Abstract
An SAR study of an HTS screening hit generated a series of pyridodiazepine amines as potent inhibitors of Helicobacter pylori glutamate racemase (MurI) showing highly selective anti-H. pylori activity, marked improved solubility, and reduced plasma protein binding. X-ray co-crystal E-I structures were obtained. These uncompetitive inhibitors bind at the MurI dimer interface.
MeSH terms
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Amines / chemistry*
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Amino Acid Isomerases / chemistry*
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Animals
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / pharmacology
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Binding, Competitive
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Chemistry, Pharmaceutical / methods*
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Dimerization
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Drug Design
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Helicobacter Infections / drug therapy*
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Helicobacter pylori / enzymology*
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Humans
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Inhibitory Concentration 50
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Mice
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Molecular Conformation
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Structure-Activity Relationship
Substances
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Amines
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Anti-Infective Agents
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Amino Acid Isomerases
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glutamate racemase