1,3-dimethyl-8-(pyridin-4-yl)-1H-imidazo[4,5-c]quinolin-2-one | 1610681-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,3-dimethyl-8-(pyridin-4-yl)-1H-imidazo[4,5-c]quinolin-2-one
• 英文别名: 1,3-Dimethyl-8-pyridin-4-ylimidazo[4,5-c]quinolin-2-one；1,3-dimethyl-8-pyridin-4-ylimidazo[4,5-c]quinolin-2-one
• CAS: 1610681-20-3
• 化学式: C₁₇H₁₄N₄O
• 分子量: 290.324
• InChiKey: ATZJMDVFRHEARB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-iodo-N-methyl-3-nitroquinolin-4-amine 在 四(三苯基膦)钯 、 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 69.25h， 生成 1,3-dimethyl-8-(pyridin-4-yl)-1H-imidazo[4,5-c]quinolin-2-one
  参考文献：
  名称：

  Establishment of a Structure–Activity Relationship of 1H-Imidazo[4,5-c]quinoline-Based Kinase Inhibitor NVP-BEZ235 as a Lead for African Sleeping Sickness

  摘要：

  Compound NVP-BEZ235 (1) is a potent inhibitor of human phospoinositide-3-kinases and mammalian target of rapamycin (mTOR) that also showed high inhibitory potency against Trypanosoma brucei cultures. With an eye toward using 1 as a starting point for anti-trypanosomal drug discovery, we report efforts to reduce host cell toxicity, to improve the physicochemical properties, and to improve the selectivity profile over human kinases. In this work, we have developed structure-activity relationships for analogues of 1 and have prepared analogues of 1 with improved solubility properties and good predicted central nervous system exposure. In this way, we have identified 4e, 9, 16e, and 16g as the most promising leads to date. We also report cell phenotype and phospholipidomic studies that suggest that these compounds exert their anti-trypanosomal effects, at least in part, by inhibition of lipid kinases.

  DOI：

  10.1021/jm500361r

文献信息

• Establishment of a Structure–Activity Relationship of 1<i>H</i>-Imidazo[4,5-<i>c</i>]quinoline-Based Kinase Inhibitor NVP-BEZ235 as a Lead for African Sleeping Sickness
  作者：João D. Seixas、Sandra A. Luengo-Arratta、Rosario Diaz、Manuel Saldivia、Domingo I. Rojas-Barros、Pilar Manzano、Silvia Gonzalez、Manuela Berlanga、Terry K. Smith、Miguel Navarro、Michael P. Pollastri

  DOI：10.1021/jm500361r

  日期：2014.6.12

  Compound NVP-BEZ235 (1) is a potent inhibitor of human phospoinositide-3-kinases and mammalian target of rapamycin (mTOR) that also showed high inhibitory potency against Trypanosoma brucei cultures. With an eye toward using 1 as a starting point for anti-trypanosomal drug discovery, we report efforts to reduce host cell toxicity, to improve the physicochemical properties, and to improve the selectivity profile over human kinases. In this work, we have developed structure-activity relationships for analogues of 1 and have prepared analogues of 1 with improved solubility properties and good predicted central nervous system exposure. In this way, we have identified 4e, 9, 16e, and 16g as the most promising leads to date. We also report cell phenotype and phospholipidomic studies that suggest that these compounds exert their anti-trypanosomal effects, at least in part, by inhibition of lipid kinases.