title: Novel antibacterial class: a series of tetracyclic derivatives.
abstract: We describe the synthesis and antibacterial activity of a series of tetracyclic naphthyridones. The members of this series act primarily via inhibition of bacterial translation and belong to the class of novel ribosome inhibitors (NRIs). In this paper we explore the structure-activity relationships (SAR) of these compounds to measure their ability both to inhibit bacterial translation and also to inhibit the growth of bacterial cells in culture. The most active of these compounds inhibit Streptococcus pneumoniae translation at concentrations of <5 microM and have minimum inhibitory concentrations (MICs) of <8 microg/mL against clinically relevant strains of bacteria.
authors.affiliation: Infectious Diseases Research, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064-6217, USA. Mira.Hinman@abbott.com
authors.forename: Mira M
authors.initials: MM
authors.lastname: Hinman
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Rosenberg
authors.forename: Darlene
authors.initials: D
authors.lastname: Balli
authors.forename: Candace
authors.initials: C
authors.lastname: Black-Schaefer
authors.forename: Linda E
authors.initials: LE
authors.lastname: Chovan
authors.forename: Douglas
authors.initials: D
authors.lastname: Kalvin
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Merta
authors.forename: Angela M
authors.initials: AM
authors.lastname: Nilius
authors.forename: Steve D
authors.initials: SD
authors.lastname: Pratt
authors.forename: Niru B
authors.initials: NB
authors.lastname: Soni
authors.forename: Frank L
authors.initials: FL
authors.lastname: Wagenaar
authors.forename: Moshe
authors.initials: M
authors.lastname: Weitzberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Wagner
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Beutel
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D009287:Naphthyridines