1.
Bioorg Med Chem Lett
; 20(17): 5039-43, 2010 Sep 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-20675133
RESUMO
SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1' pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound.
Assuntos
Inibidores de Metaloproteinases de Matriz , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Quelantes/química , Quelantes/farmacologia , Relação Estrutura-Atividade , Zinco/química
2.
Bioorg Med Chem Lett
; 19(18): 5321-4, 2009 Sep 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-19692239
RESUMO
Discovery and optimization of potency and selectivity of a non-Zn-chelating MMP-13 inhibitor with the aid of protein co-crystal structural information is reported. This inhibitor was observed to have a binding mode distinct from previously published MMP-13 inhibitors. Potency and selectivity were improved by extending the hit structure out from the active site into the S1' pocket.
