The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as beta-lactamase inhibitors

J D Buynak; V R Doppalapudi; G Adam

doi:10.1016/s0960-894x(00)00098-6

The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as beta-lactamase inhibitors

Bioorg Med Chem Lett. 2000 May 1;10(9):853-7. doi: 10.1016/s0960-894x(00)00098-6.

Authors

J D Buynak¹, V R Doppalapudi, G Adam

Affiliation

¹ Department of Chemistry, Southern Methodist University, Dallas, TX 75275-0314, USA. jbuynak@mail.smu.edu

PMID: 10853646
DOI: 10.1016/s0960-894x(00)00098-6

Abstract

A series of 3-substituted-7-(alkylidene)cephaloporin sulfones were prepared and evaluated as inhibitors of representative class A and class C serine beta-lactamase. Appropriate substituents resulted in a 1000-fold improvement in the inhibition of the class A enzymes and a simultaneous 20-fold improvement in the inhibition of class C. These new compounds have achieved the goal of creating broad scale inhibitors in the cephalosporin series.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkenes / chemical synthesis*
Alkenes / pharmacology
Cephalosporins / chemical synthesis*
Cephalosporins / pharmacology
Enterobacter cloacae / drug effects
Enterobacter cloacae / enzymology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Staphylococcus aureus / drug effects
Staphylococcus aureus / enzymology
Structure-Activity Relationship
beta-Lactamase Inhibitors*
beta-Lactamases

Substances

Alkenes
Cephalosporins
Enzyme Inhibitors
beta-Lactamase Inhibitors
beta-lactamase PC1
beta-Lactamases
beta-lactamase TEM-1