methyl 4-chloro-2-(methyl(2-nitrophenyl)amino)benzoate | 949570-66-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: methyl 4-chloro-2-(methyl(2-nitrophenyl)amino)benzoate
• CAS: 949570-66-5
• 化学式: C₁₅H₁₃ClN₂O₄
• 分子量: 320.732
• InChiKey: CIBJUMNEZMUQRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.68
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 4-chloro-2-(methyl(2-nitrophenyl)amino)benzoate 在 palladium diacetate 、 platinum on activated charcoal 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 9-(3-methoxy-4-nitrophenyl)-11-methyl-5H-benzo[b][1,4]benzodiazepin-6-one
  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：

  4-氯-2-碘苯甲酸甲酯 在 铜 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 氯苯 为溶剂， 反应 48.0h， 生成 methyl 4-chloro-2-(methyl(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