N-hydroxy-6-((3-(6-methoxyquinolin-8-yl)ureido)oxy)hexanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-hydroxy-6-((3-(6-methoxyquinolin-8-yl)ureido)oxy)hexanamide
• 英文别名: N-hydroxy-6-[(6-methoxyquinolin-8-yl)carbamoylamino]oxyhexanamide
• 化学式: C₁₇H₂₂N₄O₅
• 分子量: 362.385
• InChiKey: CLGDSTJRIXLINL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(benzyloxy)-6-bromohexaneamide 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 甲基肼 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， -10.0~70.0 ℃ 、100.0 kPa 条件下， 反应 13.0h， 生成 N-hydroxy-6-((3-(6-methoxyquinolin-8-yl)ureido)oxy)hexanamide
  参考文献：
  名称：

  Alkoxyurea-Based Histone Deacetylase Inhibitors Increase Cisplatin Potency in Chemoresistant Cancer Cell Lines

  摘要：

  The synthesis and biological evaluation of potent hydroxamate-based dual HDAC1/6 inhibitors with modest HDAC6 preference and a novel alkoxyurea connecting unit linker region are described. The biological studies included the evaluation of antiproliferative effects and HDAC inhibitory activity in the human ovarian cancer cell line A2780, the human squamous carcinoma cell line Cal27, and their cisplatin resistant sublines A2780CisR and Cal27CisR. The three most potent compounds 1gi showed IC50 values in the low mu M and sub-mu M range. 1gi revealed low nM IC50 values for HDAC6 with up to 15-fold preference over HDAC1, >3500-fold selectivity over HDAC4, and >100-fold selectivity over HDAC8. Furthermore, their ability to enhance cisplatin sensitivity was analyzed in Cal27 and Cal27CisR cells. Notably, a 48 h preincubation of 1-gi significantly enhanced the antiproliferative effects of cisplatin in Cal27 and Cal27CisR. 1-gi interacted synergistically with cisplatin. These effects were more pronounced for the cisplatin resistant subline Cal27CisR.

  DOI：

  10.1021/acs.jmedchem.6b01538

文献信息

• Alkoxyurea-Based Histone Deacetylase Inhibitors Increase Cisplatin Potency in Chemoresistant Cancer Cell Lines
  作者：Katharina Stenzel、Alexandra Hamacher、Finn K. Hansen、Christoph G. W. Gertzen、Johanna Senger、Viktoria Marquardt、Linda Marek、Martin Marek、Christophe Romier、Marc Remke、Manfred Jung、Holger Gohlke、Matthias U. Kassack、Thomas Kurz

  DOI：10.1021/acs.jmedchem.6b01538

  日期：2017.7.13

  The synthesis and biological evaluation of potent hydroxamate-based dual HDAC1/6 inhibitors with modest HDAC6 preference and a novel alkoxyurea connecting unit linker region are described. The biological studies included the evaluation of antiproliferative effects and HDAC inhibitory activity in the human ovarian cancer cell line A2780, the human squamous carcinoma cell line Cal27, and their cisplatin resistant sublines A2780CisR and Cal27CisR. The three most potent compounds 1gi showed IC50 values in the low mu M and sub-mu M range. 1gi revealed low nM IC50 values for HDAC6 with up to 15-fold preference over HDAC1, >3500-fold selectivity over HDAC4, and >100-fold selectivity over HDAC8. Furthermore, their ability to enhance cisplatin sensitivity was analyzed in Cal27 and Cal27CisR cells. Notably, a 48 h preincubation of 1-gi significantly enhanced the antiproliferative effects of cisplatin in Cal27 and Cal27CisR. 1-gi interacted synergistically with cisplatin. These effects were more pronounced for the cisplatin resistant subline Cal27CisR.