N-(4-{[(2,4-二氨基-6-蝶啶基)甲基]氨基}-3-氟苯甲酰)-L-谷氨酸 | 85803-34-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 中文名称: N-(4-{[(2,4-二氨基-6-蝶啶基)甲基]氨基}-3-氟苯甲酰)-L-谷氨酸
• 英文名称: 3'-fluoroaminopterin
• 英文别名: (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]-3-fluorobenzoyl]amino]pentanedioic acid
• CAS: 85803-34-5
• 化学式: C₁₉H₁₉FN₈O₅
• 分子量: 458.409
• InChiKey: SGJMILOGOMOIPG-LBPRGKRZSA-N

物化性质

• 密度：
  1.629±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  219
• 氢给体数：
  6
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  di-tert-butyl N-(3-fluoro-4-aminobenzoyl)-l-glutamate 在 Proton Sponge 、 异丁酰胺 、 三氟乙酸 作用下， 反应 3.0h， 生成 N-(4-{[(2,4-二氨基-6-蝶啶基)甲基]氨基}-3-氟苯甲酰)-L-谷氨酸
  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

• 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.