6-bromo-N-methyl-N-[(1R)-1-phenylethyl]thieno[2,3-d]pyrimidin-4-amine | 1580541-97-4

• 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: 6-bromo-N-methyl-N-[(1R)-1-phenylethyl]thieno[2,3-d]pyrimidin-4-amine
• CAS: 1580541-97-4
• 化学式: C₁₅H₁₄BrN₃S
• 分子量: 348.266
• InChiKey: ZDTSWBHPPNUNJJ-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-bromo-N-methyl-N-[(1R)-1-phenylethyl]thieno[2,3-d]pyrimidin-4-amine 、 2-羟基苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.5h， 以88%的产率得到(R)-2-(4-(methyl(1-phenylethyl)amino)thieno[2,3-d]pyrimidin-6-yl)phenol
  参考文献：
  名称：

  Structure–activity study leading to identification of a highly active thienopyrimidine based EGFR inhibitor

  摘要：

  Based on the thieno[2,3-d]pyrimidine scaffold, a series of new 4-amino-6-aryl thienopyrimidines have been prepared and evaluated as EGFR tyrosine kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 6-aryl ring, the stereochemistry, and the basicity at the secondary 4-amino group. A stepwise optimization by combination of active fragments led to the discovery of three structures with EGFR IC50 < 1 nM. The most potent drug candidate had an IC50 of 0.3 nM towards EGFR and its mutants L858R and L861Q. Studies using human cancer cell lines and an EGFR-L858R reporter cell system revealed good cellular potency, verifying the identified thienopyrimidines as promising lead structures. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.042
• 作为产物：
  描述：

  R-N-甲基-苯乙胺 、 6-溴-4-氯噻吩[2,3-D]嘧啶 以 正丁醇 为溶剂， 反应 18.0h， 以91%的产率得到6-bromo-N-methyl-N-[(1R)-1-phenylethyl]thieno[2,3-d]pyrimidin-4-amine
  参考文献：
  名称：

  Structure–activity study leading to identification of a highly active thienopyrimidine based EGFR inhibitor

  摘要：

  Based on the thieno[2,3-d]pyrimidine scaffold, a series of new 4-amino-6-aryl thienopyrimidines have been prepared and evaluated as EGFR tyrosine kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 6-aryl ring, the stereochemistry, and the basicity at the secondary 4-amino group. A stepwise optimization by combination of active fragments led to the discovery of three structures with EGFR IC50 < 1 nM. The most potent drug candidate had an IC50 of 0.3 nM towards EGFR and its mutants L858R and L861Q. Studies using human cancer cell lines and an EGFR-L858R reporter cell system revealed good cellular potency, verifying the identified thienopyrimidines as promising lead structures. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.042

文献信息

• Structure–activity study leading to identification of a highly active thienopyrimidine based EGFR inhibitor
  作者：Steffen Bugge、Svein Jacob Kaspersen、Synne Larsen、Unni Nonstad、Geir Bjørkøy、Eirik Sundby、Bård Helge Hoff

  DOI：10.1016/j.ejmech.2014.01.042

  日期：2014.3

  Based on the thieno[2,3-d]pyrimidine scaffold, a series of new 4-amino-6-aryl thienopyrimidines have been prepared and evaluated as EGFR tyrosine kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 6-aryl ring, the stereochemistry, and the basicity at the secondary 4-amino group. A stepwise optimization by combination of active fragments led to the discovery of three structures with EGFR IC50 < 1 nM. The most potent drug candidate had an IC50 of 0.3 nM towards EGFR and its mutants L858R and L861Q. Studies using human cancer cell lines and an EGFR-L858R reporter cell system revealed good cellular potency, verifying the identified thienopyrimidines as promising lead structures. (C) 2014 Elsevier Masson SAS. All rights reserved.