Stephane L Bogen

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. ncbi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency
    S Bogen
    Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4515-9. 2005
  2. doi request reprint Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species
    Stephane L Bogen
    Department of Medicinal Chemistry, Merck Research Labs, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem 18:1854-65. 2010
  3. doi request reprint Toward the back-up of boceprevir (SCH 503034): discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profiles
    Stephane L Bogen
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:3679-88. 2009
  4. doi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: SAR of new P1 derivatives of SCH 503034
    S Bogen
    Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 18:4219-23. 2008
  5. ncbi request reprint Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication
    Stephane L Bogen
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 49:2750-7. 2006
  6. ncbi request reprint Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity
    Stephane L Bogen
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 16:1621-7. 2006
  7. doi request reprint The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: a change in direction in the search for a second generation HCV NS3 protease inhibitor
    Frank Bennett
    Schering Plough Research Institute, K 15 A 3545, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:2617-21. 2010
  8. doi request reprint Second-generation highly potent and selective inhibitors of the hepatitis C virus NS3 serine protease
    Kevin X Chen
    Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:1370-9. 2009
  9. ncbi request reprint Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavaila
    Srikanth Venkatraman
    Schering Plough Research Institute, K 15, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 49:6074-86. 2006
  10. pmc Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034
    Vincent Madison
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Synchrotron Radiat 15:204-7. 2008

Detail Information

Publications13

  1. ncbi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency
    S Bogen
    Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 15:4515-9. 2005
    ..Modification of the P(2) and P(1) side chains of earlier P(3)-capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 resulted in the discovery of compound 24 with about 10-fold improvement in potency...
  2. doi request reprint Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species
    Stephane L Bogen
    Department of Medicinal Chemistry, Merck Research Labs, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem 18:1854-65. 2010
    ..The combination of optimal moieties led to the discovery of compound 47 which, in addition to being a potent inhibitor of HCV subgenomic RNA replication, was also found to have good PK profile in rat, dog and monkey...
  3. doi request reprint Toward the back-up of boceprevir (SCH 503034): discovery of new extended P4-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease with improved potency and pharmacokinetic profiles
    Stephane L Bogen
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:3679-88. 2009
    ..In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P(4)-capped inhibitors were also found to have improved PK profile...
  4. doi request reprint Hepatitis C virus NS3-4A serine protease inhibitors: SAR of new P1 derivatives of SCH 503034
    S Bogen
    Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 18:4219-23. 2008
    ..Substitutions on the P(1) cyclobutyl side chain of SCH 503034 were studied by introduction of hydroxyl and fluoro substituents. Additionally, effects of fluoro substitution on other P1 moieties were evaluated...
  5. ncbi request reprint Discovery of SCH446211 (SCH6): a new ketoamide inhibitor of the HCV NS3 serine protease and HCV subgenomic RNA replication
    Stephane L Bogen
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 49:2750-7. 2006
    ..In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons...
  6. ncbi request reprint Depeptidization efforts on P3-P2' alpha-ketoamide inhibitors of HCV NS3-4A serine protease: effect on HCV replicon activity
    Stephane L Bogen
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 16:1621-7. 2006
    ..We clearly established that N-methylation of the P(2) nitrogen and modification of the P(2)' carboxylic acid terminus were essential for activity in the replicon assay...
  7. doi request reprint The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: a change in direction in the search for a second generation HCV NS3 protease inhibitor
    Frank Bennett
    Schering Plough Research Institute, K 15 A 3545, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:2617-21. 2010
    ..Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration...
  8. doi request reprint Second-generation highly potent and selective inhibitors of the hepatitis C virus NS3 serine protease
    Kevin X Chen
    Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:1370-9. 2009
    ..X-ray structure of inhibitor 46 bound to the enzyme revealed that there was an additional hydrogen bonding interaction between one of the imide carbonyls and Cys159...
  9. ncbi request reprint Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavaila
    Srikanth Venkatraman
    Schering Plough Research Institute, K 15, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 49:6074-86. 2006
    ..X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed...
  10. pmc Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034
    Vincent Madison
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Synchrotron Radiat 15:204-7. 2008
    ..This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease, which is currently in clinical trials...
  11. doi request reprint Toward second generation hepatitis C virus NS3 serine protease inhibitors: discovery of novel P4 modified analogues with improved potency and pharmacokinetic profile
    Ashok Arasappan
    Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:2806-17. 2009
    ..Combining the preferred moieties, identified from comprehensive SAR studies, resulted in inhibitors that displayed superior potency and very good oral as well as target organ exposure in rats...
  12. ncbi request reprint Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II.
    Andrew J Prongay
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 50:2310-8. 2007
    ..B 1970, 257, 249-264]. This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease that is currently in clinical trials...
  13. ncbi request reprint Core modification of substituted piperidines as novel inhibitors of HDM2-p53 protein-protein interaction
    Weidong Pan
    Merck Research Laboratories, Early Development and Discovery Sciences, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States
    Bioorg Med Chem Lett 24:1983-6. 2014
    ..Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. ..