7-(((pyridin-2-yl)amino)methyl)quinolin-8-ol | 160094-92-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 7-(((pyridin-2-yl)amino)methyl)quinolin-8-ol
• 英文别名: 7-[(Pyridin-2-ylamino)methyl]quinolin-8-ol；7-[(pyridin-2-ylamino)methyl]quinolin-8-ol
• CAS: 160094-92-8
• 化学式: C₁₅H₁₃N₃O
• 分子量: 251.288
• InChiKey: IGEDQYYDZVAWDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  58
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基吡啶 、 8-羟基-7-喹啉甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 96.0h， 以34%的产率得到7-(((pyridin-2-yl)amino)methyl)quinolin-8-ol
  参考文献：
  名称：

  Identification of Clinically Viable Quinolinol Inhibitors of Botulinum Neurotoxin A Light Chain

  摘要：

  Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized hydroxyquinolines. Seventy-two compounds had IC50 values below 10 mu M, with the best compound exhibiting submicromolar inhibition (IC50 = 0.8 mu M). Structure-activity relationship trends showed that the enzyme tolerates various substitutions at R-1 but has a clear preference for bulky aryl amide groups at R-2, while methylation at R-3 increased inhibitor potency. Evaluation of the most potent compounds in an ADME panel showed that these compounds possess poor solubility at pH 6.8, but display excellent solubility at low pH, suggesting that oral dosing may be possible. Our data show the potential of quinolinol compounds as BoNT therapeutics due to their good in vitro potencies and favorable ADME properties.

  DOI：

  10.1021/jm4012164

文献信息

• Identification of Clinically Viable Quinolinol Inhibitors of Botulinum Neurotoxin A Light Chain
  作者：Dejan Caglič、Michelle C. Krutein、Kristin M. Bompiani、Deborah J. Barlow、Galit Benoni、Jeffrey C. Pelletier、Allen B. Reitz、Luke L. Lairson、Karen L. Houseknecht、Garry R. Smith、Tobin J. Dickerson

  DOI：10.1021/jm4012164

  日期：2014.2.13

  Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized hydroxyquinolines. Seventy-two compounds had IC50 values below 10 mu M, with the best compound exhibiting submicromolar inhibition (IC50 = 0.8 mu M). Structure-activity relationship trends showed that the enzyme tolerates various substitutions at R-1 but has a clear preference for bulky aryl amide groups at R-2, while methylation at R-3 increased inhibitor potency. Evaluation of the most potent compounds in an ADME panel showed that these compounds possess poor solubility at pH 6.8, but display excellent solubility at low pH, suggesting that oral dosing may be possible. Our data show the potential of quinolinol compounds as BoNT therapeutics due to their good in vitro potencies and favorable ADME properties.