National Center for
3U4R: Novel Hcv Ns5b Polymerase Inhibitors: Discovery Of Indole C2 Acyl Sulfonamides
Bioorg. Med. Chem. Lett. (2012) 22 p.713-717
Development of SAR at the C2 position of indole lead 1, a palm site inhibitor of HCV NS5B polymerase (NS5B IC(50)=0.053muM, replicon EC(50)=4.8muM), is described. Initial screening identified an acyl sulfonamide moiety as an isostere for the C2 carboxylic acid group. Further SAR investigation resulted in identification of acyl sufonamide analog 7q (NS5B IC(50)=0.039muM, replicon EC(50)=0.011muM) with >100-fold improved replicon activity.