title: Design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system.
abstract: A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised fromω-azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]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-CH2-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 orientedanti. 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.
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Bankowska
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland.
authors.forename: Iwona E
authors.initials: IE
authors.lastname: Głowacka
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland.
authors.forename: Andrzej E
authors.initials: AE
authors.lastname: Wróblewski
keywords: Conformation; Cyclizations; Cycloadditions; Heterocycles; NMR spectroscopy