Tert-butyl 4,4-difluoro-2-[[4-(methylamino)benzoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate | 178207-65-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Tert-butyl 4,4-difluoro-2-[[4-(methylamino)benzoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 178207-65-3
• 化学式: C₂₂H₃₃F₂N₃O₅
• 分子量: 457.518
• InChiKey: KXOCKBKHFKGUSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-溴乙基-喋啶-2,4-二胺 、 Tert-butyl 4,4-difluoro-2-[[4-(methylamino)benzoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate 以 N,N-二甲基乙酰胺 为溶剂， 以44%的产率得到5-Amino-2-{4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoylamino}-4,4-difluoro-pentanoic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of N^α-(4-Amino-4-deoxy-10-methylpteroyl)-dl-4,4-difluoroornithine

  摘要：

  N-alpha-(4-Amino-4-deoxy-10-methylpteroyl)-DL-4,4-difluoroornithine (AMPte-DL-4,4-F(2)Orn, 4) was synthesized and evaluated as an inhibitor of human folypoly-gamma-glutamate synthetase (FPGS), dihydrofolate reductase (DHFR), and cell growth. Synthesis of 4 involved the use of a protected form of DL-4,4-difluoroornithine 9 which was derived from DL-4,4-difluoroglutamic acid. Biological activities of 4 were compared directly to those of the corresponding nonfluorinated compound N-alpha-(4-amino-4-deoxy-10-methylpteroyl)-L-ornithine (AMPte-L-Orn, 3). Although the fluorinated analogue is a potent inhibitor of DHFR, it is a poor inhibitor of FPGS. However, the compound is transported across the cell membrane and inhibits cell growth, presumably due to the inhibition of DHFR. The data obtained with the fluorinated analogue are in contrast to those of the corresponding nonfluorinated compound 3, which is a potent inhibitor of bath FPGS and DHFR but shows very low cytotoxicity due to poor transport.

  DOI：

  10.1021/jm960046w
• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-4-(methylamino)benzoic acid 在 palladium dihydroxide 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 22.17h， 生成 Tert-butyl 4,4-difluoro-2-[[4-(methylamino)benzoyl]amino]-5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of N^α-(4-Amino-4-deoxy-10-methylpteroyl)-dl-4,4-difluoroornithine

  摘要：

  N-alpha-(4-Amino-4-deoxy-10-methylpteroyl)-DL-4,4-difluoroornithine (AMPte-DL-4,4-F(2)Orn, 4) was synthesized and evaluated as an inhibitor of human folypoly-gamma-glutamate synthetase (FPGS), dihydrofolate reductase (DHFR), and cell growth. Synthesis of 4 involved the use of a protected form of DL-4,4-difluoroornithine 9 which was derived from DL-4,4-difluoroglutamic acid. Biological activities of 4 were compared directly to those of the corresponding nonfluorinated compound N-alpha-(4-amino-4-deoxy-10-methylpteroyl)-L-ornithine (AMPte-L-Orn, 3). Although the fluorinated analogue is a potent inhibitor of DHFR, it is a poor inhibitor of FPGS. However, the compound is transported across the cell membrane and inhibits cell growth, presumably due to the inhibition of DHFR. The data obtained with the fluorinated analogue are in contrast to those of the corresponding nonfluorinated compound 3, which is a potent inhibitor of bath FPGS and DHFR but shows very low cytotoxicity due to poor transport.

  DOI：

  10.1021/jm960046w

文献信息

• Synthesis and Biological Evaluation of <i>N</i>^α-(4-Amino-4-deoxy-10-methylpteroyl)-<scp>dl</scp>-4,4-difluoroornithine
  作者：Takashi Tsukamoto、William H. Haile、John J. McGuire、James K. Coward

  DOI：10.1021/jm960046w

  日期：1996.1.1

  N-alpha-(4-Amino-4-deoxy-10-methylpteroyl)-DL-4,4-difluoroornithine (AMPte-DL-4,4-F(2)Orn, 4) was synthesized and evaluated as an inhibitor of human folypoly-gamma-glutamate synthetase (FPGS), dihydrofolate reductase (DHFR), and cell growth. Synthesis of 4 involved the use of a protected form of DL-4,4-difluoroornithine 9 which was derived from DL-4,4-difluoroglutamic acid. Biological activities of 4 were compared directly to those of the corresponding nonfluorinated compound N-alpha-(4-amino-4-deoxy-10-methylpteroyl)-L-ornithine (AMPte-L-Orn, 3). Although the fluorinated analogue is a potent inhibitor of DHFR, it is a poor inhibitor of FPGS. However, the compound is transported across the cell membrane and inhibits cell growth, presumably due to the inhibition of DHFR. The data obtained with the fluorinated analogue are in contrast to those of the corresponding nonfluorinated compound 3, which is a potent inhibitor of bath FPGS and DHFR but shows very low cytotoxicity due to poor transport.