N-hydroxy-4-(2-((1-(naphthalen-2-ylamino)isoquinolin-7-yl)amino)-2-oxoethoxy)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N-hydroxy-4-(2-((1-(naphthalen-2-ylamino)isoquinolin-7-yl)amino)-2-oxoethoxy)benzamide
• 英文别名: N-hydroxy-4-[2-[[1-(naphthalen-2-ylamino)isoquinolin-7-yl]amino]-2-oxoethoxy]benzamide
• 化学式: C₂₈H₂₂N₄O₄
• 分子量: 478.507
• InChiKey: BNIFJWDIXPWDLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲基-5-硝基苯甲酸甲酯 在 盐酸 、 羟胺 、 铁粉 、 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 12.0h， 生成 N-hydroxy-4-(2-((1-(naphthalen-2-ylamino)isoquinolin-7-yl)amino)-2-oxoethoxy)benzamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors

  摘要：

  The design, synthesis and biological evaluation of a series of isoquinoline-based hydroxamic acid compounds as novel HDACs inhibitors were reported herein. A detailed SAR study showed most of the compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10c against HDAC1, 3, 6 were 4.17 +/- 0.11 nM, 4.00 +/- 0.10 nM, 3.77 +/- 0.07 nM, respectively. Most of the compounds showed great anti-proliferative activities against RPMI 8226, HCT 116 and Hep G2 cells. The IC50 values of compounds 10a-h against RPMI 8226 cancer cell proliferation were all below 1 mu M. HCT 116 cell was sensitive to the compounds 10a, 10f-g and 18a with the IC50 values <0.3 mu M. The active compounds 10a-d did not show inhibitory activity against hERG channel. All these evidence indicated these compounds had great potential as HDACs inhibitors for the further development. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.071

文献信息

• Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors
  作者：Wei Yang、Lixuan Li、Yulan Wang、Xiaowei Wu、Tingting Li、Nan Yang、Mingbo Su、Li Sheng、Mingyue Zheng、Yi Zang、Jia Li、Hong Liu

  DOI：10.1016/j.bmc.2015.06.071

  日期：2015.9

  The design, synthesis and biological evaluation of a series of isoquinoline-based hydroxamic acid compounds as novel HDACs inhibitors were reported herein. A detailed SAR study showed most of the compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10c against HDAC1, 3, 6 were 4.17 +/- 0.11 nM, 4.00 +/- 0.10 nM, 3.77 +/- 0.07 nM, respectively. Most of the compounds showed great anti-proliferative activities against RPMI 8226, HCT 116 and Hep G2 cells. The IC50 values of compounds 10a-h against RPMI 8226 cancer cell proliferation were all below 1 mu M. HCT 116 cell was sensitive to the compounds 10a, 10f-g and 18a with the IC50 values <0.3 mu M. The active compounds 10a-d did not show inhibitory activity against hERG channel. All these evidence indicated these compounds had great potential as HDACs inhibitors for the further development. (C) 2015 Elsevier Ltd. All rights reserved.