Synthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents.
Nitrosourea derivatives 18-22 which utilize either a piperidine or pyridine ring as a carrier group were synthesized and evaluated for anticancer activity. N'-(1-Benzyl-4-piperidinyl)-N-(2-chloroethyl)-N-nitosourea hydrogen maleate (19) exhibited good activity against intracranial L1210 leukemia as well as the mouse ependymoblastoma brain tumor system. Compound 19 exhibited comparable activity in the Lewis lung carcinoma system to N,N'-bis(2-chloroethyl)-N-nitrosourea. Replacement of the N-benzyl group in both the 3-piperidinyl- and 4-piperidinylnitrosoureas resulted in less active compounds in all tumor systems tested. The 3-pyridylnitrosourea 22 was inactive in the L-1210 leukemia system.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D007942:Leukemia, Experimental / Q000188:drug therapy; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D010880:Piperidines; D011725:Pyridines