RESUMO
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.
Assuntos
Proteínas de Bactérias , Carbapenêmicos/síntese química , Bactérias Gram-Positivas/efeitos dos fármacos , Hexosiltransferases , Peptidil Transferases , Carbapenêmicos/química , Carbapenêmicos/farmacologia , Proteínas de Transporte/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , Muramilpentapeptídeo Carboxipeptidase/efeitos dos fármacos , Muramilpentapeptídeo Carboxipeptidase/metabolismo , Proteínas de Ligação às PenicilinasRESUMO
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.
