4-[(nitrooxy)methyl]piperidinium nitrate

• 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: 4-[(nitrooxy)methyl]piperidinium nitrate
• 英文别名: nitrooxy(4-piperidylmethyl) hydrogen nitrate；4-piperidinemethanol nitrate nitrate；nitrooxy(4-piperidylmethyl)-nitrate；4-Nitroxymethylpiperidine nitrate；nitric acid;piperidin-4-ylmethyl nitrate
• 化学式: C₆H₁₂N₂O₃*HNO₃
• 分子量: 223.186
• InChiKey: PNNFLVSUYSXNOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.15
• 重原子数：
  15
• 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：
  133
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(nitrooxy)methyl]piperidinium nitrate 、 缬沙坦 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以37%的产率得到N-[(1S)-2-methyl-1-[[4-[(nitrooxy)methyl]-1-piperidinyl]carbonyl]propyl]-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]pentanamide
  参考文献：
  名称：

  Nitric oxide enhancing angiotensin II antagonist compounds, compositions and methods of use

  摘要：

  该发明描述了包含至少一种一氧化氮增强的血管紧张素II拮抗剂化合物或其药用盐的组合物和试剂盒，以及包含至少一种一氧化氮增强的血管紧张素II拮抗剂化合物的新型组合物，还可以包含至少一种一氧化氮增强化合物和/或至少一种治疗剂。该发明还提供了用于(a)治疗心血管疾病；(b)治疗肾血管疾病；(c)治疗糖尿病；(d)治疗由氧化应激导致的疾病；(e)治疗内皮功能障碍；(f)治疗由内皮功能障碍引起的疾病；(g)治疗肝硬化；(h)治疗子痫前症；(j)治疗骨质疏松症；(k)治疗肾病；(l)治疗外周血管疾病；(m)治疗门静脉高压症；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；和(q)治疗高脂血症的方法。一氧化氮增强的血管紧张素II拮抗剂化合物包括至少一种一氧化氮增强基团，通过碳、氧和/或氮等一个或多个位点与血管紧张素II拮抗剂化合物连接，连接方式是通过一种不能水解的键或基团。

  公开号：

  US20070032533A1
• 作为产物：
  描述：

  4-哌啶甲醇 在 硝酸 、 乙酸酐 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 以52%的产率得到4-[(nitrooxy)methyl]piperidinium nitrate
  参考文献：
  名称：

  Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use related applications

  摘要：

  该发明描述了新型亚硝化非甾体抗炎药（NSAIDs）及其药用盐，以及包含至少一种亚硝化NSAID的新型组合物，以及可选地，至少一种提供、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物，和/或至少一种治疗剂。该发明还提供了包含至少一种亚硝化NSAID和至少一种提供、转移或释放一氧化氮、提高内源性内皮源性舒张因子水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/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亚硝化NSAID，可选地至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。该发明还提供了治疗炎症、疼痛和发热的方法；治疗胃肠道疾病的方法；促进伤口愈合的方法；治疗和/或预防由非甾体抗炎化合物使用引起的胃肠道、肾脏和/或呼吸道毒性的方法；治疗炎症性疾病状态和/或疾病的方法；以及治疗和/或预防眼科疾病和/或疾病的方法。

  公开号：

  US20040024057A1

文献信息

• Nitrosated and nitrosylated diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20050059655A1

  公开（公告）日：2005-03-17

  The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor 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; and (l) treating nephropathy.

  该发明描述了新颖的亚硝基化和/或亚硝酰化利尿化合物或其药用盐，以及包含至少一种亚硝基化和/或亚硝酰化利尿化合物的新型组合物，以及可选地至少一种一氧化氮供体和/或至少一种治疗剂。该发明还提供了包含该发明中至少一种利尿化合物的新型组合物和试剂盒，该利尿化合物可选择地亚硝基化和/或亚硝酰化，并且可选地至少一种一氧化氮供体化合物和/或至少一种治疗剂。该发明还提供了用于(a)治疗由于过多水分和/或电解贮留引起的疾病；(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；和(l)治疗肾病的方法。
• Cyclic azaaliphatic compounds with a nitroxy function, processes for the
  申请人：Boehringer Mannheim GmbH

