6-bromo-2,2-dimethyl-2,3-dihydrospiro[chromene-4,2'-[1,4]-oxazinane] | 1076221-37-8

• 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: 6-bromo-2,2-dimethyl-2,3-dihydrospiro[chromene-4,2'-[1,4]-oxazinane]
• 英文别名: 6-bromo-2,2-dimethylspiro[3H-chromene-4,2'-morpholine]
• CAS: 1076221-37-8
• 化学式: C₁₄H₁₈BrNO₂
• 分子量: 312.206
• InChiKey: JLQQLGXXYJCRFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromo-2,2-dimethyl-2,3-dihydrospiro[chromene-4,2'-[1,4]-oxazinane] 在 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 14.0h， 生成 2-(6-bromo-2,2-dimethylspiro[chroman-4,2'-morpholin]-4'-yl) acetic acid
  参考文献：
  名称：

  带有螺并苯并吡喃骨架的新型醛糖还原酶抑制剂的合成及功能评价。

  摘要：

  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，

  DOI：

  10.2174/1874104501711010009
• 作为产物：
  描述：

  6-bromo-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene-4,2'-[1,4]oxazinan]-5'-one 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 6-bromo-2,2-dimethyl-2,3-dihydrospiro[chromene-4,2'-[1,4]-oxazinane]
  参考文献：
  名称：

  Spirocyclic Benzopyran-Based Derivatives as New Anti-ischemic Activators of Mitochondrial ATP-Sensitive Potassium Channel

  摘要：

  Heart mitochondrial ATP-sensitive potassium channels mito-K-ATP channels) are deeply implicated in the self-defense mechanism of ischemic preconditioning. Therefore, exogenous molecules activating these channels are considered as a promising pharmacological tool to reduce the myocardial injury deriving from ischemia/reperfusion events. This paper reports the synthesis and pharmacological evaluation of original spiromorpholine- and spiromorpholone-benzopyran, derivatives, with the aim to obtain selective activators of mito-K-ATP channels. Some compounds of this series showed appreciable cardioprotective effects on rat isolated and perfused hearts, Submitted to ischemia/reperfusion cycles. The selective mito-K-ATP channel blocker 5-hydroxydecanoic acid antagonized the anti-ischemic activity, indicating a clear implication of this pharmacological target. Furthermore, these effects were not associated with significant hypotensive and vasorelaxing properties, which represent one of the main limiting factors for the clinical use of nonselective T K-ATP-openers against myocardial ischemia.

  DOI：

  10.1021/jm800956g

文献信息

• Spirocyclic Benzopyran-Based Derivatives as New Anti-ischemic Activators of Mitochondrial ATP-Sensitive Potassium Channel
  作者：Maria C. Breschi、Vincenzo Calderone、Maria Digiacomo、Mariaelisa Manganaro、Alma Martelli、Filippo Minutolo、Simona Rapposelli、Lara Testai、Federica Tonelli、Aldo Balsamo

  DOI：10.1021/jm800956g

  日期：2008.11.13

  Heart mitochondrial ATP-sensitive potassium channels mito-K-ATP channels) are deeply implicated in the self-defense mechanism of ischemic preconditioning. Therefore, exogenous molecules activating these channels are considered as a promising pharmacological tool to reduce the myocardial injury deriving from ischemia/reperfusion events. This paper reports the synthesis and pharmacological evaluation of original spiromorpholine- and spiromorpholone-benzopyran, derivatives, with the aim to obtain selective activators of mito-K-ATP channels. Some compounds of this series showed appreciable cardioprotective effects on rat isolated and perfused hearts, Submitted to ischemia/reperfusion cycles. The selective mito-K-ATP channel blocker 5-hydroxydecanoic acid antagonized the anti-ischemic activity, indicating a clear implication of this pharmacological target. Furthermore, these effects were not associated with significant hypotensive and vasorelaxing properties, which represent one of the main limiting factors for the clinical use of nonselective T K-ATP-openers against myocardial ischemia.
• 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，