3,4-dihydro-N-[(2S)-3-[2,3-dihydrobenzofuran-7-thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine | 470454-92-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 3,4-dihydro-N-[(2S)-3-[2,3-dihydrobenzofuran-7-thio]-2-methylpropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine
• 英文别名: (3R)-N-[(2S)-3-(2,3-dihydro-1-benzofuran-7-ylsulfanyl)-2-methylpropyl]-3,4-dihydro-2H-1,5-benzoxathiepin-3-amine
• CAS: 470454-92-3
• 化学式: C₂₁H₂₅NO₂S₂
• 分子量: 387.567
• InChiKey: YTIJTAJHGATKIA-DOTOQJQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(R)-amino-1,5-benzoxathiepine 、 2-(S)-methyl-3-(2,3-dihydrobenzofuran-7-thio)propionaldehyde 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 3,4-dihydro-N-[(2S)-3-[2,3-dihydrobenzofuran-7-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

文献信息

• Benzoaxathiepin derivatives and their use as medicines
  申请人：——

  公开号：US20040127552A1

  公开（公告）日：2004-07-01

  The invention concerns 3-arylthio-propyl-amino-3,4-dihydro-2H-1,5-aryloxathiepin derivatives of general formula (I), wherein: R1 and R2, identical or different, represent a hydrogen atom, a fluorine atom or a chlorine atom, a hydroxy group, an alkyl, cyclopropyl, alkoxy, cyclopropoxy radical or when they occupy adjacent positions, form with the carbon atoms bearing them a carbon-containing cycle or an oxygen-containing heterocycle with five non-aromatic rings; R3 represents an alkyl radical, a hydroxy group or a methoxy radical; R4 represents a hydrogen atom or a methyl radical; and R 5 ?and R6, identical or different represent a hydrogen atom, an alkyl, alkoxy, alkylthio, alkylamino radical, or the groups OR4 and R5 form with the carbons which bear them a non-aromatic heterocycle with five or six rings containing at least an oxygen atom; and their pharmaceutically acceptable additions salts. 1

  该发明涉及一般式(I)的3-芳基硫代丙基氨基-3,4-二氢-2H-1,5-芳氧硫杂环戊烷衍生物，其中：R1和R2，相同或不同，代表氢原子、氟原子或氯原子、羟基、烷基、环丙基、烷氧基、环丙氧基基团或当它们占据相邻位置时，与携带它们的碳原子形成含碳环或含氧杂环的非芳香环，R3代表烷基基团、羟基或甲氧基基团；R4代表氢原子或甲基基团；R5和R6，相同或不同，代表氢原子、烷基、烷氧基、烷硫基、烷基氨基基团，或基团OR4和R5与携带它们的碳形成含至少一个氧原子的五元或六元环的非芳香杂环；以及它们的药学上可接受的盐。
• DERIVES BENZOAXATHIEPINES ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：PIERRE FABRE MEDICAMENT

  公开号：EP1370547B1

  公开（公告）日：2004-09-15
• US7109234B2
  申请人：——

  公开号：US7109234B2

  公开（公告）日：2006-09-19
• 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.