N-(2-hydroxyethyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide | 378224-70-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(2-hydroxyethyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide
• 英文别名: N-(2-hydroxyethyl)-2-oxo-1H-benzo[cd]indole-6-sulfonamide
• CAS: 378224-70-5
• 化学式: C₁₃H₁₂N₂O₄S
• 分子量: 292.315
• InChiKey: HVGIZYVNCXVGDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxyethyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide 、 N,N-二异丙基亚磷酰胺二叔丁酯 在 四氮唑 、 双氧水 作用下， 以 四氢呋喃 、 乙腈 、 水 为溶剂， 反应 22.25h， 以67%的产率得到di-tert-butyl-2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)ethyl phosphate
  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-氧代-1,2-二氢苯并[cd]吲哚-6-磺酰氯 、 C.I.酸性橙108 以 四氢呋喃 为溶剂， 反应 12.0h， 以70%的产率得到N-(2-hydroxyethyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide
  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

文献信息

• Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase
  作者：Arindam Talukdar、Ekaterina Morgunova、Jianxin Duan、Winfried Meining、Nicolas Foloppe、Lennart Nilsson、Adelbert Bacher、Boris Illarionov、Markus Fischer、Rudolf Ladenstein、Mark Cushman

  DOI：10.1016/j.bmc.2010.03.072

  日期：2010.5

  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.