N-{4-[(3-ethynylphenyl)amino]-6-(2-pyridin-2-yl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide | 1424329-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: N-{4-[(3-ethynylphenyl)amino]-6-(2-pyridin-2-yl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide
• 英文别名: N-[4-(3-ethynylanilino)-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide
• CAS: 1424329-05-4
• 化学式: C₂₆H₂₆N₆O
• 分子量: 438.532
• InChiKey: KVGUDVKUMFSIEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  95.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{4-[(3-ethynylphenyl)amino]-6-(2-pyridin-2-yl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 10.0h， 以86%的产率得到N⁴-(3-ethynylphenyl)-6-(2-pyridin-2-yl-ethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  N2-Trimethylacetyl substituted and unsubstituted-N4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: Design, cellular receptor tyrosine kinase inhibitory activities and in vivo evaluation as antiangiogenic, antimetastatic and antitumor agents

  摘要：

  Six novel N-4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines and their N-2-trimethylacetyl substituted analogs were synthesized as receptor tyrosine kinase (RTK) inhibitors. A microwave-mediated Sonogashira reaction was used as a key step for the synthesis of these compounds. Biological evaluation, in whole cell assays, showed that some analogs had remarkable inhibitory activity against a variety of RTKs and in particular cytotoxic activity against A431 tumor cells in culture. The inhibitory data against RTKs in this study demonstrated that variation of the 4-anilino substituents of these analogs dictates both potency and specificity of inhibitory activity against various RTKs. The study also supported the hypothesis that interaction of substituents on the 2-amino group with hydrophobic site-II provides an increase in potency. Compound 8 of this series was selected for evaluation in vivo in a B16-F10 syngeneic mouse tumor model and exhibited significant reduction in tumor growth rate, in tumor vascular density and in metastases to the lung compared to the control. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.045
• 作为产物：
  描述：

  6-iodo-4(3H)-oxo-2-pivaloylamino-7H-pyrrolo<2,3-d>pyrimidine 在 盐酸 、 ammonium hydroxide 、 copper(l) iodide 、 5%-palladium/activated carbon 、 氢气 、 钯 、 三乙胺 、 三苯基膦 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 150.0 ℃ 、344.75 kPa 条件下， 反应 30.06h， 生成 N-{4-[(3-ethynylphenyl)amino]-6-(2-pyridin-2-yl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide
  参考文献：
  名称：

  N2-Trimethylacetyl substituted and unsubstituted-N4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: Design, cellular receptor tyrosine kinase inhibitory activities and in vivo evaluation as antiangiogenic, antimetastatic and antitumor agents

  摘要：

  Six novel N-4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines and their N-2-trimethylacetyl substituted analogs were synthesized as receptor tyrosine kinase (RTK) inhibitors. A microwave-mediated Sonogashira reaction was used as a key step for the synthesis of these compounds. Biological evaluation, in whole cell assays, showed that some analogs had remarkable inhibitory activity against a variety of RTKs and in particular cytotoxic activity against A431 tumor cells in culture. The inhibitory data against RTKs in this study demonstrated that variation of the 4-anilino substituents of these analogs dictates both potency and specificity of inhibitory activity against various RTKs. The study also supported the hypothesis that interaction of substituents on the 2-amino group with hydrophobic site-II provides an increase in potency. Compound 8 of this series was selected for evaluation in vivo in a B16-F10 syngeneic mouse tumor model and exhibited significant reduction in tumor growth rate, in tumor vascular density and in metastases to the lung compared to the control. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.045

文献信息

• N2-Trimethylacetyl substituted and unsubstituted-N4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: Design, cellular receptor tyrosine kinase inhibitory activities and in vivo evaluation as antiangiogenic, antimetastatic and antitumor agents
  作者：Aleem Gangjee、Ojas A. Namjoshi、Jianming Yu、Michael A. Ihnat、Jessica E. Thorpe、Lora C. Bailey-Downs

  DOI：10.1016/j.bmc.2012.12.045

  日期：2013.3

  Six novel N-4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines and their N-2-trimethylacetyl substituted analogs were synthesized as receptor tyrosine kinase (RTK) inhibitors. A microwave-mediated Sonogashira reaction was used as a key step for the synthesis of these compounds. Biological evaluation, in whole cell assays, showed that some analogs had remarkable inhibitory activity against a variety of RTKs and in particular cytotoxic activity against A431 tumor cells in culture. The inhibitory data against RTKs in this study demonstrated that variation of the 4-anilino substituents of these analogs dictates both potency and specificity of inhibitory activity against various RTKs. The study also supported the hypothesis that interaction of substituents on the 2-amino group with hydrophobic site-II provides an increase in potency. Compound 8 of this series was selected for evaluation in vivo in a B16-F10 syngeneic mouse tumor model and exhibited significant reduction in tumor growth rate, in tumor vascular density and in metastases to the lung compared to the control. (C) 2013 Elsevier Ltd. All rights reserved.