2-bromo-N-(2-methoxy-4-nitrophenyl)acetamide | 57339-09-0

• 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-bromo-N-(2-methoxy-4-nitrophenyl)acetamide
• CAS: 57339-09-0
• 化学式: C₉H₉BrN₂O₄
• 分子量: 289.085
• InChiKey: SUKQRTAHQBQIOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-bromo-N-(2-methoxy-4-nitrophenyl)acetamide 在 甲醇 、 铁粉 、 potassium carbonate 、 氯化铵 、 三氟乙酸 、 potassium iodide 作用下， 以 水 、 乙腈 、 仲丁醇 为溶剂， 反应 18.0h， 生成 N-cyclopropyl-2-[-[5-chloro-2-[4-((morpholin-4-yl)acetamido)-3-methoxyanilino]pyrimidin-4-yl]amino]benzamide
  参考文献：
  名称：

  Design and synthesis of diphenylpyrimidine derivatives (DPPYs) as potential dual EGFR T790M and FAK inhibitors against a diverse range of cancer cell lines

  摘要：

  A new class of pyrimidine derivatives were designed and synthesized as potential dual FAK and EGFR(T79)(0M) inhibitors using a fragment-based drug design strategy. This effort led to the identification of the two most active inhibitors, namely 9a and 9f, against both FAK (IC50, = 1.03 and 3.05 nM, respectively) and EGFR(T79)(0M) (IC50 = 3.89 and 7.13 nM, respectively) kinase activity. Moreover, most of these compounds also exhibited strong antiproliferative activity against the three evaluated FAK-overexpressing pancreatic cancer (PC) cells (AsPC-1, BxPC-3, Panc-1) and two drug-resistant cancer cell lines (breast cancer MCF-7/adr cells and lung cancer H1975 cells) at concentrations lower than 6.936 mu M. In addition, 9a was also effective in the in vivo assessment conducted in a FAK-driven human AsPC-1 cell xenograft mouse model. Overall, this study offers a new insight into the treatment of hard to treat cancers.

  DOI：

  10.1016/j.bioorg.2019.103408
• 作为产物：
  描述：

  溴乙酰溴 、 2-甲氧基-4-硝基苯胺 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 2-bromo-N-(2-methoxy-4-nitrophenyl)acetamide
  参考文献：
  名称：

  新型嘧啶类药物作为多靶蛋白酪氨酸激酶抑制剂，用于治疗特发性肺纤维化（IPF）。

  摘要：

  一类新的嘧啶衍生物被鉴定为有效的蛋白酪氨酸激酶（PTK）抑制剂，可用于治疗特发性肺纤维化（IPF）。这些小分子抑制剂中的大多数在浓度低于10 nM时显示出对BTK和JAK3激酶的强酶活性。代表性化合物N-（3-（（5-氯-2-（4-（（1-吗啉代）乙酰氨基）苯基氨基）-4-嘧啶基）氨基）苯基）丙烯酰胺（6a）也对两种化合物均显示出高抑制力。浓度为10 nM的BTK和JAK激酶家族以及ErbB4，抑制率高于57％。此外，体内生物学评估表明6 a可以显着降低IPF疾病的严重程度。所有这些研究表明，多PTK抑制剂6a可以用作治疗IPF的有前途的药物。

  DOI：

  10.1002/cmdc.201900606

文献信息

• Novel Quinazoline Derivatives Bearing Various 4-Aniline Moieties as Potent EGFR Inhibitors with Enhanced Activity Against NSCLC Cell Lines
  作者：Changyan Wang、Yajun Sun、Xingqi Zhu、Bin Wu、Qiao Wang、Yuhong Zhen、Xiaohong Shu、Kexin Liu、Youwen Zhou、Xiaodong Ma

  DOI：10.1111/cbdd.12692

  日期：2016.4

  the EGFR wild‐type A431 cells and 5c with an IC50 of 0.001 μm against the gefitinib‐sensitive HCC827 cells (EGFR del E746‐A750) was identified as highly active EGFR inhibitors. It was also significant that the discovered analogue 2f, not only has high potency against the gefitinib‐sensitive cells (IC50 = 0.031 μm), but also possesses remarkably improved activity against the gefitinib‐resistant cells

  合成了一类带有各种C-4苯胺部分的新型喹唑啉衍生物，并对其进行了生物学评估，认为它们是有效的表皮生长因子受体（EGFR）抑制剂，可用于治疗非小细胞肺癌（NSCLC）。这些抑制剂中的大多数在抑制这些癌细胞系方面与吉非替尼相当，其中一些甚至表现出优异的抑制活性。特别地，模拟图5b与IC 50 0.10 μ米针对EGFR野生型A431细胞和5c中有一个IC 50 0.001的μ米对吉非替尼敏感的HCC827细胞（EGFR del E746‐A750）的抗性被确定为高活性EGFR抑制剂。它也是显著所发现的类似物2F，不仅具有对吉非替尼敏感性细胞的高效力（IC 50 = 0.031 μ米），但也具有显着的对抗吉非替尼抗性细胞改善的活性。另外，用于评估典型抑制剂作用的酶促测定和蛋白质印迹分析表明，这些分子强烈干扰EGFR靶标。
• 一种苯乙酰胺类化合物及其制备方法与应用
  申请人：湖南省农业生物技术研究所

  公开号：CN114957166A

  公开（公告）日：2022-08-30

  本发明公开了一种苯乙酰胺类化合物及其制备方法与应用。该化合物的结构通式为： 其中，R1和R2分别为‑H、‑OCH3、‑NO2、‑COOCH3、‑CONH2和‑COOH中的任意一种；R3和R4分别为‑H、‑CH3、‑C2H5、‑OCH3、‑NO2、‑Br、‑Cl、‑F和‑CN中的任意一种。该类化合物具有优良的除草活性，尤其对玉米地防治一年生和多年生杂草效果显著，药后15天对总草的株防效至少达到86.22％，鲜重防效至少达到83.39％，且对玉米安全无害。该类化合物还可以有效降低除草剂用量及成本，减少残留，减轻农药对环境的潜在威胁，并且合成方法简单、经济，可以作为先导化合物，为开发安全高效环保的新型除草剂提供新的领域。
• Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines
  作者：Dan Zhao、Shanshan Huang、Menghua Qu、Changyuan Wang、Zhihao Liu、Zhen Li、Jinyong Peng、Kexin Liu、Yanxia Li、Xiaodong Ma、Xiaohong Shu

  DOI：10.1016/j.ejmech.2016.11.047

  日期：2017.1

  A new series of diphenylpyrimidine derivatives (DPPYs) bearing various aniline side chains at the C-2 position of pyrimidine core were synthesized as potent BTK inhibitors. Most of these inhibitors displayed improved activity against B leukemia cell lines compared with lead compound spebrutinib. Subsequent studies showed that the peculiar inhibitor 7j, with IC50 values of 10.5 AM against Ramos cells and 19.1 AM against Raji cells, also displayed slightly higher inhibitory ability than the novel agent ibrutinib. Moreover, compound 7j is not sensitive to normal cells PBMC, indicating low cell cytotoxicity. In addition, flow cytometry analysis indicated that 7j significantly induced the apoptosis of Ramos cells, and arrested the cell cycle at the GO/G1 phase. These explorations provided new clues to discover pyrimidine scaffold as more effective BTK inhibitors. 2017 Elsevier Masson SAS. All rights reserved.
• Novel Pyrimidines as Multitarget Protein Tyrosine Kinase Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
  作者：Bo Sun、Xiaowen Liu、Xu Zheng、Changyuan Wang、Qiang Meng、Huijun Sun、Xiaohong Shu、Kexin Liu、Xiuli Sun、Yanxia Li、Xiaodong Ma

  DOI：10.1002/cmdc.201900606

  日期：2020.1.17

  A new class of pyrimidine derivatives were identified as potent protein tyrosine kinase (PTK) inhibitors for the treatment of idiopathic pulmonary fibrosis (IPF). Most of these small-molecule inhibitors displayed strong enzymatic activity against BTK and JAK3 kinases at concentrations lower than 10 nM. The representative compound N-(3-((5-chloro-2-(4-((1-morpholino)acetylamino)phenylamino)-4-pyrim

  一类新的嘧啶衍生物被鉴定为有效的蛋白酪氨酸激酶（PTK）抑制剂，可用于治疗特发性肺纤维化（IPF）。这些小分子抑制剂中的大多数在浓度低于10 nM时显示出对BTK和JAK3激酶的强酶活性。代表性化合物N-（3-（（5-氯-2-（4-（（1-吗啉代）乙酰氨基）苯基氨基）-4-嘧啶基）氨基）苯基）丙烯酰胺（6a）也对两种化合物均显示出高抑制力。浓度为10 nM的BTK和JAK激酶家族以及ErbB4，抑制率高于57％。此外，体内生物学评估表明6 a可以显着降低IPF疾病的严重程度。所有这些研究表明，多PTK抑制剂6a可以用作治疗IPF的有前途的药物。
• Design and synthesis of diphenylpyrimidine derivatives (DPPYs) as potential dual EGFR T790M and FAK inhibitors against a diverse range of cancer cell lines
  作者：Min Ai、Changyuan Wang、Zeyao Tang、Kexin Liu、Xiuli Sun、Tengyue Ma、Yanxia Li、Xiaodong Ma、Lei Li、Lixue Chen

  DOI：10.1016/j.bioorg.2019.103408

  日期：2020.1

  A new class of pyrimidine derivatives were designed and synthesized as potential dual FAK and EGFR(T79)(0M) inhibitors using a fragment-based drug design strategy. This effort led to the identification of the two most active inhibitors, namely 9a and 9f, against both FAK (IC50, = 1.03 and 3.05 nM, respectively) and EGFR(T79)(0M) (IC50 = 3.89 and 7.13 nM, respectively) kinase activity. Moreover, most of these compounds also exhibited strong antiproliferative activity against the three evaluated FAK-overexpressing pancreatic cancer (PC) cells (AsPC-1, BxPC-3, Panc-1) and two drug-resistant cancer cell lines (breast cancer MCF-7/adr cells and lung cancer H1975 cells) at concentrations lower than 6.936 mu M. In addition, 9a was also effective in the in vivo assessment conducted in a FAK-driven human AsPC-1 cell xenograft mouse model. Overall, this study offers a new insight into the treatment of hard to treat cancers.