Design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1 H -[1,2,3]triazolo[4,5- d ]pyridazine-4,7-dione system

A series of diethyl 2-(4,5-dimethoxycarbonyl-1 -1,2,3-triazol-1-yl)alkylphosphonates was synthesised from -azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1 -[1,2,3]triazolo[4,5- ]pyridazine-4,7-diones as phosphonate analogues of acyclic nucleosides having nucleobases replaced with substituted 1,2,3-triazoles. All compounds containing P-C-C-triazole or P-C-C-CH -triazole moieties exist in single conformations in which the diethoxyphosphoryl and substituted 1,2,3-triazolyl or substituted (1,2,3-triazolyl)methyl groups are oriented . All phosphonates were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity. They were not cytostatic at 100 μM.