(E)-[1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)-3-phenyl]propenone | 1268390-58-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-[1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)-3-phenyl]propenone
• 英文别名: (E)-[3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)-1-phenyl]propenone；(E)-3-(1-hydroxy-3H-2,1-benzoxaborol-6-yl)-1-phenylprop-2-en-1-one
• CAS: 1268390-58-4
• 化学式: C₁₆H₁₃BO₃
• 分子量: 264.088
• InChiKey: KVWUSELPLQBWMH-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-[1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)-3-phenyl]propenone 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以15.8%的产率得到3-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)-1-phenyl-propanone
  参考文献：
  名称：

  Chalcone–Benzoxaborole Hybrid Molecules as Potent Antitrypanosomal Agents

  摘要：

  We report the novel chalcone-benzoxaborole hybrids and their structure-activity relationship against Trypanosoma brucei parasites. The 4-NH2 derivative 29 and 3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH2-3-OMe compound 49 showed an IC50 of 0.010 mu g/mL and resulted in 100% survival and zero parasitemia in a murine infection model, which represents one of the most potent compounds discovered to date from the benzoxaborole class that inhibit T. brucei growth.

  DOI：

  10.1021/jm2012408
• 作为产物：
  描述：

  2-溴四苯醌 在 盐酸 、 甲醇 、 锂硼氢 、 正丁基锂 、 氯化亚砜 、 对甲苯磺酸 、 三乙胺 、 pyridinium chlorochromate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.41h， 生成 (E)-[1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)-3-phenyl]propenone
  参考文献：
  名称：

  Chalcone–Benzoxaborole Hybrid Molecules as Potent Antitrypanosomal Agents

  摘要：

  We report the novel chalcone-benzoxaborole hybrids and their structure-activity relationship against Trypanosoma brucei parasites. The 4-NH2 derivative 29 and 3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH2-3-OMe compound 49 showed an IC50 of 0.010 mu g/mL and resulted in 100% survival and zero parasitemia in a murine infection model, which represents one of the most potent compounds discovered to date from the benzoxaborole class that inhibit T. brucei growth.

  DOI：

  10.1021/jm2012408

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.
• Chalcone–Benzoxaborole Hybrid Molecules as Potent Antitrypanosomal Agents
  作者：Zhitao Qiao、Qi Wang、Fenglong Zhang、Zhongli Wang、Tana Bowling、Bakela Nare、Robert T. Jacobs、Jiong Zhang、Dazhong Ding、Yangang Liu、Huchen Zhou

  DOI：10.1021/jm2012408

  日期：2012.4.12

  We report the novel chalcone-benzoxaborole hybrids and their structure-activity relationship against Trypanosoma brucei parasites. The 4-NH2 derivative 29 and 3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH2-3-OMe compound 49 showed an IC50 of 0.010 mu g/mL and resulted in 100% survival and zero parasitemia in a murine infection model, which represents one of the most potent compounds discovered to date from the benzoxaborole class that inhibit T. brucei growth.