Novel Acyclic Phosphonylated 1,2,3‐Triazolonucleosides with an Acetamidomethyl Linker: Synthesis and Biological Activity

Abstract

A new series of 4-substituted [(1,2,3-triazol-1-yl)acetamido]methylphosphonates as acyclic nucleotide analogs were synthesized from diethyl (2-chloroacetamido)methylphosphonate via azidation followed by 1,3-dipolar cycloaddition with selected alkynes derived from natural nucleobases or their mimetics. All compounds were tested for their antiviral activities against DNA and RNA viruses as well as for cytostatic activity or cytotoxicity. Among all tested compounds, [(1,2,3-triazol-1-yl)acetamido]methylphosphonate 6e substituted with the N(3)-Bz-benzuracil moiety showed activity against the vesicular stomatitis virus (EC50 = 45 µM) in HeLa cell cultures.

Synthesis and antimicrobial activity of novel 1,2,3‐triazole‐conjugates of quinazolin‐4‐ones

“…Optimized preparative procedures for all ω‐azidoalkylphosphonates 11a – j were previously elaborated in our research groups . Synthesis of N 3 ‐propargylquinazolin‐4‐ones 10a and 10b via application of a one‐pot procedure starting from anthranilic acid 12a or its derivative 12b and N , N ‐dimethylformamide dimethylacetate have been already described .…”

“…In continuation of our search for biologically active 1,2,3‐triazoles, a new class of (1,2,3‐triazol‐1‐yl)quinazolin‐4‐ones 9 was proposed. The aim of these studies was the preparation of a series of compounds having additional phosphonoalkyl group located at C4 in the 1,2,3‐triazole ring (Scheme ).…”

“…[17][18][19] Among them substituted alkylphosphonates [20][21][22] as well as derivatives with various heterocyclic systems should be mentioned. [23][24][25][26][27][28][29][30] In continuation of our search for biologically active 1,2,3triazoles, [31][32][33][34][35][36] a new class of (1,2,3-triazol-1-yl)quinazolin-4-ones 9 was proposed. The aim of these studies was the preparation of a series of compounds having additional phosphonoalkyl group located at C4 in the 1,2,3-triazole ring (Scheme 1).…”

Cycloaddition reactions for antiviral compounds

“…124 Nucleoside analogs are commonly used in HIV/AIDS therapy and as a first line therapeutics for many tumor types. Among all tested compounds, [(1,2,3-triazol-1-yl)acetamido]-methylphosphonate 280 bearing a methyl-imidazole substituent showed activity against the vesicular stomatitis virus (EC 50 5 45 μM) in HeLa cell cultures.…”

Design, Synthesis, and the Biological Evaluation of a New Series of Acyclic 1,2,3‐Triazole Nucleosides

“…In continuation of our involvement in the search for new biologically active acyclic nucleoside analogs , a new series of 1,2,3‐triazole nucleosides containing the substituted quinazoline‐2,4‐dione at C4 was designed (compounds 32–37 , Scheme ). Based on the previous observations on analogous heterocyclic conjugates 24 – 26 synthesized in our research group (Fig.…”