2,3',4'-Trichlor-4-nitro-diphenylether | 22544-09-8

• 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: 2,3',4'-Trichlor-4-nitro-diphenylether
• 英文别名: 2-Chloro-1-(3,4-dichlorophenoxy)-4-nitrobenzene
• CAS: 22544-09-8
• 化学式: C₁₂H₆Cl₃NO₃
• 分子量: 318.544
• InChiKey: STRHWUXGZOVLNQ-UHFFFAOYSA-N

物化性质

• 熔点：
  125-126.5 °C
• 沸点：
  380.8±42.0 °C(Predicted)
• 密度：
  1.533±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3',4'-Trichlor-4-nitro-diphenylether 在 10% Pt/activated carbon 、 氢气 、 铁粉 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 7.0h， 生成 1-(4-((3-chloro-4-(3,4-dichlorophenoxy)phenyl)amino)quinazolin-6-yl)urea
  参考文献：
  名称：

  Targeting EGFR/HER2 tyrosine kinases with a new potent series of 6-substituted 4-anilinoquinazoline hybrids: Design, synthesis, kinase assay, cell-based assay, and molecular docking

  摘要：

  Coexpression of EGFR and HER2 has been found in many tumors such as breast, ovarian, colon and prostate cancers, with poor prognosis of the patients. Herein, our team has designed and synthesized new eighteen compounds with 6-substituted 4-anilinoquinazoline core to selectively inhibit EGFR/HER2 tyrosine kinases. Twelve compounds (8a-8d, 9a, 9c, 9d, 10a, 10c, 11b, 14, and 15) showed nanomolar range of IC50 values on EGFR and/or HER2 kinases. Accordingly, a detailed structure activity relationship (SAR) was established. A molecular docking study demonstrated the favorable binding modes of 8d, 9b, 9d and 10d at the ATP active site of both kinases. A kinase selectivity profile performed for compound 8d showed great selectivity for EGFR and HER2. In addition, 8d, 9c, and 9d exerted selective promising cytotoxic activity over BT-474 cell line with IC50 values of 2.70, 1.82 and 1.95 mu M, respectively. From these results, we report analogs 8d, 9c, and 9d as promising candidates for the discovery of well-balanced compounds in terms of the kinase inhibitory potency and antiproliferative activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.003
• 作为产物：
  描述：

  3,4-二氯苯酚 、 2-氯-4-硝基苯酚 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 2,3',4'-Trichlor-4-nitro-diphenylether
  参考文献：
  名称：

  Targeting EGFR/HER2 tyrosine kinases with a new potent series of 6-substituted 4-anilinoquinazoline hybrids: Design, synthesis, kinase assay, cell-based assay, and molecular docking

  摘要：

  Coexpression of EGFR and HER2 has been found in many tumors such as breast, ovarian, colon and prostate cancers, with poor prognosis of the patients. Herein, our team has designed and synthesized new eighteen compounds with 6-substituted 4-anilinoquinazoline core to selectively inhibit EGFR/HER2 tyrosine kinases. Twelve compounds (8a-8d, 9a, 9c, 9d, 10a, 10c, 11b, 14, and 15) showed nanomolar range of IC50 values on EGFR and/or HER2 kinases. Accordingly, a detailed structure activity relationship (SAR) was established. A molecular docking study demonstrated the favorable binding modes of 8d, 9b, 9d and 10d at the ATP active site of both kinases. A kinase selectivity profile performed for compound 8d showed great selectivity for EGFR and HER2. In addition, 8d, 9c, and 9d exerted selective promising cytotoxic activity over BT-474 cell line with IC50 values of 2.70, 1.82 and 1.95 mu M, respectively. From these results, we report analogs 8d, 9c, and 9d as promising candidates for the discovery of well-balanced compounds in terms of the kinase inhibitory potency and antiproliferative activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.003

文献信息

• Development of new TAK-285 derivatives as potent EGFR/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines
  作者：Seohyun Son、Ahmed Elkamhawy、Anam Rana Gul、Ahmed A. Al‐Karmalawy、Radwan Alnajjar、Ahmed Abdeen、Samah F. Ibrahim、Saud O. Alshammari、Qamar A. Alshammari、Won Jun Choi、Tae Jung Park、Kyeong Lee

  DOI：10.1080/14756366.2023.2202358

  日期：2023.12.31

  the range of 1.0–7.3 nM and 0.8–2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.

  摘要 表皮生长因子受体 (EGFR) 和人表皮生长因子受体 2 (HER2) 蛋白酪氨酸激酶在卵巢癌、乳腺癌、结肠癌和前列腺癌等多种癌症中共表达。在此，新的 TAK-285 衍生物 ( 9a – h ) 作为 EGFR/HER2 双重抑制剂被合成、表征和生物学评估。化合物9f的 IC 50值比 EGFR 高 2.3 nM，比 HER2 高 234 nM，是星形孢菌素的 38 倍和 TAK-285 的 10 倍。化合物9f在小型激酶组上进行测试时也显示出高选择性。化合物9a – h显示 IC 50针对 PC3 和 22RV1 前列腺癌细胞系的值分别在 1.0-7.3 nM 和 0.8-2.8 nM 范围内。细胞周期分析、细胞凋亡诱导、分子对接、动力学和 MM-GBSA 研究证实了化合物9f作为有效的 EGFR/HER2 双重抑制剂的合理机制，对前列腺癌具有有效的抗增殖作用。
• NORSTROEM A.; CHAUDHARY S. K.; ALBRO P. W.; MCKINNEY J. D., CHEMOSPHERE, 1979, 8, NO 6, 331-343
  作者：NORSTROEM A.、 CHAUDHARY S. K.、 ALBRO P. W.、 MCKINNEY J. D.

  DOI：——

  日期：——