Potent triazolyl-proline-based inhibitors of HCV NS3 protease.
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.
Naud
Julie
J
Boehringer Ingelheim (Canada) Ltd, Research and Development, 2100 rue Cunard, Laval, QC, Canada.
Lemke
Christopher
C
Goudreau
Nathalie
N
Beaulieu
Eric
E
White
Peter D
PD
Llinàs-Brunet
Montse
M
Forgione
Pat
P
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
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