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.
Renslo
Adam R
AR
Pfizer Global Research and Development, 34790 Ardentech Ct., Fremont, CA 94555, USA. adam.renslo@ucsf.edu
Atuegbu
Andy
A
Herradura
Prudencio
P
Jaishankar
Priyadarshini
P
Ji
Mingzhe
M
Leach
Karen L
KL
Huband
Michael D
MD
Dermyer
Michael R
MR
Wu
Luping
L
Vara Prasad
J V N
JV
Gordeev
Mikhail F
MF
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