(E)-3-[3-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}phenyl]-N-hydroxyacrylamide hydrochloride | 1152131-97-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-[3-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}phenyl]-N-hydroxyacrylamide hydrochloride
• 英文别名: (E)-3-[3-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}phenyl]-N-hydroxyacrylamide hydrchloride
• CAS: 1152131-97-9
• 化学式: C₃₀H₂₂ClFN₄O₃*ClH
• 分子量: 577.442
• InChiKey: LTOZWICLEZRMGS-RRAJOLSVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.35
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  96.37
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  (E)-3-[3-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}phenyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide 在 盐酸 、 水 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以88%的产率得到(E)-3-[3-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}phenyl]-N-hydroxyacrylamide hydrochloride
  参考文献：
  名称：

  Novel Chimeric Histone Deacetylase Inhibitors: A Series of Lapatinib Hybrides as Potent Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and Histone Deacetylase Activity

  摘要：

  Reversible lysine-specific acetylation has been described as an important posttranslational modification, regulating chromatin structure and transcriptional activity in the case of core histone proteins. Histone deacetylases (HDAC) are considered as a promising target for anticancer drug development, with 2a as pan-HDAC inhibitor approved for cutanous T-cell lymphoma therapy and several other HDAC inhibitors currently in preclinical and clinical development. Protein kinases are a well-established target for cancer therapy with the EGFR/HER2 inhibitor 5 approved for treatment of advanced, HER2 positive breast cancer as a prominent example. In the present report, we present a novel strategy for cancer drug development by combination of EGFR/HER2 kinase and HDAC inhibitory activity in one molecule. By combining the structural features of 5 with an (E)-3-(aryl)-N-hydroxyacrylamide motif known from HDAC inhibitors like 1 or 3, we obtained selective inhibitors for both targets with potent cellular activity (target inhibition and cytotoxicity) of selected compounds 6a and 6c. By combining two distinct pharmacologically properties in one molecule, we postulate a broader activity spectrum and less likelihood of drug resistance in cancer patients.

  DOI：

  10.1021/jm100665z