Highly convergent synthesis and antiviral activity of (E)-but-2-enyl nucleoside phosphonoamidates.

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.

journal_name

Eur J Med Chem

authors

Bessières M,Hervin V,Roy V,Chartier A,Snoeck R,Andrei G,Lohier JF,Agrofoglio LA

doi

10.1016/j.ejmech.2018.01.086

subject

Has Abstract

pub_date

2018-02-25 00:00:00

pages

678-686

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(18)30108-9

journal_volume

146

pub_type

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