2-bromo-N-(2-methyl-4-nitrophenyl)acetamide

• 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-methyl-4-nitrophenyl)acetamide
• 化学式: C₉H₉BrN₂O₃
• mdl: MFCD02974370
• 分子量: 273.086
• InChiKey: SGTLYUYMJBRATE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromo-N-(2-methyl-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 2-[[5-chloro-2-(3-methy-4-((1-morpholin)acetylamino)ylanilino)pyrimidin-4-yl]amino]-N-cyclopropylbenzamide
  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 、 4-硝基-2-甲苯胺 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 2-bromo-N-(2-methyl-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

• Amide-Based <i>Cinchona</i> Alkaloids as Phase-Transfer Catalysts: Synthesis and Potential Application
  作者：Maciej Majdecki、Patryk Niedbala、Janusz Jurczak

  DOI：10.1021/acs.orglett.9b03065

  日期：2019.10.4

  easily and efficiently from inexpensive and commercially available substrates. We tested this class of alkaloids in the alkylation of glycine derivative, carried out under phase-transfer catalyst conditions. The presented hybrid catalysts offer both high reaction yields (up to 97%) and high enantioselectivities of the obtained product (up to 94% ee).

  本文中，我们以季铵盐的形式提供了金鸡纳生物碱的简单酰胺衍生物的文库。所获得的衍生物可以很容易和有效地从廉价的和可商购的基质中产生。我们在相转移催化剂条件下进行的甘氨酸衍生物烷基化反应中测试了这类生物碱。所提出的杂化催化剂提供了高的反应产率（高达97％）和所获得的产物的高的对映选择性（高达94％的ee）。
• 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.