Xiao Tong

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. doi P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile
    Latha G Nair
    Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:567-70. 2010
  2. doi Towards the second generation of Boceprevir: Dithianes as an alternative P2 substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors
    Latha G Nair
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:1689-92. 2010
  3. ncbi Trans-complementation of HCV replication by non-structural protein 5A
    Xiao Tong
    Virology Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Virus Res 115:122-30. 2006
  4. pmc Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease
    X Tong
    Department of Virology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Antimicrob Agents Chemother 54:2365-70. 2010
  5. ncbi Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034
    Xiao Tong
    Department of Virology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilwoth, NJ 07033, USA
    Antiviral Res 70:28-38. 2006
  6. doi Characterization of resistance mutations against HCV ketoamide protease inhibitors
    Xiao Tong
    Virology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Antiviral Res 77:177-85. 2008
  7. doi 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
  8. doi Synthesis and SAR of geminal substitutions at the C5' carbosugar position of pyrimidine-derived HCV inhibitors
    Vishal A Verma
    Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:6967-73. 2012
  9. doi A novel HCV NS3 protease mutation selected by combination treatment of the protease inhibitor boceprevir and NS5B polymerase inhibitors
    Robert Chase
    Department of Virology, K15 4945, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Antiviral Res 84:178-84. 2009
  10. doi Discovery and structure-activity relationship of P1-P3 ketoamide derived macrocyclic inhibitors of hepatitis C virus NS3 protease
    Srikanth Venkatraman
    Schering Plough Research Institute, K 15, MS 3545, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:336-46. 2009

