1. Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI): pyridodiazepine amines
- Author
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Alexander Satz, Lawrence Macpherson, Gregory S. Basarab, Bolin Geng, Ekundayo Osimboni, Pamela Hill, Charles J. Eyermann, Janelle Comita-Prevoir, Madhusudhan Reddy Gowravaram, George B. Mullen, Tomas Lundqvist, Marshall Morningstar, Andrew Kiely, and James T. Loch
- Subjects
Chemistry, Pharmaceutical ,Clinical Biochemistry ,Molecular Conformation ,Pharmaceutical Science ,Plasma protein binding ,Muri ,Biochemistry ,Binding, Competitive ,Helicobacter Infections ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,Non-competitive inhibition ,Anti-Infective Agents ,Drug Discovery ,Structure–activity relationship ,Glutamate racemase ,Animals ,Humans ,Amines ,Molecular Biology ,Antibacterial agent ,Amino Acid Isomerases ,chemistry.chemical_classification ,biology ,Helicobacter pylori ,Organic Chemistry ,Enzyme ,chemistry ,Enzyme inhibitor ,Drug Design ,biology.protein ,Molecular Medicine ,Dimerization - 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.
- Published
- 2008