
  名称：

  NO-RELEASING NITROOXY-CHROMENE CONJUGATES

  摘要：

  本发明提供了NO释放的硝基氧烷基连接的色酮共轭物，其具有如下式（1）的结构，其中R1、R2、R3、R4、X和L如详细描述中所定义；包含至少一种Formula（I）化合物的药物组合物；以及使用Formula（1）化合物有益于愈合伤口、预防和治疗癌症以及治疗光老化性角化症、囊性纤维化和痤疮的方法。

  公开号：

  US20160340330A1

文献信息

• Evaluation of nitrate-substituted pseudocholine esters of aspirin as potential nitro-aspirins
  作者：John F. Gilmer、Louise M. Moriarty、John M. Clancy

  DOI：10.1016/j.bmcl.2007.03.009

  日期：2007.6

  compounds potentially capable of releasing both aspirin and nitric oxide in vivo. A series of nitrate-bearing alkyl esters of aspirin were prepared based on the choline ester template preferred by human plasma butyrylcholinesterase. The degradation kinetics of the compounds were followed in human plasma solution. All compounds underwent hydrolysis rapidly (t(1/2) approximately 1min) but generating

  本文中，我们探讨了硝基阿司匹林的一些设计，这些化合物可能在体内释放阿司匹林和一氧化氮。基于人血浆丁酰胆碱酯酶优选的胆碱酯模板，制备了一系列阿司匹林的含硝酸烷基酯。在人血浆溶液中跟踪化合物的降解动力学。所有化合物均迅速水解（t（1/2）约1分钟），但仅生成相应的水杨酸硝基酯。一个例外是，N-丙基，N-硝基氧乙基氨基乙醇酯以摩尔计产生9.2％的阿司匹林，表明如果可以对活化酶的要求进行适当的认知，就可以实现硝基阿司匹林的目标。即使阿司匹林的释放量很低，
• COMPOUNDS FOR TREATMENT OF HEART FAILURE
  申请人：Gilmer John

  公开号：US20130338118A1

  公开（公告）日：2013-12-19

  A combination of: a first tetracycline (TC) component; and a second component capable of releasing nitric oxide (NO) or a nitrate capable of mimicking NO effects in vivo (NO mimetic). The combinations of the invention advantageously act as more effective MMP modulators with selective reductions in circulating MMP-9 levels in-vivo and inhibitory effects on MMP-2 and MMP-9 levels in-vitro. The combinations of the invention also advantageously act as modulators of inflammation mediators. The co-existence of abnormalities of MMP enzymes and inflammation in many diseases make these characteristics advantageous. Therefore, the various combinations of the invention find utility in medical applications where MMPs and/or inflammation is implicated.

  一种组合物：第一四环素（TC）成分；和第二成分，能释放一氧化氮（NO）或模拟体内NO效应的硝酸盐（NO类似物）。本发明的组合物有利地作为更有效的MMP调节剂，在体内选择性降低循环MMP-9水平，并在体外对MMP-2和MMP-9水平产生抑制作用。本发明的组合物还有利地作为炎症介质的调节剂。在许多疾病中MMP酶和炎症的异常共存使这些特性具有优势。因此，本发明的各种组合物在MMP和/或炎症参与的医学应用中具有用途。
• [EN] COMPOUNDS FOR TREATMENT OF HEART FAILURE<br/>[FR] COMPOSÉS POUR LE TRAITEMENT D'UNE INSUFFISANCE CARDIAQUE
  申请人：SOLVOTRIN INNOVATIONS LTD

  公开号：WO2012076667A1

  公开（公告）日：2012-06-14

  A combination of: a first tetracycline (TC) component; and a second component capable of releasing nitric oxide (NO) or a nitrate capable of mimicking NO effects in vivo (NO mimetic). The combinations of the invention advantageously act as more effective MMP modulators with selective reductions in circulating MMP-9 levels in-vivo and inhibitory effects on MMP-2 and MMP-9 levels in-vitro. The combinations of the invention also advantageously act as modulators of inflammation mediators. The co-existence of abnormalities of MMP enzymes and inflammation in many diseases make these characteristics advantageous. Therefore, the various combinations of the invention find utility in medical applications where MMPs and/or inflammation is implicated.

  一种组合物：第一四环素（TC）组分；以及能释放一氧化氮（NO）或在体内模拟NO效应的硝酸盐（NO模拟物）的第二组分。本发明的组合物有利地作为更有效的MMP调节剂，能在体内选择性降低循环MMP-9水平，并在体外对MMP-2和MMP-9水平具有抑制作用。本发明的组合物还有利地作为炎症介质的调节剂。在许多疾病中MMP酶和炎症的异常共存使得这些特性具有优势。因此，本发明的各种组合物在医学应用中具有用途，特别是在MMP和/或炎症被牵涉的情况下。
• Synthesis of new nitroxyalkylamides as potential prototypes of hybrid nonsteroidal anti-inflammatory drugs containing NO-donating fragment
  作者：I. V. Serkov、V. V. Bezuglov

  DOI：10.1134/s0012500809040065

  日期：2009.4
• NO-RELEASING NITROOXY-CHROMENE CONJUGATES
  申请人：EUCLISES PHARMACEUTICALS, INC.

  公开号：US20160340330A1

  公开（公告）日：2016-11-24

  The present invention provides NO-releasing nitrooxy-alkylenyl-linked-chromene conjugates, having the structure of Formula (1) wherein R1, R2, R3, R4, X, and L are as defined in the detailed description; pharmaceutical compositions comprising at least one compound o Formula (I); and methods useful for healing wounds, preventing and treating cancer and treating actinic keratosis, cystic fibrosis, and acne, using a compound of Formula (1).

  本发明提供了NO释放的硝基氧烷基连接的色酮共轭物，其具有如下式（1）的结构，其中R1、R2、R3、R4、X和L如详细描述中所定义；包含至少一种Formula（I）化合物的药物组合物；以及使用Formula（1）化合物有益于愈合伤口、预防和治疗癌症以及治疗光老化性角化症、囊性纤维化和痤疮的方法。