title: Synthesis and antiviral activity of HCV NS3/4A peptidomimetic boronic acid inhibitors.
abstract: A new series of NS3/4A protease boronic acid inhibitors is described. The compounds show good biochemical potency and cellular activity. The peptidomimetic inhibitors were evaluated against proteases from different HCV genotypes and clinically relevant NS3/4A mutants. Compound 28 displayed subnanomolar to single digit nanomolar potencies in the enzymatic assays and an EC50 of 25 nM in the replicon cell-based assay.
authors.affiliation: Phenomix Corporation, 5930 Cornerstone Court West, Suite 230, San Diego, CA 92121, USA.
authors.forename: Amogh
authors.initials: A
authors.lastname: Boloor
authors.forename: Denise
authors.initials: D
authors.lastname: Hanway
authors.forename: Maria
authors.initials: M
authors.lastname: Joshi
authors.forename: David T
authors.initials: DT
authors.lastname: Winn
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mendez
authors.forename: Marlena
authors.initials: M
authors.lastname: Walls
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Fuxin
authors.initials: F
authors.lastname: Qian
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hepperle
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Li
authors.forename: David A
authors.initials: DA
authors.lastname: Campbell
authors.forename: Juan M
authors.initials: JM
authors.lastname: Betancort
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D001897:Boronic Acids; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus