Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors

Title
Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors
Authors
서선희금교창김은경이주현신상철서영호정낙철김찬화
Keywords
Hsp90; Structure-based design; Cancer; Antiproliferative; Pyrrolo[2,3-d]pyrimidines
Issue Date
2017-01
Publisher
Bioorganic & medicinal chemistry letters
Citation
VOL 27, NO 2-241
Abstract
A novel series of heat shock protein 90 (Hsp90) inhibitors was identified by X-ray crystal analysis of complex structures at solvent-exposed exit pocket C. The 2-amino-pyrrolo[2,3-d]pyrimidine derivatives, 7-deazapurines substituted with a benzyl moiety at C5, showed potent Hsp90 inhibition and broad-spectrum antiproliferative activity against NCI-60 cancer cell lines. The most potent compound, 6a, inhibited Hsp90 with an IC50 of 36 nM and showed a submicromolar mean GI50 value against NCI-60 cell lines. The interaction of 6a at the ATP-binding pocket of Hsp90 was confirmed by X-ray crystallography and Western blot analysis.
URI
http://pubs.kist.re.kr/handle/201004/65265
ISSN
0960-894X
Appears in Collections:
KIST Publication > Article
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