2-(4-((3-amino-6-iodoquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile | 1628077-36-0

• 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-(4-((3-amino-6-iodoquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile
• CAS: 1628077-36-0
• 化学式: C₁₉H₁₇IN₄
• 分子量: 428.275
• InChiKey: RQCAOZHRNNFSOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  74.73
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(4-((3-amino-6-iodoquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile 在 四(三苯基膦)钯 、 四丁基溴化铵 、 potassium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 乙二醇二乙醚 、 水 为溶剂， 反应 26.25h， 生成 2-methyl-2-(4-(3-methyl-2-oxo-8-phenyl-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
• 作为产物：
  描述：

  5-iodo-2-((2-nitrovinyl)amino)benzoic acid 在 potassium acetate 、 乙酸酐 、 铁粉 、 氯化铵 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 、 水 为溶剂， 反应 8.5h， 生成 2-(4-((3-amino-6-iodoquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile
  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

• Structure–property studies of an imidazoquinoline chemotype with antitrypanosomal activity
  作者：Dana M. Klug、Rosario Diaz-Gonzalez、Travis J. DeLano、Eftychia M. Mavrogiannaki、Melissa J. Buskes、Raeann M. Dalton、John K. Fisher、Katherine M. Schneider、Vivian Hilborne、Melanie G. Fritsche、Quillon J. Simpson、Westley F. Tear、William G. Devine、Guiomar Pérez-Moreno、Gloria Ceballos-Pérez、Raquel García-Hernández、Cristina Bosch-Navarrete、Luis Miguel Ruiz-Pérez、Francisco Gamarro、Dolores González-Pacanowska、Maria Santos Martinez-Martinez、Pilar Manzano-Chinchon、Miguel Navarro、Michael P. Pollastri、Lori Ferrins

  DOI：10.1039/d0md00103a

  日期：——

  Structure–property and structure–activity studies identify regions that positively modulate aqueous solubility; though maintaining potent anti-trypanosomal potency proves challenging.

  结构-性质和结构-活性研究确定了能够正面调节水溶性的区域；尽管保持有效的抗锥虫活性证明具有挑战性。