4-((2-((4-chloro-3-(trifluoromethyl)phenyl)amino)quinolin-5-yl)oxy)-N-methylpicolinamide

• 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: 4-((2-((4-chloro-3-(trifluoromethyl)phenyl)amino)quinolin-5-yl)oxy)-N-methylpicolinamide
• 英文别名: 4-((2-((4-Chloro-3-(trifluoromethyl)phenyl)amino)quinolin-5-yl)oxy)-N-methylpicolinamide (6j)；4-[2-[4-chloro-3-(trifluoromethyl)anilino]quinolin-5-yl]oxy-N-methylpyridine-2-carboxamide
• 化学式: C₂₃H₁₆ClF₃N₄O₂
• 分子量: 472.854
• InChiKey: AYFIGOMGVCPKEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-methoxyquinoline N-oxide 在 三溴化硼 、 potassium carbonate 、 caesium carbonate 、 对甲苯磺酰氯 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 19.0h， 生成 4-((2-((4-chloro-3-(trifluoromethyl)phenyl)amino)quinolin-5-yl)oxy)-N-methylpicolinamide
  参考文献：
  名称：

  Design and synthesis of new 2-anilinoquinolines bearing N -methylpicolinamide moiety as potential antiproliferative agents

  摘要：

  A series of new 2‐anilinoquinolines 6a–o possessing the substantial N‐methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogs. The antiproliferative activities of the target compounds were preliminarily appraised against a panel of three human cancer cell lines (MCF‐7, SK‐BR3, and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10 μM concentration. Interestingly, compounds 6c, 6d, 6j, 6k, and 6l showed promising selective anticancer activities (growth inhibition >80%) toward certain cancer cells at 10 μM testing dose. Compounds 6d and 6j were advanced to five‐dose testing mode to determine their GI50 values and compared with our previously reported ureidoquinoline B and sorafenib as reference compounds. The 4‐chloro‐3‐trifluoromethylaniline derivative 6j manifested superior potency than both compound B and sorafenib over eleven and eight cell lines, respectively. It showed GI50 values of 0.36, 0.66, 0.68, and 0.60 μM against the breast MDA‐MB‐468, renal A498, and melanoma SK‐MEL‐5 and UACC‐62 cell lines, respectively. Moreover, both 6d and 6j exerted low cytotoxic effects against HFF‐1 normal cell line. Furthermore, compounds 6d and 6j were tested against both B‐RafV600E and C‐Raf kinases and displayed modest inhibitory activities, which were justified by molecular docking study. Compound 6j could serve as a promising candidate for further development of potent anticancer chemotherapeutics.

  DOI：

  10.1111/cbdd.12836