Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 1. The "B" group.
The synthesis and structure/activity studies of the effect of varying the "B" group in a series of oxazolidinone antibacterials (I) are described. Two synthetic routes were used: (1) alkylation of aniline with glycidol followed by dialkyl carbonate heterocyclization to afford I (A = H, B = OH), whose arene ring was further elaborated by using electrophilic aromatic substitution methodology; (2) cycloaddition of substituted aryl isocyanates with epoxides to give A and B with a variety of values. I with B = OH or Br were converted to other "B" functionalities by using SN2 methodology. Antibacterial evaluation of compounds I with A = acetyl, isopropyl, methylthio, methylsulfinyl, methylsulfonyl, and sulfonamido and a variety of different "B" groups against Staphylococcus aureus and Enterococcus faecalis concluded that the compounds with B = aminoacyl, and particularly acetamido, were the most active of those examined in each A series, possessing MICs in the range of 0.5-4 micrograms/mL for the most active compounds described.
Gregory
W A
WA
Medical Products Department, E. I. du Pont de Nemours and Co., Wilmington, Delaware 19898.
Brittelli
D R
DR
Wang
C L
CL
Wuonola
M A
MA
McRipley
R J
RJ
Eustice
D C
DC
Eberly
V S
VS
Bartholomew
P T
PT
Slee
A M
AM
Forbes
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D010080:Oxazoles