methyl 4-{5-cyano-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]-5-(ethoxycarbonyl)pentyl}benzoate | 553681-14-4

• 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-{5-cyano-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]-5-(ethoxycarbonyl)pentyl}benzoate
• CAS: 553681-14-4
• 化学式: C₂₁H₂₆F₃N₃O₄
• 分子量: 441.45
• InChiKey: BWESLQULRMZAGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.91
• 重原子数：
  31.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  91.99
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 4-{5-cyano-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]-5-(ethoxycarbonyl)pentyl}benzoate 在 lithium hydroxide 、 sodium hydroxide 、 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.75h， 生成 4-carbamoyl-4-{4-[4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(2,2,2-trifluoroacetyl)butyl]benzoylamino}butyric acid hydrochloride
  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 在 sodium hexamethyldisilazane 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.75h， 生成 methyl 4-{5-cyano-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]-5-(ethoxycarbonyl)pentyl}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