Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted-naphthyridones.
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.
Di Cesare
P
P
Bristol-Myers Squibb Pharmaceutical Research Institute, Marne-la-Vallée, France.
Bouzard
D
D
Essiz
M
M
Jacquet
J P
JP
Ledoussal
B
B
Kiechel
J R
JR
Remuzon
P
P
Kessler
R E
RE
Fung-Tomc
J
J
Desiderio
J
J
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
D000900:Anti-Bacterial Agents; D009287:Naphthyridines