Structure-activity relationships of C-17-substituted estratriene-3-O-sulfamates as anticancer agents.
J Med Chem
; 54(13): 4863-79, 2011 Jul 14.
Article
em En
| MEDLINE
| ID: mdl-21604672
ABSTRACT
The synthesis and antiproliferative activities of analogues of 2-substituted estradiol-3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent confirm that an H-bond acceptor is essential for high activity; its optimal linkage to C-17 and the local environment in which it resides are defined. In the non-sulfamoylated series 17ß-acyl substitution delivers 48b, the most potent compound identified to date. In the sulfamate series a number of permutations of linker and H-bond acceptor deliver excellent activity, with 55, 61, 65, 49a, and 49b proving especially promising. The in vivo potential of these compounds was explored in the NCI hollow fiber assay and also in a mouse Matrigel model of antiangiogenesis in which 49 and 55 show significant inhibitory activity.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ácidos Sulfônicos
/
Estradiol
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido