title: Synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones: novel analogs of linezolid.
abstract: The synthesis and antibacterial activity of oxazolidinones containing dihydro-1,2-oxazine and 2-pyrazoline ring systems are described. Linezolid analogs utilizing dihydro-1,2-oxazines as morpholine mimics were prepared utilizing a nitrosoamine/diene 4+2 cycloaddition strategy. Pyrazolidine, hexahydro-pyridazine, and 2-pyrazoline analogs more closely related to eperezolid were also prepared. The most active of these new oxazolidinones were the dihydro-1,2-oxazine 6 and the 2-pyrazoline 20 both of which had potency similar to linezolid against a panel of Gram-positive bacteria.
authors.affiliation: Bristol-Myers Squibb, Discovery Chemistry, Pharmaceutical Research Institute, Wallingford, CT 06492, USA. stanley.dandrea@bms.com
authors.forename: Stan
authors.initials: S
authors.lastname: D'Andrea
authors.forename: Zhizhen Barbara
authors.initials: ZB
authors.lastname: Zheng
authors.forename: Kenneth
authors.initials: K
authors.lastname: Denbleyker
authors.forename: Joan C
authors.initials: JC
authors.lastname: Fung-Tomc
authors.forename: Hyekyung
authors.initials: H
authors.lastname: Yang
authors.forename: Junius
authors.initials: J
authors.lastname: Clark
authors.forename: Dennis
authors.initials: D
authors.lastname: Taylor
authors.forename: Joanne
authors.initials: J
authors.lastname: Bronson
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D000069349:Linezolid; D051379:Mice; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D010080:Oxazoles; D023303:Oxazolidinones; D000069349:Linezolid