尼可地尔杂质26 | 20830-49-3

• 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
• 中文名称: 尼可地尔杂质26
• 英文名称: bis-(2-nitryloxy-ethyl)-amine
• 英文别名: 2,2'-iminobis-ethanol dinitrate；Bis-(2-nitryloxy-aethyl)-amin；2-(2-Nitrooxyethylamino)ethyl nitrate
• CAS: 20830-49-3
• 化学式: C₄H₉N₃O₆
• 分子量: 195.132
• InChiKey: UCRKMCMOUNBJIB-UHFFFAOYSA-N

物化性质

• 沸点：
  295.2±25.0 °C(Predicted)
• 密度：
  1.377±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  尼可地尔杂质26 在 硝酸 、 乙酸酐 、 zinc(II) chloride 作用下， 以 二氧化碳 为溶剂， 40.0 ℃ 、10.0 MPa 条件下， 反应 8.0h， 以83%的产率得到Di-(2-nitro-ethyl)-nitramin
  参考文献：
  名称：

  在液态或超临界二氧化碳中由仲硝酸铵合成 N,N-二烷基硝胺

  摘要：

  开发了一种有效的防爆方法，通过在液态或超临界二氧化碳中在 ZnCl2 存在下用硝酸和乙酸酐的混合物处理二烷基硝酸铵来制备 N,N-二烷基硝胺。

  DOI：

  10.1007/s11172-009-0282-1
• 作为产物：
  描述：

  二乙醇胺 在 硝酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 生成 尼可地尔杂质26
  参考文献：
  名称：

  COMPOUNDS FOR TREATMENT OF HEART FAILURE

  摘要：

  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。

  公开号：

  US20130338118A1

文献信息

• Nitric oxide enhancing diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20060189603A1

  公开（公告）日：2006-08-24

  The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

  该发明描述了包含至少一种增强一氧化氮利尿化合物或其药用盐的新型组合物和试剂盒，以及可选地，至少一种增强一氧化氮化合物和/或至少一种治疗剂的试剂盒。该发明还提供了以下方法：(a)治疗由过多水分和/或电解贮留引起的症状；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；(l)治疗肾病；(m)治疗外周血管疾病；(n)治疗门静脉高压；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；(q)治疗性功能障碍；以及(r)高脂血症。增强一氧化氮利尿化合物包括至少一种增强一氧化氮基团，通过碳、氧和/或氮等一个或多个位点与利尿化合物连接，连接通过不能水解的键或基团。
• [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。
• Design of Barbiturate–Nitrate Hybrids that Inhibit MMP-9 Activity and Secretion
  作者：Jun Wang、Shane O’Sullivan、Shona Harmon、Ray Keaveny、Marek W. Radomski、Carlos Medina、John F. Gilmer

  DOI：10.1021/jm201352k

  日期：2012.3.8

  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.
• Synthesis of N,N-dialkylnitramines from secondary ammonium nitrates in liquid or supercritical carbon dioxide
  作者：I. V. Kuchurov、I. V. Fomenkov、S. G. Zlotin

  DOI：10.1007/s11172-009-0282-1

  日期：2009.10

  An efficient explosion-proof method was developed for the preparation of N,N-dialkylnitramines by treatment of dialkylammonium nitrates with a mixture of nitric acid and acetic anhydride in the presence of ZnCl2 in liduid or supercritical carbon dioxide.

  开发了一种有效的防爆方法，通过在液态或超临界二氧化碳中在 ZnCl2 存在下用硝酸和乙酸酐的混合物处理二烷基硝酸铵来制备 N,N-二烷基硝胺。
• 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。