Research Topics
| David R LangleySummaryAffiliation: Bristol-Myers Squibb Country: USA Publications
| Collaborators
|
Detail Information
Publications
Inhibition of hepatitis B virus polymerase by entecavirDavid 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...
Balancing oral exposure with Cyp3A4 inhibition in benzimidazole-based IGF-IR inhibitorsKurt 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...- The terminal (catalytic) adenosine of the HIV LTR controls the kinetics of binding and dissociation of HIV integrase strand transfer inhibitorsDavid 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... 
Respiratory syncytial virus fusion inhibitors. Part 6: an examination of the effect of structural variation of the benzimidazol-2-one heterocycle moietyKeith 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...- E-novo: an automated workflow for efficient structure-based lead optimizationBradley 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... - Communication: Quantum polarized fluctuating charge model: a practical method to include ligand polarizability in biomolecular simulationsS 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.... - MORPH: a new tool for ligand designBrett 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... - 2-(1H-Imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chain variants of the IGF-1R inhibitor BMS-536924Mark 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... - Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as corticotropin-releasing factor1 receptor ligandsRichard 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%... - 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... - X-ray crystal structures of human immunodeficiency virus type 1 protease mutants complexed with atazanavirHerbert 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... - In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043Nannan 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... - 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-11Mark 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... - Targeting a binding pocket within the trimer-of-hairpins: small-molecule inhibition of viral fusionChristopher 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... - 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 carbonMark 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... - 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 developmentMark 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... - Expanding GPCR homology model binding sites via a balloon potential: A molecular dynamics refinement approachS 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... - Nucleophilic capture of the imino-quinone methide type intermediates generated from 2-aminothiazol-5-yl carbinolsMark 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... - Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomersSamuel 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... - Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effectMin Gao
Department of Virology, Bristol Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA
Nature 465:96-100. 2010.... - Changes to the HIV long terminal repeat and to HIV integrase differentially impact HIV integrase assembly, activity, and the binding of strand transfer inhibitorsIra 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... - Respiratory syncytial virus fusion inhibitors. Part 5: Optimization of benzimidazole substitution patterns towards derivatives with improved activityXiangdong 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.... - Biochemical and genetic characterizations of a novel human immunodeficiency virus type 1 inhibitor that blocks gp120-CD4 interactionsQi 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... - Electrostatic interaction of pi-acidic amides with hydrogen-bond acceptorsYi 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... - Molecular basis for increased susceptibility of isolates with atazanavir resistance-conferring substitution I50L to other protease inhibitorsJoseph 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...