Synthesis and antitumor activity of 1,2-dihydro-1-(2-deosy-beta-D-erythro-pentofuranosyl)-2-oxo-5-methylpyrazine 4-oxide, a structural analogue of thymidine.
1,2-Dihydro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-2-oxo-5-methylpyrazine 4-oxide was synthesized by condensation of the silylated pyrazine base with the blocked chloro sugar, followed by removal of the protecting groups. The compound inhibited the growth of leukemia L1210 cells in vitro by 50% at 2 x 10-7 M. At 400 mg/kg/day x 6 it increased the life-span of leukemia L1210 bearing mice by approximately 55%, without apparent toxicity to the host.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D008722:Methods; D051379:Mice; D008811:Mice, Inbred DBA; D013291:Streptococcus / Q000187:drug effects; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D013936:Thymidine