Faculty Advisor

Dempski, Robert E.

Project Center

University of Massachusetts Medical Center


Hepatitis C virus (HCV) infection can cause serious liver disease. Efforts to eliminate the virus involve the development of novel drugs designed to disrupt viral replication. One of the ways to inhibit the virus is by targeting the HCV enzyme NS3/4A protease. MK-5172 is a potent protease inhibitor recently approved by the FDA for the treatment of HCV. As part of this project, I synthesized four new analogues of MK-5172. These analogues, which lack the methoxy group on the quinoxaline, are either linear or have different macrocyclization than MK-5172. The compounds were tested for enzyme inhibitory activity using kinetic assays. The new macrocyclic analogues show potent inhibitory activity against wild-type NS3/4A protease and the D168A drug resistant variant.


Worcester Polytechnic Institute

Date Accepted

April 2016



Project Type

Major Qualifying Project


Restricted-WPI community only

Advisor Department

Chemistry and Biochemistry

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