(S)-2-methyl 3-(N-t-butoxycarbonylindol-7-thio)-propanol | 1169760-37-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-2-methyl 3-(N-t-butoxycarbonylindol-7-thio)-propanol
• 英文别名: tert-butyl 7-[(2S)-3-hydroxy-2-methylpropyl]sulfanylindole-1-carboxylate
• CAS: 1169760-37-5
• 化学式: C₁₇H₂₃NO₃S
• 分子量: 321.441
• InChiKey: YVPNUQYXYJYTTA-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-methyl 3-(N-t-butoxycarbonylindol-7-thio)-propanol 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成
  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：

  (S)-2-methyl 3-(N-t-butoxycarbonylindol-7-thio)-propyl t-butyldimethylsilyl ether 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以72%的产率得到(S)-2-methyl 3-(N-t-butoxycarbonylindol-7-thio)-propanol
  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

文献信息

• Na⁺ Currents in Cardioprotection: Better to Be Late
  作者：Bruno Le Grand、Christophe Pignier、Robert Létienne、Francis Colpaert、Florence Cuisiat、Françoise Rolland、Agnes Mas、Maud Borras、Bernard Vacher

  DOI：10.1021/jm900296e

  日期：2009.7.23

  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.