ethyl 5-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)pentanoate | 1214998-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 5-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)pentanoate
• 英文别名: Ethyl 5-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]oxypentanoate
• CAS: 1214998-21-6
• 化学式: C₂₄H₂₅N₃O₄
• 分子量: 419.48
• InChiKey: BUMLXUHKNOAIQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 5-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)pentanoate 在 羟胺 作用下， 以 甲醇 为溶剂， 以40%的产率得到5-(4-((3-ethynylphenyl)amino)-7-methoxyquinazolin-6-yloxy)-N-hydroxypentanamide
  参考文献：
  名称：

  Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer

  摘要：

  By incorporating historic deacetylase (HDAC) inhibitory functionality into the pharmacophore of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors, we synthesized a novel series OF compounds with potent, multiacting HDAC, EGFR, and HER2 inhibition and identified 7-(4-(3-ethylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8 (CUDC-101) as a drug Candidate, which is now in clinical development. 8 displays potent in vitro inhibitory activity against HDAC, EGFR, and HER2 with an IC50 of 4.4, 2.4, and 15.7 nM, respectively. In most tumor Cell lines tested, 8 exhibits efficient antiproliferative activity with greater potency than vorinostat (SAHA), erlotinib, lapatinib, and combinations of vorinostat/erlotinib and vorinostat/lapatinib. In vivo, 8 promotes tumor regression or inhibition in various cancer xenograft models including nonsmall cell lung cancer (NSCLC), liver, breast, head and neck, colon, and pancreatic cancers. These results Suggest that a single compound that simultaneously inhibits HDAC, EGFR, and HER2 may offer greater therapeutic benefits in cancer over single-acting agents through the interference with multiple pathways and potential synergy among HDAC and EGFR/HER2 inhibitors.

  DOI：

  10.1021/jm901453q
• 作为产物：
  描述：

  4-[(3-乙炔基苯基)氨基]-7-甲氧基-喹唑啉-6-醇 、 5-溴戊酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以72%的产率得到ethyl 5-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)pentanoate
  参考文献：
  名称：

  Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer

  摘要：

  By incorporating historic deacetylase (HDAC) inhibitory functionality into the pharmacophore of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors, we synthesized a novel series OF compounds with potent, multiacting HDAC, EGFR, and HER2 inhibition and identified 7-(4-(3-ethylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8 (CUDC-101) as a drug Candidate, which is now in clinical development. 8 displays potent in vitro inhibitory activity against HDAC, EGFR, and HER2 with an IC50 of 4.4, 2.4, and 15.7 nM, respectively. In most tumor Cell lines tested, 8 exhibits efficient antiproliferative activity with greater potency than vorinostat (SAHA), erlotinib, lapatinib, and combinations of vorinostat/erlotinib and vorinostat/lapatinib. In vivo, 8 promotes tumor regression or inhibition in various cancer xenograft models including nonsmall cell lung cancer (NSCLC), liver, breast, head and neck, colon, and pancreatic cancers. These results Suggest that a single compound that simultaneously inhibits HDAC, EGFR, and HER2 may offer greater therapeutic benefits in cancer over single-acting agents through the interference with multiple pathways and potential synergy among HDAC and EGFR/HER2 inhibitors.

  DOI：

  10.1021/jm901453q

文献信息

• Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-<i>N</i>-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer
  作者：Xiong Cai、Hai-Xiao Zhai、Jing Wang、Jeffrey Forrester、Hui Qu、Ling Yin、Cheng-Jung Lai、Rudi Bao、Changgeng Qian

  DOI：10.1021/jm901453q

  日期：2010.3.11

  By incorporating historic deacetylase (HDAC) inhibitory functionality into the pharmacophore of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) inhibitors, we synthesized a novel series OF compounds with potent, multiacting HDAC, EGFR, and HER2 inhibition and identified 7-(4-(3-ethylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide 8 (CUDC-101) as a drug Candidate, which is now in clinical development. 8 displays potent in vitro inhibitory activity against HDAC, EGFR, and HER2 with an IC50 of 4.4, 2.4, and 15.7 nM, respectively. In most tumor Cell lines tested, 8 exhibits efficient antiproliferative activity with greater potency than vorinostat (SAHA), erlotinib, lapatinib, and combinations of vorinostat/erlotinib and vorinostat/lapatinib. In vivo, 8 promotes tumor regression or inhibition in various cancer xenograft models including nonsmall cell lung cancer (NSCLC), liver, breast, head and neck, colon, and pancreatic cancers. These results Suggest that a single compound that simultaneously inhibits HDAC, EGFR, and HER2 may offer greater therapeutic benefits in cancer over single-acting agents through the interference with multiple pathways and potential synergy among HDAC and EGFR/HER2 inhibitors.