3-(2-羟基乙基氨基甲酰)苯硼酸 | 955422-14-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(2-羟基乙基氨基甲酰)苯硼酸
• 英文名称: (3-((2-Hydroxyethyl)carbamoyl)phenyl)boronic acid
• 英文别名: [3-(2-hydroxyethylcarbamoyl)phenyl]boronic acid
• CAS: 955422-14-7
• 化学式: C₉H₁₂BNO₄
• mdl: MFCD09878355
• 分子量: 209.01
• InChiKey: HVVLWQCKVRJBBU-UHFFFAOYSA-N

物化性质

• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.21
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 海关编码：
  2931900090

反应信息

• 作为反应物：
  描述：

  2-amino-6-iodo-3-(4-(trifluoromethyl)phenyl)quinazolin-4(3H)-one 、 3-(2-羟基乙基氨基甲酰)苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成
  参考文献：
  名称：

  显示抗分枝杆菌活性的氨基喹唑啉酮的合成，结构-活性关系和机理研究。

  摘要：

  表型全细胞筛选针对补充有吐温80和铁（GASTE-Fe）的甘油-丙氨酸-盐中的结核分枝杆菌（Mtb）导致鉴定出2-氨基喹唑啉酮命中化合物砜1，该化合物可通过替换来优化溶解度带有亚砜的砜部分2。合成和结构-活性关系（SAR）研究确定了几种具有有效抗分枝杆菌活性的化合物，它们在代谢上稳定且无细胞毒性。化合物2表现出良好的体外特性，因此被选择用于体内药代动力学（PK）研究，发现它被广泛代谢为砜1。两种衍生物均显示出有希望的PK参数。但是，当评估2在急性TB感染小鼠模型中的体内功效时，发现它没有活性。为了了解体外和体内差异，随后使用在不同培养基中培养的不同Mtb菌株在体外对化合物2进行了重新测试。这表明仅在含甘油的介质中观察到了活性，并导致了以下假设：甘油不被Mtb用作主要碳源。如先前所观察到的，在小鼠肺中的这种作用。自发抗性突变体的产生和全基因组测序研究提供了对这一假说的支持，该研究揭示了映射到

  DOI：

  10.1021/acsinfecdis.0c00252

文献信息

• Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1
  作者：Claire Le Manach、Diego Gonzàlez Cabrera、Frederic Douelle、Aloysius T. Nchinda、Yassir Younis、Dale Taylor、Lubbe Wiesner、Karen L. White、Eileen Ryan、Corinne March、Sandra Duffy、Vicky M. Avery、David Waterson、Michael J. Witty、Sergio Wittlin、Susan A. Charman、Leslie J. Street、Kelly Chibale

  DOI：10.1021/jm500098s

  日期：2014.3.27

  A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound 35 was highly active (IC50: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.
• Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 2
  作者：Claire Le Manach、Tanya Paquet、Diego Gonzàlez Cabrera、Yassir Younis、Dale Taylor、Lubbe Wiesner、Nina Lawrence、Sylva Schwager、David Waterson、Michael J. Witty、Sergio Wittlin、Leslie J. Street、Kelly Chibale

  DOI：10.1021/jm500887k

  日期：2014.11.13

  On the basis of our recent results on a novel series of imidazopyridazine-based antimalarials, we focused on identifying compounds with improved aqueous solubility and hERG profile while maintaining metabolic stability and in vitro potency. Toward this objective, 41 compounds were synthesized and evaluated for antiplasmodial activity against NF54 (sensitive) and K1 (multidrug resistant) strains of the malaria parasite Plasmodium falciparum and evaluated for both aqueous solubility and metabolic stability. Selected compounds were tested for in vitro hERG activity and in vivo efficacy in the P. berghei mouse model. Several compounds were identified with significantly improved aqueous solubility, good metabolic stability, and a clean hERG profile relative to a previous frontrunner lead compound. A sulfoxide-based imidazopyridazine analog 45, arising from a prodrug-like strategy, was completely curative in the Plasmodium berghei mouse model at 4 x 50 mg/kg po.