2-氨基-5-(3-氯丙氧基)-4-甲氧基苯甲酸甲酯 | 380844-26-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氨基-5-(3-氯丙氧基)-4-甲氧基苯甲酸甲酯
• 英文名称: methyl 2-amino-5-(3-chloropropoxy)-4-methoxybenzoate
• 英文别名: methyl 5-(3-chloropropoxy)-2-amino-4-methoxybenzoate；methyl 2-amino-4-methoxy-5-(3-chloropropoxy)benzoate
• CAS: 380844-26-8
• 化学式: C₁₂H₁₆ClNO₄
• 分子量: 273.716
• InChiKey: MMBSMYNVNCVFFZ-UHFFFAOYSA-N

物化性质

• 熔点：
  96-98℃
• 密度：
  1.232

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2922509090

反应信息

• 作为反应物：
  描述：

  2-氨基-5-(3-氯丙氧基)-4-甲氧基苯甲酸甲酯 在 正丁基锂 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 9.25h， 生成 4-chloro-6-(3-chloropropoxy)-7-methoxy-3-quinolinecarbonitrile
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250
• 作为产物：
  描述：

  3-(3-chloropropoxy)-4-methoxybenzoic acid 在 氯化亚砜 、 硝酸 、 乙酸酐 、 铁粉 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 2-氨基-5-(3-氯丙氧基)-4-甲氧基苯甲酸甲酯
  参考文献：
  名称：

  Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors

  摘要：

  We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4] octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.049

文献信息

• Design, Synthesis, and In vitro Antitumor Activity Evaluation of Novel 4-pyrrylamino Quinazoline Derivatives
  作者：Xiaoqing Wu、Mingdong Li、Wenhua Tang、Youguang Zheng、Jiqin Lian、Liang Xu、Min Ji

  DOI：10.1111/j.1747-0285.2011.01234.x

  日期：2011.12

  Here, we describe the design and synthesis of two series of 4‐pyrrylamino quinazolines as new analogs of the epidermal growth factor receptor inhibitor gefitinib. In vitro antitumor activity of these novel compounds against pancreatic (Miapaca2) and prostate (DU145) cancer cell lines was evaluated. Compared with the parental gefitinib, all 18 derivatives show a greatly increased cytotoxicity to cancer

  在这里，我们描述了两个系列的 4-吡咯氨基喹唑啉作为表皮生长因子受体抑制剂吉非替尼的新类似物的设计和合成。评估了这些新化合物对胰腺 (Miapaca2) 和前列腺 (DU145) 癌细胞系的体外抗肿瘤活性。与亲本吉非替尼相比，所有 18 种衍生物都显示出对癌细胞的细胞毒性大大增加。还研究了对表皮生长因子受体的体外激酶抑制活性。其中，化合物GI-6、GII-4、GII-6、GII-8和GII-9是更有潜力的受体酪氨酸激酶 (RTK) 抑制剂。基于这些结果，我们提出了简单的构效关系，为设计和开发更有效的抗肿瘤药物提供信息。
• Novel EGFR inhibitors prepared by combination of dithiocarbamic acid esters and 4-anilinoquinazolines
  作者：Ri-Dong Li、Xin Zhang、Qiao-Yan Li、Ze-Mei Ge、Run-Tao Li

  DOI：10.1016/j.bmcl.2011.04.096

  日期：2011.6

  basis of combination strategy, a novel series of EGFR inhibitors were designed and synthesized by combination of dithiocarbamic acid esters and 4-anilinoquinazolines. The effect of the synthesized compounds on cell proliferation was evaluated by MTT assay in three human cancer cell lines: MDA-MB-468, SK-BR-3 and HCT-116. Two compounds (11d and 11f) were found more potent against all three cell lines and

