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 Chemjournal_title
European journal of medicinal chemistryauthors
Bessières M,Hervin V,Roy V,Chartier A,Snoeck R,Andrei G,Lohier JF,Agrofoglio LAdoi
10.1016/j.ejmech.2018.01.086subject
Has Abstractpub_date
2018-02-25 00:00:00pages
678-686eissn
0223-5234issn
1768-3254pii
S0223-5234(18)30108-9journal_volume
146pub_type
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