Collaborators

Detail Information

Publications28

  1. doi P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile
    Latha G Nair
    Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:567-70. 2010
    ..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...
  2. doi Towards the second generation of Boceprevir: Dithianes as an alternative P2 substituent for 2,2-dimethyl cycloproyl proline in HCV NS3 protease inhibitors
    Latha G Nair
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:1689-92. 2010
    ..1.0]hexane-2-carboxylic acid. The systematic investigation led to the discovery of highly potent inhibitor 25 (K(i)( *)=7nM, EC(90)=30nM) with improved rat exposure of 2.56microM h...
  3. ncbi Trans-complementation of HCV replication by non-structural protein 5A
    Xiao Tong
    Virology Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Virus Res 115:122-30. 2006
    ..These studies strongly suggest that HCV non-structural proteins, with the exception of NS5A, can only act in cis on the RNA from which they were translated...
  4. pmc Preclinical characterization of the antiviral activity of SCH 900518 (narlaprevir), a novel mechanism-based inhibitor of hepatitis C virus NS3 protease
    X Tong
    Department of Virology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Antimicrob Agents Chemother 54:2365-70. 2010
    ..In summary, the results of the preclinical characterization of the antiviral activity of SCH 900518 support its evaluation in clinical studies...
  5. ncbi Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034
    Xiao Tong
    Department of Virology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilwoth, NJ 07033, USA
    Antiviral Res 70:28-38. 2006
    ..Combination therapy with IFN-alpha should also greatly reduce the potential emergence of resistance...
  6. doi Characterization of resistance mutations against HCV ketoamide protease inhibitors
    Xiao Tong
    Virology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Antiviral Res 77:177-85. 2008
    ..Changes at V36 and R155 had more severe impact on VX-950, whereas mutations at Q41, F43 and V170 conferred higher resistance to SCH 503034. Structural analysis of resistance mutations on inhibitor binding is discussed...
  7. doi 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...
  8. doi Synthesis and SAR of geminal substitutions at the C5' carbosugar position of pyrimidine-derived HCV inhibitors
    Vishal A Verma
    Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:6967-73. 2012
    ..Expanded SAR at the C2 amino position led to the utilization of C2 ethers. These compounds exhibited good potency, high selectivity, and excellent plasma exposure and bioavailability in rodent as well as in higher species...
  9. doi A novel HCV NS3 protease mutation selected by combination treatment of the protease inhibitor boceprevir and NS5B polymerase inhibitors
    Robert Chase
    Department of Virology, K15 4945, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Antiviral Res 84:178-84. 2009
    ..These findings support the rationale for clinical evaluation of combination treatment of HCV protease and polymerase inhibitors...
  10. doi Discovery and structure-activity relationship of P1-P3 ketoamide derived macrocyclic inhibitors of hepatitis C virus NS3 protease
    Srikanth Venkatraman
    Schering Plough Research Institute, K 15, MS 3545, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 52:336-46. 2009
    ..X-ray structure of 52 bound to NS3 protease and biological data are also discussed...
  11. doi Cyclic sulfones as novel P3-caps for hepatitis C virus NS3/4A (HCV NS3/4A) protease inhibitors: synthesis and evaluation of inhibitors with improved potency and pharmacokinetic profiles
    Francisco Velazquez
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033 1300, USA
    J Med Chem 53:3075-85. 2010
    ..The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration...
  12. doi 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...
  13. doi Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors
    Vinay M Girijavallabhan
    Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:5652-7. 2012
    ..Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC(50)), PK parameters in all species studied, and cross genotype activity...
  14. doi Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings
    Kevin X Chen
    Infectious Disease Tumor Biology, Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 A 3545, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 19:1105-9. 2009
    ..This compound had the best overall profile in potency and PK profile: excellent K(i)(*) of 5.3 nM and activity in replicon (EC(90)) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 microMh...
  15. doi 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...
  16. doi Design, synthesis, and evaluation of oxygen-containing macrocyclic peptidomimetics as inhibitors of HCV NS3 protease
    Francisco Velazquez
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033 1300, USA
    J Med Chem 52:700-8. 2009
    ....
  17. pmc Identification of HCV protease inhibitor resistance mutations by selection pressure-based method
    Ping Qiu
    Molecular Design and Informatics, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Nucleic Acids Res 37:e74. 2009
    ....
  18. doi Analysis of HCV resistance mutations during combination therapy with protease inhibitor boceprevir and PEG-IFN alpha-2b using TaqMan mismatch amplification mutation assay
    Stephanie Curry
    Virology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    J Virol Methods 153:156-62. 2008
    ..These results show that TaqMAMA can be used to detect minor resistant variants in pretreatment samples and to study in detail the evolution of mutant viruses during targeted antiviral therapy...
  19. doi Pyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors
    Frank Bennett
    Merck Research Laboratories, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:5144-9. 2012
    ....
  20. doi Discovery of novel P3 sulfonamide-capped inhibitors of HCV NS3 protease. Inhibitors with improved cellular potencies
    Srikanth Venkatraman
    Schering Plough Research Institute, K 15, Kenilworth, NJ 07033, United States
    Bioorg Med Chem 17:4486-95. 2009
    ..X-ray structure of one of these inhibitors bound to the enzyme revealed a hydrogen bond of the P(3) sulfonamide group to Cys-159 which resulted in improved binding and cellular potency...
  21. doi 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...
  22. ncbi Impact of naturally occurring variants of HCV protease on the binding of different classes of protease inhibitors
    Xiao Tong
    Antiviral Therapy, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    Biochemistry 45:1353-61. 2006
    ..The identification of naturally occurring variations which can affect inhibitor binding is an important step in the design of broad-spectrum, second generation protease inhibitors...
  23. doi 5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors
    Ashok Arasappan
    Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:3229-34. 2012
    ..Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol...
  24. doi Correlation between PAMPA permeability and cellular activities of hepatitis C virus protease inhibitors
    Cheng Li
    Schering Plough Research Institute, K 15 2 2700, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Biochem Pharmacol 75:1186-97. 2008
    ....
  25. ncbi Mutations conferring resistance to SCH6, a novel hepatitis C virus NS3/4A protease inhibitor. Reduced RNA replication fitness and partial rescue by second-site mutations
    Minkyung Yi
    Center for Hepatitis Research, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston 77555 1019, USA
    J Biol Chem 281:8205-15. 2006
    ....
  26. ncbi Amino acid mutations of the infectious clone from Chinese EIAV attenuated vaccine resulted in reversion of virulence
    Tao Shen
    National Center for AIDS STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
    Vaccine 24:738-49. 2006
    ....
  27. doi Molecular epidemiology of human immunodeficiency virus type 1 and hepatitis C virus in former blood donors in central China
    Pingping Liu
    The State Key Laboratory of Virology, Wuhan Institution of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
    AIDS Res Hum Retroviruses 24:1-6. 2008
    ..4%) were detected. No recombinant form of HIV-1 was identified. Non-B' subtypes occurring among FBDs indicate the complexity of the HIV-1 prevalence in central China, where HIV is beginning to spread into the general population...
  28. ncbi Full-length clone and characterization of a human immunodeficiency virus type 1 subtype B' isolated from Hubei Province, China
    Jian Xin Tan
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    Chin Med J (Engl) 120:831-3. 2007