title: Antibacterial oxazolidinones possessing a novel C-5 side chain. (5R)-trans-3-[3-Fluoro-4- (1-oxotetrahydrothiopyran-4-yl)phenyl]-2- oxooxazolidine-5-carboxylic acid amide (PF-00422602), a new lead compound.
abstract: Oxazolidinones possessing a C-5 carboxamide functionality (reverse amides) represent a new series of compounds that block bacterial protein synthesis. These reverse amides also exhibited less potency against monoamine oxidase (MAO) enzymes and thus possess less potential for the side effects associated with MAO inhibition. The title compound (14) showed reduced in vivo myelotoxicity compared to linezolid in a 14-day safety study in rats, potent in vivo efficacy in murine systemic infection models, and excellent pharmacokinetic properties.
authors.affiliation: Michigan Laboratories, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
authors.forename: Toni-Jo
authors.initials: TJ
authors.lastname: Poel
authors.forename: Richard C
authors.initials: RC
authors.lastname: Thomas
authors.forename: Wade J
authors.initials: WJ
authors.lastname: Adams
authors.forename: Paul A
authors.initials: PA
authors.lastname: Aristoff
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barbachyn
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Boyer
authors.forename: Joan
authors.initials: J
authors.lastname: Brieland
authors.forename: Roger
authors.initials: R
authors.lastname: Brideau
authors.forename: Joanne
authors.initials: J
authors.lastname: Brodfuehrer
authors.forename: Alan P
authors.initials: AP
authors.lastname: Brown
authors.forename: Allison L
authors.initials: AL
authors.lastname: Choy
authors.forename: Michael
authors.initials: M
authors.lastname: Dermyer
authors.forename: Michael
authors.initials: M
authors.lastname: Dority
authors.forename: Charles W
authors.initials: CW
authors.lastname: Ford
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gadwood
authors.forename: Debra
authors.initials: D
authors.lastname: Hanna
authors.forename: Cai
authors.initials: C
authors.lastname: Hongliang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Huband
authors.forename: Christopher
authors.initials: C
authors.lastname: Huber
authors.forename: Rose
authors.initials: R
authors.lastname: Kelly
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Martin
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pagano
authors.forename: Daniel
authors.initials: D
authors.lastname: Ross
authors.forename: Laura
authors.initials: L
authors.lastname: Skerlos
authors.forename: Mark C
authors.initials: MC
authors.lastname: Sulavik
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Zurenko
authors.forename: J V N Vara
authors.initials: JV
authors.lastname: Prasad
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001682:Biological Availability; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004285:Dogs; D024881:Drug Resistance, Bacterial; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007275:Injections, Intravenous; D000069349:Linezolid; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus; D013290:Streptococcal Infections / Q000188:drug therapy; D013297:Streptococcus pyogenes; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D003499:Cyclic S-Oxides; D008996:Monoamine Oxidase Inhibitors; D023303:Oxazolidinones; C526807:PF 00422602; D000069349:Linezolid