RESUMEN
1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI.
Asunto(s)
Antibacterianos/farmacología , Imidazoles/farmacología , Oxidorreductasas/antagonistas & inhibidores , Antibacterianos/síntesis química , Antibacterianos/química , Enoil-ACP Reductasa (NADH) , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli , Acido Graso Sintasa Tipo II , Imidazoles/síntesis química , Imidazoles/química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacosRESUMEN
In a 3-oxo-1,4-benzodiazepine-2-acetic acid series of vitronectin receptor (alpha v beta 3) antagonists containing a benzimidazole as a novel arginine mimetic, we examined the effects of benzimidazole modifications and amide substitutions on both activity and pharmacokinetics.
Asunto(s)
Bencimidazoles/farmacología , Benzodiazepinas/farmacología , Receptores de Vitronectina/antagonistas & inhibidores , Arginina , Relación Estructura-ActividadRESUMEN
In the 3-oxo-1,4-benzodiazepine-2-acetic acid series of vitronectin receptor (alpha v beta 3) antagonists, a compound containing an imidazopyridine arginine mimetic was discovered which had sufficient potency and i.v. pharmacokinetics for demonstration of efficacy in a rat restenosis model.