(+/-)-3,3-dimethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one hydrochloride

• 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: (+/-)-3,3-dimethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a]isoindol-6(2H)-one hydrochloride
• 英文别名: 3,3-Dimethyl-7-(trifluoromethyl)-1,2,4,10b-tetrahydropyrazino[1,2-b]isoindol-6-one;hydrochloride
• 化学式: C₁₄H₁₅F₃N₂O*ClH
• 分子量: 320.742
• InChiKey: ITXBPWAIXHOPNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-三氟甲基苯甲酰氯 在 palladium on activated charcoal 盐酸 、 四甲基乙二胺 、 氢气 、 仲丁基锂 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， -78.0~100.0 ℃ 、551.58 kPa 条件下， 反应 125.5h， 生成 (+/-)-3,3-dimethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[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

文献信息

• Discovery of (<i>R</i>)-9-Ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-<i>a</i>]isoindol- 6(2<i>H</i>)-one, a Selective, Orally Active Agonist of the 5-HT_2C Receptor
  作者：Dean A. Wacker、Jeffrey G. Varnes、Sarah E. Malmstrom、Xueying Cao、Chen-Pin Hung、Thao Ung、Ginger Wu、Ge Zhang、Eva Zuvich、Michael A. Thomas、William J. Keim、Mary Jane Cullen、Kenneth W. Rohrbach、Qinling Qu、Rangaraj Narayanan、Karen Rossi、Evan Janovitz、Lois Lehman-McKeeman、Mary F. Malley、James Devenny、Mary Ann Pelleymounter、Keith J. Miller、Jeffrey A. Robl

  DOI：10.1021/jm0612968

  日期：2007.3.1

  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.