Synthesis and evaluation of novel flexible nucleoside analogues against H1N1 influenza virus

Flexible nucleoside analogues (fleximers) are viewed as a new class of inhibitors against numerous highly lethal RNA virus infections and pandemics. In this work, we chemically synthesized a series of novel fleximers featuring a flexible base moiety connected to a pentose sugar ring and tested them for activity against H1N1 influenza virus. The novel flexible nucleoside analogues exhibit low micromolar levels of antiviral activity. The most potent 7c is able to potently inhibit the multiplication of the H1N1 influenza strains with an
in vitro
anti-H1N1 EC
50
of 1.371 μM. Most importantly, 7c demonstrated an excellent safety profile with cytotoxicity CC
50
>200μM and an
in vivo
mouse LD
50
> 2000 mg/kg. As such, 7c could serve as a novel lead compound for the further development of antiviral drug candidate.