  公开号：US05030641A1

  公开（公告）日：1991-07-09

  The present invention provides anti-angina pharmaceutical compositions containing at least one compound of the formula: ##STR1## wherein n is 1 or 2, R is a hydrogen atom or an H-(C.sub.1 -C.sub.8)-alkylene, hydroxy-(C.sub.1 -C.sub.8)-alkylene, R.sup.1 R.sup.2 N-(C.sub.1 -C.sub.8)-alkylene, R.sup.1 R.sup.2 N-(C.sub.1 -C.sub.8)-alkylene-CO--, R.sup.1 R.sup.2 N-CO-NR.sup.3 -(C.sub.1 -C.sub.8)-alkylene or R.sup.1 R.sup.2 N-CO-- radical, A is a valency bond or an --NR.sup.4 --CO-- or --CO--NR.sup.4 -- radical, R.sup.4 is a hydrogen atom or a straight-chained or branched, saturated or unsaturated of cyclic alkyl radical containing up to 6 carbon atoms and B is a valency bond or a straight-chained or branched alkylene chain containing up to 8 carbon atoms, in which a --CH.sub.2 -- group can be replaced by a cycloalkylene radical containing 3 to 7 carbon atoms.

  本发明提供一种抗心绞痛药物组合物，其中至少包含以下一种化合物：##STR1## 其中n为1或2，R为氢原子或H-(C.sub.1-C.sub.8)-烷基，羟基-(C.sub.1-C.sub.8)-烷基，R.sup.1 R.sup.2 N-(C.sub.1-C.sub.8)-烷基，R.sup.1 R.sup.2 N-(C.sub.1-C.sub.8)-烷基-CO--，R.sup.1 R.sup.2 N-CO-NR.sup.3-(C.sub.1-C.sub.8)-烷基或R.sup.1 R.sup.2 N-CO--基团，A为一个价键或--NR.sup.4--CO--或--CO--NR.sup.4--基团，R.sup.4为氢原子或含有最多6个碳原子的直链或支链、饱和或不饱和的环烷基基团，B为一个价键或含有最多8个碳原子的直链或支链烷基链，其中一个--CH.sub.2--基团可以被含有3到7个碳原子的环烷基团所替代。
• Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria
  作者：Massimo Bertinaria、Stefano Guglielmo、Barbara Rolando、Marta Giorgis、Cristina Aragno、Roberta Fruttero、Alberto Gasco、Silvia Parapini、Donatella Taramelli、Yuri C. Martins、Leonardo J.M. Carvalho

  DOI：10.1016/j.ejmech.2011.02.029

  日期：2011.5

  The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive, 010 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound 40, which is potent and fast amodiaquine-derived NO-donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Synthesis and anti-inflammatory activity of a series of N-substituted naproxen glycolamides: Nitric oxide-donor naproxen prodrugs
  作者：Ramani R. Ranatunge、Michael E. Augustyniak、Vijay Dhawan、James L. Ellis、David S. Garvey、David R. Janero、L. Gordon Letts、Stewart K. Richardson、Mathew J. Shumway、A. Mark Trocha、Delano V. Young、Irina S. Zemtseva

  DOI：10.1016/j.bmc.2005.11.040

  日期：2006.4

  A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These Compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, 5a, 5b, 7b, and 7c exhibited anti-inflammatory activity equivalent to that of the parent NSAID, naproxen-Na, in the rat carrageenan paw edema model. At equimolar doses relative to naproxen-Na. the NO-donor glycolamide derivatives 4a, 4b, 5a.. 5b, 7b, and 7c were gastro-sparing in the rat. Naproxen formation from these NO-donor glycolamides varied among the structures examined, with the N-substituent on the amide group having a particular influence, and demonstrated their prodrug nature. Compound 7b was selected for exemplary demonstration that the glycolamide nitrates can be bioactivated to release NO. These data open the possibility that naproxen glycolainide nitrates may represent a safer alternative to naproxen as anti-inflammatory medicines. (c) 2005 Elsevier Ltd. All rights reserved.
• US5030641A
  申请人：——

  公开号：US5030641A

  公开（公告）日：1991-07-09