(5-methyl-4-phenyl-1H-pyrazol-3-yl)(4-trifluoromethyl-phenyl)amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (5-methyl-4-phenyl-1H-pyrazol-3-yl)(4-trifluoromethyl-phenyl)amine
• 英文别名: (5-Methyl-4-phenyl-1H-pyrazol-3-yl)-(4-trifluoromethyl-phenyl)-amine；5-methyl-4-phenyl-N-[4-(trifluoromethyl)phenyl]-1H-pyrazol-3-amine
• 化学式: C₁₇H₁₄F₃N₃
• 分子量: 317.313
• InChiKey: QEEIPIODSXKDCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)异硫氰酸苯酯 在 sodium hydride 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.0h， 生成 (5-methyl-4-phenyl-1H-pyrazol-3-yl)(4-trifluoromethyl-phenyl)amine
  参考文献：
  名称：

  Pyrazole Bioisosteres of Leflunomide as B-Cell Immunosuppressants for Xenotransplantation and Chronic Rejection:  Scope and Limitations

  摘要：

  T-cell immunosuppressant-based therapies efficiently control early graft rejection in allotransplantation settings. They fail, however, to prevent those rejection events which are mediated by transplant-induced antibody (Ab) responses such as those involved in xenograft and chronic allograft rejection. This is mainly due to their inability to block T-cell-independent Ab production against the transplanted organs. The bioactive metabolite 2(Z) of leflunomide (1) inhibits the formation of such Ab, but the drug has pharmacokinetic properties and a therapeutic window incompatible with transplantation indications. Pyrazole 3, a constrained analogue of 2(Z), was designed and shown to be conformationally and biologically similar to 2(Z). Further investigations with derivatives of 3 demonstrated that the pyrazoles had very tight structure-activity relationships, the only equipotent compound being 3o. However, in contrast to 2(Z), both 3 and 3o were inactive in vivo due to short half-life and drug concentrations lower than the in vitro obtained IC50 values, Compound 3o inhibits T-cell-independent Ab production by a different biochemical mechanism from that of 2(Z) and 3 and may therefore represent a valuable tool for the identification of new targets for B-cell inhibition.

  DOI：

  10.1021/jm981028c