A distal methyl substituent attenuates mitochondrial protein synthesis inhibition in oxazolidinone antibacterials.
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.
Pfizer Global Research and Development, 34790 Ardentech Ct., Fremont, CA 94555, USA. adam.renslo@ucsf.edu
Adam R
AR
Renslo
Andy
A
Atuegbu
Prudencio
P
Herradura
Priyadarshini
P
Jaishankar
Mingzhe
M
Ji
Karen L
KL
Leach
Michael D
MD
Huband
Michael R
MR
Dermyer
Luping
L
Wu
J V N
JV
Vara Prasad
Mikhail F
MF
Gordeev
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000378:metabolism*; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D011500:Protein Synthesis Inhibitors