Antitumor agents II: nitrogen analogs of mycophenolic acid.
Mycophenolic acid, a novel antibiotic of low toxicity containing no nitrogen atoms in its structure, induces tumor regression in several murine solid tumor assays. It has been reported in extensive structure-activity studies that chemical modifications on the antibiotic itself reduce or eliminate antitumor activity. With the objective of antitumor activity enhancement, nitrogen-containing analogs of mycophenolic acid were synthesized according to a program directed toward the ultimate synthesis of close bioisosteres of the antibiotic. Intial efforts reported here describe the terpenoid side-chain degradation of N-geranyl-2(1H)-pyridones and N-geranylglutarimides, where the terminal isopropylidene is replaced with a carboxyl group as it occurs in mycophenolic acid. The resulting nitrogen-containing analogs of the antitumor antibiotic were inactive in the l-1210 and Walker 256 tumor systems.
D000447:Aldehydes; D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000138:chemical synthesis / Q000627:therapeutic use*; D002264:Carboxylic Acids / Q000138:chemical synthesis; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000627:therapeutic use; D051381:Rats; D012510:Sarcoma 180 / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D009173:Mycophenolic Acid