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Design, synthesis, and evaluation of 2 beta-alkenyl penam sulfone acids as inhibitors of beta-lactamases.

Abstract：

:A general method for synthesis of 2 beta-alkenyl penam sulfones has been developed. The new compounds inhibited most of the common types of beta-lactamase. The level of activity depended very strongly on the nature of the substituent in the 2 beta-alkenyl group. The inhibited species formed with the beta-lactamase from Citrobacter freundii 1205 was sufficiently stable for X-ray crystallographic studies. These, together with UV absorption spectroscopy and studies of chemical degradation, suggested a novel reaction mechanism for the new inhibitors that might account for their broad spectrum of action. The (Z)-2 beta-acrylonitrile penam sulfone Ro 48-1220 was the most active inhibitor from this class of compound. The inhibitor enhanced the action of, for example, ceftriaxone against a broad selection of organisms producing beta-lactamases. The organisms included strains of Enterobacteriaceae that produce cephalosporinases, which is an exceptional activity for penam sulfones.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Richter HG,Angehrn P,Hubschwerlen C,Kania M,Page MG,Specklin JL,Winkler FK

doi

10.1021/jm9601967

subject

Has Abstract

pub_date

1996-09-13 00:00:00

pages

3712-22

issue

19

eissn

0022-2623

issn

1520-4804

pii

jm9601967

journal_volume

39

pub_type

杂志文章

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