ethyl 7-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ylsulfonyl)heptanoate | 1214998-22-7

• 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 7-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ylsulfonyl)heptanoate
• 英文别名: Ethyl 7-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]sulfonylheptanoate
• CAS: 1214998-22-7
• 化学式: C₂₄H₂₇ClFN₃O₅S
• 分子量: 524.013
• InChiKey: HYOWPPQFWAFMOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 7-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ylsulfonyl)heptanoate 在 羟胺 作用下， 以 甲醇 为溶剂， 以26%的产率得到7-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ylsulfonyl)-N-hydroxyheptanamide
  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：

  ethyl 7-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ylthio)heptanoate 在 potassium permanganate 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以25%的产率得到ethyl 7-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-ylsulfonyl)heptanoate
  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

• AMINO QUINAZOLINES AS KINASE INHIBITORS
  申请人：Bury Michael Jonathan

  公开号：US20140206688A1

  公开（公告）日：2014-07-24

  Disclosed are compounds having the formula (Formula I)): wherein R 1 , R 2 , R 3 and Z are as defined herein, and methods of making and using the same.

  公开了具有以下公式（公式I）的化合物：其中R1，R2，R3和Z的定义如本文所述，并公开了制备和使用这些化合物的方法。
• Amino quinazolines as kinase inhibitors
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10717711B2

  公开（公告）日：2020-07-21

  Disclosed are compounds having the formula: wherein R1, R2, R3, and Z are as defined herein, and methods of making and using the same.

  所公开的是具有以下式子的化合物 其中 R1、R2、R3 和 Z 如本文所定义，以及制造和使用它们的方法。
• US9604938B2
  申请人：——

  公开号：US9604938B2

  公开（公告）日：2017-03-28
• US9994529B2
  申请人：——

  公开号：US9994529B2

  公开（公告）日：2018-06-12
• 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.