Francisco Velazquez

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. doi request reprint A novel class of highly potent irreversible hepatitis C virus NS5B polymerase inhibitors
    Kevin X Chen
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 55:2089-101. 2012
  2. doi request reprint 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
  3. ncbi request reprint Application of ring-closing metathesis for the synthesis of macrocyclic peptidomimetics as inhibitors of HCV NS3 protease
    Francisco Velazquez
    Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, New Jersey 07033 1300, USA
    Org Lett 9:3061-4. 2007
  4. doi request reprint 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
  5. doi request reprint II. Novel HCV NS5B polymerase inhibitors: discovery of indole C2 acyl sulfonamides
    Gopinadhan N Anilkumar
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:713-7. 2012
  6. doi request reprint 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
  7. doi request reprint 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
  8. doi request reprint Structure-activity relationship (SAR) development and discovery of potent indole-based inhibitors of the hepatitis C virus (HCV) NS5B polymerase
    Kevin X Chen
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
    J Med Chem 55:754-65. 2012
  9. 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
  10. doi request reprint Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups
    Srikanth Venkatraman
    Schering Plough Research Institute, K15 MS 3545, 2015, Galloping Hill Road, Kenilworth, NJ 07033, United States
    Bioorg Med Chem Lett 20:2151-5. 2010

Collaborators

Detail Information

Publications18

  1. doi request reprint A novel class of highly potent irreversible hepatitis C virus NS5B polymerase inhibitors
    Kevin X Chen
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    J Med Chem 55:2089-101. 2012
    ..The overall excellent profile of 47 made it an interesting candidate for further investigation...
  2. doi request reprint 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...
  3. ncbi request reprint Application of ring-closing metathesis for the synthesis of macrocyclic peptidomimetics as inhibitors of HCV NS3 protease
    Francisco Velazquez
    Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 3 3545, Kenilworth, New Jersey 07033 1300, USA
    Org Lett 9:3061-4. 2007
    ..The methyl ester moiety in the RCM products was synthetically manipulated to install a keto-amide moiety via a Passerini reaction...
  4. doi request reprint 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
    ....
  5. doi request reprint II. Novel HCV NS5B polymerase inhibitors: discovery of indole C2 acyl sulfonamides
    Gopinadhan N Anilkumar
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 22:713-7. 2012
    ..Further SAR investigation resulted in identification of acyl sufonamide analog 7q (NS5B IC(50)=0.039μM, replicon EC(50)=0.011μM) with >100-fold improved replicon activity...
  6. doi request reprint 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...
  7. doi request reprint 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...
  8. doi request reprint Structure-activity relationship (SAR) development and discovery of potent indole-based inhibitors of the hepatitis C virus (HCV) NS5B polymerase
    Kevin X Chen
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States
    J Med Chem 55:754-65. 2012
    ..02 μM) assays and a good oral PK profile with area-under-the curve (AUC) of 14 and 8 μM·h in rats and dogs, respectively. X-ray structure of inhibitor 56 bound to the enzyme was also reported...
  9. 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...
  10. doi request reprint Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups
    Srikanth Venkatraman
    Schering Plough Research Institute, K15 MS 3545, 2015, Galloping Hill Road, Kenilworth, NJ 07033, United States
    Bioorg Med Chem Lett 20:2151-5. 2010
    ..In this manuscript we describe alpha quaternized P(1) group that result in potent inhibitors in the enzyme assay and demonstrate cellular activity comparable to boceprevir...
  11. doi request reprint 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...
  12. 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...
  13. doi request reprint Optimization of potency and pharmacokinetics of tricyclic indole derived inhibitors of HCV NS5B polymerase. Identification of ester prodrugs with improved oral pharmacokinetics
    Srikanth Venkatraman
    Merck Research Laboratories, K15, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States Electronic address
    Bioorg Med Chem 22:447-58. 2014
    ..These analogs also demonstrate excellent PK in rats and monkeys when administered as a dimethyl ethyl amino ester prodrug. ..
  14. doi request reprint 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...
  15. doi request reprint Synthesis of new 4,5-dihydrofuranoindoles and their evaluation as HCV NS5B polymerase inhibitors
    Francisco Velazquez
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033 1300, USA
    Org Lett 14:556-9. 2012
    ..These new indole compounds were used to synthesize potent HCV NS5B inhibitors. The binding mode of the dihydrofuranoindole-derived inhibitors was established via X-ray crystallographic studies...
  16. ncbi request reprint 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...
  17. doi request reprint Discovery of an irreversible HCV NS5B polymerase inhibitor
    Qingbei Zeng
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 23:6585-7. 2013
    ..The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays...
  18. doi request reprint I. Novel HCV NS5B polymerase inhibitors: discovery of indole 2-carboxylic acids with C3-heterocycles
    Gopinadhan N Anilkumar
    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 21:5336-41. 2011
    ..SAR development resulted in leads 7q (NS5B IC(50)=0.032 μM, replicon EC(50)=1.4 μM) and 7r (NS5B IC(50)=0.017 μM, replicon EC(50)=0.3 μM) with improved enzyme and replicon activity...