In an attempt to identify potential HCV NS3 protease inhibitors lead compounds, 
a series of novel indoles (10a-g) was designed. Molecular modeling study, 
including fitting to a 3D-pharmacophore model of the designed molecules (10a-g), 
with HCV NS3 protease hypothesis using catalyst program was fulfilled. Also, the 
molecular docking into the NS3 active site was examined using Discovery Studio 
2.5 software. Several compounds showed significant high simulation docking score 
and fit values. The designed compounds with high docking score and fit values 
were synthesized and biologically evaluated in vitro using an NS3 protease 
binding assay. It appears that most of the tested compounds reveal promising 
inhibitory activity against NS3 protease. Of these, compounds 10a and 10b 
demonstrated potent HCV NS3 protease inhibitors with IC(50) values of 9 and 
12μg/mL, respectively. The experimental serine protease inhibitor activities of 
compounds 10a-g were consistent with their molecular modeling results. 
Inhibitors from this class have promising characteristics for further 
development as anti-HCV agents.