ethyl 4-hydroxy-3,5-bis((2-(benzo[d][1,3]dioxol-5-carbonyl)hydrazinylidene)methyl)benzoate | 1246354-34-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-hydroxy-3,5-bis((2-(benzo[d][1,3]dioxol-5-carbonyl)hydrazinylidene)methyl)benzoate
• CAS: 1246354-34-6
• 化学式: C₂₇H₂₂N₄O₉
• 分子量: 546.493
• InChiKey: FJZMUYWQVYIRNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 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：
  0.15
• 拓扑面积：
  166.37
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  4-羟基-3,5-二甲基苯甲酸 在 chromium(VI) oxide 、 硫酸 、 乙酸酐 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 58.0h， 生成 ethyl 4-hydroxy-3,5-bis((2-(benzo[d][1,3]dioxol-5-carbonyl)hydrazinylidene)methyl)benzoate
  参考文献：
  名称：

  Discovery of Novel Small Molecule Inhibitors of Dengue Viral NS2B-NS3 Protease Using Virtual Screening and Scaffold Hopping

  摘要：

  By virtual screening, compound 1 was found to be active against NS2B-NS3 protease (IC50 = 13.12 +/- 1.03 mu M). Fourteen derivatives (22) of compound 1 were synthesized, leading to the discovery of four new inhibitors with biological activity. In order to expand the chemical diversity of the inhibitors, small-molecule-based scaffold hopping was performed on the basis of the common scaffold of compounds 1 and 22. Twenty-one new compounds (23, 24) containing quinoline (new scaffold) were designed and synthesized. Protease inhibition assays revealed that 12 compounds with the new scaffold are inhibitors of NS2B-NS3 protease. Taken together, 17 new compounds were discovered as NS2B-NS3 protease inhibitors with IC50 values of 7.46 +/- 1.15 to 48.59 +/- 3.46 mu M, and 8 compounds belonging to two different scaffolds are active to some extent against DENY based on luciferase reporter replicon-based assays. These novel chemical entities could serve as lead structures for discovering therapies against DENY.

  DOI：

  10.1021/jm300146f

文献信息

• Discovery of Novel Small Molecule Inhibitors of Dengue Viral NS2B-NS3 Protease Using Virtual Screening and Scaffold Hopping
  作者：Jing Deng、Ning Li、Hongchuan Liu、Zhili Zuo、Oi Wah Liew、Weijun Xu、Gang Chen、Xiankun Tong、Wei Tang、Jin Zhu、Jianping Zuo、Hualiang Jiang、Cai-Guang Yang、Jian Li、Weiliang Zhu

  DOI：10.1021/jm300146f

  日期：2012.7.26

  By virtual screening, compound 1 was found to be active against NS2B-NS3 protease (IC50 = 13.12 +/- 1.03 mu M). Fourteen derivatives (22) of compound 1 were synthesized, leading to the discovery of four new inhibitors with biological activity. In order to expand the chemical diversity of the inhibitors, small-molecule-based scaffold hopping was performed on the basis of the common scaffold of compounds 1 and 22. Twenty-one new compounds (23, 24) containing quinoline (new scaffold) were designed and synthesized. Protease inhibition assays revealed that 12 compounds with the new scaffold are inhibitors of NS2B-NS3 protease. Taken together, 17 new compounds were discovered as NS2B-NS3 protease inhibitors with IC50 values of 7.46 +/- 1.15 to 48.59 +/- 3.46 mu M, and 8 compounds belonging to two different scaffolds are active to some extent against DENY based on luciferase reporter replicon-based assays. These novel chemical entities could serve as lead structures for discovering therapies against DENY.