2-methyl-4-{[(4-nitronaphthalen-1-yl)amino]methyl}-1H-isoindole-1,3(2H)-dione | 1314499-86-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-methyl-4-{[(4-nitronaphthalen-1-yl)amino]methyl}-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-Methyl-4-[[(4-nitronaphthalen-1-yl)amino]methyl]isoindole-1,3-dione
• CAS: 1314499-86-9
• 化学式: C₂₀H₁₅N₃O₄
• 分子量: 361.357
• InChiKey: KEQYAJRFPIOSLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-Dihydro-2,4-dimethyl-1H-isoindole-1,3-dione 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 2-methyl-4-{[(4-nitronaphthalen-1-yl)amino]methyl}-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Identification of the Binding Modes of N-Phenylphthalimides Inhibiting Bacterial Thymidylate Synthase through X-Ray Crystallography Screening

  摘要：

  To identify specific bacterial thymidylate synthase (TS) inhibitors, we exploited phenolphthalein (PTH), which inhibits both bacterial and human enzymes. The X-ray crystal structure of Lactobacillus casei TS (LcTS) that binds PTH showed multiple binding modes of the inhibitor, which prevented a classical structure-based drug design approach. To overcome this issue, we synthesized two phthalimidic libraries that were tested against TS enzymes and then we performed X-ray crystallographic screening of the active compounds. Compounds 6A, 8A, and 12A showed 40-fold higher affinity for bacterial TS than human TS. The X-ray crystallographic screening characterized the binding mode of six inhibitors in complexes with LcTS. Of these, 20A, 23A, and 24A showed a common unique binding mode, whereas 8A showed a different, unique binding mode. A comparative analysis of the LcTS X-ray complexes that were obtained with the pathogenic TS enabled the selection of compounds 8A and 23A as specific compounds and starting points to be exploited for the specific inhibition of pathogen enzymes.

  DOI：

  10.1021/jm2005018

文献信息

• Identification of the Binding Modes of <i>N</i>-Phenylphthalimides Inhibiting Bacterial Thymidylate Synthase through X-Ray Crystallography Screening
  作者：Stefano Mangani、Laura Cancian、Rosalida Leone、Cecilia Pozzi、Sandra Lazzari、Rosaria Luciani、Stefania Ferrari、M. Paola Costi

  DOI：10.1021/jm2005018

  日期：2011.8.11

  To identify specific bacterial thymidylate synthase (TS) inhibitors, we exploited phenolphthalein (PTH), which inhibits both bacterial and human enzymes. The X-ray crystal structure of Lactobacillus casei TS (LcTS) that binds PTH showed multiple binding modes of the inhibitor, which prevented a classical structure-based drug design approach. To overcome this issue, we synthesized two phthalimidic libraries that were tested against TS enzymes and then we performed X-ray crystallographic screening of the active compounds. Compounds 6A, 8A, and 12A showed 40-fold higher affinity for bacterial TS than human TS. The X-ray crystallographic screening characterized the binding mode of six inhibitors in complexes with LcTS. Of these, 20A, 23A, and 24A showed a common unique binding mode, whereas 8A showed a different, unique binding mode. A comparative analysis of the LcTS X-ray complexes that were obtained with the pathogenic TS enabled the selection of compounds 8A and 23A as specific compounds and starting points to be exploited for the specific inhibition of pathogen enzymes.