5-(4-tert-butylphenyl)-3-hydroxy-1-(2-(indol-3-yl)ethyl)-4-(4-methoxybenzoyl)-1,5-dihydro-2H-pyrrol-2-one | 728886-05-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 5-(4-tert-butylphenyl)-3-hydroxy-1-(2-(indol-3-yl)ethyl)-4-(4-methoxybenzoyl)-1,5-dihydro-2H-pyrrol-2-one
• CAS: 728886-05-3
• 化学式: C₃₂H₃₂N₂O₄
• 分子量: 508.617
• InChiKey: IQAICBGMIWHYDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  38.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  82.63
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  对甲氧基苯乙酮 在 lithium hexamethyldisilazane 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 24.75h， 生成 5-(4-tert-butylphenyl)-3-hydroxy-1-(2-(indol-3-yl)ethyl)-4-(4-methoxybenzoyl)-1,5-dihydro-2H-pyrrol-2-one
  参考文献：
  名称：

  Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis

  摘要：

  Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei, is a neglected fatal disease. Leucyl-tRNA synthetase (LeuRS), which has been successfully applied in the development of antifungal agent, represents a potential antiprotozoal drug target. In this study, a 3D model of T. brucei LeuRS (TbLeuRS) synthetic active site was constructed and subjected to virtual screening using a combination of pharmacophore- and docking-based methods. A new 2-pyrrolinone scaffold was discovered and the structure-activity relationship (SAR) studies aided by the docking model and organic synthesis were carried out. Compounds with various substituents on R-1, R-2 and R-3 were synthesized and their SAR was discussed. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.035

文献信息

• Identification of Trypanosoma brucei leucyl-tRNA synthetase inhibitors by pharmacophore- and docking-based virtual screening and synthesis
  作者：Yaxue Zhao、Qing Wang、Qingqing Meng、Dazhong Ding、Huaiyu Yang、Guangwei Gao、Dawei Li、Weiliang Zhu、Huchen Zhou

  DOI：10.1016/j.bmc.2011.12.035

  日期：2012.2

  Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei, is a neglected fatal disease. Leucyl-tRNA synthetase (LeuRS), which has been successfully applied in the development of antifungal agent, represents a potential antiprotozoal drug target. In this study, a 3D model of T. brucei LeuRS (TbLeuRS) synthetic active site was constructed and subjected to virtual screening using a combination of pharmacophore- and docking-based methods. A new 2-pyrrolinone scaffold was discovered and the structure-activity relationship (SAR) studies aided by the docking model and organic synthesis were carried out. Compounds with various substituents on R-1, R-2 and R-3 were synthesized and their SAR was discussed. (C) 2012 Elsevier Ltd. All rights reserved.