David R Langley

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. pmc Inhibition of hepatitis B virus polymerase by entecavir
    David R Langley
    Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06443, USA
    J Virol 81:3992-4001. 2007
  2. doi request reprint Balancing oral exposure with Cyp3A4 inhibition in benzimidazole-based IGF-IR inhibitors
    Kurt Zimmermann
    Bristol Myers Squibb Co, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 18:4075-80. 2008
  3. doi request reprint The terminal (catalytic) adenosine of the HIV LTR controls the kinetics of binding and dissociation of HIV integrase strand transfer inhibitors
    David R Langley
    Department of Computer Assisted Drug Design, Bristol Myers Squibb Research and Development, Wallingford, Connecticut 06492, USA
    Biochemistry 47:13481-8. 2008
  4. ncbi request reprint Respiratory syncytial virus fusion inhibitors. Part 6: an examination of the effect of structural variation of the benzimidazol-2-one heterocycle moiety
    Keith D Combrink
    Department of Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 17:4784-90. 2007
  5. doi request reprint E-novo: an automated workflow for efficient structure-based lead optimization
    Bradley C Pearce
    Bristol Myers Squibb, Computer Assisted Drug Design, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Chem Inf Model 49:1797-809. 2009
  6. doi request reprint Communication: Quantum polarized fluctuating charge model: a practical method to include ligand polarizability in biomolecular simulations
    S Roy Kimura
    Department of Computer Assisted Drug Design, Bristol Myers Squibb R and D, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Chem Phys 135:231101. 2011
  7. doi request reprint MORPH: a new tool for ligand design
    Brett R Beno
    Computer Assisted Drug Design Department, Applied Biotechnology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Chem Inf Model 50:1159-64. 2010
  8. doi request reprint 2-(1H-Imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chain variants of the IGF-1R inhibitor BMS-536924
    Mark G Saulnier
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 18:1702-7. 2008
  9. pmc X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir
    Herbert E Klei
    Macromolecular Crystallography, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    J Virol 81:9525-35. 2007
  10. ncbi request reprint Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)
    Upender Velaparthi
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 17:2317-21. 2007

