Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication

Journal of Medicinal Chemistry
Stephane L BogenF George Njoroge

Abstract

Introduction of various modified prolines at P(2) and optimization of the P(1) side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K(i)*= 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC(50) and IC(90) of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

References

Oct 1, 1994·Clinical Microbiology Reviews·J A Cuthbert
Dec 24, 1998·Antiviral Research·A D KwongS A Raybuck
May 21, 1999·Analytical Biochemistry·R ZhangB A Malcolm
Feb 24, 2001·Bioorganic & Medicinal Chemistry Letters·J M BennettF X Wilson
Jan 31, 2003·Expert Opinion on Investigational Drugs·Frank NarjesChristian Steinkühler
May 10, 2003·The Journal of Organic Chemistry·Juan R Del Valle, Murray Goodman
Jun 18, 2005·Science·Guo-Cheng YuanOliver J Rando
Aug 10, 2005·Bioorganic & Medicinal Chemistry Letters·A ArasappanA K Ganguly

❮ Previous
Next ❯

Citations

Dec 1, 2007·Nature Reviews. Drug Discovery·Erik De Clercq
Nov 23, 2006·FEBS Letters·Marlyse BuissonWim P Burmeister
Oct 2, 2013·Expert Opinion on Drug Discovery·David P Rotella
Nov 21, 2007·Journal of Molecular Graphics & Modelling·Hsin-Yuan WeiThy-Hou Lin
Sep 28, 2007·Advanced Drug Delivery Reviews·Masanori Ikeda, Nobuyuki Kato
Jul 7, 2007·Archives of Medical Research·Roberto J Firpi, David R Nelson
Jul 19, 2013·Annals of the New York Academy of Sciences·Daria J HazudaSrikanth Venkatraman
Sep 1, 2015·Chemical Reviews·Vedanjali GogineniMark T Hamann
Nov 27, 2007·Virus Research·Sandra FrancoMiguel Angel Martínez
Mar 30, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sandra FrancoMiguel Angel Martinez
Jan 22, 2009·Journal of Medicinal Chemistry·Francisco VelázquezF George Njoroge
Jan 8, 2015·Journal of Medicinal Chemistry·Arun K Ghosh, Margherita Brindisi
Aug 12, 2016·Journal of the American Chemical Society·Djadé I SoumanaCelia A Schiffer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.