SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF THIAZOLOPYRAZINE-INCORPORATEDTETRACYCLIC QUINOLONE ANTIBACTERIALS

A novel series of oro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic a cids 5a-q having a unique thiazolopyrazine-incorporated tetracyclic st ructure were synthesized, and the in vitro and in vivo activities were determined against Gram-positive and Gram-negative bacteria. All comp ounds 5a-q had more potent activity than ofloxacin (6), which is one o f the most popular quinolones, against Gram-positive and Gram-negative bacteria. The 8-pyrrolidinyl, 5a-e, and 8-morpholino, 5p, derivatives showed the most potent activity against Gram-positive bacteria. It is also significant that these compounds, 5a-q, showed more potent antib acterial activity against methicillin-resistant Staphylococcus aureus isolates (MRSA) than ofloxacin (6). The combination of the morpholino group and this unique tetracyclic thiazolopyrazine skeleton contribute s to the enhancement of the antibacterial activity against MRSA isolat es. The in vivo antibacterial activities of these compounds, 5a-q, wer e limited and depended on the structure of the 8-substituent. The 8-(4 -alkyl-1-piperazinyl) derivatives 5g, 5h, 5j, and 5n provided good ora l efficacy and exhibited more potent activity than ofloxacin (6) again st the systematic infection with S. aureus IID 803 in mice.