Synthesis and antitumor activity of 5-azacytosine arabinoside.
5-Azacytosine arabinoside (ara-AC) can be considered a combination of structural elements derived from the antitumor nucleosides cytosine arabinoside (ara-C) and 5-azacytidine (5-AC). The synthesis of ara-AC, for which standard methods were inadequate, was accomplished using the stable dihydro derivative as a synthetic intermediate. A novel dehydrogenation of the latter through the application of a trimethylsilylation-oxidation procedure gave ara-AC in good yield. Using murine L1210 leukemia as a test system, ara-AC was evaluated for antitumor properties in parallel determinations with 5-AC and ara-C. Although higher dose levels were necessary, ara-AC demonstrated a reproducibly greater efficacy in the L1210 system (% ILS = 144-148) than that shown by 5-AC (% ILS = 126-124) or ara-C (% ILS=127-121 ). Moreover, initial data suggest that ara-AC exhibits less host toxicity than either 5-AC or ARA-C. Although ara-AC can equally be considered an analogue of either 5-AC or ara-C, preliminary results indicate that ara-AC is chemically similar to 5-AC but biologically more closely related to ara-C.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001374:Azacitidine / Q000138:chemical synthesis* / Q000494:pharmacology / Q000031:analogs & derivatives; D055598:Chemical Phenomena; D002621:Chemistry; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013237:Stereoisomerism
D000970:Antineoplastic Agents; C022121:fazarabine; D001374:Azacitidine