title: Side chain SAR of bicyclic beta-lactamase inhibitors (BLIs). 1. Discovery of a class C BLI for combination with imipinem.
abstract: Bridged monobactam beta-lactamase inhibitors were prepared and evaluated as potential partners for combination with imipenem to overcome class C beta-lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective in both in vitro and in vivo assays and was selected for preclinical development.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Labs, Rahway, NJ 07065, USA. tim_blizzard@merck.com
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Blizzard
authors.forename: Helen
authors.initials: H
authors.lastname: Chen
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: Amy
authors.initials: A
authors.lastname: Ogawa
authors.forename: Susan
authors.initials: S
authors.lastname: Raghoobar
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Painter
authors.forename: Nichelle
authors.initials: N
authors.lastname: Hairston
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Andrew
authors.initials: A
authors.lastname: Misura
authors.forename: Tom
authors.initials: T
authors.lastname: Felcetto
authors.forename: Paula
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: Nandini
authors.initials: N
authors.lastname: Sharma
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Sookhee
authors.initials: S
authors.lastname: Ha
authors.forename: Emily
authors.initials: E
authors.lastname: Hickey
authors.forename: Jeff
authors.initials: J
authors.lastname: Hermes
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology; D015780:Carbapenems / Q000737:chemistry* / Q000494:pharmacology; D004338:Drug Combinations; D055808:Drug Discovery / Q000379:methods*; D015378:Imipenem / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000201:enzymology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D018440:beta-Lactam Resistance / Q000187:drug effects / Q000502:physiology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D015780:Carbapenems; D004338:Drug Combinations; D065093:beta-Lactamase Inhibitors; D015378:Imipenem; D001618:beta-Lactamases