RESUMEN
A series of 6-(substituted oxyethyl)penem esters having the (5S) stereochemistry which are potent inhibitors of Escherichia coli leader peptidase is described. Structure-activity relationships are discussed.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Escherichia coli/enzimología , Lactamas/química , Lactamas/farmacología , Proteínas de la Membrana , Serina Endopeptidasas/efectos de los fármacos , Inhibidores Enzimáticos/síntesis química , Lactamas/síntesis química , Relación Estructura-ActividadRESUMEN
The synthesis and antibacterial activity of 7 beta-[D-2-(aryl)-2-[(4-ethyl-2,3-dioxopiperazin-1-yl) carbonylamino] acetamido]-7 alpha-formamidocephalosporins with various substituents at the C-3 position of the cephalosporin nucleus is described. Inhibition of Gram-positive and Gram-negative bacteria including beta-lactamase producing strains was observed with phenyl as the aryl residue. The 3,4-dihydroxyphenyl group further enhanced the activity against Gram-negative organisms; in this series, the 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl] and 3-[(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl] analogues (2 and 12b) exhibited exceptional activity against Gram-negative bacteria, including Pseudomonas aeruginosa.