D J Kempf

Summary

Affiliation: Abbott Laboratories
Country: USA

Publications

  1. ncbi request reprint Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine
    Dale J Kempf
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois, USA
    J Infect Dis 189:51-60. 2004
  2. pmc Practical preclinical model for assessing the potential for unconjugated hyperbilirubinemia produced by human immunodeficiency virus protease inhibitors
    Dale J Kempf
    Global Pharmaceutical Research and Development, Abbott, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 50:762-4. 2006
  3. ncbi request reprint Pharmacokinetic enhancement of the hepatitis C virus protease inhibitors VX-950 and SCH 503034 by co-dosing with ritonavir
    Dale J Kempf
    Global Pharmaceutical Research and Development Division Abbott, Abbott Park, IL, USA
    Antivir Chem Chemother 18:163-7. 2007
  4. pmc Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients
    D J Kempf
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Virol 75:7462-9. 2001
  5. ncbi request reprint Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir therapy
    Dale J Kempf
    Global Pharmaceutica Research and Development, Abbott Laboratories, Abbott Park, Ill, USA
    Antivir Ther 7:165-74. 2002
  6. pmc Activity of a potent hepatitis C virus polymerase inhibitor in the chimpanzee model
    Chih Ming Chen
    Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA
    Antimicrob Agents Chemother 51:4290-6. 2007
  7. pmc ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease
    H L Sham
    Departments of Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 42:3218-24. 1998
  8. pmc Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir
    D J Kempf
    Department of Infectious Diseases Research, Abbott Laboratories, Illinois 60064, USA
    Antimicrob Agents Chemother 41:654-60. 1997
  9. pmc Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication
    Hongmei Mo
    Global Pharmaceutical Research and Development, Department R4CQ, Building AP52N, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064 6217, USA
    Antimicrob Agents Chemother 51:732-5. 2007
  10. pmc In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor
    A Carrillo
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Virol 72:7532-41. 1998

