4-(2,4-dichlorobenzyloxy)-2-hydroxybenzaldehyde | 1387637-34-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2,4-dichlorobenzyloxy)-2-hydroxybenzaldehyde
• CAS: 1387637-34-4
• 化学式: C₁₄H₁₀Cl₂O₃
• 分子量: 297.138
• InChiKey: SGONBZNQSYGLIC-UHFFFAOYSA-N

物化性质

• 沸点：
  443.3±40.0 °C(Predicted)
• 密度：
  1.427±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-(2,4-dichlorobenzyloxy)-2-hydroxybenzaldehyde 、 N4-[4-(dimethylaminomethyl)phenyl]semicarbazide 在 溶剂黄146 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以59%的产率得到(E)-2-(4-((2,4-dichlorobenzyl)oxy)-2-hydroxybenzylidene)-N-(4-((dimethylamino)methyl)phenyl)hydrazine-1-carboxamide hydrochloride
  参考文献：
  名称：

  带有苯基部分的半脲衍生物：合成，抗癌活性，细胞周期，细胞凋亡诱导和代谢稳定性研究。

  摘要：

  合成了一系列带有苯基部分的半脲衍生物，并评估了其在四种人类癌细胞系（人类结肠癌（HT29），人类神经母细胞瘤（SK-N-SH），人类乳腺癌（MDA-MB）中的体外抗癌活性-231）和人胃癌（MKN45））。生物学评估导致鉴定出11q和11s，它们对被测癌细胞具有优异的抗癌活性，IC50值分别为0.32至1.57 µM，而对正常细胞（人脐静脉内皮细胞（HUVEC））的细胞毒性较弱）。流式细胞仪检测细胞周期和细胞凋亡表明11q和11s导致Sub-G1细胞周期停滞，并通过剂量依赖性方式诱导细胞凋亡来抑制癌细胞的增殖。进一步的酶促测定表明11q和11s可以将procaspase-3显着激活为caspase-3。代谢稳定性研究表明，11q和11s在人和大鼠肝微粒体中显示出适度的体外稳定性。鉴于11q和11s具有良好的药理活性，已成为进一步发展癌症治疗的有价值的先导。

  DOI：

  10.1248/cpb.c18-00738
• 作为产物：
  描述：

  2,4-二氯氯苄 、 2,4-二羟基苯甲醛 在 碳酸氢钠 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 36.0h， 以82.6%的产率得到4-(2,4-dichlorobenzyloxy)-2-hydroxybenzaldehyde
  参考文献：
  名称：

  带有邻羟基-N-酰基腙部分的苯并噻唑衍生物作为有效抗肿瘤剂的合成和生物学评价

  摘要：

  设计、合成了一系列带有邻羟基-N-酰基腙部分的新型苯并噻唑衍生物，并评估了它们对五种癌细胞系（NCI-H226、SK-N-SH、 HT29、MKN-45 和 MDA-MB-231）。大多数目标化合物对所有五个测试的癌症系都显示出中等至极好的细胞毒活性。最有希望的化合物 18e（procaspase-3 EC50 = 0.31 µM）对所有测试细胞系的 IC50 值范围为 0.24 至 0.92 µM，其活性是 PAC-1（procaspase-3 EC50 = 0.41 µM）的 4.24-12.2 倍。构效关系研究表明，2-羟基苯环上的苯基（A 部分）对体外药理活性至关重要。此外，在 A 部分引入苄氧基和在苄氧基的 4 位引入单吸电子基团更有利于抗肿瘤活性。此外，苄氧基苯环中电子密度的降低导致 procaspase-3 激酶活化活性的显着降低。

  DOI：

  10.1002/ardp.201400230

文献信息

• Discovery of Hybrid Dual N-Acylhydrazone and Diaryl Urea Derivatives as Potent Antitumor Agents: Design, Synthesis and Cytotoxicity Evaluation
  作者：Xin Zhai、Qiang Huang、Nan Jiang、Di Wu、Hongyu Zhou、Ping Gong

  DOI：10.3390/molecules18032904

  日期：——

  Based on the hybrid pharmacophore design concept, a novel series of dual diaryl urea and N-acylhydrazone derivatives were synthesized and evaluated for their in vitro cytotoxicity by the standard MTT assay. The pharmacological results indicated that most compounds exhibited moderate to excellent activity. Moreover, compound 2g showed the most potent cytotoxicity against HL-60, A549 and MDA-MB-231 cell lines, with IC50 values of 0.22, 0.34 and 0.41 μM, respectively, which was 3.8 to 22.5 times more active than the reference compounds sorafenib and PAC-1. The promising compound 2g thus emerges as a lead for further structural modifications.

  基于混合药效团设计概念，合成了一系列新型的双芳基脲和N-酰肼衍生物，并通过标准的MTT法评估其体外细胞毒性。药理结果表明，大多数化合物表现出中等到优良的活性。此外，化合物2g对HL-60、A549和MDA-MB-231细胞系表现出最强的细胞毒性，IC50值分别为0.22、0.34和0.41 μM，是参考化合物索拉非尼和PAC-1的3.8到22.5倍活性。因此，前景良好的化合物2g显现出作为进一步结构修饰的候选药物的潜力。
• Design, synthesis, and structure–activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents
  作者：Junjie Ma、Dong Chen、Kuan Lu、Lihui Wang、Xiaoqi Han、Yanfang Zhao、Ping Gong

  DOI：10.1016/j.ejmech.2014.08.058

  日期：2014.10

  A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 15g (procaspase-3 EC50 = 1.42 mu M) and 16b (procaspase-3 EC50 = 0.25 mu M) exhibited excellent antitumor activity with IC50 values ranging from 0.14 mu M to 0.98 mu M against all cancer cell lines, which were 1.8-8.7 times more active than the first procaspase activating compound (PAC-1) (procaspase-3 EC50 = 4.08 mu M). The structure activity relationship (SAR) analyses indicated that the introduction of a lipophilic group (a benzyloxy or heteroaryloxy group) at the 4-position of the 2-hydroxy phenyl ring was beneficial to antitumor activity, and the presence of substituents containing nitrogen that are positively charged at physiological pH could also improve antitumor activity. It was also confirmed that the steric effect of the 4-position substituent of the benzyloxy group had a significant influence on cytotoxic activity. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and antiproliferative activities of diaryl urea derivatives bearing N-acylhydrazone moiety
  作者：Bei Zhang、Yan Fang Zhao、Xin Zhai、Wei Jie Fan、Jun Ling Ren、Chun Fu Wu、Ping Gong

  DOI：10.1016/j.cclet.2012.06.009

  日期：2012.8

  A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line (HL-60), human lung adenocarcinoma epithelial cell line (A549) and human breast cancer cell line (MDA-MB-231) in vitro by standard MTT assay. The pharmacological results indicated that some compounds exhibited promising antitumor activities. Compound 1j showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 mu mol/L, 0.7 mu mol/L and 0.5 mu mol/L, respectively. (C) 2012 Ping Gong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.