N-(tert-butoxycarbonyl)-(+/-)-8-ethenyl-7-methoxy-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one | 934634-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(tert-butoxycarbonyl)-(+/-)-8-ethenyl-7-methoxy-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one
• 英文别名: Tert-butyl 8-ethenyl-7-methoxy-6-oxo-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindole-2-carboxylate
• CAS: 934634-59-0
• 化学式: C₁₉H₂₄N₂O₄
• 分子量: 344.411
• InChiKey: LZYHCQQEGJDVRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)-(+/-)-8-ethenyl-7-methoxy-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 1.08h， 生成 (R)-8-ethyl-7-methoxy-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one hydrochloride
  参考文献：
  名称：

  Discovery of (R)-9-Ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol- 6(2H)-one, a Selective, Orally Active Agonist of the 5-HT_2C Receptor

  摘要：

  Robust pharmaceutical treatment of obesity has been limited by the undesirable side-effect profile of currently marketed therapies. This paper describes the synthesis and optimization of a new class of pyrazinoisoindolone-containing, selective 5-HT2C agonists as antiobesity agents. Key to optimization of the pyrazinoisoindolone core was the identification of the appropriate substitution pattern and functional groups which led to the discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one (58), a 5-HT2C agonist with > 300-fold functional selectivity over 5-HT2B and > 70-fold functional selectivity over 5-HT2A. Oral dosing of 58 reduced food intake in an acute rat feeding model, which could be completely reversed by a selective 5-HT2C antagonist and caused a reduction in body weight gain in a 4-day rat model.

  DOI：

  10.1021/jm0612968
• 作为产物：
  描述：

  N-(tert-butoxycarbonyl)-(+/-)-8-chloro-7-methoxy-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one 、 alkaline earth salt of/the/ methylsulfuric acid 在 bis(tri-tert-butylphosphine)palladium⁽⁰⁾ potassium fluoride 作用下， 以 1,4-二氧六环 为溶剂， 反应 14.0h， 以88%的产率得到N-(tert-butoxycarbonyl)-(+/-)-8-ethenyl-7-methoxy-1,3,4,10b-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one
  参考文献：
  名称：

  Discovery of (R)-9-Ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol- 6(2H)-one, a Selective, Orally Active Agonist of the 5-HT_2C Receptor

  摘要：

  Robust pharmaceutical treatment of obesity has been limited by the undesirable side-effect profile of currently marketed therapies. This paper describes the synthesis and optimization of a new class of pyrazinoisoindolone-containing, selective 5-HT2C agonists as antiobesity agents. Key to optimization of the pyrazinoisoindolone core was the identification of the appropriate substitution pattern and functional groups which led to the discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one (58), a 5-HT2C agonist with > 300-fold functional selectivity over 5-HT2B and > 70-fold functional selectivity over 5-HT2A. Oral dosing of 58 reduced food intake in an acute rat feeding model, which could be completely reversed by a selective 5-HT2C antagonist and caused a reduction in body weight gain in a 4-day rat model.

  DOI：

  10.1021/jm0612968