3KN2

HCV NS3 Protease Domain with ketoamide inhibitor

Summary for 3KN2

• Entry DOI: 10.2210/pdb3kn2/pdb
• Descriptor: HCV NS3 Protease Domain, Peptide KK-NS4A-KK, ZINC ION, ... (5 entities in total)
• Functional Keywords: hepatitis c virus, ns3 protease domain, serine protease, ketoamide inhibitor, atp-binding, capsid protein, envelope protein, helicase, host membrane, hydrolase, membrane, nucleotide-binding, rna replication, transmembrane, virion
• Biological source: Hepatitis C virus subtype 1a; More
• Total number of polymer chains: 4
• Total formula weight: 48104.27

Authors

Nair, L.G.,Sannigrahi, M.,Pinto, P.,Bogen, S.,Chen, K.X.,Njoroge, G.,Prongay, A. (deposition date: 2009-11-11, release date: 2010-01-19, Last modification date: 2021-10-13)

Primary citation

Nair, L.G.,Sannigrahi, M.,Bogen, S.,Pinto, P.,Chen, K.X.,Prongay, A.,Tong, X.,Cheng, K.C.,Girijavallabhan, V.,George Njoroge, F.
P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile.
Bioorg.Med.Chem.Lett., 20:567-570, 2010

PubMed Abstract: SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4, 4-dimethyl lactam as the new P4 cap unit with improved potency (K(i)( *)=15nM, EC 90=70nM) and pharmacokinetic properties (Rat AUC (PO)=3.52microMh) compared to 1.

PubMed: 20004570
DOI: 10.1016/j.bmcl.2009.11.094

Experimental method

X-RAY DIFFRACTION (2.3 Å)