title: Discovery of a series of novel compounds with moderate anti-hepatitis C virus NS3 protease activity in vitro.
abstract: The hepatitis C virus (HCV) NS3/4A protease that plays an important role in the viral life cycle has been proven to be an excellent target for the discovery of anti-HCV drugs. Enlightened by some P2-triazole and amide compounds, which had been found as HCV NS3 protease inhibitors, we designed and synthesized a series of novel compounds by incorporating different amino acid residues in P1/P1' and P3/P3' position to develop novel antiviral agents. The result of enzyme inhibition assay indicated that all the designed compounds showed moderate anti-HCV NS3 protease activity. On the basis of the biological result, a detailed structure-activity relationship (SAR) was derived and discussed.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China. Electronic address: wenfxu@163.com.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D016174:Hepacivirus / Q000201:enzymology*; D066298:In Vitro Techniques; D015394:Molecular Structure; D057786:Peptidomimetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D057786:Peptidomimetics; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Acylsulfonamide; HCV; Peptidomimetics; Protease inhibitors; Triazole