Synthesis and antitumor activity of cytosine and adenine nucleosides of unsaturated 5-(aminoacyl)aminopentofuranoses.
Direct synthesis of the 1- and 9-(5-azido-2,3,5-trideoxy-beta-D-glycero-pent-2-enofuranosyl) derivatives (3a and 3b) of cytosine and adenine, respectively, has been accomplished via treatment of the corresponding 2',3'-unsaturated nucleosides (1a and 1b) with triphenylphosphine and carbon tetrabromide in the presence of lithium azide. Members of a new type of (aminoacyl)amino nucleoside, the 1- and 9-[5-(aminoacyl)amino-2,3,5-trideoxy-beta-D-glycero-pent-2-enofuranosyl] derivatives of cytosine and adenine, respectively, have been obtained by condensation of the corresponding, unsaturated amino nucleosides with the active esters of several amino acid derivatives, followed by deprotection. These nucleosides were examined for in vivo antitumor activity against leukemia L-1210 and Sarcoma 180 (solid tumor) in mice; none of them exhibited antitumor activity against L-1210 in mice, but compounds 1a, 3a, and 1-[2,3,5-trideoxy-5-(L-methionyl)amino-beta-D-glycero-pent-2-enofuranosyl]cytosine exhibited weak activity against Sarcoma 180 (solid tumor).
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D000596:Amino Acids / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D012510:Sarcoma 180 / Q000188:drug therapy
D000596:Amino Acids; D000970:Antineoplastic Agents; D003596:Cytosine; D000225:Adenine