3U4R: 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 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.
PDB ID: 3U4RDownload
MMDB ID: 95585
PDB Deposition Date: 2011/10/10
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 3U4R: monomeric; determined by author and by software (PISA)
Molecular Components in 3U4R
Label Count Molecule
Protein (1 molecule)
RNA-directed RNA Polymerase
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB