期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 26, 期 11, 页码 2706-2712出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2016.04.002
关键词
Phosphatidylinositol 4-kinase; Purine; PI4K III beta; Antiviral agent; Hepatitis C virus
资金
- Czech Science Foundation
- Academy of Sciences of the Czech Republic [RVO: 61388963]
- Project NPU I from the Ministry of Education, Youth and Sports [LO 1302]
- Gilead Sciences Inc.
We report on an extensive structure-activity relationship study of novel PI4K III beta inhibitors. The purine derivative of the potent screening hit T-00127-HEV1 has served as a suitable starting point for a thorough investigation of positions 8 and 2. While position 8 of the purine scaffold can only bear a small substituent to maintain the inhibitory activity, position 2 is opened for extensive modification and can accommodate even substituted phenyl rings without the loss of PI4K III beta inhibitory activity. These empirical observations nicely correlate with the results of our docking study, which suggests that position 2 directs towards solution and can provide the necessary space for the interaction with remote residues of the enzyme, whereas the cavity around position 8 is strictly limited. The obtained compounds have also been subjected to antiviral screening against a panel of (+) ssRNA viruses. (C) 2016 Published by Elsevier Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据