Synthesis of alpha-methylenebeutyrolactams as potential antitumor agents.
A series of 1-aryl-3-methylene-2-pyrrolidinones was synthesized via a three-step reaction sequence. 1,4-Bis-[N-(3-methylene-2-oxopyrrolidino)]benzene, which can undergo alkylation at two sites, was also prepared. These compounds are related to the known antitumor agents alpha-methylenebutyrolactones. Attempts to prepare bis-alpha-methylenelactams, in which the heterocyclic rings are joined through their nitrogen atoms by an alkylene bridge, were unsuccessful. All of the alpha-methylenelactams were screened in B16 melanocarcinoma and P-388 lymphocytic leukemia tumor systems but failed to show significant activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D007942:Leukemia, Experimental / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy
D000970:Antineoplastic Agents; D007769:Lactams