4-(tert-butyl) 1-(4-chlorophenyl) 2-((pyridin-3-yloxy)methyl)piperazine-1,4-dicarboxylate | 1609464-37-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(tert-butyl) 1-(4-chlorophenyl) 2-((pyridin-3-yloxy)methyl)piperazine-1,4-dicarboxylate
• CAS: 1609464-37-0
• 化学式: C₂₂H₂₆ClN₃O₅
• 分子量: 447.919
• InChiKey: WARNVMQBRDZXPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.23
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  81.2
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-(tert-butyl) 1-(4-chlorophenyl) 2-((pyridin-3-yloxy)methyl)piperazine-1,4-dicarboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 1.0h， 以63 mg的产率得到4-chlorophenyl 2-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate dihydrochloride
  参考文献：
  名称：

  Discovery of Novel 2-((Pyridin-3-yloxy)methyl)piperazines as α7 Nicotinic Acetylcholine Receptor Modulators for the Treatment of Inflammatory Disorders

  摘要：

  Herein we report the design, synthesis, and structure activity relationships for a new class of alpha 7 nicotinic acetylcholine receptor (nAChR) modulators based on the 2-((pyridin-3-yloxy)methyl)piperazine scaffold. The oxazolo[4,5-b]pyridine, (R)-18, and 4-methoxyphenylurea, (R)-47, were identified as potent and selective modulators of the alpha 7 nAChR with favorable in vitro safety profiles and good oral bioavailability in mouse. Both compounds were shown to significantly inhibit cellular infiltration in a murine model of allergic lung inflammation. Despite the structural and in vivo functional similarities in the compounds, only (R)-18 was shown to be an agonist. Compound (R)-47 demonstrated silent agonist activity. These data support the hypothesis that the anti-inflammatory activity of the alpha 7 nAChR is mediated by a signal transduction pathway that is independent of ion current.

  DOI：

  10.1021/jm5004599
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 硼烷四氢呋喃络合物 、 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 130.5h， 生成 4-(tert-butyl) 1-(4-chlorophenyl) 2-((pyridin-3-yloxy)methyl)piperazine-1,4-dicarboxylate
  参考文献：
  名称：

  Discovery of Novel 2-((Pyridin-3-yloxy)methyl)piperazines as α7 Nicotinic Acetylcholine Receptor Modulators for the Treatment of Inflammatory Disorders

  摘要：

  Herein we report the design, synthesis, and structure activity relationships for a new class of alpha 7 nicotinic acetylcholine receptor (nAChR) modulators based on the 2-((pyridin-3-yloxy)methyl)piperazine scaffold. The oxazolo[4,5-b]pyridine, (R)-18, and 4-methoxyphenylurea, (R)-47, were identified as potent and selective modulators of the alpha 7 nAChR with favorable in vitro safety profiles and good oral bioavailability in mouse. Both compounds were shown to significantly inhibit cellular infiltration in a murine model of allergic lung inflammation. Despite the structural and in vivo functional similarities in the compounds, only (R)-18 was shown to be an agonist. Compound (R)-47 demonstrated silent agonist activity. These data support the hypothesis that the anti-inflammatory activity of the alpha 7 nAChR is mediated by a signal transduction pathway that is independent of ion current.

  DOI：

  10.1021/jm5004599