title: Design, synthesis and biological evaluation of oxazolidinone-quinolone hybrids.
abstract: Oxazolidinone-quinolone hybrids that combine the pharmacophores of a quinolone and an oxazolidinone were synthesised and shown to be active against a variety of resistant and susceptible Gram-positive and fastidious Gram-negative organisms. The best compounds in this series overcome all types of resistance in relevant clinical Gram-positive pathogens. The nature of the spacer greatly influences the antibacterial activity. The dual mode of action could be demonstrated for compounds having a piperazinyl spacer. Antibacterial activity was higher at acidic pH.
authors.affiliation: Morphochem AG, Schwarzwaldallee 215, CH-4058 Basel, Switzerland. christian.hubschwerlen@morphochem.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Hubschwerlen
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Specklin
authors.forename: Christine
authors.initials: C
authors.lastname: Sigwalt
authors.forename: Susanne
authors.initials: S
authors.lastname: Schroeder
authors.forename: Hans H
authors.initials: HH
authors.lastname: Locher
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D018432:Drug Resistance, Multiple; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014176:Protein Biosynthesis; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase