N-(2-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenoxy)ethyl)isoxazole-5-carboxamide

• 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: N-(2-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenoxy)ethyl)isoxazole-5-carboxamide
• 英文别名: N-[2-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenoxy]ethyl]-1,2-oxazole-5-carboxamide
• 化学式: C₂₁H₁₈F₃N₃O₄
• 分子量: 433.387
• InChiKey: AZDOANPZBGQTAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  93.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-硝基-2-甲基苯酚 在 盐酸 、 5%-palladium/activated carbon 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 N-(2-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenoxy)ethyl)isoxazole-5-carboxamide
  参考文献：
  名称：

  Discovery of N-(3-((1-Isonicotinoylpiperidin-4-yl)oxy)-4-methylphenyl)-3-(trifluoromethyl)benzamide (CHMFL-KIT-110) as a Selective, Potent, and Orally Available Type II c-KIT Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  c-KIT kinase is a validated drug discovery target for gastrointestinal stromal tumors (GISTs). Clinically used c-KIT kinase inhibitors, i.e., Imatinib and Sunitinib, bear other important targets such as ABL or FLT3 kinases. Here we report our discovery of a more selective c-KIT inhibitor, compound 13 (CHMFL-KIT-110), which completely abolished ABL and FLT3 kinase activity. KinomeScan selectivity profiling (468 kinases) of 13 exhibited a high selectivity (S score (1) = 0.01). 13 displayed great antiproliferative efficacy against GISTs cell lines GIST-T1 and GIST-882 (GI50: 0.021 and 0.043 mu M, respectively). In the cellular context, it effectively affected c-KIT-mediated signaling pathways and induced apoptosis as well as cell cycle arrest. In addition, 13 possessed acceptable bioavailability (36%) and effectively suppressed the tumor growth in GIST-T1 cell inoculated xenograft model without apparent toxicity. 13 currently is undergoing extensive preclinical evaluation and might be a potential drug candidate for GISTs.

  DOI：

  10.1021/acs.jmedchem.6b00200