N-(4-(2-(thiazolo[5,4-c]pyridin-2-yl)phenoxy)phenyl)acetamide

• 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: N-(4-(2-(thiazolo[5,4-c]pyridin-2-yl)phenoxy)phenyl)acetamide
• 英文别名: N-{4-[2-([1,3]thiazolo[5,4-C]pyridin-2-Yl)phenoxy]phenyl}acetamide；N-[4-[2-([1,3]thiazolo[5,4-c]pyridin-2-yl)phenoxy]phenyl]acetamide
• 化学式: C₂₀H₁₅N₃O₂S
• 分子量: 361.424
• InChiKey: OPOGWEXFOKBMCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(N,N-diisopropyldithiocarbamato)-4-(pivaloylamino)pyridine 在 盐酸 、 caesium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 4.5h， 生成 N-(4-(2-(thiazolo[5,4-c]pyridin-2-yl)phenoxy)phenyl)acetamide
  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.