MOLECULAR MODELING OF γ-LACTAM ANALOGUES OF β-LACTAM ANTIBACTERIAL AGENTS: SYNTHESIS AND BIOLOGICAL EVALUATION OF SELECTED PENEM AND CARBAPENEM ANALOGUES

Article abstract of DOI:10.1016/S0040-4020(01)80055-7

Computational chemistry made possible the prediction of the three-dimensional structures of γ-lactam analogues of penems and carbapenems before the analogues were made.Molecular superpositioning showed that these novel structures with a 7β-acylamino side-chain present the pharmacophoric groups in close spatial similarity to the groups in biologically active cephalosporin and penicillin antibiotics.This suggest that 8-oxo-7-acylamino-1-azabicyclo<3.3.0>oct-2-ene-2-carboxylates and 4-thia-analogues can be accommodated in the same active sites of essential bacterical penicillin-binding proteins where cephalosporins and penicillins are recognized.The syntheses of these compounds are reported.The γ-lactams exhibit low, but detectable levels of antibacterial activity and suggest promise that substantial activity can be achieved with other γ-lactams.