3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)butan-3-one | 1268390-47-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)butan-3-one
• 英文别名: 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)butan-2-one；3-[(1-hydroxy-3H-2,1-benzoxaborol-6-yl)oxy]butan-2-one
• CAS: 1268390-47-1
• 化学式: C₁₁H₁₃BO₄
• 分子量: 220.033
• InChiKey: XAOLARAFQGZJQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.26
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-(benzyloxy)benzo[c][1,2]oxaborol-1(3H)-ol 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yloxy)butan-3-one
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of Trypanosoma brucei Leucyl-tRNA Synthetase Inhibitors as Antitrypanosomal Agents

  摘要：

  African trypanosomiasis, caused by the protozoal pathogen Tlypanosoma brucei (T. brucei), is one of the most neglected tropical diseases that are in great need of new drugs. We report the design and synthesis of T. bruceileucyl-tRNA synthetase (TbLeuRS) inhibitors and their structure activity relationship. Benzoxaborole was used as the core structure and C(6) was modified to achieve improved affinity bared on docking results that showed further binding space at this position. Indeed, compounds with C(7) substitutions showed diminished activity due to clash with the eukaryote specific I4ae helix while substitutions at C(6) gave enhanced affinity. TbLeuRS inhibitors with IC50 as low as 1.6 mu M were discovered, and the structure activity relationship was discussed. The most potent enzyme inhibitors also showed excellent T.brucei parasite growth inhibition activity. This is the first time that TbLeuRS inhibitors are reported, and this study suggests that leucyl-tRNA synthetase (LeuRS) could be a potential target for antiparasitic drug development.

  DOI：

  10.1021/jm101225g

文献信息

• Design, Synthesis, and Structure−Activity Relationship of <i>Trypanosoma brucei</i> Leucyl-tRNA Synthetase Inhibitors as Antitrypanosomal Agents
  作者：Dazhong Ding、Qingqing Meng、Guangwei Gao、Yaxue Zhao、Qing Wang、Bakela Nare、Robert Jacobs、Fernando Rock、Michael R. K. Alley、Jacob J. Plattner、Guoqiang Chen、Dawei Li、Huchen Zhou

  DOI：10.1021/jm101225g

  日期：2011.3.10

  African trypanosomiasis, caused by the protozoal pathogen Tlypanosoma brucei (T. brucei), is one of the most neglected tropical diseases that are in great need of new drugs. We report the design and synthesis of T. bruceileucyl-tRNA synthetase (TbLeuRS) inhibitors and their structure activity relationship. Benzoxaborole was used as the core structure and C(6) was modified to achieve improved affinity bared on docking results that showed further binding space at this position. Indeed, compounds with C(7) substitutions showed diminished activity due to clash with the eukaryote specific I4ae helix while substitutions at C(6) gave enhanced affinity. TbLeuRS inhibitors with IC50 as low as 1.6 mu M were discovered, and the structure activity relationship was discussed. The most potent enzyme inhibitors also showed excellent T.brucei parasite growth inhibition activity. This is the first time that TbLeuRS inhibitors are reported, and this study suggests that leucyl-tRNA synthetase (LeuRS) could be a potential target for antiparasitic drug development.