Synthesis of antimicrobial agents. II. Syntheses and antibacterial activities of optically active 7-(3-hydroxypyrrolidin-1-yl)quinolones

• Published in: Journal of heterocyclic chemistry Vol. 24; no. 4; pp. 1025 - 1028
• Main Authors: Uno, Toshio, Iuch, Koji, Kawahata, Yoshihiro, Tsukamoto, Goro
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley-Blackwell 01-07-1987; Wiley‐Blackwell; HeteroCorporation
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Preparations and properties; Stereoisomer; Five membered ring; Nitrogen heterocycle; Bicyclic compound; Racemate; Aromatic compound; Antibacterial agent; Biological activity
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.5570240423

Two optically active isomers of 1‐ethyl‐6,8‐difluoro‐1,4‐dihydro‐7‐(3‐hydroxypyrrolidin‐1‐yl)‐4‐oxoquinoline‐3‐carboxylic acid (10) were prepared. One of the isomer, 7‐[(3S)‐hydroxypyrrolidin‐1‐yl] derivative 8, was about 4 times more potent in vitro than the other, 7‐[(3R)‐hydroxypyrrolidin‐1‐yl] derivative 4, and approximately two times more active than the racemate, 7‐[(3RS)‐hydroxypyrrolidine‐1‐yl] derivative 10.
Optical active 8 was the most active in in vivo, followed by 10, and 4 was the least active compound. But, they were more potent than CI‐934 12 and norfloxacin.
From the results, (3S)‐hydroxypyrrolidinyl group was found to be one of the beneficial group for PCA‐anti‐bacterial agent.