1-(4-(4-amino-2-(trifluoromethyl)phenyl)-3,6-dihydropyridin-1(2H)-yl)propan-1-one | 1252048-22-8

• 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: 1-(4-(4-amino-2-(trifluoromethyl)phenyl)-3,6-dihydropyridin-1(2H)-yl)propan-1-one
• CAS: 1252048-22-8
• 化学式: C₁₅H₁₇F₃N₂O
• 分子量: 298.308
• InChiKey: RZOJIROARMENSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  46.33
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-(4-(4-amino-2-(trifluoromethyl)phenyl)-3,6-dihydropyridin-1(2H)-yl)propan-1-one 、 4,6-二氯喹啉-3-羧酸乙酯 以 1,4-二氧六环 为溶剂， 反应 4.0h， 生成 ethyl 6-chloro-4-[4-(1-propanoyl-3,6-dihydro-2H-pyridin-4-yl)-3-(trifluoromethyl)anilino]quinoline-3-carboxylate
  参考文献：
  名称：

  Discovery of 1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a Highly Potent, Selective Mammalian Target of Rapamycin (mTOR) Inhibitor for the Treatment of Cancer

  摘要：

  The mTOR It protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline I, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin 1), which inhibited phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin I exhibits 1000-fold selectivity for mTOR over P13K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. Torin was efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrated good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and per tissues. These results demonstrate that Torin I is a useful probe of mTOR-dependent phenomena and that benzo-naphthridinones represent a promising scaffold for the further development of mTOR-specific inhibitors with the potential for clinical utility.

  DOI：

  10.1021/jm101144f