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
en 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfonas
/
Inhibidores Enzimáticos
/
Inhibidores de la Metaloproteinasa de la Matriz
/
Amidas
/
Compuestos Heterocíclicos
/
Ácidos Hidroxámicos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos