7-fluorobenzo[c][1,2]oxaborole-1,6(3H)-diol

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 7-fluorobenzo[c][1,2]oxaborole-1,6(3H)-diol
• 英文别名: 7-fluoro-1-hydroxy-3H-2,1-benzoxaborol-6-ol
• 化学式: C₇H₆BFO₃
• 分子量: 167.932
• InChiKey: VUKNUBXFXYOUGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.25
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-fluorobenzo[c][1,2]oxaborole-1,6(3H)-diol 在 sodium cyanoborohydride 、 sodium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 24.0h， 生成 (3aR,4R,5R,7S,8S,9R,9aS,12R)-7-((dimethylamino)methyl)-8-hydroxy-4,7,9,12-tetramethyl-3-oxodecahydro-4,9a-propanocyclopenta[8]annulen-5-yl 2-((7-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)oxy)acetate
  参考文献：
  名称：

  Boron-Pleuromutilins as Anti-Wolbachia Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis

  摘要：

  A series of pleuromutilins modified by introduction of a boron-containing heterocycle on C(14) of the polycyclic core are described. These analogs were found to be potent anti-Wolbachia antibiotics and, as such, may be useful in the treatment of filarial infections caused by Onchocerca volvulus, resulting in Onchocerciasis or river blindness, or Wuchereria bancrofti and Brugia malayi and related parasitic nematodes resulting in lymphatic filariasis. These two important neglected tropical diseases disproportionately impact patients in the developing world. The lead preclinical candidate compound containing 7-fluoro-6-oxybenzoxaborole (15, AN11251) was shown to have good in vitro anti-Wolbachia activity and physicochemical and pharmacokinetic properties providing high exposure in plasma. The lead was effective in reducing the Wolbachia load in filarial worms following oral administration to mice.

  DOI：

  10.1021/acs.jmedchem.8b01854
• 作为产物：
  描述：

  2,3-二氟苯酚 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium tetrahydroborate 、 正丁基锂 、 palladium on activated charcoal 、 氢气 、 potassium acetate 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， -78.0~70.0 ℃ 、344.75 kPa 条件下， 反应 45.0h， 生成 7-fluorobenzo[c][1,2]oxaborole-1,6(3H)-diol
  参考文献：
  名称：

  [EN] BORON-CONTAINING SMALL MOLECULES
  [FR] PETITES MOLÉCULES CONTENANT DU BORE

  摘要：

  化合物、药物配方和治疗细菌感染的方法被披露。

  公开号：

  WO2017151489A1

文献信息

• [EN] 1 -HYDROXY-BENZOOXABOROLES AS ANTIPARASITIC AGENTS<br/>[FR] 1-HYDROXY-BENZOOXABOROLES COMME AGENTS ANTIPARASITAIRES
  申请人：LILLY CO ELI

  公开号：WO2014149793A1

  公开（公告）日：2014-09-25

  Provided are compounds useful for controlling endoparasites both in animals and agriculture. Further provided are methods for controlling endoparasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling endoparasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. The claimed compounds are described by the following Markush formula:A typical example for a compound according to above formula is: A typical example for a compound according to above formula is:

  提供了一些在动物和农业中控制内寄生虫的化合物。此外，还提供了一种通过向动物施用上述化合物或其药学上可接受的盐的有效量来控制动物内寄生虫侵染的方法，以及使用上述化合物或其可接受的盐以及可接受的载体来控制内寄生虫侵染的配方。所述的化合物由以下Markush公式描述：根据上述公式的化合物的典型示例是：
• [EN] BORON-CONTAINING SMALL MOLECULES<br/>[FR] PETITES MOLÉCULES CONTENANT DU BORE
  申请人：ANACOR PHARMACEUTICALS INC

  公开号：WO2017151489A1

  公开（公告）日：2017-09-08

  Compounds, pharmaceutical formulations, and methods of treating bacterial infections are disclosed.

  化合物、药物配方和治疗细菌感染的方法被披露。
• A hit deconstruction approach for the discovery of fetal hemoglobin inducers
  作者：Andrew B. Benowitz、H. Christian Eberl、Connie L. Erickson-Miller、Aidan G. Gilmartin、Elizabeth R. Gore、Monica N. Montoute、Zining Wu

  DOI：10.1016/j.bmcl.2018.10.032

  日期：2018.12

  unmet medical need. De-repression of fetal hemoglobin in erythrocytes is a clinically validated approach for the management of sickle cell disease, but the only FDA-approved medicine for this purpose has limitations to its use. We conducted a phenotypic screen in human erythroid progenitor cells to identify molecules with the ability to de-repress fetal hemoglobin, which resulted in the identification

  β-血红蛋白病（例如镰状细胞病）代表了全球主要的未满足医疗需求。抑制胎儿红血球中血红蛋白的含量是临床验证的治疗镰状细胞疾病的方法，但是唯一获得FDA批准的用于此目的的药物在使用中受到限制。我们在人类红系祖细胞中进行了表型筛选，以鉴定具有抑制胎儿血红蛋白抑制能力的分子，从而鉴定出含有苯并氧杂硼酸的命中化合物1。发现该化合物具有适度的细胞效价和铅样药代动力学，但没有可优化的可识别SAR。密切相关的类似物1的系统解构揭示了片段状羧酸12，然后对其进行优化以提供四唑31，与1相比，四唑31的细胞效能提高了约100倍，在大鼠中的口服暴露水平较高，并且具有出色的溶解度。
• Boron-Pleuromutilins as Anti-<i>Wolbachia</i> Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis
  作者：Robert T. Jacobs、Christopher S. Lunde、Yvonne R. Freund、Vincent Hernandez、Xianfeng Li、Yi Xia、David S. Carter、Pamela W. Berry、Jason Halladay、Fernando Rock、Rianna Stefanakis、Eric Easom、Jacob J. Plattner、Louise Ford、Kelly L. Johnston、Darren A. N. Cook、Rachel Clare、Andrew Cassidy、Laura Myhill、Hayley Tyrer、Joanne Gamble、Ana F. Guimaraes、Andrew Steven、Franziska Lenz、Alexandra Ehrens、Stefan J. Frohberger、Marianne Koschel、Achim Hoerauf、Marc P. Hübner、Case W. McNamara、Malina A. Bakowski、Joseph D. Turner、Mark J. Taylor、Stephen A. Ward

  DOI：10.1021/acs.jmedchem.8b01854

  日期：2019.3.14

  A series of pleuromutilins modified by introduction of a boron-containing heterocycle on C(14) of the polycyclic core are described. These analogs were found to be potent anti-Wolbachia antibiotics and, as such, may be useful in the treatment of filarial infections caused by Onchocerca volvulus, resulting in Onchocerciasis or river blindness, or Wuchereria bancrofti and Brugia malayi and related parasitic nematodes resulting in lymphatic filariasis. These two important neglected tropical diseases disproportionately impact patients in the developing world. The lead preclinical candidate compound containing 7-fluoro-6-oxybenzoxaborole (15, AN11251) was shown to have good in vitro anti-Wolbachia activity and physicochemical and pharmacokinetic properties providing high exposure in plasma. The lead was effective in reducing the Wolbachia load in filarial worms following oral administration to mice.