3-methylnitrate piperidine | 104963-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-methylnitrate piperidine
• 英文别名: 3-nitrooxymethyl piperidine；Piperidin-3-ylmethyl nitrate
• CAS: 104963-89-5
• 化学式: C₆H₁₂N₂O₃
• 分子量: 160.173
• InChiKey: FEEOZZVENPLKFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• 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 、 3-methylnitrate piperidine 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以39.8%的产率得到5-(4-phenoxyphenyl)-5-(3-(1-nitrooxy-methyl)piperidin-1-yl)-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：

  3-哌啶甲醇 在 硝酸 、 乙酸酐 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.91h， 生成 3-methylnitrate piperidine
  参考文献：
  名称：

  [EN] COMPOUNDS FOR TREATMENT OF HEART FAILURE
  [FR] COMPOSÉS POUR LE TRAITEMENT D'UNE INSUFFISANCE CARDIAQUE

  摘要：

  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。

  公开号：

  WO2012076667A1

文献信息

• 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。
• Nitrosated glutamic acid compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20070037821A1

  公开（公告）日：2007-02-15

  The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.

  该发明描述了新型的硝化谷氨酸化合物及其药学上可接受的盐，以及包含至少一种硝化谷氨酸化合物，和/或至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。该发明还提供了包含至少一种硝化谷氨酸化合物，和/或至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。该发明还提供了治疗心血管疾病、肾血管疾病、糖尿病、氧化应激引起的疾病、内皮功能障碍、内皮功能障碍引起的疾病、肝硬化、先兆子痫、骨质疏松症、肾病、γ-谷氨酰转移酶水平升高引起的疾病以及将化合物和一氧化氮有针对性地输送到含有γ-谷氨酰转移酶的器官、细胞或组织的方法。
• EP1673384A4
  申请人：——

  公开号：EP1673384A4

  公开（公告）日：2007-02-07
• NITROSATED GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Nitromed, Inc.

  公开号：EP1673384A2

  公开（公告）日：2006-06-28
• US9566342B2
  申请人：——

  公开号：US9566342B2

  公开（公告）日：2017-02-14