II. Novel HCV NS5B polymerase inhibitors: discovery of indole C2 acyl sulfonamides.

Development of SAR at the C2 position of indole lead 1, a palm site inhibitor of HCV NS5B polymerase (NS5B IC50 = 0.053 mu M, replicon EC50 = 4.8 mu M), 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 IC50 = 0.039 mu M, replicon EC50 = 0.011 mu M) with >100-fold improved replicon activity. (C) 2011 Elsevier Ltd. All rights reserved.