4'-(4-trifluoromethylbenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene4,2'-[1,4]-oxazinan]-5'-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: 4'-(4-trifluoromethylbenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene4,2'-[1,4]-oxazinan]-5'-one
• 英文别名: 4'-(4-trifluoromethylbenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromen-4,2'-[1,4]oxazinan]-5'-one；2,2-dimethyl-4'-[[4-(trifluoromethyl)phenyl]methyl]spiro[3H-chromene-4,6'-morpholine]-3'-one
• 化学式: C₂₂H₂₂F₃NO₃
• 分子量: 405.417
• InChiKey: CKMSOIOZIUVENL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4'-(4-trifluoromethylbenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene4,2'-[1,4]-oxazinan]-5'-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 4'-(4-trifluoromethylbenzyl)-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
• 作为产物：
  描述：

  2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene-4,2'-[1,4]oxazinan]-5'-one 、 1-溴-三氟对二甲苯 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87%的产率得到4'-(4-trifluoromethylbenzyl)-2,2-dimethyl-2,3-dihydro-5'H-spiro[chromene4,2'-[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