(2S)-3-tert-butoxy-1-(2-nitroimidazol-1-yl)-2-propanol | 765305-19-9

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: (2S)-3-tert-butoxy-1-(2-nitroimidazol-1-yl)-2-propanol
• 英文别名: TX-1894
• CAS: 765305-19-9
• 化学式: C₁₀H₁₇N₃O₄
• 分子量: 243.263
• InChiKey: UARGHWZXNCKZAM-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.97
• 重原子数：
  17.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  90.42
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S)-3-tert-butoxy-1-(2-nitroimidazol-1-yl)-2-propanol 、 4-[(三氟乙酰基)氨基]苯甲酸 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以82.5%的产率得到(2S)-3-tert-butoxy-1-(2-nitroimidazol-1-yl)-prop-2-yl 4'-(trifluoroacetamido)benzoate
  参考文献：
  名称：

  Design of antiangiogenic hypoxic cell radiosensitizers: 2-Nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety

  摘要：

  We designed chiral 2-nitroimidazole derivatives containing a 2-aminomethylene- 4-cyclopentene-1,3-dione moiety as antiangiogenic hypoxic cell radiosensitizers. Based on results of molecular orbital calculations, the 2-aminomethylene-4-cyclopentene1,3-dione moiety is expected to show high electrophilicity comparable to that of the 2-methylene-4-cyclopentene-1,3-dione moiety included in TX-1123 and tyrphostin AG17. We evaluated the antiangiogenic and radiosensitizing effects of the new compounds, along with other biological properties including their activities as hypoxic cytotoxicities and protein tyrosine kinase (PTK) inhibitory activities. Among the compounds tested, 5 (TX-2036) proved to be the strongest antiangiogenic hypoxic cell radiosensitizer. All the other chiral 2-nitroimidazole derivatives having 2-aminomethylene-4-cyclopentene-1,3-dione moiety tested were also antiangiogenic hypoxic cell radiosensitizers. The PTK inhibitory activity of 5 (TX-2036) showed this to be a promising and potent EGFR kinase inhibitor, having an IC50 value of lower than 2 mu M. This compound also was an Flt-1 kinase inhibitor having an IC50 value of lower than 20 mu M. Our results show that these chiral 2- nitroimidazole derivatives that contain the 2- aminomethylene-4- cyclopentene1,3-dione moiety as a potent antiangiogenic pharmacophoric descriptor are promising lead candidates for the development of antiangiogenic hypoxic cell radiosensitizers. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.04.041
• 作为产物：
  描述：

  2-硝基咪唑 、 (S)-t-叔丁基缩水甘油醚 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以85%的产率得到(2S)-3-tert-butoxy-1-(2-nitroimidazol-1-yl)-2-propanol
  参考文献：
  名称：

  Angiogenesis inhibitor TX-1898: syntheses of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers

  摘要：

  (R)- and (S)-Epichlorohydrins were used to prepare the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazoles that function as hypoxic cell radiosensitizers. The synthetic design allowed for introduction of a side chain of varying bulk that permitted an examination of the steric effects on enantio-discrimination in biological assay systems. The single stereocenter also connected the two pharmacophores-a 2-nitroimidazole moiety critical to hypoxic cell radiosensitization, and a haloacetylcarbamoyl group to function as an anti-angiogenesis pharmacophore. In the chick embryo chorioallantoic membrane (CAM) assay, the R-enantiomers possessing the bulky p-tert-butylphenyl group showed higher anti-angiogenic activity than the corresponding S-enantiomers, while there were no differences in the activity between the enantiomers containing the less bulky methyl and tert-butyl groups. Among the compounds we report, R-p-tert-butylphenyl-bromoacetylcarbamoyl-2-nitroimidazole, TX-1898, was found to be the most promising candidate for further development of as anti-angiogenic hypoxic cell radiosensitizer. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.039