| 884315-36-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• CAS: 884315-36-0
• 化学式: C₂₄H₃₁F₃N₆O₄
• 分子量: 524.543
• InChiKey: WOCJCICHUTUTEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.39
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  113.73
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  、 特戊胺 在 N,N-二异丙基乙胺 作用下， 反应 12.0h， 生成 1-{4-[4-(2-tert-Butyl-6-trifluoromethyl-pyrimidin-4-yl)-piperazin-1-yl]-butyl}-3-(2,2-dimethyl-propyl)-urea
  参考文献：
  名称：

  Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: Variations on the 1H-pyrimidin-2-one theme

  摘要：

  In our efforts to further pursue one of the most selective dopamine D-3-receptor antagonists reported to date, we now describe the synthesis and SAR of novel and highly selective dopamine D-3 antagonists based on a 1H-pyridin-2-one or on a urea scaffold. The most potent compounds exhibited K-i values toward the D-3 receptor in the nano- to subnanomolar range and high selectivity versus the related D-2 dopamine receptor. Thus, 1H-pyridin-2-one 7b displays oral bioavailability (F = 37%) as well as brain penetration (brain plasma ratio 3.7) in rat. Within the urea series, an excellent D-3 versus D-2 selectivity (>100-fold) could be achieved by removal of one NH group (compound 6), although bioavailability (rat) was suboptimal (F < 10%). These data significantly enhance our understanding of the D-3 Pharmacophore and are expected to lead to novel approaches for the treatment of schizophrenia. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.079
• 作为产物：
  描述：

  4-(4-(2-(tert-butyl)-6-(trifluoromethyl)pyrimidin-4-yl)piperazin-1-yl)butan-1-amine 、 对硝基苯基氯甲酸酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: Variations on the 1H-pyrimidin-2-one theme

  摘要：

  In our efforts to further pursue one of the most selective dopamine D-3-receptor antagonists reported to date, we now describe the synthesis and SAR of novel and highly selective dopamine D-3 antagonists based on a 1H-pyridin-2-one or on a urea scaffold. The most potent compounds exhibited K-i values toward the D-3 receptor in the nano- to subnanomolar range and high selectivity versus the related D-2 dopamine receptor. Thus, 1H-pyridin-2-one 7b displays oral bioavailability (F = 37%) as well as brain penetration (brain plasma ratio 3.7) in rat. Within the urea series, an excellent D-3 versus D-2 selectivity (>100-fold) could be achieved by removal of one NH group (compound 6), although bioavailability (rat) was suboptimal (F < 10%). These data significantly enhance our understanding of the D-3 Pharmacophore and are expected to lead to novel approaches for the treatment of schizophrenia. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.079