title: A Journey around the Medicinal Chemistry of Hepatitis C Virus Inhibitors Targeting NS4B: From Target to Preclinical Drug Candidates.
abstract: Hepatitis C virus (HCV) infection is a global health burden with an estimated 130-170 million chronically infected individuals and is the cause of serious liver diseases such as cirrhosis and hepatocellular carcinoma. HCV NS4B protein represents a validated target for the identification of new drugs to be added to the combination regimen recently approved. During the last years, NS4B has thus been the object of impressive medicinal chemistry efforts, which led to the identification of promising preclinical candidates. In this context, the present review aims to discuss research published on NS4B functional inhibitors focusing the attention on hit identification, hit-to-lead optimization, ADME profile evaluation, and the structure-activity relationship data raised for each compound family taken into account. The information delivered in this review will be a useful and valuable tool for those medicinal chemists dealing with research programs focused on NS4B and aimed at the identification of innovative anti-HCV compounds.
authors.affiliation: Department of Pharmaceutical Sciences, Università degli Studi di Perugia , Via A. Fabretti, 48-06123 Perugia, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Cannalire
authors.affiliation: Department of Pharmaceutical Sciences, Università degli Studi di Perugia , Via A. Fabretti, 48-06123 Perugia, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.affiliation: Department of Pharmaceutical Sciences, Università degli Studi di Perugia , Via A. Fabretti, 48-06123 Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manfroni
authors.affiliation: Department of Pharmaceutical Sciences, Università degli Studi di Perugia , Via A. Fabretti, 48-06123 Perugia, Italy.
authors.forename: Violetta
authors.initials: V
authors.lastname: Cecchetti
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D057166:High-Throughput Screening Assays; D006801:Humans; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C080107:NS4B protein, flavivirus; D017361:Viral Nonstructural Proteins