2-methyl-2-(4-(2-oxo-8-(pyridin-3-ylethynyl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)propanenitrile | 1610681-28-1

• 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: 2-methyl-2-(4-(2-oxo-8-(pyridin-3-ylethynyl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)propanenitrile
• CAS: 1610681-28-1
• 化学式: C₂₇H₁₉N₅O
• 分子量: 429.481
• InChiKey: QDKQDDHKSBEZQJ-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  2-methyl-2-(4-(2-oxo-8-(pyridin-3-ylethynyl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)propanenitrile 、 碘甲烷 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以20%的产率得到2-methyl-2-(4-(3-methyl-2-oxo-8-(pyridin-3-ylethynyl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)propanenitrile
  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