40597-86-2

Upstream product

• 4922-98-9 3-phenyl-1H-1,2,4-triazol-5-amine 
• 40597-80-6 2-phenyl-7-thioxo-6,7-dihydro-4H-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-one 
• 74-88-4 methyl iodide 
• 19923-10-5 C₁₂H₁₃N₅O₂S 

Downstream Products

• 1431968-81-8 2-phenyl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5,7(4H,6H)-dione 

Relevant academic research and scientific papers

Fused heterocyclic systems with an s-triazine ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines

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.

Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors

In our lead finding program, a series of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positions showed varying degrees of TP inhibitory activity comparable with positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 μm). Enzyme inhibition kinetics study suggested that compound IVn behaved as a mixed-type inhibitor of the enzyme with respect to thymidine (dThd) as a variable substrate. Compound IVn was also found to inhibit PMA-induced MMP-9 expression in MDA-MB-231 cells at sublethal concentrations. Computational docking study was performed to illustrate the enzyme inhibition kinetics and to explore the ligand-enzyme interactions.