2,2-dimethyl-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-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one
• 英文别名: 2,2-dimethyl-2,3-dihydro-2'H-spiro[chromen-4,5'-[1,3]oxazolidin]-2'-one；2',2'-dimethylspiro[1,3-oxazolidine-5,4'-3H-chromene]-2-one
• 化学式: C₁₃H₁₅NO₃
• mdl: MFCD23061865
• 分子量: 233.267
• InChiKey: ICPFAFANWFOCPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-2,3-dihydro-2'H-spiro[chromene-4,5'-[1,3]oxazolidin]-2'-one 在 iron(III) chloride 、 sodium hydride 、 potassium carbonate 、 甲烷 、 一水合肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 2.5h， 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：

  3,4-dihydro-2,2-dimethyl-4-[(trimethylsilyl)oxy]-2H-1-benzopyran-4-carbonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 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

文献信息

• Synthesis and Functional Evaluation of Novel Aldose Reductase Inhibitors Bearing a Spirobenzopyran Scaffold
  作者：Maria Digiacomo、Stefania Sartini、Giulia Nesi、Simona Sestito、Vito Coviello、Concettina La Motta、Simona Rapposelli

  DOI：10.2174/1874104501711010009

  日期：2017.1.31

  their benzyloxy analogs, developed as aldose reductase inhibitors. RESULTS Most of them proved to inhibit the target enzyme, showing IC50 values in the micromolar/low micromolar range. SARs observed among the three different series allowed to highlight their key pharmacophoric elements, thus creating sound basis for the design of novel and more effective inhibitors. CONCLUSION Although further substitution

  背景技术醛糖还原酶是多元醇途径的第一种酶，是长期糖尿病并发症发病机理的关键决定因素。因此，其抑制代表了治疗这种病理的主要治疗策略。目的在这项工作中，我们描述了作为醛糖还原酶抑制剂开发的许多螺-恶唑烷酮和螺-吗啉酮乙酸衍生物及其苄氧基类似物的合成和功能评估。结果大多数被证明可抑制目标酶，IC50值在微摩尔/低微摩尔范围内。在三个不同系列中观察到的SAR可以突出显示其关键的药效学元素，从而为设计新型更有效的抑制剂奠定了良好的基础。结论尽管还需要其他替代方式，
• 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.