FA-103

A number of new quinolone antibacterial agents such as ofloxacin, norfloxacin, ciprofloxacin and sparfloxacin have been developed and introduced to the market. They possess a broad spectrum of activity against Gram-positive and Gram-negative bacteria. Ciprofloxacin has the highest activity against Gram-positive is higher than other quinolones. The activity of these quinolones against Gram-negative bacteria is generally higher than against Gram-positive bacteria. The substitution group of quinolones at C-7 position is responsible to show similar antibacterial activity with broad spectrum and similar pharmacokinetic properties, and variety of the substituents have been synthesized in many laboratories. Most of the substituents are piperazinyl of six-membered ring or pyrrolidinyl of five-membered ring, being modified with an alkyl group or another group. The development of potent quinolones against bacteria involved in pneumonia was seemed to be useful, and we investigated structure-activity relationships of new quinolones with a stronger activity against Gram-positive bacteria. A quinolone derivative with a seven-membered ring, perhydrodiazepinone, at the C-7 position was found to be a candidate for further evaluation. No previous attempts have been made to synthesize this type of derivatives. The compound FA103, 5-amino-1-cyclopropyl-6,8-difluoro-7-(2,3,4,5,6,7-hexahydro-1 H-1,4-diazepin-5-on-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, was synthesized and evaluated. Chemical structure of FA103 is shown in Fig. 1. This is a new difluoroquinolone with a broad antibacterial spectrum and improved activity against Gram-positive bacteria. In this paper, we compare the in vitro activity of FA103 with that of ofloxacin, norfloxacin, sparfloxacin against Gram-positive and Gram-negative bacteria.