title: Antibacterials. synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 4. Multiply-substituted aryl derivatives.
abstract: The synthesis and structure-activity relationship (SAR) studies of the effect of different polysubstitution patterns in the aromatic ring of 5-(acetamidomethyl)oxazolidinone antibacterials (I) on antibacterial activity are presented. Compounds I were prepared by the six-step synthesis described previously (Gregory, W. A.; et al. J. Med. Chem. [formula: see text] 1989, 32, 1673), electrophilic aromatic substitution reactions of 3-substituted compounds, and functional-group interchange reactions of 3,4-disubstituted compounds. Antibacterial evaluation of compounds I against Staphylococcus aureus and Enterococcus faecalis gave the following results. The 2,4- and 2,5-disubstituted derivatives have weak or no antibacterial activity. Antibacterial activities of 3,4-disubstituted compounds are comparable to those of the 4-monosubstituted analogues for small 3-substituents (smaller than Br), but decline rapidly for larger 3-substituents. 3,4-Annulated derivatives are comparable in activity to their open-chain analogues. 3,5-Disubstituted and 3,4,5- and 2,4,6-trisubstituted derivatives are devoid of antibacterial activity.
authors.affiliation: Du Pont Merck Pharmaceutical Company, Drug Discovery Research, Wilmington, Delaware 19880-0353.
authors.forename: C H
authors.initials: CH
authors.lastname: Park
authors.forename: D R
authors.initials: DR
authors.lastname: Brittelli
authors.forename: C L
authors.initials: CL
authors.lastname: Wang
authors.forename: F D
authors.initials: FD
authors.lastname: Marsh
authors.forename: W A
authors.initials: WA
authors.lastname: Gregory
authors.forename: M A
authors.initials: MA
authors.lastname: Wuonola
authors.forename: R J
authors.initials: RJ
authors.lastname: McRipley
authors.forename: V S
authors.initials: VS
authors.lastname: Eberly
authors.forename: A M
authors.initials: AM
authors.lastname: Slee
authors.forename: M
authors.initials: M
authors.lastname: Forbes
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010080:Oxazoles