The synthesis and evaluation of 6-alkylidene-2'beta-substituted penam sulfones as beta-lactamase inhibitors

J D Buynak; A S Rao; V R Doppalapudi; G Adam; P J Petersen; S D Nidamarthy

doi:10.1016/s0960-894x(99)00325-x

The synthesis and evaluation of 6-alkylidene-2'beta-substituted penam sulfones as beta-lactamase inhibitors

Bioorg Med Chem Lett. 1999 Jul 19;9(14):1997-2002. doi: 10.1016/s0960-894x(99)00325-x.

Authors

J D Buynak¹, A S Rao, V R Doppalapudi, G Adam, P J Petersen, S D Nidamarthy

Affiliation

¹ Department of Chemistry, Southern Methodist University, Dallas, TX 75275-0314, USA.

PMID: 10450969
DOI: 10.1016/s0960-894x(99)00325-x

Abstract

Penicillin sulfones, which structurally incorporate both a 6-position alkylidene substituent and a 2'beta substituent, have been synthesized and evaluated as inhibitors of class C and class A serine beta-lactamases. Incorporation of the 2'beta-substituent generally improves inhibitory activity. Substituents that improve transport across the bacterial cell membrane have also been incorporated.

MeSH terms

Cloxacillin / analogs & derivatives*
Cloxacillin / chemical synthesis*
Cloxacillin / chemistry*
Cloxacillin / pharmacology
Drug Therapy, Combination / pharmacology
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Inhibitory Concentration 50
Microbial Sensitivity Tests
Penicillin Resistance
Piperacillin / pharmacology
Structure-Activity Relationship
Sulfones / chemistry
beta-Lactamase Inhibitors*
beta-Lactamases

Substances

Enzyme Inhibitors
Sulfones
beta-Lactamase Inhibitors
beta-Lactamases
beta-lactamase TEM-1
Cloxacillin
Piperacillin