title: Discovery of novel phosphonate derivatives as hepatitis C virus NS3 protease inhibitors.
abstract: A novel class of phosphonate derivatives was designed to mimic the interaction of product-like carboxylate based inhibitors of HCV NS3 protease. A phosphonic acid (compound 2) was demonstrated to be a potent HCV NS3 protease inhibitor, and a potential candidate for treating HCV infection. The syntheses and preliminary biological evaluation of this phosphonate class of inhibitor are described.
authors.affiliation: Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA. csheng@gilead.com
authors.forename: X Christopher
authors.initials: XC
authors.lastname: Sheng
authors.forename: Hyung-Jung
authors.initials: HJ
authors.lastname: Pyun
authors.forename: Kleem
authors.initials: K
authors.lastname: Chaudhary
authors.forename: Jianying
authors.initials: J
authors.lastname: Wang
authors.forename: Edward
authors.initials: E
authors.lastname: Doerffler
authors.forename: Melissa
authors.initials: M
authors.lastname: Fleury
authors.forename: Darren
authors.initials: D
authors.lastname: McMurtrie
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Chen
authors.forename: William E
authors.initials: WE
authors.lastname: Delaney
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004285:Dogs; D055808:Drug Discovery; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases