Molecular design and synthesis of HCV inhibitors based on thiazolone scaffold

A series of thiazolone derivatives was designed and synthesized as potential HCV NS5B allosteric polymerase inhibitors at the allosteric site thumb II. Their antiviral activity was evaluated and molecular modeling was utilized to give further envision on their probable binding modes in the allosteric binding site. Among the tested molecules, compound 9b displayed sub-micromolar inhibitory activity with an EC50 of 0.79 mu M indicating excellent potency profile. It also showed good safety profile (CC50 >= 75 mu M and SI >= 94.3). (C) 2013 Elsevier Masson SAS. All rights reserved.