methyl 4-{4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate | 553681-15-5

• 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-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate
• 英文别名: Methyl-4-[4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-(2,2,2-trifluoro-1-di-methylhydrazonoethyl)butyl]benzoate；methyl 4-[6-(2,4-diamino-6-oxo-1H-pyrimidin-5-yl)-2-(dimethylhydrazinylidene)-1,1,1-trifluorohexan-3-yl]benzoate
• CAS: 553681-15-5
• 化学式: C₂₀H₂₅F₃N₆O₃
• 分子量: 454.452
• InChiKey: HOZQDSCEFDMVON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 4-{4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以100%的产率得到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-{4-chloro-1-[1-(dimethylhydrazono)-2,2,2-trifluoroethyl]butyl}benzoate 在 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.5h， 生成 methyl 4-{4-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5-yl)-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

文献信息

• Inhibitors of glycinamide ribonucleotide transformylase
  申请人：Boger L Dale

  公开号：US20070167377A1

  公开（公告）日：2007-07-19

  Potent human inhibitors of human glycinamide ribonucleotide transformylase and of aminoimidazole carboxamide ribonucleotide transformylase are designed, synthesized, and characterized.

  设计、合成并表征了强效的人类甘氨酰核苷酸转移酶和氨基咪唑甲酸核苷酸转移酶的人类抑制剂。
• Synthesis and biological evaluation of α- and γ-carboxamide derivatives of 10-CF3CO-DDACTHF
  作者：Youhoon Chong、Inkyu Hwang、Ali Tavassoli、Yan Zhang、Ian A. Wilson、Stephen J. Benkovic、Dale L. Boger

  DOI：10.1016/j.bmc.2004.11.050

  日期：2005.5

  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.