2,2-dimethyl-3'-(4-nitrobenzyl)-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2,2-dimethyl-3'-(4-nitrobenzyl)-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one
• 英文别名: 3'-(4-nitrobenzyl)-2,2-dimethyl-2,3-dihydro-2'H-spiro[chromen-4,5'-[1,3]oxazolidin]-2'-one；2',2'-dimethyl-3-[(4-nitrophenyl)methyl]spiro[1,3-oxazolidine-5,4'-3H-chromene]-2-one
• 化学式: C₂₀H₂₀N₂O₅
• 分子量: 368.389
• InChiKey: VURSQLZUTRGDSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-3'-(4-nitrobenzyl)-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one 在 iron(III) chloride 、 potassium carbonate 、 甲烷 、 一水合肼 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 1.0h， 生成 3'-(4-acetamidobenzyl)-2,2-dimethyl-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-membered spiro heterocycle-benzopyran derivatives against myocardial ischemia

  摘要：

  The activation of ATP-sensitive potassium channels (K-ATP), play a key role in an endogenous "self-defence" mechanism, known as ischemic preconditioning (IPC), which is fundamentally involved in the protection of the heart against the ischemia/reperfusion injury. Presently, it is widely accepted that IPC is mainly (albeit not exclusively) mediated by the activation of K-ATP channels expressed in the mitochondrial inner membrane (mito-K-ATP) rather than the sarcoplasmatic ones (sarc-K-ATP). Consistently, exogenous activation of K-ATP channels by pharmacological tools can be viewed as one of the most promising strategies for the therapy of myocardial ischemia. As part of our research program devoted to the synthesis and the evaluation of new cardioprotective agents, we extensively studied several six-membered spiro-heterocycle-benzopyran compounds endowed of a significant anti-ischemic activity. The positive results obtained, prompted us to further explore the influence on the biopharmacological effects, of the spiro-substitution at C4 benzopyran nucleus by replacing the six-membered spirocycle of the most active compounds with 5-membered-one.The preliminary evaluation of the new compounds on cultured H9c2 cardiomyoblasts exposed to anoxia/reperfusion and on Langendorff-perfused rat hearts submitted to ischemia/reperfusion cycles, showed that some of them can exert a cardioprotective effect. This anti-ischemic activity was antagonized by 5-hydroxydecanoic acid, a selective blocker of mito-K-ATP channels, confirming the involvement of this channel in the cardioprotective activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.003
• 作为产物：
  描述：

  4-(aminomethyl)-2,2-dimethylchroman-4-ol 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.5h， 生成 2,2-dimethyl-3'-(4-nitrobenzyl)-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-membered spiro heterocycle-benzopyran derivatives against myocardial ischemia

  摘要：

  The activation of ATP-sensitive potassium channels (K-ATP), play a key role in an endogenous "self-defence" mechanism, known as ischemic preconditioning (IPC), which is fundamentally involved in the protection of the heart against the ischemia/reperfusion injury. Presently, it is widely accepted that IPC is mainly (albeit not exclusively) mediated by the activation of K-ATP channels expressed in the mitochondrial inner membrane (mito-K-ATP) rather than the sarcoplasmatic ones (sarc-K-ATP). Consistently, exogenous activation of K-ATP channels by pharmacological tools can be viewed as one of the most promising strategies for the therapy of myocardial ischemia. As part of our research program devoted to the synthesis and the evaluation of new cardioprotective agents, we extensively studied several six-membered spiro-heterocycle-benzopyran compounds endowed of a significant anti-ischemic activity. The positive results obtained, prompted us to further explore the influence on the biopharmacological effects, of the spiro-substitution at C4 benzopyran nucleus by replacing the six-membered spirocycle of the most active compounds with 5-membered-one.The preliminary evaluation of the new compounds on cultured H9c2 cardiomyoblasts exposed to anoxia/reperfusion and on Langendorff-perfused rat hearts submitted to ischemia/reperfusion cycles, showed that some of them can exert a cardioprotective effect. This anti-ischemic activity was antagonized by 5-hydroxydecanoic acid, a selective blocker of mito-K-ATP channels, confirming the involvement of this channel in the cardioprotective activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.003

文献信息

• WO2008/7210
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and biological evaluation of 5-membered spiro heterocycle-benzopyran derivatives against myocardial ischemia
  作者：Simona Rapposelli、Maria Cristina Breschi、Vincenzo Calderone、Maria Digiacomo、Alma Martelli、Lara Testai、Michael Vanni、Aldo Balsamo

  DOI：10.1016/j.ejmech.2011.01.003

  日期：2011.3

  The activation of ATP-sensitive potassium channels (K-ATP), play a key role in an endogenous "self-defence" mechanism, known as ischemic preconditioning (IPC), which is fundamentally involved in the protection of the heart against the ischemia/reperfusion injury. Presently, it is widely accepted that IPC is mainly (albeit not exclusively) mediated by the activation of K-ATP channels expressed in the mitochondrial inner membrane (mito-K-ATP) rather than the sarcoplasmatic ones (sarc-K-ATP). Consistently, exogenous activation of K-ATP channels by pharmacological tools can be viewed as one of the most promising strategies for the therapy of myocardial ischemia. As part of our research program devoted to the synthesis and the evaluation of new cardioprotective agents, we extensively studied several six-membered spiro-heterocycle-benzopyran compounds endowed of a significant anti-ischemic activity. The positive results obtained, prompted us to further explore the influence on the biopharmacological effects, of the spiro-substitution at C4 benzopyran nucleus by replacing the six-membered spirocycle of the most active compounds with 5-membered-one.The preliminary evaluation of the new compounds on cultured H9c2 cardiomyoblasts exposed to anoxia/reperfusion and on Langendorff-perfused rat hearts submitted to ischemia/reperfusion cycles, showed that some of them can exert a cardioprotective effect. This anti-ischemic activity was antagonized by 5-hydroxydecanoic acid, a selective blocker of mito-K-ATP channels, confirming the involvement of this channel in the cardioprotective activity. (C) 2011 Elsevier Masson SAS. All rights reserved.