Steven Harper

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase
    Steven Harper
    IRBM Merck Research Laboratories, Rome, Pomezia, Italy
    J Med Chem 48:4547-57. 2005
  2. doi request reprint 2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp
    Barbara Pacini
    IRBM, Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    Bioorg Med Chem Lett 19:6245-9. 2009
  3. ncbi request reprint Development and preliminary optimization of indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase
    Steven Harper
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    J Med Chem 48:1314-7. 2005
  4. doi request reprint Inhibitors of the hepatitis C virus NS3 protease with basic amine functionality at the P3-amino acid N-terminus: discovery and optimization of a new series of P2-P4 macrocycles
    Steven Harper
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    J Med Chem 52:4820-37. 2009
  5. ncbi request reprint Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors
    Paola Pace
    Istituto di Ricerche di Biologia Molecolare, P Angeletti S p A Merck Research Laboratories, Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 50:2225-39. 2007
  6. ncbi request reprint 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis
    Uwe Koch
    Istituto di Ricerche di Biologia Molecolare, P Angeletti S p A Merck Research Laboratories, Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 49:1693-705. 2006
  7. doi request reprint Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection
    Cristina Gardelli
    Department of Medicinal Chemistry, Istituto di Ricerche di Biologia Molecolare, P Angeletti SpA IRBM MRL Rome, Pomezia, Italy
    J Med Chem 52:5394-407. 2009
  8. ncbi request reprint Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid
    Ian Stansfield
    Department of Medicinal Chemistry, IRBM MRL Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 14:5085-8. 2004
  9. ncbi request reprint The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease
    Jesus M Ontoria
    IRBM MRL Rome, Via Pontina Km 30, 600, 00040 Rome, Italy
    J Med Chem 47:6443-6. 2004
  10. pmc Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs
    Jesus M Ontoria
    Departments of Chemistry and Biology, IRBM Science Park, Via Pontina Km 30, 600, 00071 Pomezia, Rome, Italy
    ACS Med Chem Lett 7:454-9. 2016

Detail Information

Publications12

  1. ncbi request reprint Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase
    Steven Harper
    IRBM Merck Research Laboratories, Rome, Pomezia, Italy
    J Med Chem 48:4547-57. 2005
    ..Optimized analogues devoid of PXR activation (e.g., 55, EC(50) = 127 nM) retain strong cell-based efficacy under high serum conditions and show acceptable pharmacokinetics parameters in rat and dog...
  2. doi request reprint 2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp
    Barbara Pacini
    IRBM, Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    Bioorg Med Chem Lett 19:6245-9. 2009
    ..The results generated are in broad agreement with the previously proposed binding model for this compound class...
  3. ncbi request reprint Development and preliminary optimization of indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase
    Steven Harper
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    J Med Chem 48:1314-7. 2005
    ..Inhibitors from this class have promising characteristics for further development as anti-HCV agents...
  4. doi request reprint Inhibitors of the hepatitis C virus NS3 protease with basic amine functionality at the P3-amino acid N-terminus: discovery and optimization of a new series of P2-P4 macrocycles
    Steven Harper
    IRBM Merck Research Laboratories Rome, Via Pontina Km 30, 600, 00040 Pomezia, Rome, Italy
    J Med Chem 52:4820-37. 2009
    ..Optimization of this new class of P3-amine based inhibitors gave compounds such as 25 and 26 that combine excellent cell based activity with pharmacokinetic properties that are attractive for an antiviral targeting HCV...
  5. ncbi request reprint Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors
    Paola Pace
    Istituto di Ricerche di Biologia Molecolare, P Angeletti S p A Merck Research Laboratories, Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 50:2225-39. 2007
    ..The compound has favorable pharmacokinetic properties in preclinical species (rats, dogs, and monkeys) and shows no liabilities in several counterscreening assays, highlighting its potential as a clinically useful antiviral agent...
  6. ncbi request reprint 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis
    Uwe Koch
    Istituto di Ricerche di Biologia Molecolare, P Angeletti S p A Merck Research Laboratories, Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 49:1693-705. 2006
    ..We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions...
  7. doi request reprint Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection
    Cristina Gardelli
    Department of Medicinal Chemistry, Istituto di Ricerche di Biologia Molecolare, P Angeletti SpA IRBM MRL Rome, Pomezia, Italy
    J Med Chem 52:5394-407. 2009
    ..Our SAR studies ultimately led to compounds that gave high levels of NTP in hamster and rat liver after subcutaneous dosing and that were devoid of the toxic phenol moiety usually found in ProTides...
  8. ncbi request reprint Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid
    Ian Stansfield
    Department of Medicinal Chemistry, IRBM MRL Rome, Via Pontina Km 30, 600, Pomezia, 00040 Rome, Italy
    Bioorg Med Chem Lett 14:5085-8. 2004
    ..This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series...
  9. ncbi request reprint The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease
    Jesus M Ontoria
    IRBM MRL Rome, Via Pontina Km 30, 600, 00040 Rome, Italy
    J Med Chem 47:6443-6. 2004
    ..The crystal structure of the ternary NS3/NS4A/inhibitor complex for the most active molecule in this series highlights its suitability as an N-terminal capping group of a dipeptide inhibitor of the NS3 protease...
  10. pmc Discovery of a Selective Series of Inhibitors of Plasmodium falciparum HDACs
    Jesus M Ontoria
    Departments of Chemistry and Biology, IRBM Science Park, Via Pontina Km 30, 600, 00071 Pomezia, Rome, Italy
    ACS Med Chem Lett 7:454-9. 2016
    ..Inhibition of parasital HDACs as the mechanism of action of this new class of selective growth inhibitors is supported by hyperacetylation studies. ..
  11. pmc Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase
    Licia Tomei
    Istituto di Ricerche di Biologia Molecolare P Angeletti, 00040 Pomezia Rome, Italy
    J Virol 77:13225-31. 2003
    ..Interestingly, proline 495 lies in a recently identified noncatalytic GTP-binding site, thus validating it as a potential allosteric site that can be targeted by small-molecule inhibitors of HCV polymerase...
  12. ncbi request reprint Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site
    Stefania Di Marco
    Istituto di Ricerche di Biologia Molecolare P Angeletti, Pomezia Rome, Italy
    J Biol Chem 280:29765-70. 2005
    ..Our structures identify a novel mechanism by which a new class of allosteric inhibitors inhibits the HCV polymerase and open the way to the development of novel antiviral agents against this clinically relevant human pathogen...