Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Herein, we report the synthesis and in vitro evaluation of anti-NS5B polymerase activity of a molecular hybrid of our previously reported lead compounds 1 (IC50= 7.7 μM) and 2 (IC50= 10.6 μM) as represented by hybrid compound 27 (IC50= 6.7 μM). We have explored the optimal substituents on the terminal phenyl ring of the 3- ...