[Pyrazine-1,4-dioxides fused to heterocycles / 2nd comm.: Synthesis and antibacterial activity of substituted...

The position selective synthesis of substituted pyrido[2,3-b]-pyrazine-1,4-dioxides is reported. Compound 3g was subjected to a series of screening-tests for antibacterial activity and compared to therapeutical standards. The range of antibacterial activity mainly comprises enterobacteriaceae, above all E. coli, Klebsiella, Proteus and Shigella strains. Activity against gram-positive organisms and Serratia is much weaker and completely lacking with Pseudomonas. Therapeutic activity in septicaemic infections of the mouse is very good, especially in the case of E. coli infection with an ED50 of 13 mg/kg mouse for s.c. application. With p.o. application 3g shows activity comparable to nalidixic acid and nitrofurantoin in the experimental acute pyelonephritis in the mouse. The activity of 3g, however, is clearly inferior to that of gentamicin.