Novel antibacterial class: a series of tetracyclic derivatives.
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.
Hinman
Mira M
MM
Infectious Diseases Research, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064-6217, USA. Mira.Hinman@abbott.com
Rosenberg
Teresa A
TA
Balli
Darlene
D
Black-Schaefer
Candace
C
Chovan
Linda E
LE
Kalvin
Douglas
D
Merta
Philip J
PJ
Nilius
Angela M
AM
Pratt
Steve D
SD
Soni
Niru B
NB
Wagenaar
Frank L
FL
Weitzberg
Moshe
M
Wagner
Rolf
R
Beutel
Bruce A
BA
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
D000900:Anti-Bacterial Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D009287:Naphthyridines