di-tert-butyl N-(3-fluoro-4-nitrobenzoyl)-l-glutamate | 85803-26-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: di-tert-butyl N-(3-fluoro-4-nitrobenzoyl)-l-glutamate
• 英文别名: di-tert-butyl (3-fluoro-4-nitrobenzoyl)-L-glutamate；Di-tert-butyl 3-fluoro,4-nitrobenzoyl-L-glutamate；ditert-butyl (2S)-2-[(3-fluoro-4-nitrobenzoyl)amino]pentanedioate
• CAS: 85803-26-5
• 化学式: C₂₀H₂₇FN₂O₇
• 分子量: 426.442
• InChiKey: UTZQCFYMHAIMPC-AWEZNQCLSA-N

物化性质

• 沸点：
  535.4±50.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  di-tert-butyl N-(3-fluoro-4-nitrobenzoyl)-l-glutamate 在 palladium on activated charcoal ammonium formate 作用下， 以 甲醇 为溶剂， 以99%的产率得到di-tert-butyl N-(3-fluoro-4-aminobenzoyl)-l-glutamate
  参考文献：
  名称：

  衍生自2-氟-和3-氟苯甲酸的烷基化剂的新型前药，用于抗体指导的酶前药治疗。

  摘要：

  描述了用于抗体指导的酶前药治疗的六种新型氟化潜在前药的合成。[2-和3-氟-4- [双（2-氯乙基）氨基]苯甲酰基] -L-谷氨酸（9和21），其双（甲氧基）乙基衍生物（7和19）和其氯乙基（甲磺酰氧基）-乙基衍生物（8和20）是双官能烷基化剂，其中离子化羧基官能团的活化作用通过与谷氨酸残基的酰胺键被掩盖。通过事先施用与细菌羧肽酶G2（CPG2）偶联的单克隆抗体，可以设计这些化合物在肿瘤部位活化为相应的苯甲酸烷基化剂。类似的新型母体药物2-和3-氟-4- [双（2-氯乙基）氨基]苯甲酸的合成（12和24），还描述了它们的双（甲磺酰氧基）乙基衍生物（10和22）以及它们的氯乙基（甲磺酰氧基）乙基衍生物（11和23）。在CPG2存在的情况下，用六个潜在的前药和单独的母体药物来监测结直肠细胞系的生存力。化合物19-21显示出显着的前药活性，被CPG2激活分别导致可与22-24相比的细胞毒性。确定

  DOI：

  10.1021/jm00041a015
• 作为产物：
  描述：

  3-氟-4-硝基甲苯 在 potassium permanganate 、 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 6.0h， 生成 di-tert-butyl N-(3-fluoro-4-nitrobenzoyl)-l-glutamate
  参考文献：
  名称：

  Novel fluorinated antifolates. Enzyme inhibition and cytotoxicity studies on 2'- and 3'-fluoroaminopterin

  摘要：

  Two novel analogues of aminopterin with a single fluorine substitution in the 2' (compound 8) or in the 3' (compound 9) position of the p-aminobenzoyl group were synthesized and evaluated as inhibitors of dihydrofolate reductase from two bacterial species and from human HeLa cells. The 2'-fluoro compound was bound essentially the same as aminopterin itself, while the 3'-fluoro derivative bound two- to threefold more tightly in all cases. UV spectral shifts indicated normal binding of the pteridine. Cytotoxicity studies against mouse leukemia L1210 cells and the human stomach cancer line HuTu80 indicated equivalent toxicity of the parent drug with the 2'-fluoro analogue. 3'-Fluoroaminopterin was, however, twice as toxic as aminopterin to both cell lines.

  DOI：

  10.1021/jm00362a019

文献信息

• Fluoromethotrexates and uses therefor
  申请人：——

  公开号：US20040259878A1

  公开（公告）日：2004-12-23

  Provided herein is are novel fluorine-substituted methotrexates and methods of using magnetic resonance spectroscopy of these novel compounds to determine the sensitivity of or resistance of a tumor to methotrexate. Such methods may be used to predict the efficacy of methotrexate therapy or to devise alternate therapeutic strategies. Also provided are methods of treating tumors sensitive to methotrexate.

  本文提供了一种新型的氟代甲氨蝶呤和使用这些新化合物的核磁共振光谱法来确定肿瘤对甲氨蝶呤的敏感性或耐药性的方法。这些方法可用于预测甲氨蝶呤治疗的疗效或制定替代治疗策略。还提供了治疗对甲氨蝶呤敏感的肿瘤的方法。
• 4-amino-fluorobenzamides and their use as cytotoxic prodrugs
  申请人：Cancer Research Campaign Technology Limited

  公开号：US05811454A1

  公开（公告）日：1998-09-22

  The invention provides a compound which is a 3-fluorobenzamide of the formula (A) ##STR1## wherein R-NH is the residue of an .alpha.-amino acid R-NH.sub.2 or oligopeptide R-NH.sub.2, and M is a nitrogen mustard group of the formula ##STR2## wherein Y and L, which may be the same or different in a molecule, are leaving groups; or a pharmaceutically acceptable salt thereof. The compounds are useful as prodrugs for treating cancer.

  本发明提供了一种化合物，其为式（A）的3-氟苯甲酰胺 ##STR1## 其中R-NH为α-氨基酸R-NH.sub.2或寡肽R-NH.sub.2的残基，M为式的氮芥基团 ##STR2## 其中Y和L在分子中可以相同也可以不同，为离去基团；或其药学上可接受的盐。该化合物可作为治疗癌症的前药而有用。
• 4-AMINO-FLUOROBENZAMIDES AND THEIR USE AS CYTOTOXIC PRODRUGS
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：EP0696270B1

  公开（公告）日：1998-11-04
• US5811454A
  申请人：——

  公开号：US5811454A

  公开（公告）日：1998-09-22
• Novel fluorinated antifolates. Enzyme inhibition and cytotoxicity studies on 2'- and 3'-fluoroaminopterin
  作者：Jack Henkin、Wendy L. Washtien

  DOI：10.1021/jm00362a019

  日期：1983.8

  Two novel analogues of aminopterin with a single fluorine substitution in the 2' (compound 8) or in the 3' (compound 9) position of the p-aminobenzoyl group were synthesized and evaluated as inhibitors of dihydrofolate reductase from two bacterial species and from human HeLa cells. The 2'-fluoro compound was bound essentially the same as aminopterin itself, while the 3'-fluoro derivative bound two- to threefold more tightly in all cases. UV spectral shifts indicated normal binding of the pteridine. Cytotoxicity studies against mouse leukemia L1210 cells and the human stomach cancer line HuTu80 indicated equivalent toxicity of the parent drug with the 2'-fluoro analogue. 3'-Fluoroaminopterin was, however, twice as toxic as aminopterin to both cell lines.