(2R)-3-methoxy-1-(2-nitroimidazol-1-yl)-2-propanol | 95120-45-9

• 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: (2R)-3-methoxy-1-(2-nitroimidazol-1-yl)-2-propanol
• 英文别名: (R)-misonidazole；TX-1860；misonidazole；(2R)-1-methoxy-3-(2-nitro-1H-imidazol-1-yl)propan-2-ol；(2R)-1-methoxy-3-(2-nitroimidazol-1-yl)propan-2-ol
• CAS: 95120-45-9
• 化学式: C₇H₁₁N₃O₄
• 分子量: 201.182
• InChiKey: OBBCSXFCDPPXOL-ZCFIWIBFSA-N

物化性质

• 沸点：
  438.5±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  氯乙酰异氰酸酯 、 (2R)-3-methoxy-1-(2-nitroimidazol-1-yl)-2-propanol 以 二氯甲烷 为溶剂， 反应 0.5h， 以96%的产率得到[(2R)-1-methoxy-3-(2-nitroimidazol-1-yl)propan-2-yl] N-(2-chloroacetyl)carbamate
  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
• 作为产物：
  描述：

  2-硝基咪唑 、 (R)-(-)-环氧丙基甲基醚 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 3.5h， 以28%的产率得到(2R)-3-methoxy-1-(2-nitroimidazol-1-yl)-2-propanol
  参考文献：
  名称：

  (S)-和 (R)-咪唑作为 GPX 抑制剂的评价：合成、表征，包括圆二色性和牛 GPx-1 的体外测试

  摘要：

  外消旋米索尼达唑是一种正式用于癌症放射治疗的放射增敏剂，至今仍在使用，曾被报道对小鼠谷胱甘肽过氧化物酶 (GPX) 表现出强烈的抑制作用。这似乎使米索尼达唑成为开发新型 GPX 抑制剂的先导结构，以在化疗耐药肿瘤中引起氧化应激。米索尼达唑作为 GPX 抑制剂的一个独特特征是不存在硫醇官能团。因此，有望选择性地靶向抑制，而不会与阳离子和巯基发生混杂的相互作用。我们合成了米索尼达唑的异构体，并分析了手性高效液相色谱 (HPLC) 鉴定特定对映体的能力。由于手性池合成，可以验证正确配置的分配。最后，我们评估了两种异构体对牛红细胞 GPx-1 的抑制活性，GPx-1 与人类酶有 87% 的同源性。尽管先前报道了消旋咪唑对同源性较低的小鼠 GPx-1 的抑制作用，但我们没有发现任何一种异构体对牛酶的任何显着抑制活性。尽管米索尼达唑似乎不太可能是人类 GPx-1 活性的抑制剂，但我们仍然将米索尼达唑作

  DOI：

  10.1002/ardp.201300285

文献信息

• Design of antiangiogenic hypoxic cell radiosensitizers: 2-Nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety
  作者：Yoshihiro Uto、Hideko Nagasawa、Cheng-Zhe Jin、Shinichi Nakayama、Ayako Tanaka、Saori Kiyoi、Hitomi Nakashima、Mariko Shimamura、Seiichi Inayama、Tomoya Fujiwara、Yoshio Takeuchi、Yoshimasa Uehara、Kenneth L. Kirk、Eiji Nakata、Hitoshi Hori

  DOI：10.1016/j.bmc.2008.04.041

  日期：2008.6

  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.
• Angiogenesis inhibitor TX-1898: syntheses of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers
  作者：Cheng-Zhe Jin、Hideko Nagasawa、Mariko Shimamura、Yoshihiro Uto、Seiichi Inayama、Yoshio Takeuchi、Kenneth L. Kirk、Hitoshi Hori

  DOI：10.1016/j.bmc.2004.06.039

  日期：2004.9

  (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.
• Evaluation of (<i>S</i>)- and (<i>R</i>)-Misonidazole as GPX Inhibitors: Synthesis, Characterization Including Circular Dichroism and<i>In Vitro</i>Testing on Bovine GPx-1
  作者：Felix Wilde、Chamseddin Chamseddin、Heidi Lemmerhirt、Patrick J. Bednarski、Thomas Jira、Andreas Link

  DOI：10.1002/ardp.201300285

  日期：2014.3

  exhibit strong inhibitory effects on mouse glutathione peroxidases (GPX). This appeared to qualify misonidazole as a lead structure for the development of novel GPX inhibitors to cause oxidative stress in chemotherapy‐resistant tumors. A unique feature of misonidazole as an inhibitor of GPX is the absence of a thiol functionality. Therefore, it was expected to selectively target inhibition devoid of promiscuous

  外消旋米索尼达唑是一种正式用于癌症放射治疗的放射增敏剂，至今仍在使用，曾被报道对小鼠谷胱甘肽过氧化物酶 (GPX) 表现出强烈的抑制作用。这似乎使米索尼达唑成为开发新型 GPX 抑制剂的先导结构，以在化疗耐药肿瘤中引起氧化应激。米索尼达唑作为 GPX 抑制剂的一个独特特征是不存在硫醇官能团。因此，有望选择性地靶向抑制，而不会与阳离子和巯基发生混杂的相互作用。我们合成了米索尼达唑的异构体，并分析了手性高效液相色谱 (HPLC) 鉴定特定对映体的能力。由于手性池合成，可以验证正确配置的分配。最后，我们评估了两种异构体对牛红细胞 GPx-1 的抑制活性，GPx-1 与人类酶有 87% 的同源性。尽管先前报道了消旋咪唑对同源性较低的小鼠 GPx-1 的抑制作用，但我们没有发现任何一种异构体对牛酶的任何显着抑制活性。尽管米索尼达唑似乎不太可能是人类 GPx-1 活性的抑制剂，但我们仍然将米索尼达唑作