6-(2,6-dimethoxyphenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-(2,6-dimethoxyphenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
• 英文别名: 6-(2,6-Dimethoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole；6-(2,6-dimethoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
• 化学式: C₁₁H₁₀N₄O₂S
• 分子量: 262.292
• InChiKey: AFOFVENDZCJNEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  89.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,6-二甲氧基苯甲酸 、 4-氨基-3-巯基-4H-1,2,4-三唑 在 三氯氧磷 作用下， 以64.2%的产率得到6-(2,6-dimethoxyphenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
  参考文献：
  名称：

  Fragment-Based Discovery of Dual JC Virus and BK Virus Helicase Inhibitors

  摘要：

  There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 mu M for the early 6-(2-methoxyphenyl) - and the 6-(2-ethoxypheny1)- [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazole hits la and 1b to 0.6 mu M for triazolopyridine 12i. In addition, we were able to demonstrate measurable antiviral activity in Vero cells for our thiazolopyridine series in the absence of marked cytotoxicity, thus confirming the usefulness of this approach.

  DOI：

  10.1021/acs.jmedchem.6b00486

文献信息

• Fragment-Based Discovery of Dual JC Virus and BK Virus Helicase Inhibitors
  作者：Dominique Bonafoux、Suganthini Nanthakumar、Upul K. Bandarage、Christine Memmott、Derek Lowe、Alex M. Aronov、Govinda Rao Bhisetti、Kenneth C. Bonanno、Joyce Coll、Joshua Leeman、Christopher A. Lepre、Fan Lu、Emanuele Perola、Rene Rijnbrand、William P. Taylor、Dean Wilson、Yi Zhou、Jacque Zwahlen、Ernst ter Haar

  DOI：10.1021/acs.jmedchem.6b00486

  日期：2016.8.11

  There are currently no treatments for life-threatening infections caused by human polyomaviruses JCV and BKV. We therefore report herein the first crystal structure of the hexameric helicase of JCV large T antigen (apo) and its use to drive the structure-based design of dual JCV and BKV ATP-competitive inhibitors. The crystal structures obtained by soaking our early inhibitors into the JCV helicase allowed us to rapidly improve the biochemical activity of our inhibitors from 18 mu M for the early 6-(2-methoxyphenyl) - and the 6-(2-ethoxypheny1)- [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazole hits la and 1b to 0.6 mu M for triazolopyridine 12i. In addition, we were able to demonstrate measurable antiviral activity in Vero cells for our thiazolopyridine series in the absence of marked cytotoxicity, thus confirming the usefulness of this approach.