methyl 4-{4-chloro-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate | 878380-60-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl 4-{4-chloro-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate
• CAS: 878380-60-0
• 化学式: C₁₆H₂₀ClF₃N₂O₂
• 分子量: 364.795
• InChiKey: NCUXVAQSSTYONT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.06
• 重原子数：
  24.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.9
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 4-{4-chloro-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate 在 lithium hydroxide 、 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.5h， 生成 4-[4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(2,2,2-trifluoroacetyl)butyl]benzoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of α- and γ-carboxamide derivatives of 10-CF3CO-DDACTHF

  摘要：

  Structurally-related, but non-polyglutamylatable, derivatives of 10-CF3CO-DDACTHF (1), which incorporate L-glutamine (2) and L-isoglutamine (3) in place Of L-glutamate, were prepared and evaluated as inhibitors of recombinant human (rh) GAR Tfase. While the L-glutamate alpha-carboxamide derivative 3 was much less effective as a rhGAR Tfase inhibitor (K-i = 4.8 mu M) and inactive in cellular functional assays, the gamma-carboxamide derivative 2 was found to be a potent and selective rhGAR Tfase inhibitor (K-i = 0.056 mu M) being only 4-fold less potent than 1 (K-i = 0.0 15 mu M). Moreover, 2 was effective in cellular functional assays exhibiting purine sensitive cytotoxic activity (IC50 = 300 nM, CCRF-CEM) only 20-fold less potent than 1 (IC50 = 16 nM), consistent with inhibition of de novo purine biosynthesis via selective inhibition of GAR Tfase. Like 1, 2 is transported into the cell by the reduced folate carrier. Unlike 1, the functional activity of 2 is not dependent upon FPGS polyglutamylation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.050
• 作为产物：
  描述：

  Methyl 4-(3,3,3-trifluoro-2-dimethylhydrazonopropyl)benzoate 、 1-氯-3-碘丙烷 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以63%的产率得到methyl 4-{4-chloro-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate
  参考文献：
  名称：

  Synthesis and biological evaluation of α- and γ-carboxamide derivatives of 10-CF3CO-DDACTHF

  摘要：

  Structurally-related, but non-polyglutamylatable, derivatives of 10-CF3CO-DDACTHF (1), which incorporate L-glutamine (2) and L-isoglutamine (3) in place Of L-glutamate, were prepared and evaluated as inhibitors of recombinant human (rh) GAR Tfase. While the L-glutamate alpha-carboxamide derivative 3 was much less effective as a rhGAR Tfase inhibitor (K-i = 4.8 mu M) and inactive in cellular functional assays, the gamma-carboxamide derivative 2 was found to be a potent and selective rhGAR Tfase inhibitor (K-i = 0.056 mu M) being only 4-fold less potent than 1 (K-i = 0.0 15 mu M). Moreover, 2 was effective in cellular functional assays exhibiting purine sensitive cytotoxic activity (IC50 = 300 nM, CCRF-CEM) only 20-fold less potent than 1 (IC50 = 16 nM), consistent with inhibition of de novo purine biosynthesis via selective inhibition of GAR Tfase. Like 1, 2 is transported into the cell by the reduced folate carrier. Unlike 1, the functional activity of 2 is not dependent upon FPGS polyglutamylation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.050