Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines
| Autor: | Yvonne Peijun Zhou, Wai Keung Chui, Anton V. Dolzhenko, Felicia Phei Lin Lim, Ahmad Junaid |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Guanine
Isoguanine Triazole Pharmaceutical Science Antineoplastic Agents 010402 general chemistry Ring (chemistry) 01 natural sciences Article Analytical Chemistry lcsh:QD241-441 purine isostere chemistry.chemical_compound Nucleophile lcsh:Organic chemistry Drug Discovery Reactivity (chemistry) Physical and Theoretical Chemistry Enzyme Inhibitors Triazine azapurine 010405 organic chemistry Triazines Organic Chemistry Regioselectivity Purine Nucleosides Combinatorial chemistry 0104 chemical sciences triazole chemistry Purine-Nucleoside Phosphorylase Chemistry (miscellaneous) Electrophile Molecular Medicine triazine |
| Zdroj: | Molecules Molecules, Vol 24, Iss 8, p 1453 (2019) Volume 24 Issue 8 |
| ISSN: | 1420-3049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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