title: Acyclic nucleoside phosphonates containing the amide bond.
abstract: To study the influence of a linker rigidity and donor-acceptor properties, the P-CH2-O-CHR- fragment in acyclic nucleoside phosphonates (e.g., acyclovir, tenofovir) was replaced by the P-CH2-HN-C(O)- residue. The respective phosphonates were synthesized in good yields by coupling the straight chain ofω-aminophosphonates and nucleobase-derived acetic acids with EDC. Based on the1H and13C NMR data, the unrestricted rotation within the methylene and 1,2-ethylidene linkers in phosphonates from seriesaandbwas confirmed. For phosphonates containing 1,3-propylidene (seriesc) fragments, antiperiplanar disposition of the bulkyO,O-diethylphosphonate and substituted amidomethyl groups was established. The synthesized ANPs P-X-HNC(O)-CH2B (X = CH2, CH2CH2, CH2CH2CH2, CH2OCH2CH2) appeared inactive in antiviral assays against a wide variety of DNA and RNA viruses at concentrations up to 100 μM while marginal antiproliferative activity (L1210 cells, IC50= 89 ± 16 μM and HeLa cells, IC50= 194 ± 19 μM) was noticed for the analog derived from (5-fluorouracyl-1-yl)acetic acid andO,O-diethyl (2-aminoethoxy)methylphosphonate.
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, 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 Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.
authors.forename: Dorota G
authors.initials: DG
authors.lastname: Piotrowska
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Louvain, Belgium.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Louvain, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Louvain, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.
authors.forename: Andrzej E
authors.initials: AE
authors.lastname: Wróblewski
keywords: Amide bond formation; NMR spectroscopy; Nucleotides; Phosphonates