3,4-dihydro-N-[(2S)-3-[(2-methoxyphenyl)thio]-2-n-propoxypropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine | 1038864-94-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,4-dihydro-N-[(2S)-3-[(2-methoxyphenyl)thio]-2-n-propoxypropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine
• 英文别名: (3R)-N-[(2S)-3-(2-methoxyphenyl)sulfanyl-2-propoxypropyl]-3,4-dihydro-2H-1,5-benzoxathiepin-3-amine
• CAS: 1038864-94-6
• 化学式: C₂₂H₂₉NO₃S₂
• 分子量: 419.609
• InChiKey: XTGYNIBAARSQAR-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  90.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(R)-amino-1,5-benzoxathiepine 、 (2S)-3-[(2-methoxyphenyl)thio]-2-propyloxyl-propanal 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 2.33h， 生成 3,4-dihydro-N-[(2S)-3-[(2-methoxyphenyl)thio]-2-n-propoxypropyl]-2H-(3R)-1,5-benzoxathiepin-3-amine
  参考文献：
  名称：

  Sodium Late Current Blockers in Ischemia Reperfusion: Is the Bullet Magic?

  摘要：

  We describe the discovery of the first selective, potent, and voltage-dependent inhibitor of the late current mediated by the cardiac sodium channel Na(V)1.5. The compound 3,4-dihydro-N-[(2S)-3-[(2-methoxyphenyl)thio]-2-methylpropyll-2H-(3R)-1,5-benzoxathiepin-3-amine, 2a (F 15845), was identified from a novel family of 3-amino-1,5-benzoxathiepine derivatives. The late sodium current inhibition and antiischemic effects of 2a were studied in various models in vitro and in vivo. In a rabbit model of ischemia-reperfusion, 2a exhibited more potent antiischemic effects than reference compounds KC 12291, ranolazine, and ivabradine. Thus, after a single administration, 2a almost abolished ST segment elevation in response to a transient coronary occlusion. Further, the antiischemic activity of 2a is maintained over a wide range of doses and is not associated with any hemodynamic changes, contrary to conventional antiischemic agents. The unique pharmacological profile of 2a opens new and promising opportunities for the treatment of ischemic heart diseases.

  DOI：

  10.1021/jm800100z

文献信息

• Sodium Late Current Blockers in Ischemia Reperfusion: Is the Bullet Magic?
  作者：Bruno Le Grand、Christophe Pignier、Robert Létienne、Florence Cuisiat、Françoise Rolland、Agnes Mas、Bernard Vacher

  DOI：10.1021/jm800100z

  日期：2008.7

  We describe the discovery of the first selective, potent, and voltage-dependent inhibitor of the late current mediated by the cardiac sodium channel Na(V)1.5. The compound 3,4-dihydro-N-[(2S)-3-[(2-methoxyphenyl)thio]-2-methylpropyll-2H-(3R)-1,5-benzoxathiepin-3-amine, 2a (F 15845), was identified from a novel family of 3-amino-1,5-benzoxathiepine derivatives. The late sodium current inhibition and antiischemic effects of 2a were studied in various models in vitro and in vivo. In a rabbit model of ischemia-reperfusion, 2a exhibited more potent antiischemic effects than reference compounds KC 12291, ranolazine, and ivabradine. Thus, after a single administration, 2a almost abolished ST segment elevation in response to a transient coronary occlusion. Further, the antiischemic activity of 2a is maintained over a wide range of doses and is not associated with any hemodynamic changes, contrary to conventional antiischemic agents. The unique pharmacological profile of 2a opens new and promising opportunities for the treatment of ischemic heart diseases.