N-((8-hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2).
Bioorg Med Chem Lett
; 18(24): 6454-7, 2008 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-18974001
ABSTRACT
N-((8-Hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared. Selected compounds 10, 14, 25, and 53 show sub-microM ADAMTS-5 potency and good selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP-13, and MMP-12. Compound 53 shows a good balance of potent ADAMTS-5 inhibition, moderate CYP3A4 inhibition and good rat liver microsome stability. This series of compounds represents progress towards selective ADAMTS-5 inhibitors as disease modifying osteoarthritis agents.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas ADAM
/
Acetamidas
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article