Antibacterial pyrazine (1,4)-dioxide derivs. - prepd. by reacting pyrido- or pyrimido-furoxan cpds. with oxo cpds.

摘要

New, N, N-dioxide derivs. are cpds. of formula (I). In this formula, R1 and R2 are H, lower alkyl, phenyl, -CHO, -CN, -CH=N(right arrow O) -CH3 or -CHR3R4; R3 is OH, lower alkoxy, lower alkylthio, -COCH3, -cOOR5 or -CONR6R7; R4 is H, lower alkyl, lower alkoxy, -CONR6R7, -COOR5 or -CH=NR9; or R3+R4 is -O-(CH2)n-O-; R5 is lower alkyl, -(CH2)nOH or -CONR6R7; R6 and R7 are H, lower alkyl or lower hydroxyalkyl, or NR6R7 is a pyrrolidine ring or a 6-membered heterocycle which can contain O or N (N opt. substd. by lower alkyl) is a second heteroatom in the 4-position; R9 is OH, ureido, thioureido, 2-oxo-3-oxazolidinyl or -NH-COOCH3; n is 2 or 3; and A is 2, 3-pyridylene or 2-R10-6-amino-4, 5-pyrimidinylene, R10 being H or lower alkoxy. (I) are chemotherapeutic agents with low toxicity. In particular, (I) are inhibitors of bacterial growth. Thus, in vitro inhibition is seen at concn. of from ca. 5 mug./ml., and in vivo in the mouse E. coli pyelonephritis model activity is seen at dosages of ca. 13-80 mg./kg. p.o. or s.c. Specific cpds. (I) include 2-methylpyrido 2,3-b pyrazine-1, 4-dioxide. In an example, this is prepd. by dropwise addn. of an acetone soln. of pyrido 2, 3 furoxan to a refluxing acetone soln. of morpholine in the presence of a 4 angstroms molecular sieve.