Synthesis of 4-substituted imidazo[4,5-d][1,2,3]triazine (2-azapurine)nucleosides.
Several methods for functionalization of the 4-position of imidazo[4,5-d][1,2,3]triazin-4-one were investigated. These investigations were successful and led to the preparation of 4-amino, 4-triazol-1-yl, 4-methoxy, 4-methylthio, 4-methylamino, 4-thio, 4-nitrobenzyl, and 4-unsubstituted 9-(beta-D-ribofuranosyl)-imidazo-[4,5-d][1,2,3]triazine (2-azapurine ribosides). The 4-unsubstituted compound (19) was slightly active against HCMV in plaque and yield reduction experiments and was not cytotoxic at 100 microM. The methylamino (15), hydrazino (16), and p-nitrobenzylthio (20) were inactive against HCMV but slightly cytotoxic. The thiomethyl-substituted analog (21) was the most active with activity comparable to ganciclovir but with greater cytotoxicity. We conclude that even though none of the tested compounds had antiviral activity superior to ganciclovir, the new synthetic methods will provide a route to more interesting compounds.
Krawczyk
S
S
Department of Chemistry, College of Literature, Science and the Arts, University of Michigan, Ann Arbor 48109-1065, USA.
Migawa
M T
MT
Drach
J C
JC
Townsend
L B
LB
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003587:Cytomegalovirus / Q000187:drug effects*; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D009705:Nucleosides; D011687:Purines; D014227:Triazines