2-[(2,5-Dimethoxyphenyl)methoxy]-4-nitroaniline | 1372688-53-3

• 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: 2-[(2,5-Dimethoxyphenyl)methoxy]-4-nitroaniline
• CAS: 1372688-53-3
• 化学式: C₁₅H₁₆N₂O₅
• 分子量: 304.302
• InChiKey: RVSSLXPGBUGZAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  99.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[(2,5-Dimethoxyphenyl)methoxy]-4-nitroaniline 在 sodium hydride 、 potassium carbonate 、 氯化铵 、 锌 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4,4'-((2,2'-oxybis(acetyl))bis(azanediyl))bis(N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido)phenyl)benzamide)
  参考文献：
  名称：

  胶质母细胞瘤中雄激素受体 HSP27 干扰剂的先导优化

  摘要：

  胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤，在目前的标准治疗下预后较差。开发新方法来选择性地对抗这种疾病至关重要。 GBM 性别差异表明雄激素受体 (AR) 是治疗 AR 过度表达的 GBM 的潜在治疗靶点。热休克 27 kDa 蛋白 (HSP27) 是一种有据可查的稳定 AR 的伴侣蛋白。 HSP27 的抑制导致 AR 降解，表明 HSP27 抑制剂可以抑制 GBM 中的 AR 活性。我们已经鉴定出一种可诱导 AR 降解的主要 HSP27 抑制剂。先导化合物优化产生了两种新的衍生物（化合物4和26 ），与先导化合物相比，它们表现出有效的抗 GBM 活性并改善了药物分布。化合物4和6的IC 50分别为35和23 nM，抑制细胞增殖，并且还表现出显着的降低体内肿瘤生长的活性。

  DOI：

  10.1021/acs.jmedchem.2c02022
• 作为产物：
  描述：

  2,5-二甲氧基苄氯 、 2-氨基-5-硝基苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[(2,5-Dimethoxyphenyl)methoxy]-4-nitroaniline
  参考文献：
  名称：

  胶质母细胞瘤中雄激素受体 HSP27 干扰剂的先导优化

  摘要：

  胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤，在目前的标准治疗下预后较差。开发新方法来选择性地对抗这种疾病至关重要。 GBM 性别差异表明雄激素受体 (AR) 是治疗 AR 过度表达的 GBM 的潜在治疗靶点。热休克 27 kDa 蛋白 (HSP27) 是一种有据可查的稳定 AR 的伴侣蛋白。 HSP27 的抑制导致 AR 降解，表明 HSP27 抑制剂可以抑制 GBM 中的 AR 活性。我们已经鉴定出一种可诱导 AR 降解的主要 HSP27 抑制剂。先导化合物优化产生了两种新的衍生物（化合物4和26 ），与先导化合物相比，它们表现出有效的抗 GBM 活性并改善了药物分布。化合物4和6的IC 50分别为35和23 nM，抑制细胞增殖，并且还表现出显着的降低体内肿瘤生长的活性。

  DOI：

  10.1021/acs.jmedchem.2c02022

文献信息

• AMIDE DERIVATIVES OF BENZENE-SULFONANILIDE, PHARMACEUTICAL COMPOSITION THEREOF AND METHOD FOR CANCER TREATMENT USING THE SAME
  申请人：Su Bin

  公开号：US20120095092A1

  公开（公告）日：2012-04-19

  The invention provides a compound of formula (I), a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. The invention exhibits merits against cancers such as significantly higher potency and effectiveness over a broader range of cancers. In formula (I), R a is a benzyl group with alkyl and/or alkoxy; R b is selected from H and alkyl groups; R f is an alkyl; and R 3 is selected from a substituted phenyl, a heterocyclic group, and wherein Rc is selected from a fused ring, fused rings, and any bivalent cyclic group.

  该发明提供了一种式(I)的化合物，其药物组成物，用于治疗癌症的药物制备方法，以及治疗癌症的方法。该发明展示了针对癌症的优点，如在更广泛的癌症范围内具有显着更高的效力和有效性。在式(I)中，R是含有烷基和/或烷氧基的苄基；R被选自H和烷基；Rf是烷基；而R3被选自取代苯基、杂环基，以及其中Rc被选自融合环、融合环和任何二价环状基团。
• Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors
  作者：Bo Zhong、Snigdha Chennamaneni、Rati Lama、Xin Yi、Werner J. Geldenhuys、John J. Pink、Afshin Dowlati、Yan Xu、Aimin Zhou、Bin Su

  DOI：10.1021/jm4004736

  日期：2013.7.11

  Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development.
• Lead optimization of dual tubulin and Hsp27 inhibitors
  作者：Bo Zhong、Rati Lama、Daniel G. Kulman、Bibo Li、Bin Su

  DOI：10.1016/j.ejmech.2014.04.038

  日期：2014.6

  Tubulin and heat shock protein 27 (Hsp27) are well-characterized molecular targets for anti-cancer drug development. We previously identified lead compounds that inhibited both Hsp27 and tubulin. These compounds exhibited extensive anti-cancer activities against the proliferation of various human cancer cell lines. In the current study, a systematic ligand based structural optimization led to new analogs that significantly inhibited the growth of a panel of breast cancer cell lines. Furthermore, the most potent compounds were examined with tubulin polymerization assay and Hsp27 chaperone activity assay. The compounds showed potent tubulin polymerization inhibition but no Hsp27 inhibitory effect. The structural optimization dissected the dual activity and improved the selectivity of the compounds for tubulin. The results revealed several structural moieties of the lead compounds that are critical for Hsp27 inhibition. The modification of these structural fragments eliminated Hsp27 inhibition, but did not harm tubulin-targeting effects of the compounds. This result further defined the structure-activity relationship between the tubulin and Hsp27 effects of these compounds.
• Synthesis and biological evaluation of imidamide analogs as selective anti-trypanosomal agents
  作者：Viharika Bobba、Yaxin Li、Marjia Afrin、Raina Dano、Wenjing Zhang、Bibo Li、Bin Su

  DOI：10.1016/j.bmc.2022.116740

  日期：2022.5
• US8802895B2
  申请人：——

  公开号：US8802895B2

  公开（公告）日：2014-08-12