Discovery of isoxazolinone antibacterial agents. Nitrogen as a replacement for the stereogenic center found in oxazolidinone antibacterials.
A series of potential antimicrobial derivatives possessing bioisosteric replacements for the central oxazolidinone ring found in oxazolidinone antibacterials have been prepared. The design concept involved replacement of the requisite sp(3)-hybridized stereogenic center found at the 5-position of the oxazolidinone with a nitrogen atom. The synthesis and antibacterial activity of three such ring systems, the benzisoxazolinones, pyrroles, and isoxazolinones is described.
Snyder
Lawrence B
LB
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. lawrence.snyder@bms.com
Meng
Zhaoxing
Z
Mate
Robert
R
D'Andrea
Stanley V
SV
Marinier
Anne
A
Quesnelle
Claude A
CA
Gill
Patrice
P
DenBleyker
Kenneth L
KL
Fung-Tomc
Joan C
JC
Frosco
MaryBeth
M
Martel
Alain
A
Barrett
John F
JF
Bronson
Joanne J
JJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry*; D023303:Oxazolidinones / Q000737:chemistry*; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007555:Isoxazoles; D023303:Oxazolidinones; D011758:Pyrroles; D010081:Oxazolone; D009584:Nitrogen