Pyrazolo[1,5-<i>a</i>]-1,3,5-triazine C-Nucleoside as Deoxyadenosine Analogue: Synthesis, Pairing, and Resistance to Hydrolysis

Lefoix, Myriam; Mathis, Gérald; Kleinmann, Tirtsa; Truffert, Jean-Christophe; Asseline, Ulysse

doi:10.1021/jo5000253

Cited by 14 publications

(6 citation statements)

References 50 publications

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“…This seems confirmed by comparing the 1 H NMR spectra in SM Section with data given in [13] (for 4a) and in Ref. [42] (see Supplementary Information).…”

Section: General Informationsupporting

confidence: 74%

Microwave-Assisted Sequential One-Pot Synthesis of 8-Substituted Pyrazolo[1,5-a][1,3,5]triazines

2021

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This paper reports a convenient sequential one-pot approach for the synthesis of an array of 14 pyrazolo[1,5-a][1,3,5]triazines, substituted in C8 by halogen (Br), various functions (CN and CO2Et) and alkyl or (het)aryl groups. This study confirms the interest of combining the efficient heating obtained under dielectric microwave heating and the achievement of sequential one-pot reactions, avoiding the tedious work-up and purification of intermediate compounds, achieving sustainable synthesis processes. Considering usual conventional methods, this microwave protocol is featured by advantages in terms of yields, reaction times, and convenient gram scale synthesis.

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“…This seems confirmed by comparing the 1 H NMR spectra in SM Section with data given in [13] (for 4a) and in Ref. [42] (see Supplementary Information).…”

Section: General Informationsupporting

confidence: 74%

Microwave-Assisted Sequential One-Pot Synthesis of 8-Substituted Pyrazolo[1,5-a][1,3,5]triazines

2021

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“…98 Compound 37 was synthesized as a deoxyadenosine analogue (Figure 8) that was more resistant to acid-catalyzed hydrolysis than dA, yet able to base-pair with 2′-deoxythymidine. 99 Whether it would possess any antitumor and/or antiviral properties was not explored. A number of mono-and diindole C-nucleoside analogues have been synthesized, 100 but again, their biological properties were not assessed.…”

Section: C-nucleoside Hcv Polymerase Inhibitormentioning

confidence: 99%

“…Likewise, 36 (Figure ) has been synthesized, but again, these C-nucleoside analogues did not show antiviral activity (against HIV) . Compound 37 was synthesized as a deoxyadenosine analogue (Figure ) that was more resistant to acid-catalyzed hydrolysis than dA, yet able to base-pair with 2′-deoxythymidine . Whether it would possess any antitumor and/or antiviral properties was not explored.…”

Section: Showdomycin (32) L-showdomycin (33) Formycin (34) Carbocycli...mentioning

confidence: 99%

C-Nucleosides To Be Revisited

2015

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Two new C-nucleoside analogues, BCX4430, an imino-C-nucleoside, and GS-6620, a phosphoramidate derivative of 1'-cyano-2'-C-methyl-4-aza-7,9-dideazaadenosine C-nucleoside, have been recently described as effective against filovirus infections (Marburg) and hepatitis C virus (HCV), respectively. The first C-nucleoside analogues were described about half a century ago. The C-nucleoside pseudouridine is a natural component of RNA, and various other C-nucleoside analogues have been reported previously for their antiviral and/or anticancer potential, the most prominent being pyrazofurin, tiazofurin, and selenazofurin. In the meantime, showdomycin, formycin, and various triazole, pyrazine, pyridine, dihydroxyphenyl, thienopyrimidine, pyrazolotriazine, and porphyrin C-nucleoside analogues have been described. It would be worth revisiting these C-nucleosides and derivatives thereof, including their phosphoramidates, for their therapeutic potential in the treatment of virus infections and, where appropriate, cancer as well.

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“…However, to the best of our knowledge, no examples on transaminations at the position 7 of 1,2,4-triazolo[1,5- a ][1,3,5]triazines have been reported. For similar pyrazolo[1,5- a ][1,3,5]triazines, the replacement of a N-methylanilino substituent in the corresponding position with other amines was effectively employed in drug-discovery programs to prepare a variety of compounds with a diverse substitution pattern [33,34,35,36,37,38,39,40].…”

Section: Resultsmentioning

confidence: 99%

Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines

et al. 2019

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Purine isosteres present excellent opportunities in drug design and development. Using isosteres of natural purines as scaffolds for the construction of new therapeutic agents has been a valid strategy of medicinal chemistry. Inspired by the similarity to isoguanine, we attempted to develop a practical method for the preparation of 5-aza-isoguanines. Several synthetic approaches were explored to establish a robust general protocol for the preparation of these compounds. The significant difference in the reactivity of the C-5 and C-7 electrophilic centers of 1,2,4-triazolo[1,5-a][1,3,5]triazines (5-azapurines) towards nucleophiles was demonstrated. The most practical and general method for the preparation of 5-aza-isoguanines involved a regioselective reaction of ethoxycarbonyl isothiocyanate with a 5-aminotriazole. The intramolecular ring closure of the resulted product followed by the S-methylation afforded 7-methylthio-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-one, which could be effectively aminated with various amines. The resulted 5-aza-isoguanines resemble a known purine nucleoside phosphorylase inhibitor and could be interesting for further investigations as potential anticancer agents.

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Pyrazolo[1,5-a]-1,3,5-triazine C-Nucleoside as Deoxyadenosine Analogue: Synthesis, Pairing, and Resistance to Hydrolysis

Cited by 14 publications

References 50 publications

Microwave-Assisted Sequential One-Pot Synthesis of 8-Substituted Pyrazolo[1,5-a][1,3,5]triazines

Microwave-Assisted Sequential One-Pot Synthesis of 8-Substituted Pyrazolo[1,5-a][1,3,5]triazines

C-Nucleosides To Be Revisited

Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines

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