title: Potent triazolyl-proline-based inhibitors of HCV NS3 protease.
abstract: The design and synthesis of tripeptide-based inhibitors of the HCV NS3 protease containing a novel P2-triazole is described. Replacement of the P2 quinoline with a triazole moiety provided a versatile handle which could be expediently modified to generate a diverse series of inhibitors. Further refinement by the incorporation of an aryl-substituted triazole and replacement of the P1 acid with an acyl sulfonamide ultimately provided inhibitors with interesting cellular activity.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 rue Cunard, Laval, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Naud
authors.forename: Christopher
authors.initials: C
authors.lastname: Lemke
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goudreau
authors.forename: Eric
authors.initials: E
authors.lastname: Beaulieu
authors.forename: Peter D
authors.initials: PD
authors.lastname: White
authors.forename: Montse
authors.initials: M
authors.lastname: Llinàs-Brunet
authors.forename: Pat
authors.initials: P
authors.lastname: Forgione
mesh_terms: D020650:Combinatorial Chemistry Techniques; D016174:Hepacivirus / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D011392:Proline; D011480:Protease Inhibitors; D014230:Triazoles; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases