title: Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted-naphthyridones.
abstract: A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3- carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Marne-la-Vallée, France.
authors.forename: P
authors.initials: P
authors.lastname: Di Cesare
authors.forename: D
authors.initials: D
authors.lastname: Bouzard
authors.forename: M
authors.initials: M
authors.lastname: Essiz
authors.forename: J P
authors.initials: JP
authors.lastname: Jacquet
authors.forename: B
authors.initials: B
authors.lastname: Ledoussal
authors.forename: J R
authors.initials: JR
authors.lastname: Kiechel
authors.forename: P
authors.initials: P
authors.lastname: Remuzon
authors.forename: R E
authors.initials: RE
authors.lastname: Kessler
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
authors.forename: J
authors.initials: J
authors.lastname: Desiderio
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009287:Naphthyridines