Synthesis of a New Series of Phosphonylated 1,2,3‐<scp>T</scp>riazoles as Acyclic Analogs of Ribavirin

Głowacka, Iwona E.; Balzarini, Jan; Wróblewski, Andrzej E.

doi:10.1002/ardp.201300156

Cited by 12 publications

(14 citation statements)

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“…Although organic azides can be explosive and toxic, they are very attractive reagents for the pharmaceutical industry. In this paper, azides 12 , 15 and 16 were synthesized via nucleophilic bimolecular substitution through nucleophilic attack by azide anion on the leaving group; the reactions required heating, and reaction times varied from 4–24 hr . Yields of the azides varied between 49% and 85% (Scheme ), and the chemical structures were confirmed by mass spectrometry with electrospray ionization mass spectrometry (MS‐ESI) and IR.…”

Section: Resultsmentioning

confidence: 99%

“…Yields of the azides varied between 49% and 85% (Scheme ), and the chemical structures were confirmed by mass spectrometry with electrospray ionization mass spectrometry (MS‐ESI) and IR. The results of the analyses were compared with the literature data as these intermediates are already described …”

Section: Resultsmentioning

confidence: 99%

“…Azides 12 , 15 and 16 were prepared according to the methodologies previously described in the literature …”

Section: Methodsmentioning

confidence: 99%

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New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Głowacka

Andrei

Schols

et al. 2017

Archiv der Pharmazie

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A new strategy for the synthesis of N -benzoylated- and N -benzylated N -propargylquinazoline-2,4-diones 30a-d and 31a-d from isatoic anhydride 41 is reported. The alkynes 30a-d and 31a-d were applied in the 1,3-dipolar cycloadditions with azides 27 and 28 to synthesize acyclic 1,2,3-triazole nucleosides. The obtained alkynes and 1,2,3-triazole were evaluated for antiviral activity against a broad range of DNA and RNA viruses. The alkyne 30d showed activity against adenovirus-2 (EC = 8.3 μM), while compounds 37a and 37d were also active toward herpes simplex virus-1 wild-type and thymidine kinase deficient (HSV-1 TK ) strains (EC values in the range of 4.6-13.8 μM). In addition, compounds 30a, 30b, 37b, and 37c exhibited activity toward varicella-zoster virus (VZV) TK and TK strains (EC = 2.1-9.5 μM). The compound 30b proved to be the most selective against VZV and displayed marginal activity against human cytomegalovirus (HCMV). Although the compound 30a had improved anti-HCMV activity, the increase in anti-HCMV activity was accompanied by significant toxicity. Compounds 37a and 37d showed inhibitory effects toward the human T lymphocyte (CEM) cell line (IC = 21 ± 7 and 22 ± 1 μM, respectively), while compound 35 exhibited cytostatic activity toward HMEC-1 cells (IC = 28 ± 2 μM).

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“…In continuation of our involvement in the search for new biologically active nucleotide analogs , the synthesis and biological evaluation of a new series of acyclic phosphonylated 1,2,3‐triazolonucleosides 5a – e and 6a – h containing an acetamidomethyl linker located between a phosphorus atom and a 1,2,3‐triazole ring substituted at C4 with selected nucleobases are presented (Scheme ). In addition to the canonical nucleobases (in 4a – 4d ) and their close mimetics (in 4e and 4f ), several nucleobase analogs containing substituted heterocyclic (in 3e , 4g , and 4h ) and benzene (in 3a – 3d ) rings were used.…”

Section: Introductionmentioning

confidence: 99%

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

Głowacka

Balzarini

Wróblewski

2014

Archiv der Pharmazie

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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.

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Synthesis of a New Series of Phosphonylated 1,2,3‐Triazoles as Acyclic Analogs of Ribavirin

Cited by 12 publications

References 72 publications

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

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

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

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