4'-(4-bromobenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene-4,2'-[1,4]-oxazinan]-5'-one | 1076221-27-6

• 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: 4'-(4-bromobenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene-4,2'-[1,4]-oxazinan]-5'-one
• 英文别名: 4'-[(4-bromophenyl)methyl]-2,2-dimethylspiro[3H-chromene-4,6'-morpholine]-3'-one
• CAS: 1076221-27-6
• 化学式: C₂₁H₂₂BrNO₃
• 分子量: 416.315
• InChiKey: IWOMHISQLWDWBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene-4,2'-[1,4]oxazinan]-5'-one 、 对溴溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.5h， 以38%的产率得到4'-(4-bromobenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene-4,2'-[1,4]-oxazinan]-5'-one
  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.