Discovery of 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7, 8-dihydro pteridin-6(5H)-ones as potent and selective Hsp90 inhibitors

A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7, 8-dihydro pteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 de...

Full description

Saved in:
Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 19; no. 10; pp. 2860 - 2864
Main Authors Li, Xiaoyuan, Shocron, Ellyn, Song, Aimin, Patel, Neela, Sun, Connie L
Format Journal Article
LanguageEnglish
Published 01.05.2009
Online AccessGet full text

Cover

More Information
Summary:A new series of compounds, 5-substituted 2-amino-4-chloro-8-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7, 8-dihydro pteridin-6(5H)-ones, have been designed and identified as potent and selective inhibitors of Hsp90. These compounds demonstrated nanomolar potency toward both Hsp90-regulated Her2 degradation and the growth of a panel of human tumor cell lines in cell-based assays. High selectivity of these compounds toward Hsp90 was evident given that they did not inhibit a panel of 34 kinases at 10 is a subset of M. The structure-activity relationship (SAR) of this series is reported here.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
content type line 23
ObjectType-Feature-2
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.03.074