(E)-N-(4-((3-chloro-4-fluorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)but-2-enamide | 1595286-03-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: (E)-N-(4-((3-chloro-4-fluorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)but-2-enamide
• 英文别名: (E)-N-[4-(3-chloro-4-fluoroanilino)thieno[2,3-d]pyrimidin-6-yl]-4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)but-2-enamide
• CAS: 1595286-03-5
• 化学式: C₂₃H₂₃ClFN₅O₂S
• 分子量: 487.985
• InChiKey: SZLAQBNHGVKZED-OWOJBTEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-chloro-6-nitrothieno[2,3-d]pyrimidine 在 氯化亚砜 、 铁粉 、 氯化铵 作用下， 以 乙醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 3.0h， 生成 (E)-N-(4-((3-chloro-4-fluorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)but-2-enamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors

  摘要：

  A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives was designed, synthesized and evaluated as irreversible inhibitors of the epidermal growth factor receptor (EGFR). Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020 mu M, and those of 12 compounds were less than 0.010 mu M. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005 mu M. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1 mu M. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1 mu M), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method. (c) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.01.035

文献信息

• Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors
  作者：Xun Ji、Ting Peng、Xu Zhang、Jian Li、Wei Yang、Linjiang Tong、Rong Qu、Hualiang Jiang、Jian Ding、Hua Xie、Hong Liu

  DOI：10.1016/j.bmc.2014.01.035

  日期：2014.4

  A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives was designed, synthesized and evaluated as irreversible inhibitors of the epidermal growth factor receptor (EGFR). Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020 mu M, and those of 12 compounds were less than 0.010 mu M. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005 mu M. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1 mu M. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1 mu M), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method. (c) 2014 Published by Elsevier Ltd.