Collaborators

Detail Information

Publications27

  1. pmc Inhibition of hepatitis B virus polymerase by entecavir
    David R Langley
    Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06443, USA
    J Virol 81:3992-4001. 2007
    ..Overall, these studies explain the potency, mechanism, and cross-resistance profile of ETV against HBV and account for the successful treatment of naive and LVD- or ADV-experienced chronic HBV patients...
  2. doi request reprint Balancing oral exposure with Cyp3A4 inhibition in benzimidazole-based IGF-IR inhibitors
    Kurt Zimmermann
    Bristol Myers Squibb Co, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 18:4075-80. 2008
    ..The use of malonate as methyl anion synthon via S(N)Ar reaction and double decarboxylation under mild conditions is demonstrated...
  3. doi request reprint The terminal (catalytic) adenosine of the HIV LTR controls the kinetics of binding and dissociation of HIV integrase strand transfer inhibitors
    David R Langley
    Department of Computer Assisted Drug Design, Bristol Myers Squibb Research and Development, Wallingford, Connecticut 06492, USA
    Biochemistry 47:13481-8. 2008
    ..These findings further our understanding of the details of the inhibitor binding site of specific strand transfer inhibitors...
  4. ncbi request reprint Respiratory syncytial virus fusion inhibitors. Part 6: an examination of the effect of structural variation of the benzimidazol-2-one heterocycle moiety
    Keith D Combrink
    Department of Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 17:4784-90. 2007
    ..The introduction of an aminomethyl substituent to the benzimidazole ring enhanced antiviral activity in the 6,6-fused ring systems...
  5. doi request reprint E-novo: an automated workflow for efficient structure-based lead optimization
    Bradley C Pearce
    Bristol Myers Squibb, Computer Assisted Drug Design, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Chem Inf Model 49:1797-809. 2009
    ..The E-Novo protocol provides a convenient all-in-one structure-based design process for rapid assessment and scoring of lead optimization libraries...
  6. doi request reprint Communication: Quantum polarized fluctuating charge model: a practical method to include ligand polarizability in biomolecular simulations
    S Roy Kimura
    Department of Computer Assisted Drug Design, Bristol Myers Squibb R and D, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Chem Phys 135:231101. 2011
    ....
  7. doi request reprint MORPH: a new tool for ligand design
    Brett R Beno
    Computer Assisted Drug Design Department, Applied Biotechnology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Chem Inf Model 50:1159-64. 2010
    ..The MORPH program and its application to two ligands extracted from cocrystal structures with cyclin-dependent kinase 2 (CDK2)/cyclin A and CDK2 are discussed below...
  8. doi request reprint 2-(1H-Imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chain variants of the IGF-1R inhibitor BMS-536924
    Mark G Saulnier
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 18:1702-7. 2008
    ..This may be the due to the improved protein binding in human and mouse serum for imidazole 16a and the excellent oral exposure of pyrazole 17f...
  9. pmc X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavir
    Herbert E Klei
    Macromolecular Crystallography, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    J Virol 81:9525-35. 2007
    ..Because of its nearly symmetrical chemical structure, atazanavir is able to make several analogous contacts with each monomer of the biological dimer...
  10. ncbi request reprint Discovery and initial SAR of 3-(1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-ones as inhibitors of insulin-like growth factor 1-receptor (IGF-1R)
    Upender Velaparthi
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 17:2317-21. 2007
    ..Installing amine containing side chains at the 4-position of pyridone ring significantly improved the enzyme potency. SAR and biological activity of these compounds is presented...
  11. ncbi request reprint Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as corticotropin-releasing factor1 receptor ligands
    Richard A Hartz
    Discovery Chemistry, Bristol Myers Squibb Company, Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 16:934-7. 2006
    ..Selected compounds were examined in a rat pharmacokinetic study and were found to have oral bioavailabilities ranging from 16 to 35%...
  12. pmc In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043
    Nannan Zhou
    Virology, Bristol Myers Squibb, Wallingford, CT 06492, USA
    Antimicrob Agents Chemother 55:729-37. 2011
    ..Most importantly, the substitutions described here are not associated with resistance to other approved antiretrovirals, and therefore, attachment inhibitors could complement the current arsenal of anti-HIV agents...
  13. ncbi request reprint Discovery of a fluoroindolo[2,3-a]carbazole clinical candidate with broad spectrum antitumor activity in preclinical tumor models superior to the marketed oncology drug, CPT-11
    Mark G Saulnier
    The Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    J Med Chem 48:2258-61. 2005
    ..The lead clinical candidate from this series, BMS-250749, displays broad spectrum antitumor activity superior to CPT-11 against some preclinical xenograft models, including curative antitumor activity against Lewis lung carcinoma...
  14. ncbi request reprint Novel 3',6'-anhydro and N12,N13-bridged glycosylated fluoroindolo[2,3-a]carbazoles as topoisomerase I inhibitors. Fluorine as a leaving group from sp3 carbon
    Mark G Saulnier
    Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    Org Lett 7:1271-4. 2005
