Design,synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-b]pyridine,imidazo[4,5-b]pyridine and imidazo[4,5-b]pyridin-2(3H)-one systems |
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Authors: | Anna Hartwich Nee Zdzienicka Dominique Schols Graciela Andrei Robert Snoeck |
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Affiliation: | 1. Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of ?ód?, ?ód?, Poland;2. Rega Institute for Medical Research, KU Leuven, Leuven, Belgium |
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Abstract: | AbstractA new series of phosphonylated triazolo[4,5-b]pyridine (1-deaza-8-azapurine), imidazo[4,5-b]pyridine (1-deazapurine) and imidazo[4,5-b]pyridin-2(3H)-one (1-deazapurin-8-one) were synthesized from 2-chloro-3-nitropyridine and selected diethyl ?-aminoalkylphosphonates followed by reduction of the nitro group and cyclization. In the final step O,O-diethylphosphonates were transformed into the corresponding phosphonic acids. All synthesized compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses and their cytotoxic potencies were also established. Compound 12f showed marginal activity against cytomegalovirus Davis strain (EC50?=?76.47?μM) in human embryonic lung (HEL) cells while compounds 10g (EC50?=?52.53?μM) and 12l (EC50?=?61.70?μM) were minimally active against the varicella-zoster virus Oka strain in HEL cells. Compounds under investigation were not cytotoxic at the maximum concentration evaluated (100?µM). |
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Keywords: | Aminoalkylophosphonates acyclonucleotides synthesis antiviral activity |
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