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ID: ALA4196014
Journal: Eur J Med Chem
Title: Highly convergent synthesis and antiviral activity of (E)-but-2-enyl nucleoside phosphonoamidates.
Authors: Bessières M, Hervin V, Roy V, Chartier A, Snoeck R, Andrei G, Lohier JF, Agrofoglio LA.
Abstract: Several hitherto unknown (E)-but-2-enyl nucleoside phosphonoamidate analogs (ANPs) were prepared directed with nitrogen reagents by cross-metathesis in water-under ultrasound irradiation. Two diastereoisomers were formally identified by X-ray diffraction. These compounds were evaluated against a large spectrum of DNA and RNA viruses. Among them, the phosphonoamidate thymine analogue 19 emerged as the best prodrug against varicella-zoster virus (VZV) with EC50 values of 0.33 and 0.39 μM for wild-type and thymidine kinase deficient strains, respectively, and a selectivity index ≥200 μM. This breakthrough approach paves the way for new purine and pyrimidine (E)-but-2-enyl phosphonoamidate analogs.
CiteXplore: 29407990