Sang J. Chung, D. H. Kim
1997
Citations
0
Influential Citations
2
Citations
Journal
Archiv der Pharmazie
Abstract
3‐Fluoro‐2‐piperazinyl‐5,8,13‐trihydro‐5‐oxoquino[1,2‐a][3,1]‐benzoxazine‐6‐carboxylic acids were designed and synthesized as potential DNA gyrase inhibitors and antibacterial agents. The design rationale rests on the proposition made by Ohta and Koga that in order for N1‐aryl substituted quinolones to posses antibacterial activity the N1‐aryl ring should be oriented out of the plane of the quinolone ring. α‐[Bis(methylthio)methylene]‐2,4,5‐trifluoro‐β‐oxobenzenepropanoic acid tert‐butyl ester (6) obtained by the treatment of 2,4,5‐trifluoro‐β‐oxobenzenepropanoic acid tert‐butyl ester (5) with carbon disulfide and methyl iodide in the presence of cesium carbonate was used as a key intermediate, yielding tert‐butyl 2,3‐difluoro‐5,8,13‐trihydro‐5‐oxoquino[1,2‐a][3,1]benzoxazine‐6‐carboxylate (8) upon treatment with 2‐aminobenzyl alcohol. The coupling of 8 with piperazines followed by the hydrolysis of the ester under acidic conditions afforded the desired product (3). Contrary to expectation, both compounds (3a,b) were, however, devoid of antibacterial activity, suggesting that for N1‐aryl substituted quinolones to exhibit antimicrobial activity important structural feature(s) other than the conformational requirement of the N1‐aryl ring with respect to the quinolone nucleus should also be satisfied.