Synthesis of Antitumor Pyridine and Pyridazine N-Oxides having (2-Chloroethyl) nitrosoureidomethyl and Bis (2-chloroethyl)-aminomethyl Groups

Treatment of 1-(2-chloroethyl)-1-nitroso-3-(3-pyridylmethyl) urea (Ia) and the 3-nitroso isomer (Ib) with m-chloroperbenzoic acid, gave the corresponding N-oxides, IIa and IIb. The 3-nitrosoureas (Ib, IIb) isomerized to the 1-nitroso isomers (Ia, IIa) by dissolving them in formic acid. The reaction of 6-bis (2-chloroethyl) aminomethyl-3-hydroxypyridazine 1-oxide (III) with bromine gave the 4-bromo derivative (IV). 1-(2-Chloroethyl)-1-nitroso-3-(3-pyridylmethyl) urea N-oxide (IIa) showed the most marked activity against rat ascites hepatom AH-13 and mouse lymphoid leukemia L-1210.