N-(6-(5-((2,4-difluorophenyl)sulfonamido)-6-methoxypyridin-3-yl)-4-methoxyquinolin-3-yl)acetamide

• 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: N-(6-(5-((2,4-difluorophenyl)sulfonamido)-6-methoxypyridin-3-yl)-4-methoxyquinolin-3-yl)acetamide
• 英文别名: N-(6-(5-(2,4-difluorobenzenesulfonamido)-6-methoxypyridin-3-yl)-4-methoxyquinoline-3-yl)acetamide；N-[6-[5-[(2,4-difluorophenyl)sulfonylamino]-6-methoxypyridin-3-yl]-4-methoxyquinolin-3-yl]acetamide
• 化学式: C₂₄H₂₀F₂N₄O₅S
• 分子量: 514.509
• InChiKey: AWZBQRRDOVSYAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  6-溴-4-氯-3-喹啉羧酸乙酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 叠氮磷酸二苯酯 、 potassium carbonate 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 54.58h， 生成 N-(6-(5-((2,4-difluorophenyl)sulfonamido)-6-methoxypyridin-3-yl)-4-methoxyquinolin-3-yl)acetamide
  参考文献：
  名称：

  Discovery of a series of N -(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as PI3K/mTOR dual inhibitors

  摘要：

  Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been considered as promising targets for the treatment of cancer. Herein, we synthesized a series of N-(5(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual inhibitors for cancer therapy. In the biological evaluation, compound 17e was identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. Moreover, 17e display high potency against PC-3 cells (IC50 = 80 nM) in the anti-proliferative assay, and showed acceptable pharmacokinetic properties in vivo. (c) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.01.016

文献信息

• Discovery of a series of N -(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as PI3K/mTOR dual inhibitors
  作者：Jiankang Zhang、Xiaoqing Lv、Xiaodong Ma、Yongzhou Hu

  DOI：10.1016/j.ejmech.2017.01.016

  日期：2017.2

  Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been considered as promising targets for the treatment of cancer. Herein, we synthesized a series of N-(5(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual inhibitors for cancer therapy. In the biological evaluation, compound 17e was identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. Moreover, 17e display high potency against PC-3 cells (IC50 = 80 nM) in the anti-proliferative assay, and showed acceptable pharmacokinetic properties in vivo. (c) 2017 Elsevier Masson SAS. All rights reserved.