説明
Prulifloxacin was launched as the third fluoroquinone. It was introduced in
Japan as an oral treatment for urinary tract infections (UTls), respiratory tract infections
(RTls) and bacterial pneumoniae. It can be synthesized in 10 steps from commercially
available 3,4-difluoroaniline. Key steps involve the cyclization of 6,7-difluoro-rl-hydroxy-2-
thioquinoline-3carboxylic acid ethyl ester with 1 ,I-dibromomethane to give the
corresponding thiazeto-[3,2a]quinoline. Aromatic nucleophilic substitution of the 7-fluoro
atom with piperazine followed by hydrolysis of the ethyl ester and finally alkylation of the
piperazinyl moiety with 4-(bromomethyl)-5-methyl-l ,bdioxol-Bone complete the synthesis.
Prulifloxacin is a lipophilic prodrug, which is rapidly hydrolyzed to the corresponding Ndealkylated
piperazine, NM 394, by paraoxonase type enzymes in blood and liver following
intestinal absorption. The DNA gyrase inhibitor NM 394 accounts for all antimicrobial
activity: it shows a similar or greater activity against gram-positive bacteria compared to
ciprofloxacin, and a greater activity in the case of gram-negative bacteria. In clinical
studies, prulifloxacin has shown good efficacy against UTls and RTls. The drug is mainly
excreted in the urine and in the feces as unchanged NM 394, which has a plasma half-life
of approximately 8 h. Phototoxicity in animal models is less severe than with other
quinolones. Prulifloxacin is well tolerated with an adverse effect profile similar to that of
other fluoroquinolones.
