title: The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones.
abstract: The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 microg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of alpha-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.
authors: Pfizer, 7000 Portage Road, Kalamazoo, MI 49001, USA.
authors: Fred L
authors: FL
authors: Ciske
authors: Michael R
authors: MR
authors: Barbachyn
authors: Michael J
authors: MJ
authors: Genin
authors: Kevin C
authors: KC
authors: Grega
authors: Chi Sing
authors: CS
authors: Lee
authors: Lester A
authors: LA
authors: Dolak
authors: Eric P
authors: EP
authors: Seest
authors: William
authors: W
authors: Watt
authors: Wade J
authors: WJ
authors: Adams
authors: Janice M
authors: JM
authors: Friis
authors: Charles W
authors: CW
authors: Ford
authors: Gary E
authors: GE
authors: Zurenko
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006873:Hydroquinones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010078:Oxazines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006873:Hydroquinones; D007211:Indoles; D010078:Oxazines; D023303:Oxazolidinones