Antitumor effect of pyridine N-oxides having 1-(2-chloroethyl)-1-nitrosoureidoalkyl and 1-methyl-1-nitrosoureidoalkyl groups.
Pyridine N-oxides having 1-(2-chloroethyl)-1-nitrosoureidoalkyl or 1-methyl-1-nitrosoureidoalkyl groups were evaluated for their antitumor activity against AH13 hepatoma and L1210 leukemia. Among them, 1-(2-chloroethyl)-1-nitroso-3-(2-pyridylmethyl)urea N-oxide (1), its tosylate (2), 1-(2-chloroethyl)-1-nitroso-3-(2-pyridylethyl)urea N-oxide (4), and 1-(2-chloroethyl)-1-nitroso-3-(3-pyridylmethyl)urea N-oxide (6) were highly active against both tumors in ip-ip system. These compounds were also active in ip-iv and ip-po systems of L1210. On the other hand, pyridine N-oxides having 1-methyl-1-nitrosoureidoalkyl group were all inactive against AH13 and weakly active against L1210. Effect on blood cells in Donryu rats bearing EDEN-5 erythroblastic leukemia cells was tested with these 1-(2-chloroethyl)-1-nitrosoureidoalkylureas. These compounds caused leucopenia and compound (4) was only slightly effective against EDEN-5.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002621:Chemistry; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D007939:Leukemia L1210 / Q000188:drug therapy; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy; D008770:Methylnitrosourea / Q000627:therapeutic use; D051379:Mice; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D012995:Solubility; D013997:Time Factors
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D009588:Nitrogen Mustard Compounds; D009607:Nitrosourea Compounds; D011725:Pyridines; D008770:Methylnitrosourea