Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one , a novel broad-spectrum antitumor agent.
Interaction of 5-diazoimidazole-4-carboxamide and alkyl and aryl isocyanates in the dark affords 8-carbamoyl-3-substituted-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-on es. In cold methanol or ethanol, the 3-(2-chloroethyl) derivative 7a decomposes to afford 2-azahypoxanthine (14) and methyl and ethyl N-(2-chloroethyl)carbamates, respectively. Compound 7a has curative activity against L-1210 and P388 leukemia and may act as a prodrug modification of the acyclic triazene 5-[3-(2-chloroethyl)triazen-1-yl]imidazole-4-carboxamide (MCTIC), since it ring opens to form the triazene in aqueous sodium carbonate.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000627:therapeutic use; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D009588:Nitrogen Mustard Compounds; D013057:Spectrum Analysis; D014867:Water
D000970:Antineoplastic Agents; D007093:Imidazoles; D009588:Nitrogen Mustard Compounds; D014867:Water; C040369:mitozolomide