RESUMEN
A series of 1beta-methyl carbapenems substituted at the 2-position with lipophilic, acyclic and cyclic (sulfonamido)methyl groups was prepared and evaluated for activity against resistant gram-positive bacteria. From these studies, the 1,8-naphthosultamyl group emerged as a novel, PBP2a-binding, anti-MRSA pharmacophore worthy of further exploration.
Asunto(s)
Proteínas Bacterianas , Carbapenémicos/síntesis química , Bacterias Grampositivas/efectos de los fármacos , Hexosiltransferasas , Peptidil Transferasas , Carbapenémicos/química , Carbapenémicos/farmacología , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/metabolismo , Farmacorresistencia Microbiana , Pruebas de Sensibilidad Microbiana , Muramoilpentapéptido Carboxipeptidasa/efectos de los fármacos , Muramoilpentapéptido Carboxipeptidasa/metabolismo , Proteínas de Unión a las PenicilinasRESUMEN
A series of 1beta-methyl-2-(naphthosultamyl)methyl-carbapenems bearing dicationic groups on the naphthosultamyl moiety was prepared and evaluated for activity against resistant gram-positive bacteria. Based on a combination of excellent in vitro antibacterial activity, acceptable mouse acute toxicity, and a desirable fragmentation pattern on beta-lactam ring opening, the analog 2g (L-786,392) was selected for extended evaluation.
