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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.

Bankowska E, Balzarini J, Głowacka IE, Wróblewski AE - Monatsh. Chem. (2014)

Bottom Line: 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 oriented anti.None of the compounds were endowed with antiviral activity.They were not cytostatic at 100 μM.

View Article: PubMed Central - PubMed

Affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland.

ABSTRACT

Abstract: A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-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 oriented anti. 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.

No MeSH data available.


Related in: MedlinePlus

Preferred conformations of the phosphonates described in this study
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Fig7: Preferred conformations of the phosphonates described in this study

Mentions: Detailed analyses of 1H and 13C NMR spectral data revealed conformational preferences of phosphonates described in this paper. Compounds 8a–11a contain an 1,2-substituted ethylene fragment which does not freely rotate around a C–C bond because their 1H NMR spectra display AA′XX′P patterns. A similar spectrum was also noticed for 2-azidoethylphosphonate [31]. Antiperiplanar disposition of the diethoxyphosphoryl groups and substituted 1,2,3-triazoles 14a (Fig. 7) was proved by the presence of two identical 3J(P–HX) = 10.5 Hz couplings which were calculated from the 1H{31P} NMR spectrum of 8a.Fig. 7


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.

Bankowska E, Balzarini J, Głowacka IE, Wróblewski AE - Monatsh. Chem. (2014)

Preferred conformations of the phosphonates described in this study
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4494773&req=5

Fig7: Preferred conformations of the phosphonates described in this study
Mentions: Detailed analyses of 1H and 13C NMR spectral data revealed conformational preferences of phosphonates described in this paper. Compounds 8a–11a contain an 1,2-substituted ethylene fragment which does not freely rotate around a C–C bond because their 1H NMR spectra display AA′XX′P patterns. A similar spectrum was also noticed for 2-azidoethylphosphonate [31]. Antiperiplanar disposition of the diethoxyphosphoryl groups and substituted 1,2,3-triazoles 14a (Fig. 7) was proved by the presence of two identical 3J(P–HX) = 10.5 Hz couplings which were calculated from the 1H{31P} NMR spectrum of 8a.Fig. 7

Bottom Line: 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 oriented anti.None of the compounds were endowed with antiviral activity.They were not cytostatic at 100 μM.

View Article: PubMed Central - PubMed

Affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland.

ABSTRACT

Abstract: A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-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 oriented anti. 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.

No MeSH data available.


Related in: MedlinePlus