  在联合策略的基础上，通过二硫代氨基甲酸酯与4-苯胺基喹唑啉的结合，设计合成了一系列新的EGFR抑制剂。通过MTT测定法在三种人癌细胞系：MDA-MB-468，SK-BR-3和HCT-116中评估了合成化合物对细胞增殖的作用。发现两种化合物（11d和11f）对所有三种细胞系均更有效力，而五种化合物（11a，11d – 11g））被发现对MDA-MB-468和SK-BR-3都比拉帕替尼更有效。SAR研究表明，喹唑啉C6和C7位置的取代基，二硫代氨基甲酸酯部分的胺成分和连接基极大地影响了活性。这项工作为有效的酪氨酸激酶抑制剂的制备提供了有希望的新策略。
• Synthesis of Gefitinibfrom Methyl 3-Hydroxy-4-methoxy-benzoate
  作者：Ming Li、You Zheng、Min Ji

  DOI：10.3390/12030673

  日期：——

  gefitinib starting from methyl 3-hydroxy-4-methoxybenzoate. The process starts with alkylation of the starting material, followed by nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1H-NMR, 13C-NMR, MS and the purities of all these compounds were determined by HPLC. This novel synthetic route produced overall

  本文报道了从3-羟基-4-甲氧基苯甲酸甲酯开始的吉非替尼的新型合成方法。该方法开始于原料的烷基化，然后进行硝化，还原，环化，氯化和两个连续的胺化反应。中间体和目标分子通过1 H-NMR，13 C-NMR，MS表征，所有这些化合物的纯度均通过HPLC测定。这种新颖的合成途径产生的总产率高达37.4％。
• Design and synthesis of novel Gefitinib analogues with improved anti-tumor activity
  作者：Xiaoqing Wu、Mingdong Li、Yang Qu、Wenhua Tang、Youguang Zheng、Jiqin Lian、Min Ji、Liang Xu

  DOI：10.1016/j.bmc.2010.04.046

  日期：2010.6.1

  design and develop new and more potent EGFR inhibitors with improved anti-tumor activity. Here we describe the design and synthesis of two series of 4-benzothienyl amino quinazolines as new analogues of the EGFR inhibitor Gefitinib. The anti-tumor activity of these novel Gefitinib analogues in 6 human cancer cell lines was examined. Compared with the parental Gefitinib, most of the new compounds show

  迫切需要设计和开发具有改进的抗肿瘤活性的新型和更有效的 EGFR 抑制剂。在这里，我们描述了两个系列的 4-苯并噻吩基氨基喹唑啉作为 EGFR 抑制剂吉非替尼的新类似物的设计和合成。检查了这些新型吉非替尼类似物在 6 种人类癌细胞系中的抗肿瘤活性。与母体吉非替尼相比，大多数新化合物对癌细胞的细胞毒性显着增加。此外，7 位侧链含有甲基或乙基的几种 B 系列化合物是有效的泛 RTK 抑制剂。此类中的两种代表性化合物，15和17，与亲本吉非替尼相比，具有增强的体外抑制癌细胞生长和诱导细胞凋亡的能力，并在具有高 HER-2 的人类癌细胞中抑制体内肿瘤形成。因此，它们可能是有前景的先导化合物，可作为当前吉非替尼疗法或吉非替尼耐药患者的替代品，可能通过同时阻断多个 RTK 信号通路。
• Design, Synthesis of Novel Quinazolone Alkaloids Derivatives as Potential Antitumor Agents
  作者：Youguang Zheng、Min Sun、Yi Liu、Mingdong Li、Min Ji

  DOI：10.2174/157340611796150987

  日期：2011.7.1

  Several novel quinazolone alkaloids derivatives were synthesized. Some of the target compounds were determined against human prostate cancer DU145 and pancreatic cancer Miacapa2 cells in vitro. The entire compounds had been identified by 1HNMR, 13CNMR, IR, MS and EA.

  合成了几种新型喹唑啉酮生物碱衍生物。其中一些目标化合物对人类前列腺癌 DU145 和胰腺癌 Miacapa2 细胞具有体外抗癌作用。通过 1HNMR、13CNMR、IR、MS 和 EA 对整个化合物进行了鉴定。