(E)-N-[2-[4-[3-chloro-4-[3-(trifluoromethyl)phenoxy]anilino]pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-4-(dimethylamino)but-2-enamide | 1415813-89-6

• 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: (E)-N-[2-[4-[3-chloro-4-[3-(trifluoromethyl)phenoxy]anilino]pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-4-(dimethylamino)but-2-enamide
• CAS: 1415813-89-6
• 化学式: C₂₇H₂₆ClF₃N₆O₂
• 分子量: 558.991
• InChiKey: FXXJFJZPESCIJK-QPJJXVBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-[4-[3-Chloro-4-(3-trifluoromethylphenoxy)phenylamino]-5H-pyrrolo[3,2-d]pyrimidine-5-yl]ethylamine 、 反式-4-二甲基氨基巴豆酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 以37%的产率得到(E)-N-[2-[4-[3-chloro-4-[3-(trifluoromethyl)phenoxy]anilino]pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-4-(dimethylamino)but-2-enamide
  参考文献：
  名称：

  Structure-Based Approach for the Discovery of Pyrrolo[3,2-d]pyrimidine-Based EGFR T790M/L858R Mutant Inhibitors

  摘要：

  The epidermal growth factor receptor (EGFR) family plays a critical role in vital cellular processes and in various cancers. Known EGFR inhibitors exhibit distinct antitumor responses against the various EGFR mutants associated with nonsmall-cell lung cancer. The L858R mutation enhances clinical sensitivity to gefitinib and erlotinib as compared with wild type and reduces the relative sensitivity to lapatinib. In contrast, the T790M mutation confers drug resistance to gefitinib and erlotinib. We determined crystal structures of the wild-type and T790M/L858R double mutant EGFR kinases with reversible and irreversible pyrrolo[3,2-d]pyrimidine inhibitors based on analogues of TAK-285 and neratinib. In these structures, M790 adopts distinct conformations to accommodate different inhibitors, whereas R858 allows conformational variations of the activation loop. These results provide structural insights for understanding the structure-activity relationships that should contribute to the development of potent inhibitors against drug-sensitive or -resistant EGFR mutations.

  DOI：

  10.1021/ml300327z