    ..A novel N12,N13-bridged sugar analogue 2 results from loss of 4'-fluorine from beta-N-glycosylated analogue 4. Both analogues 1 and 2 display topo I inhibitory potencies similar to camptothecin...
  15. pmc Targeting a binding pocket within the trimer-of-hairpins: small-molecule inhibition of viral fusion
    Christopher Cianci
    Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA
    Proc Natl Acad Sci U S A 101:15046-51. 2004
    ..Because analogous cavities are present in many class I viruses, including HIV, these results demonstrate the feasibility of this approach as a strategy for drug discovery...
  16. doi request reprint Characterizations of HCV NS5A replication complex inhibitors
    Donald R O'Boyle Ii
    Bristol Myers Squibb Research and Development, Department of Virology Discovery, 5 Research Parkway, Wallingford, CT 06492, USA Electronic address
    Virology 444:343-54. 2013
    ..The functional data supports a model of inhibition that implicates inhibitor binding by covalently combining distinct pharmacophores across an NS5A dimer interface to achieve maximal inhibition of HCV replication. ..
  17. doi request reprint Nucleophilic capture of the imino-quinone methide type intermediates generated from 2-aminothiazol-5-yl carbinols
    Mark G Saulnier
    Department of Discovery Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    Org Lett 11:5154-7. 2009
    ..Generation of imino-quinone methide type intermediates from 2-aminothiazole-5-carbinols using alkylsulfonic acids in nitromethane followed by trapping with a wide range of nucleophiles effects C-C, C-O, C-N, C-S, and C-P bond formation...
  18. doi request reprint Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development
    Mark D Wittman
    Bristol Myers Squibb Co, Wallingford, Connecticut 06492, USA
    J Med Chem 52:7360-3. 2009
    ..This report describes the biological activity, characterization, and SAR leading to 9d (BMS-754807) a small molecule IGF-1R kinase inhibitor in clinical development...
  19. doi request reprint Expanding GPCR homology model binding sites via a balloon potential: A molecular dynamics refinement approach
    S Roy Kimura
    Computer Assisted Drug Design, Bristol Myers Squibb, Wallingford, CT 06492, USA
    Proteins 71:1919-29. 2008
    ..In both cases, we show that the MD expansion algorithm makes it possible to dock the ligands in poses that agree with the crystal structure or mutagenesis data...
  20. doi request reprint Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 12. Structure-activity relationships associated with 4-fluoro-6-azaindole derivatives leading to the identification of 1-(4-benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1h-p
    Alicia Regueiro-Ren
    Department of Medicinal Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States
    J Med Chem 56:1656-69. 2013
    ..The predicted low clearance in humans, modest protein binding, and good potency in the presence of 40% human serum for 12m led to its selection for human clinical studies. ..
  21. doi request reprint Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
    Min Gao
    Department of Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
    Nature 465:96-100. 2010
    ....
  22. pmc Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers
    Samuel W Gerritz
    Bristol Myers Squibb Research and Development, Wallingford, CT 06492, USA
    Proc Natl Acad Sci U S A 108:15366-71. 2011
    ..Optimization of the initial screening hit produced an analog that protects mice from influenza-induced weight loss and mortality by reducing viral titers to undetectable levels throughout the course of treatment...
  23. ncbi request reprint Changes to the HIV long terminal repeat and to HIV integrase differentially impact HIV integrase assembly, activity, and the binding of strand transfer inhibitors
    Ira B Dicker
    Department of Virology, Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA
    J Biol Chem 282:31186-96. 2007
    ..4) Gln(148) interacts with G(2), T(1), and C(-1) at the 5' end of the viral LTR, with these four determinants playing important and overlapping roles in assembly, strand transfer catalysis and high affinity inhibitor binding...
  24. ncbi request reprint Respiratory syncytial virus fusion inhibitors. Part 5: Optimization of benzimidazole substitution patterns towards derivatives with improved activity
    Xiangdong Alan Wang
    Department of Chemistry, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 17:4592-8. 2007
    ....
  25. pmc Biochemical and genetic characterizations of a novel human immunodeficiency virus type 1 inhibitor that blocks gp120-CD4 interactions
    Qi Guo
    Department of Virology, Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA
    J Virol 77:10528-36. 2003
    ..BMS-378806 therefore serves as a prototype for this new class of antiretroviral agents and validates gp120 as a viable target for small-molecule inhibitors...
  26. ncbi request reprint Electrostatic interaction of pi-acidic amides with hydrogen-bond acceptors
    Yi Li
    Computer Assisted Drug Design, The Bristol Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA
    Bioorg Med Chem Lett 13:3261-6. 2003
    ..Examples of such interactions were identified through a search of the CSD database...
  27. pmc Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitors
    Joseph Yanchunas
    Gene Expression and Protein Biochemistry Department, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Antimicrob Agents Chemother 49:3825-32. 2005
    ..The results of this study provide a molecular understanding of the novel hypersusceptibility of atazanavir-resistant I50L/A71V-containing clinical isolates to other currently approved PIs...