The synthesis and biological activity of certain pentaazaacenaphthylenes, hexaazaacenaphthylenes and their corresponding nucleosides.
Synthesis of the tricyclic nucleoside 8-amino-6-N-methyl-2-(beta-D-ribo-furanosyl)-1,2,3,5,6,7-hexaazaacena phthylene (5) has been accomplished by the ring closure of an appropriately substituted pyrazolo[3,4-d]-pyrimidine nucleoside followed by the requisite chemical conversions. The formation, isolation and structural elucidation of two unexpected nucleosides formed by a reductive ring cleavage of the hexaazaacenaphthylene ring system is discussed. A comparison of the antitumor and biological activity of 5 with the structurally related tricyclic pentaazaacenaphthylene nucleoside which is currently in phase II clinical trials at the 5'-phosphate pro-drug is also presented.
D000073:Acenaphthenes; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis*; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D012265:Ribonucleotides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000073:Acenaphthenes; D000964:Antimetabolites, Antineoplastic; D007202:Indicators and Reagents; D012263:Ribonucleosides; D012265:Ribonucleotides; C051669:8-amino-6(N)-methyl-2-ribofuranosyl-1,2,3,5,6,7-hexaazaacenaphthylene; C023764:triciribine; C014205:triciribine phosphate