A distal methyl substituent attenuates mitochondrial protein synthesis inhibition in oxazolidinone antibacterials

Adam R Renslo; Andy Atuegbu; Prudencio Herradura; Priyadarshini Jaishankar; Mingzhe Ji; Karen L Leach; Michael D Huband; Michael R Dermyer; Luping Wu; J V N Vara Prasad; Mikhail F Gordeev

doi:10.1016/j.bmcl.2007.07.022

A distal methyl substituent attenuates mitochondrial protein synthesis inhibition in oxazolidinone antibacterials

Bioorg Med Chem Lett. 2007 Sep 15;17(18):5036-40. doi: 10.1016/j.bmcl.2007.07.022. Epub 2007 Jul 13.

Authors

Adam R Renslo¹, Andy Atuegbu, Prudencio Herradura, Priyadarshini Jaishankar, Mingzhe Ji, Karen L Leach, Michael D Huband, Michael R Dermyer, Luping Wu, J V N Vara Prasad, Mikhail F Gordeev

Affiliation

¹ Pfizer Global Research and Development, 34790 Ardentech Ct., Fremont, CA 94555, USA. adam.renslo@ucsf.edu

PMID: 17681758
DOI: 10.1016/j.bmcl.2007.07.022

Abstract

Oxazolidinone analogs bearing substituted piperidine or azetidine C-rings are described. Analogs with a methyl group at the 3-position of the azetidine ring or the 4-position of the piperidine ring exhibited reduced mitochondrial protein synthesis inhibition while retaining good antibacterial potency.

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Enterococcus faecalis / drug effects
Microbial Sensitivity Tests
Mitochondria / metabolism*
Oxazolidinones / chemistry
Oxazolidinones / pharmacology*
Protein Biosynthesis / drug effects*
Protein Synthesis Inhibitors / chemistry
Protein Synthesis Inhibitors / pharmacology*
Staphylococcus aureus / drug effects
Streptococcus pneumoniae / drug effects

Substances

Anti-Bacterial Agents
Oxazolidinones
Protein Synthesis Inhibitors