6-cyclohexylmethoxy-1,3-dihydro-1-hydroxy-2,1-benzoxaborole | 1268390-25-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-cyclohexylmethoxy-1,3-dihydro-1-hydroxy-2,1-benzoxaborole
• 英文别名: 6-(cyclohexylmethoxy)-1-hydroxy-3H-2,1-benzoxaborole
• CAS: 1268390-25-5
• 化学式: C₁₄H₁₉BO₃
• 分子量: 246.114
• InChiKey: GLUBIFLETOCGRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

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 为溶剂， 生成 6-cyclohexylmethoxy-1,3-dihydro-1-hydroxy-2,1-benzoxaborole
  参考文献：
  名称：

  [EN] BORON-CONTAINING SMALL MOLECULES AS ANTIPROTOZOAL AGENTS
  [FR] PETITES MOLÉCULES CONTENANT DU BORE COMME AGENTS ANTIPROTOZOAIRES

  摘要：

  本发明提供了具有以下通式的新颖化合物，这些化合物可用于治疗原虫感染，包含此类化物的药物组合物，以及这些化合物与至少一种其他治疗有效成分的组合。

  公开号：

  WO2011049971A1

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.