title: Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI): pyridodiazepine amines.
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.
authors.affiliation: AstraZeneca R&D Boston, Infection Discovery, 35 Gatehouse Drive, Waltham, MA 02451, USA. bolin.geng@astrazeneca.com
authors.forename: Bolin
authors.initials: B
authors.lastname: Geng
authors.forename: Gregory
authors.initials: G
authors.lastname: Basarab
authors.forename: Janelle
authors.initials: J
authors.lastname: Comita-Prevoir
authors.forename: Madhusudhan
authors.initials: M
authors.lastname: Gowravaram
authors.forename: Pamela
authors.initials: P
authors.lastname: Hill
authors.forename: Andrew
authors.initials: A
authors.lastname: Kiely
authors.forename: James
authors.initials: J
authors.lastname: Loch
authors.forename: Lawrence
authors.initials: L
authors.lastname: MacPherson
authors.forename: Marshall
authors.initials: M
authors.lastname: Morningstar
authors.forename: George
authors.initials: G
authors.lastname: Mullen
authors.forename: Ekundayo
authors.initials: E
authors.lastname: Osimboni
authors.forename: Alexander
authors.initials: A
authors.lastname: Satz
authors.forename: Charles
authors.initials: C
authors.lastname: Eyermann
authors.forename: Tomas
authors.initials: T
authors.lastname: Lundqvist
mesh_terms: D000588:Amines / Q000737:chemistry*; D000591:Amino Acid Isomerases / Q000737:chemistry*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019281:Dimerization; D015195:Drug Design; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D000591:Amino Acid Isomerases; C062292:glutamate racemase