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https://doi.org/10.3390/molecules24081453
Title: | Fused heterocyclic systems with an s-triazine ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines | Authors: | Junaid, A. Lim, F.P.L. Zhou, Y.P. Chui, W.K. Dolzhenko, A.V. |
Keywords: | Azapurine Purine isostere Triazine Triazole |
Issue Date: | 2019 | Publisher: | MDPI AG | Citation: | Junaid, A., Lim, F.P.L., Zhou, Y.P., Chui, W.K., Dolzhenko, A.V. (2019). Fused heterocyclic systems with an s-triazine ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines. Molecules 24 (8) : 1453. ScholarBank@NUS Repository. https://doi.org/10.3390/molecules24081453 | Rights: | Attribution 4.0 International | Abstract: | 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. © 2019 by the authors. | Source Title: | Molecules | URI: | https://scholarbank.nus.edu.sg/handle/10635/209983 | ISSN: | 1420-3049 | DOI: | 10.3390/molecules24081453 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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