3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-methoxycarbonylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine | 1169760-18-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-methoxycarbonylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine
• CAS: 1169760-18-2
• 化学式: C₂₁H₂₅NO₄S₂
• 分子量: 419.566
• InChiKey: YWKNWKRUCFSHOG-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.05
• 重原子数：
  28.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  67.79
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-methoxycarbonylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine 在 ammonium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-carboxamidophenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine
  参考文献：
  名称：

  Na⁺ Currents in Cardioprotection: Better to Be Late

  摘要：

  We report the discovery of a selective, potent inhibitor of the late current mediated by the cardiac isoform of the sodium channel (Nav 1.5). The compound, 3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-methylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine (2d) (F 15741), blocks the late component of the Na+ currents and greatly reduces veratridine- or ischemia-induced contracture in isolated tissue and whole heart. The cardioprotective action of 2d was further established in a model of myocardial infarction in the pig in which 2d prevents ischemia-reperfusion damage after 60 min of coronary occlusion and 48 h reperfusion. Under these experimental conditions, only 2d and cariporide reduce infarct size. Remarkably, myocardial protection afforded by 2d occurs in the absence of hemodynamic effects. These data expand the therapeutic potential of late I-Na blockers and suggest that 2d could be useful in pathologies for which pharmacological treatments are not yet available.

  DOI：

  10.1021/jm900296e
• 作为产物：
  描述：

  3,4-dihydro-N-[(2S)-3-[(2-methoxymethoxy-3-methoxycarbonylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine 在 盐酸 、 水 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以2.59 g的产率得到3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-methoxycarbonylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine
  参考文献：
  名称：

  Na⁺ Currents in Cardioprotection: Better to Be Late

  摘要：

  We report the discovery of a selective, potent inhibitor of the late current mediated by the cardiac isoform of the sodium channel (Nav 1.5). The compound, 3,4-dihydro-N-[(2S)-3-[(2-hydroxy-3-methylphenyl)thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine (2d) (F 15741), blocks the late component of the Na+ currents and greatly reduces veratridine- or ischemia-induced contracture in isolated tissue and whole heart. The cardioprotective action of 2d was further established in a model of myocardial infarction in the pig in which 2d prevents ischemia-reperfusion damage after 60 min of coronary occlusion and 48 h reperfusion. Under these experimental conditions, only 2d and cariporide reduce infarct size. Remarkably, myocardial protection afforded by 2d occurs in the absence of hemodynamic effects. These data expand the therapeutic potential of late I-Na blockers and suggest that 2d could be useful in pathologies for which pharmacological treatments are not yet available.

  DOI：

  10.1021/jm900296e