2-哌啶-4-基乙基硝酸酯 | 129999-77-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 2-哌啶-4-基乙基硝酸酯
• 英文名称: 4-(2-nitroxyethyl)piperidine
• 英文别名: 2-piperidin-4-ylethyl nitrate
• CAS: 129999-77-5
• 化学式: C₇H₁₄N₂O₃
• 分子量: 174.2
• InChiKey: CBGXVHOGJBNZLS-UHFFFAOYSA-N

物化性质

• 沸点：
  257.7±13.0 °C(Predicted)
• 密度：
  1.094±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  12
• 可旋转键数：
  3
• 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 、 2-哌啶-4-基乙基硝酸酯 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以30.9%的产率得到5-(4-phenoxyphenyl)-5-(4-(2-nitrooxy-ethyl)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

文献信息

• 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。
• 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。
• Cyclische Azaaliphaten mit Nitroxyfunktion, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0366004A1

  公开（公告）日：1990-05-02

  Die vorliegende Erfindung betrifft Verbindungen der Formel I in der n 1 oder 2 bedeutet, R Wasserstoff, H-(C₁-C₈)-Alkylen, Hydroxy-(C₁-C₈)-Alkylen, R¹R²N-(C₁-C₈)-Alkylen, R¹R²N-(C₁-C₈)-Alkylen-CO-, R¹R²N-CO-­NR³-(C₁-C₈)-Alkylen, oder R₁R₂N-CO- bedeutet, worin R¹ Wasserstoff oder eine geradkettige oder verzweigte, gesättigte oder ungesättigte, oder cyclische Alkyl-Gruppe von 1-6 C-Atomen bedeutet, R² Wasserstoff oder eine geradkettige oder verzweigte, gesättigte oder ungesättigte, oder cyclische Alkyl-Gruppe von 1-6 C-Atomen bedeutet, oder R² gemeinsam mit einer -­(CH₂)-Gruppe der benachbarten (C₁-C₈)-Alkyl-Gruppe und dem Stickstoff-Atom einen heteroaliphatischen Ring von 2- 6 C-­Atomen aufspannen kann, R³ Wasserstoff oder eine geradkettige oder verzweigte, gesättigte oder ungesättigte, oder cyclische Alkyl-Gruppe von 1-6 C-Atomen bedeutet, A eine Bindung, eine -NR⁴-CO-Gruppe oder eine -CO-NR⁴-Gruppe bedeutet, worin R⁴ Wasserstoff oder eine geradkettige oder verzweigte, gesättigte oder ungesättigte oder cyclische Alkyl-Gruppe von 1-6 C-Atomen bedeutet, B eine Bindung oder eine geradkettige oder verzweigte Alkylenkette von 1-8 C-Atomen, wobei eine -CH₂-Gruppe durch eine Cycloalkylen-Gruppe mit 3-7 C-Atomen ersetzt sein kann, bedeutet, sowie Arzneimittel enthaltend diese Verbindungen. Gegenstand der Erfindung sind auch Verfahren zur Herstellung der Verbindungen der Formel I sowie neue Zwischenprodukte.

  本发明涉及式 I 的化合物 其中 n 是 1 或 2、 R 是氢、H-(C₁-C₈)-亚烷基、羟基-(C₁-C₈)-亚烷基、R¹R²N-(C₁-C₈)-亚烷基、R¹R²N-(C₁-C₈)-亚烷基-CO-、R¹R²N-CO-NR³-(C₁-C₈)-亚烷基或 R₁R₂N-CO- ，其中 R¹ 表示氢或 1-6 个 C 原子的直链或支链、饱和或不饱和或环状烷基、 R² 表示氢或 1-6 个 C 原子的直链或支链、饱和或不饱和或环状烷基，或 R² 与邻近 (C₁-C₈) 烷基的-(CH₂) 基团和氮原子一起可形成 2-6 个 C 原子的杂脂环、 R³ 表示氢或 1-6 个 C 原子的直链或支链、饱和或不饱和或环状烷基、 A 表示键、-NR⁴-CO 基团或-CO-NR⁴ 基团，其中 R⁴ 表示氢或 1-6 个 C 原子的直链或支链、饱和或不饱和或环状烷基 B 表示键或 1-8 个 C 原子的直链或支链亚烷基链，其中 -CH₂ 基团可由 3-7 个 C 原子的环亚烷基取代、 以及含有这些化合物的药物。 本发明还涉及式 I 化合物和新中间体的制备工艺。
• Organic Nitric Oxide Donor Salts of Angiotensin Converting Enzyme Inhibitors, Compositions and Methods of Use
  申请人：Garvey David S.

  公开号：US20080293678A1

  公开（公告）日：2008-11-27

  The invention describes compositions and kits comprising at least qrie organic nitric oxide enhancing salt of an angiotensin converting enzyme inhibitor, and, optionally, at least one nitric oxide enhancing 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; Q) treating osteoporosis; (k) treating nephropathy; (l) treating peripheral vascular diseases; (m) treating portal hypertension; (n) treating ophthalmic disorders; (o) treating metabolic syndrome; and (p) treating hyperlipidemia. The organic nitric oxide enhancing compounds that form salts with the angiotensin converting enzyme inhibitors are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.
• ORGANIC NITRIC OXIDE DONOR SALTS OF NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Garvey David S.

  公开号：US20090048219A1

  公开（公告）日：2009-02-19

  The invention describes novel organic nitric oxide enhancing salts of nonsteroidal antiinflammatory drugs (NSAIDs) and novel compositions comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders; (c) facilitating wound healing; (d) treating gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; (e) treating inflammatory disease states and/or disorders; (f) treating ophthalmic disorders; (h) treating peripheral vascular diseases; (i) treating diseases resulting from oxidative stress; (j) treating endothelial dysfunctions; and (k) treating diseases caused by endothelial dysfunctions. The organic nitric oxide enhancing compounds that form salts with the NSAIDs are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.