Synthesis and antibacterial activity of dihydro-1,2-oxazine and 2-pyrazoline oxazolidinones: novel analogs of linezolid.
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.
D'Andrea
Stan
S
Bristol-Myers Squibb, Discovery Chemistry, Pharmaceutical Research Institute, Wallingford, CT 06492, USA. stanley.dandrea@bms.com
Zheng
Zhizhen Barbara
ZB
Denbleyker
Kenneth
K
Fung-Tomc
Joan C
JC
Yang
Hyekyung
H
Clark
Junius
J
Taylor
Dennis
D
Bronson
Joanne
J
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*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D010080:Oxazoles; D023303:Oxazolidinones; D000069349:Linezolid