Abstract
The synthesis and antibacterial activity of heterocyclic methylsulfone hydroxamates is presented. Compounds in this series are potent inhibitors of the LpxC enzyme, a key enzyme involved in the production of lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria. SAR evaluation of compounds in this series revealed analogs with potent antibacterial activity against challenging Gram-negative species such as Pseudomonas aeruginosa and Klebsiella pneumoniae.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
-
Amidohydrolases / antagonists & inhibitors*
-
Amidohydrolases / metabolism
-
Anti-Bacterial Agents / chemical synthesis
-
Anti-Bacterial Agents / chemistry*
-
Anti-Bacterial Agents / pharmacology
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology
-
Gram-Negative Bacteria / drug effects*
-
Heterocyclic Compounds / chemistry
-
Hydroxamic Acids / chemical synthesis
-
Hydroxamic Acids / chemistry*
-
Hydroxamic Acids / pharmacology
-
Klebsiella pneumoniae / drug effects
-
Microbial Sensitivity Tests
-
Pseudomonas aeruginosa / drug effects
-
Pseudomonas aeruginosa / enzymology
-
Structure-Activity Relationship
-
Sulfones / chemistry
Substances
-
Anti-Bacterial Agents
-
Enzyme Inhibitors
-
Heterocyclic Compounds
-
Hydroxamic Acids
-
Sulfones
-
Amidohydrolases
-
LpxC deacetylase, Pseudomonas