2-氨基-4-(7-乙氧基-7-氧代庚氧基)-5-甲氧基苯甲酸乙酯 | 1012058-12-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氨基-4-(7-乙氧基-7-氧代庚氧基)-5-甲氧基苯甲酸乙酯
• 英文名称: ethyl 2-amino-4-(7-ethoxy-7-oxoheptyloxy)-5-methoxybenzoate
• 英文别名: Ethyl 2-amino-4-(7-ethoxy-7-oxoheptoxy)-5-methoxybenzoate
• CAS: 1012058-12-6
• 化学式: C₁₉H₂₉NO₆
• 分子量: 367.442
• InChiKey: FILPRGSGOXBBNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-氨基-4-(7-乙氧基-7-氧代庚氧基)-5-甲氧基苯甲酸乙酯 、 甲酸铵 在 formamide 作用下， 反应 3.0h， 以67%的产率得到ethyl 7-(6-methoxy-4-oxo-3,4-dihydroquinazolin-7-yloxy)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
• 作为产物：
  描述：

  ethyl 4-(7-ethoxy-7-oxoheptyloxy)-5-methoxy-2-nitrobenzoate 在 盐酸 、 铁粉 作用下， 以 乙醇 、 水 为溶剂， 以84%的产率得到2-氨基-4-(7-乙氧基-7-氧代庚氧基)-5-甲氧基苯甲酸乙酯
  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

• QUINAZOLINE BASED EGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
  申请人：Qian Changgeng

  公开号：US20080194578A1

  公开（公告）日：2008-08-14

  The present invention relates to quinazoline containing zinc-binding moiety based derivatives that have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

  本发明涉及含有锌结合基团的喹唑啉衍生物，具有增强和意外的抑制表皮生长因子受体酪氨酸激酶（EGFR-TK）的性质，并可用于治疗EGFR-TK相关的疾病和疾病，如癌症。所述衍生物还可以作为HDAC抑制剂。
• Multi-Functional Small Molecules as Anti-Proliferative Agents
  申请人：Cai Xiong

  公开号：US20080221132A1

  公开（公告）日：2008-09-11

  The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

  本发明涉及一种新型选择性抑制多种细胞或分子靶点的组合物、方法和应用。更具体地说，本发明涉及多功能小分子，其中一种功能能够抑制组蛋白去乙酰化酶（HDAC），另一种功能能够抑制与异常细胞增殖、分化或存活有关的不同细胞或分子途径。
• [EN] MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS<br/>[FR] PETITES MOLÉCULES MULTIFONCTIONNELLES SERVANT D'AGENTS ANTI-PROLIFÉRATIFS
  申请人：CURIS INC

  公开号：WO2008033747A3

  公开（公告）日：2008-12-04
• MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS
  申请人：Curis, Inc.

  公开号：EP2061772A2

  公开（公告）日：2009-05-27
• US8604044B2
  申请人：——

  公开号：US8604044B2

  公开（公告）日：2013-12-10