Synthesis and antibacterial activity of [6,5,5] and [6,6,5] tricyclic fused oxazolidinones.
A series of conformationally restricted, [6,5,5] and [6,6,5] tricyclic fused oxazolidinones were synthesized and tested for antibacterial activity. Several compounds in the trans-[6,5,5] series demonstrated potent in vitro and in vivo activity. This work provides valuable information regarding the preferred conformational orientation of the oxazolidinones at the binding site.
Gleave
D M
DM
Pharmacia & Upjohn, Kalamazoo, MI 49001, USA.
Brickner
S J
SJ
Manninen
P R
PR
Allwine
D A
DA
Lovasz
K D
KD
Rohrer
D C
DC
Tucker
J A
JA
Zurenko
G E
GE
Ford
C W
CW
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy*; D007202:Indicators and Reagents; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D010080:Oxazoles