Synthesis and evaluation of 3-(carboxymethylidene)- and 3-(carboxymethyl)penicillinates as inhibitors of beta-lactamase

J Org Chem. 2005 May 27;70(11):4510-3. doi: 10.1021/jo050004s.

Abstract

Penicillin-resistant bacteria can often be treated through the co-administration of an antibiotic and a beta-lactamase inhibitor. Current inhibitors target only class A beta-lactamases. We report two new series of C3-modified penicillin sulfones, having either a simple methylene group (i.e., a homologue) or exocyclic unsaturation between the thiazolidine ring and the C3 carboxylate. The homologue has 10-fold better activity against a class C beta-lactamase than does sulbactam itself. By contrast, the exocyclic C3 unsaturated compounds are less active.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / enzymology
  • Combinatorial Chemistry Techniques*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Penicillin Resistance
  • Penicillins / chemical synthesis*
  • Penicillins / pharmacology*
  • Structure-Activity Relationship
  • beta-Lactamase Inhibitors*

Substances

  • Enzyme Inhibitors
  • Penicillins
  • beta-Lactamase Inhibitors