Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo4,5-bpyridine, imidazo4,5-bpyridine and imidazo4,5-bpyridin-2(3H)-one systems

摘要

A new series of phosphonylated triazolo4,5-bpyridine (1-deaza-8-azapurine), imidazo4,5-bpyridine (1-deazapurine) and imidazo4,5-bpyridin-2(3H)-one (1-deazapurin-8-one) were synthesized from 2-chloro-3-nitropyridine and selected diethyl x277;-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 mu M) in human embryonic lung (HEL) cells while compounds 10g (EC50 = 52.53 mu M) and 12l (EC50 = 61.70 mu M) 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 mu M).