title: Side chain SAR of bicyclic β-lactamase inhibitors (BLIs). 2. N-Alkylated and open chain analogs of MK-8712.
abstract: The bridged monobactam β-lactamase inhibitor MK-8712 (1) effectively inhibits class C β-lactamases. Side chain N-alkylated and ring-opened analogs of 1 were prepared and evaluated for combination with imipenem to overcome class C β-lactamase mediated resistance. Although some analogs were more potent inhibitors of AmpC, none exhibited better synergy with imipenem than 1.
authors.affiliation: Departments of Medicinal Chemistry, Merck Research Labs, Rahway, NJ 07065, USA. helen_chen@merck.com
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Blizzard
authors.forename: Seongkon
authors.initials: S
authors.lastname: Kim
authors.forename: Jane
authors.initials: J
authors.lastname: Wu
authors.forename: Katherine
authors.initials: K
authors.lastname: Young
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Park
authors.forename: Aimie M
authors.initials: AM
authors.lastname: Ogawa
authors.forename: Susan
authors.initials: S
authors.lastname: Raghoobar
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Painter
authors.forename: Doug
authors.initials: D
authors.lastname: Wisniewski
authors.forename: Nichelle
authors.initials: N
authors.lastname: Hairston
authors.forename: Paula
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: Nandini
authors.initials: N
authors.lastname: Sharma
authors.forename: Giovanna
authors.initials: G
authors.lastname: Scapin
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Jeff
authors.initials: J
authors.lastname: Hermes
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000138:chemical synthesis* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; C561926:MK 8712; D008997:Monobactams; D065093:beta-Lactamase Inhibitors; D015378:Imipenem; D001618:beta-Lactamases