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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

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Mentions: Based on the active compounds already discussed, a novel series of phosphonate analogues 11 having the 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system was designed as potential antiviral agents (Scheme 1). Furthermore, because their immediate precursor dihydrazides 10 as well as diamides 9 share several common structural features with ribavirin, they also may show antiviral activity. The key step of our synthetic plan involves the 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate and ω-azidoalkylphosphonates 7 which contain structurally diversified alkyl chains to provide the intermediate diesters 8.


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)

© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Mentions: Based on the active compounds already discussed, a novel series of phosphonate analogues 11 having the 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-dione system was designed as potential antiviral agents (Scheme 1). Furthermore, because their immediate precursor dihydrazides 10 as well as diamides 9 share several common structural features with ribavirin, they also may show antiviral activity. The key step of our synthetic plan involves the 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate and ω-azidoalkylphosphonates 7 which contain structurally diversified alkyl chains to provide the intermediate diesters 8.

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