Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.
Bioorg Med Chem Lett
; 21(11): 3411-6, 2011 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-21515049
ABSTRACT
A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration, consistent with elevated and prolonged exposure in the tumor.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Biomarcadores
/
Desenho de Fármacos
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Proteínas de Choque Térmico HSP90
/
Lactamas Macrocíclicas
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Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos