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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
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.
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
ISSN: 1420-3049
DOI: 10.3390/molecules24081453
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications

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