Virtual Screening to Successfully Identify Novel Janus Kinase 3 Inhibitors: A Sequential Focused Screening Approach

被引：14

作者：

Chen, Xin ^{[1
]}

Wilson, Lawrence J. ^{[2
]}

Malaviya, Ravi ^{[3
]}

Argentieri, Rochelle L. ^{[3
]}

Yang, Shyh-Ming ^{[2
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Comp Assisted Drug Discovery, Raritan, NJ 08869 USA

[2] Johnson & Johnson Pharmaceut Res & Dev LLC, Highthroughput Chem, Raritan, NJ 08869 USA

[3] Johnson & Johnson Pharmaceut Res & Dev LLC, Inflammat Therapeut, Raritan, NJ 08869 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 21期

关键词：

D O I：

10.1021/jm800662z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In an effort to identify novel Janus kinase 3 inhibitors, a sequential focused screening approach was adopted to search our in-house chemical database. By biologically testing only 79 selected compounds, we successfully identified 19 compounds showing IC50 < 20 mu M, with four of them in the nanomolar range. Particularly, a 3,5-disubstituted pyrazolo[4,3-d]pyrimidine scaffold emerged as a promising candidate for further lead optimization. With the advantages of efficiency and flexibility, this approach may be utilized to identify leads for other therapeutic targets.

引用

页码：7015 / 7019

页数：5

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