MMP-13 selective α-sulfone hydroxamates: a survey of P1' heterocyclic amide isosteres.
Bioorg Med Chem Lett
; 21(10): 2820-2, 2011 May 15.
Article
em En
| MEDLINE
| ID: mdl-21507637
ABSTRACT
Seeking compounds preferentially potent and selective for MMP-13, we reported in the preceding Letter on a series of hydroxamic acids with a flexible benzamide tail groups.(1a) Here, we replace the amide moiety with non-hydrolyzable heterocycles in an effort to improve half-life. We identify a hydroxamate tetrazole 4e that spares MMP-1 and -14, shows >400-fold selectivity versus MMP-8 and >600-fold selectivity versus MMP-2, and has a 4.8 h half-life in rats. X-ray data (1.9 Å) for tetrazole 4c is presented.
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Base de dados:
MEDLINE
Assunto principal:
Sulfonas
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Inibidores Enzimáticos
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Inibidores de Metaloproteinases de Matriz
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Amidas
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Compostos Heterocíclicos
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Ácidos Hidroxâmicos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article