1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl 4-(1-acetyl-3-p-tolyl-4,5-dihydro-1H-pyrazol-5-yl)benzoate

• 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: 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl 4-(1-acetyl-3-p-tolyl-4,5-dihydro-1H-pyrazol-5-yl)benzoate
• 英文别名: 1-(2-Methyl-5-nitroimidazol-1-yl)propan-2-yl 4-[2-acetyl-5-(4-methylphenyl)-3,4-dihydropyrazol-3-yl]benzoate；1-(2-methyl-5-nitroimidazol-1-yl)propan-2-yl 4-[2-acetyl-5-(4-methylphenyl)-3,4-dihydropyrazol-3-yl]benzoate
• 化学式: C₂₆H₂₇N₅O₅
• 分子量: 489.531
• InChiKey: WXFJAWWXWDNJPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(3-oxo-3-p-tolylpropenyl)benzoic acid 在 4-二甲氨基吡啶 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-yl 4-(1-acetyl-3-p-tolyl-4,5-dihydro-1H-pyrazol-5-yl)benzoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors

  摘要：

  A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13 mu M to 128.06 mu M in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26 mu M/0.51 mu M, respectively, comparable to the positive control erlotinib (IC50 = 0.41 mu M for HER-2 and IC50 = 0.20 mu M for EGFR) and lapatinib (IC50 = 0.54 mu M for HER-2 and IC50 = 0.28 mu M for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity of the proposed compounds and activity relationship (SAR) of these pyrazole-nitroimidazole derivatives. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.040

文献信息

• Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors
  作者：Xiang-Xiang Tao、Yong-Tao Duan、Long-Wang Chen、Dan-Jie Tang、Meng-Ru Yang、Peng-Fei Wang、Chen Xu、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2015.11.040

  日期：2016.1

  A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13 mu M to 128.06 mu M in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26 mu M/0.51 mu M, respectively, comparable to the positive control erlotinib (IC50 = 0.41 mu M for HER-2 and IC50 = 0.20 mu M for EGFR) and lapatinib (IC50 = 0.54 mu M for HER-2 and IC50 = 0.28 mu M for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity of the proposed compounds and activity relationship (SAR) of these pyrazole-nitroimidazole derivatives. (C) 2015 Elsevier Ltd. All rights reserved.