methyl 4-chloro-2-{[4-(2-methoxy-2-oxoethyl)-2-nitrophenyl]amino}benzoate | 755026-46-1

• 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: methyl 4-chloro-2-{[4-(2-methoxy-2-oxoethyl)-2-nitrophenyl]amino}benzoate
• 英文别名: Methyl 2-(4-((methoxycarbonyl)methyl)-2-nitrophenylamino)-4-chlorobenzoate；methyl 4-chloro-2-[4-(2-methoxy-2-oxoethyl)-2-nitroanilino]benzoate
• CAS: 755026-46-1
• 化学式: C₁₇H₁₅ClN₂O₆
• 分子量: 378.769
• InChiKey: RAJBTFQYWBGVHR-UHFFFAOYSA-N

物化性质

• 沸点：
  490.0±45.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-chloro-2-{[4-(2-methoxy-2-oxoethyl)-2-nitrophenyl]amino}benzoate 在 palladium diacetate 、 platinum on activated charcoal lithium hydroxide 、 氢气 、 对甲苯磺酸 、 cesium fluoride 作用下， 以 甲醇 、 乙二醇二甲醚 、 甲苯 为溶剂， 反应 60.0h， 生成 [3-(3-methoxy-4-nitrophenyl)-11-oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-8-yl]acetic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of 5,10-Dihydro-dibenzo[b,e][1,4]diazepin-11-one-Based Potent and Selective Chk-1 Inhibitors

  摘要：

  A novel series of 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones have been synthesized as potent and selective checkpoint kinase 1 (Chk1) inhibitors via structure-based design. Aided by protein X-ray crystallography, medicinal chemistry efforts led to the identification of compound 46d, with potent enzymatic activity against Chk1 kinase. While maintaining a low cytotoxicity of its own, compound 46d exhibited a strong ability to abrogate G2 arrest and increased the cytotoxicity of camptothecin by 19-fold against SW620 cells. Pharmacokinetic studies revealed that it had a moderate bioavailabilty of 20% in mice. Two important binding interactions between compound 46b and Chk1 kinase, revealed by X-ray cocrystal structure, were hydrogen bonds between the hinge region and the amide bond of the core structure and a hydrogen bond between the methoxy group and Lys38 of the protein.

  DOI：

  10.1021/jm070105d
• 作为产物：
  描述：

  2-(4-氨基-3-硝基苯基)乙酸甲酯 、 4-氯-2-碘苯甲酸甲酯 在 palladium diacetate 1,1'-双(二苯基膦)二茂铁 、 caesium carbonate 作用下， 反应 16.0h， 以87%的产率得到methyl 4-chloro-2-{[4-(2-methoxy-2-oxoethyl)-2-nitrophenyl]amino}benzoate
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of 5,10-Dihydro-dibenzo[b,e][1,4]diazepin-11-one-Based Potent and Selective Chk-1 Inhibitors

  摘要：

  A novel series of 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones have been synthesized as potent and selective checkpoint kinase 1 (Chk1) inhibitors via structure-based design. Aided by protein X-ray crystallography, medicinal chemistry efforts led to the identification of compound 46d, with potent enzymatic activity against Chk1 kinase. While maintaining a low cytotoxicity of its own, compound 46d exhibited a strong ability to abrogate G2 arrest and increased the cytotoxicity of camptothecin by 19-fold against SW620 cells. Pharmacokinetic studies revealed that it had a moderate bioavailabilty of 20% in mice. Two important binding interactions between compound 46b and Chk1 kinase, revealed by X-ray cocrystal structure, were hydrogen bonds between the hinge region and the amide bond of the core structure and a hydrogen bond between the methoxy group and Lys38 of the protein.

  DOI：

  10.1021/jm070105d

文献信息

• [EN] HETEROCYCLIC KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE HETEROCYCLIQUE
  申请人：ABBOTT LAB

  公开号：WO2004076424A1

  公开（公告）日：2004-09-10

  Compounds having the formula (I) are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式(I)的化合物对于抑制蛋白激酶是有用的。还公开了制造这些化合物的方法、包含这些化合物的组合物以及使用这些化合物的治疗方法。
• Heterocyclic kinase inhibitors
  申请人：——

  公开号：US20040254159A1

  公开（公告）日：2004-12-16

  Compounds having the formula 1 are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有1式的化合物对于抑制蛋白激酶非常有用。还揭示了制备该化合物的方法，含有该化合物的组合物，以及使用该化合物进行治疗的方法。
• Heterocyclic Kinase Inhibitors
  申请人：Hasvold A. Lisa

  公开号：US20070254867A1

  公开（公告）日：2007-11-01

  Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  具有公式的化合物对于抑制蛋白激酶很有用。还公开了制备这些化合物的方法、含有这些化合物的组合物和使用这些化合物的治疗方法。
• 5,10-DIHYDRO-11H-DIBENZO[B,E][1,4]DIAZEPIN-11-ONE AS KINASE INHIBITORS
  申请人：AbbVie Inc.

  公开号：EP1606268B1

  公开（公告）日：2015-05-20
• US7456169B2
  申请人：——

  公开号：US7456169B2

  公开（公告）日：2008-11-25