(5-氯-2-(甲基磺酰基)嘧啶-4-基)氨基甲酸叔丁酯 | 955112-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: (5-氯-2-(甲基磺酰基)嘧啶-4-基)氨基甲酸叔丁酯
• 英文名称: 2-methylsulfonyl-4-tert-butoxycarbonylamino-5-chloropyrimidine
• 英文别名: tert-Butyl (5-chloro-2-(methylsulfonyl)pyrimidin-4-yl)carbamate；tert-butyl N-(5-chloro-2-methylsulfonylpyrimidin-4-yl)carbamate
• CAS: 955112-59-1
• 化学式: C₁₀H₁₄ClN₃O₄S
• 分子量: 307.758
• InChiKey: BRQMVVSECBWDCA-UHFFFAOYSA-N

物化性质

• 密度：
  1.407±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  (5-氯-2-(甲基磺酰基)嘧啶-4-基)氨基甲酸叔丁酯 、 硫酸二甲酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 8.25h， 以1.96 g的产率得到2-methylsulfonyl-4-(tert-butoxycarbonyl-methylamino)-5-chloropyrimidine
  参考文献：
  名称：

  High-Efficacy 5-HT_1A Agonists for Antidepressant Treatment:  A Renewed Opportunity

  摘要：

  We report the discovery of novel 5-HT1A receptor agonists and describe the process that led to the antidepressant candidate 9 (F 15599). 9 has nanomolar affinity for 5-HT1A binding sites and is over 1000-fold selective with respect to the other 5-HT1 receptor subtypes, 5-HT2-7 receptor families, and also numerous GPCRs, transporters, ion channels, and enzymes. In a cellular model of signal transduction, 9 activates h5-HT1A receptors with an efficacy superior to that of the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT and comparators undergoing clinical trials. After acute oral administration in rats, 9 totally reverses immobility in the forced swimming test and produces behaviors characteristic of 5-HT1A receptor activation. However, these effects occurred at widely separated doses, suggesting that 9 discriminates between distinct populations of 5-HT1A receptors. While the clinical relevance of these observations is still unknown, this opens new perspectives for the treatment of depressive disorders.

  DOI：

  10.1021/jm070714l
• 作为产物：
  描述：

  叔丁醇 、 5-氯-2-(甲磺酰基)嘧啶-4-羧酸 在 二苯基膦叠氮化物 、 三乙胺 作用下， 反应 8.0h， 以52%的产率得到(5-氯-2-(甲基磺酰基)嘧啶-4-基)氨基甲酸叔丁酯
  参考文献：
  名称：

  High-Efficacy 5-HT_1A Agonists for Antidepressant Treatment:  A Renewed Opportunity

  摘要：

  We report the discovery of novel 5-HT1A receptor agonists and describe the process that led to the antidepressant candidate 9 (F 15599). 9 has nanomolar affinity for 5-HT1A binding sites and is over 1000-fold selective with respect to the other 5-HT1 receptor subtypes, 5-HT2-7 receptor families, and also numerous GPCRs, transporters, ion channels, and enzymes. In a cellular model of signal transduction, 9 activates h5-HT1A receptors with an efficacy superior to that of the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT and comparators undergoing clinical trials. After acute oral administration in rats, 9 totally reverses immobility in the forced swimming test and produces behaviors characteristic of 5-HT1A receptor activation. However, these effects occurred at widely separated doses, suggesting that 9 discriminates between distinct populations of 5-HT1A receptors. While the clinical relevance of these observations is still unknown, this opens new perspectives for the treatment of depressive disorders.

  DOI：

  10.1021/jm070714l

文献信息

• High-Efficacy 5-HT_1A Agonists for Antidepressant Treatment:  A Renewed Opportunity
  作者：Jean Louis Maurel、Jean-Marie Autin、Philippe Funes、Adrian Newman-Tancredi、Francis Colpaert、Bernard Vacher

  DOI：10.1021/jm070714l

  日期：2007.10.1

  We report the discovery of novel 5-HT1A receptor agonists and describe the process that led to the antidepressant candidate 9 (F 15599). 9 has nanomolar affinity for 5-HT1A binding sites and is over 1000-fold selective with respect to the other 5-HT1 receptor subtypes, 5-HT2-7 receptor families, and also numerous GPCRs, transporters, ion channels, and enzymes. In a cellular model of signal transduction, 9 activates h5-HT1A receptors with an efficacy superior to that of the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT and comparators undergoing clinical trials. After acute oral administration in rats, 9 totally reverses immobility in the forced swimming test and produces behaviors characteristic of 5-HT1A receptor activation. However, these effects occurred at widely separated doses, suggesting that 9 discriminates between distinct populations of 5-HT1A receptors. While the clinical relevance of these observations is still unknown, this opens new perspectives for the treatment of depressive disorders.