1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)pyrrole-2-carboxylic acid | 1615684-94-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)pyrrole-2-carboxylic acid
• 英文别名: 1-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-1H-pyrrole-2-carboxylic acid；1-(1-hydroxy-3H-2,1-benzoxaborol-6-yl)pyrrole-2-carboxylic acid
• CAS: 1615684-94-0
• 化学式: C₁₂H₁₀BNO₄
• 分子量: 243.027
• InChiKey: YFGVWLJIHAKPRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.39
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  71.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)pyrrole-2-carboxylic acid 、 4-甲氧基苄胺 在 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以44.4%的产率得到1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)pyrrole-2-carboxylic acid 4-methoxybenzylamide
  参考文献：
  名称：

  Novel pyrrolobenzoxaboroles: Design, synthesis, and biological evaluation against Trypanosoma brucei

  摘要：

  Human African trypanosomiasis is a fatal parasitic infection caused by the protozoan Trypanosoma brucei. The development of novel antitrypanosomal agents is urgently needed. Here we report the synthesis and structure-activity relationship of a new class of benzoxaboroles as antitrypanosomal agents. These compounds showed antiparasitic IC50 values ranging from 4.02 to 0.03 mu g/mL and satisfactory cytotoxicity profile. Three of the lead compounds were demonstrated to cure the parasitic infection in a murine acute infection model. The structure activity relationship of the pyrrolobenzoxaboroles are also discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.079
• 作为产物：
  描述：

  2-溴-4-硝基苯甲酸 在 盐酸 、 锂硼氢 、 正丁基锂 、 氯化亚砜 、 tin(II) chloride dihdyrate 、 silver nitrate 、 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 14.75h， 生成 1-(1,3-dihydro-1-hydroxy-2,1-benzoxaborol-6-yl)pyrrole-2-carboxylic acid
  参考文献：
  名称：

  Novel pyrrolobenzoxaboroles: Design, synthesis, and biological evaluation against Trypanosoma brucei

  摘要：

  Human African trypanosomiasis is a fatal parasitic infection caused by the protozoan Trypanosoma brucei. The development of novel antitrypanosomal agents is urgently needed. Here we report the synthesis and structure-activity relationship of a new class of benzoxaboroles as antitrypanosomal agents. These compounds showed antiparasitic IC50 values ranging from 4.02 to 0.03 mu g/mL and satisfactory cytotoxicity profile. Three of the lead compounds were demonstrated to cure the parasitic infection in a murine acute infection model. The structure activity relationship of the pyrrolobenzoxaboroles are also discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.079

文献信息

• 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。
• Novel pyrrolobenzoxaboroles: Design, synthesis, and biological evaluation against Trypanosoma brucei
  作者：Puhua Wu、Jiong Zhang、Qingqing Meng、Bakela Nare、Robert T. Jacobs、Huchen Zhou

  DOI：10.1016/j.ejmech.2014.04.079

  日期：2014.6

  Human African trypanosomiasis is a fatal parasitic infection caused by the protozoan Trypanosoma brucei. The development of novel antitrypanosomal agents is urgently needed. Here we report the synthesis and structure-activity relationship of a new class of benzoxaboroles as antitrypanosomal agents. These compounds showed antiparasitic IC50 values ranging from 4.02 to 0.03 mu g/mL and satisfactory cytotoxicity profile. Three of the lead compounds were demonstrated to cure the parasitic infection in a murine acute infection model. The structure activity relationship of the pyrrolobenzoxaboroles are also discussed. (C) 2014 Elsevier Masson SAS. All rights reserved.