diethyl 1,1-difluoro-4-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)-hexyl-phosphonate | 1234567-74-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: diethyl 1,1-difluoro-4-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)-hexyl-phosphonate
• CAS: 1234567-74-8
• 化学式: C₂₁H₂₇F₂N₂O₆PS
• 分子量: 504.492
• InChiKey: JJYBMWROVFDJGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  110.8
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  diethyl 1,1-difluoro-4-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)-hexyl-phosphonate 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 以68%的产率得到1,1-difluoro-4-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)hexylphosphonic acid
  参考文献：
  名称：

  Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase

  摘要：

  Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid ( 9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a K-i of 70 mu M. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (K-i 38 mu M). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve pi-pi stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.072
• 作为产物：
  描述：

  2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide 、 diethyl 1,1-difluoro-6-iodohexylphosphonate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以59%的产率得到diethyl 1,1-difluoro-4-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)-hexyl-phosphonate
  参考文献：
  名称：

  Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase

  摘要：

  Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid ( 9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a K-i of 70 mu M. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (K-i 38 mu M). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve pi-pi stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.072