Abstract

The major cause of chronic liver disease, cirrhosis, liver carcinoma and liver failure is Hepatitis C virus (HCV). NS3 is one of the attractive targets for therapy development for HCV as the N-terminal domain of the NS3 protein is a serine protein. NS3 protease acts by interfering with cellular mechanisms which are involved in the host immune response to an HCV infection and the inhibition of the protease is an efficient antiviral approach. NS3 protease inhibitors initially developed were: BILN 2061 (Ciluprevir), VX-950 (Telaprevir) and SCH503034. A combination therapy of injected pegylated interferon-α and oral ribavirin is regarded as the current standard therapy for HCV infection. Leucopenia, flu-like symptoms, thrombocytopenia, depression and anemia are some of the adverse effects of ribavirin. The compounds which constitute a benzoxaborole moiety interact with many biological targets and presents appreciable qualities. The acyl sulfinamide and the acyl cyanamide were shown to be potent P1 C-terminal groups in the enzyme assay. In a study, it is indicated that the aminobenzoyl sulfonamide fragment was identified as a novel P1 structural motif. New P2–P4 macrocycle inhibitors of NS3/4A were made up of a P1 C-terminal carboxylic acid have recently been developed. Potent tetrapeptidic inhibitors of the HCV NS3 protease have been developed by incorporating 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid as a new N-acyl-L-hydroxyproline were developed for the treatment of Hepatitis C. α-Amino cyclic boronates was designed and synthesized and incorporated successfully in several acyclic templates at the P1 position as HCV inhibitors. The boronic acid compounds acts as the HCV NS3 serine protease inhibitors. Some of the HCV-protease inhibitors are developed which are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2 phenylglycine or a glycine. NS3/4A protease inhibitors constituting of quinazoline derivatives as P2 substituent were synthesized. The tripeptide-based inhibitors of the HCV NS3 protease containing a novel P2-triazole had been synthesized. A protease domain (NS3pro) and RNA helicase domain (NS3hel) makes a multifunctional enzyme: Flaviviridae non-structural 3 proteins (NS3). Crude ethanol extract from rhizomes of the Chinese medicinal herb Rhodiola kirilowii (Regel) Maxim was also used for the cure of Hepatitis C. A new series of HCV NS3/4A protease inhibitors bearing a P2-P4 macrocycle and a P1- P10 a-ketoamide serine trap has been studied.

Key words: Hepatitis C virus, non-structural protein inhibitors.