2-methylsulfonyl-4-(tert-butoxycarbonyl-methylamino)-5-chloropyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-methylsulfonyl-4-(tert-butoxycarbonyl-methylamino)-5-chloropyrimidine
• 英文别名: tert-butyl N-(5-chloro-2-methylsulfonylpyrimidin-4-yl)-N-methylcarbamate
• 化学式: C₁₁H₁₆ClN₃O₄S
• 分子量: 321.785
• InChiKey: HCPMTCYOMAPACZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  97.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methylsulfonyl-4-(tert-butoxycarbonyl-methylamino)-5-chloropyrimidine 、 氰化钠 以 二甲基亚砜 为溶剂， 反应 0.5h， 以100%的产率得到2-cyano-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：

  (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

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.