Detail Information

Publications60

  1. ncbi request reprint Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivudine to nelfinavir plus stavudine and lamivudine
    Dale J Kempf
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois, USA
    J Infect Dis 189:51-60. 2004
    ..These differences suggest substantially different genetic and pharmacological barriers to resistance for these 2 protease inhibitors and may have implications for strategies for initiating antiretroviral therapy...
  2. pmc Practical preclinical model for assessing the potential for unconjugated hyperbilirubinemia produced by human immunodeficiency virus protease inhibitors
    Dale J Kempf
    Global Pharmaceutical Research and Development, Abbott, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 50:762-4. 2006
    ..This model was used to disqualify an exploratory protease inhibitor from development...
  3. ncbi request reprint Pharmacokinetic enhancement of the hepatitis C virus protease inhibitors VX-950 and SCH 503034 by co-dosing with ritonavir
    Dale J Kempf
    Global Pharmaceutical Research and Development Division Abbott, Abbott Park, IL, USA
    Antivir Chem Chemother 18:163-7. 2007
    ..A human pharmacokinetic model of VX-950 co-administered with low-dose ritonavir suggested that improved efficacy and/or dosing convenience may be feasible by pharmacokinetic enhancement with ritonavir...
  4. pmc Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients
    D J Kempf
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Virol 75:7462-9. 2001
    ....
  5. ncbi request reprint Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir therapy
    Dale J Kempf
    Global Pharmaceutica Research and Development, Abbott Laboratories, Abbott Park, Ill, USA
    Antivir Ther 7:165-74. 2002
    ..These results provide guidance for clinically relevant interpretation of phenotypic and genotypic resistance tests when applied to lopinavir/ritonavir...
  6. pmc Activity of a potent hepatitis C virus polymerase inhibitor in the chimpanzee model
    Chih Ming Chen
    Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA
    Antimicrob Agents Chemother 51:4290-6. 2007
    ..These findings validate the antiviral efficacy and resistance development of benzothiadiazine HCV polymerase inhibitors in vivo...
  7. pmc ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease
    H L Sham
    Departments of Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 42:3218-24. 1998
    ..These results demonstrate the potential utility of ABT-378 as a therapeutic intervention against AIDS...
  8. pmc Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir
    D J Kempf
    Department of Infectious Diseases Research, Abbott Laboratories, Illinois 60064, USA
    Antimicrob Agents Chemother 41:654-60. 1997
    ..Because of potentially substantial drug level increases, however, such combinations require further investigation to establish safe regimens for clinical use...
  9. pmc Identification and structural characterization of I84C and I84A mutations that are associated with high-level resistance to human immunodeficiency virus protease inhibitors and impair viral replication
    Hongmei Mo
    Global Pharmaceutical Research and Development, Department R4CQ, Building AP52N, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064 6217, USA
    Antimicrob Agents Chemother 51:732-5. 2007
    ....
  10. pmc In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor
    A Carrillo
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Virol 72:7532-41. 1998
    ..Doyon et al., J. Virol. 70:3763-3769, 1996; Y. M. Zhang et al., J. Virol. 71:6662-6670, 1997)...
  11. ncbi request reprint Metabolism and disposition of the HIV-1 protease inhibitor lopinavir (ABT-378) given in combination with ritonavir in rats, dogs, and humans
    Gondi N Kumar
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Pharm Res 21:1622-30. 2004
    ..The objective of this study was to examine the metabolism and disposition of the HIV protease inhibitor lopinavir in humans and animal models...
  12. pmc Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodeficiency virus-infected patients
    Ann Hsu
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 47:350-9. 2003
    ..Multiple stepwise logistic regressions confirmed the significance of the IQ parameters, as well as other baseline characteristics, in predicting virologic response at 24 weeks in this patient population...
  13. ncbi request reprint Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides
    A Chris Krueger
    Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 16:3367-70. 2006
    ..Substituted N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed...
  14. ncbi request reprint A human immunodeficiency virus protease inhibitor is a novel functional inhibitor of human pregnane X receptor
    Christine Healan-Greenberg
    Abbott Laboratories, Global Pharmaceutical Research and Development, Abbott Park, Illinois 60064 6104, USA
    Drug Metab Dispos 36:500-7. 2008
    ..Among the class of HIV-PIs, which are typically PXR activators, A-792611 seems to have a unique property for PXR antagonism and could be a useful tool for studying nuclear receptor pathway regulation...
  15. ncbi request reprint In vitro metabolism of the HIV-1 protease inhibitor ABT-378: species comparison and metabolite identification
    G N Kumar
    Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064 3500, USA
    Drug Metab Dispos 27:86-91. 1999
    ..The results of the current study indicate that ABT-378 is highly susceptible to oxidative metabolism in vitro, and possibly in vivo, in humans...
  16. ncbi request reprint Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of unsymmetrical 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives
    A Chris Krueger
    Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 17:2289-92. 2007
    ..Structure-activity relationship patterns for this class of compounds are discussed. It was found that the saturated alkane dialkyl units provided the most active analogs...
  17. ncbi request reprint Design and characterization of an engineered gp41 protein from human immunodeficiency virus-1 as a tool for drug discovery
    Kent D Stewart
    Department of Structural Biology, Abbott Laboratories, Building AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    J Comput Aided Mol Des 21:121-30. 2007
    ..This engineered version of gp41 protein will be potentially useful in research programs aimed at discovery of new drugs for therapy of HIV-infection in humans...
  18. pmc Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease
    Thomas P Young
    Abbott Molecular, 1300 East Touhy Avenue, Des Plaines, IL 60018 3315, USA
    Antimicrob Agents Chemother 54:4903-6. 2010
    ..L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir...
  19. ncbi request reprint Synthesis and SAR of novel 1,1-dialkyl-2(1H)-naphthalenones as potent HCV polymerase inhibitors
    Todd D Bosse
    Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:568-70. 2008
    ..This investigation led to the discovery of potent inhibitors of the hepatitis C virus at low nanomolar concentrations in both enzymatic and cell-based HCV genotype 1a assays...
  20. pmc Relative replication capacity and selective advantage profiles of protease inhibitor-resistant hepatitis C virus (HCV) NS3 protease mutants in the HCV genotype 1b replicon system
    Yupeng He
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6217, USA
    Antimicrob Agents Chemother 52:1101-10. 2008
    ....
  21. pmc Predictive genotypic algorithm for virologic response to lopinavir-ritonavir in protease inhibitor-experienced patients
    Martin S King
    Global Pharmaceutical Research and Development, Abbott, 100 Abbott Park Rd, R436 AP9A 2, Abbott Park, IL 60064, USA
    Antimicrob Agents Chemother 51:3067-74. 2007
    ..The refined algorithm may be useful in making clinical treatment decisions and in refining genetic and pharmacologic methods for assessing the activity of LPV/r...
  22. pmc Characterization of a novel human immunodeficiency virus type 1 protease inhibitor, A-790742
    Tatyana Dekhtyar
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 52:1337-44. 2008
    ..The selection of the uncommon V82L and V82G mutations in protease by A-790742 suggests the potential for an advantageous resistance profile with this protease inhibitor...
  23. doi request reprint Synthesis of potent pyrrolidine influenza neuraminidase inhibitors
    A Chris Krueger
    Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, AP 52N, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:1692-5. 2008
    ..The synthesis of several pyrrolidine inhibitor analogs is described that possess nanomolar in vitro potencies against the neuraminidase enzymes expressed by the B/Memphis/3/89 and A/N1/PR/8/34 influenza strains...
  24. doi request reprint Synthesis and evaluation of inhibitors of cytochrome P450 3A (CYP3A) for pharmacokinetic enhancement of drugs
    Charles A Flentge
    Abbott Laboratories, Departments of Antiviral Research D R4CQ, Building AP 52, 200 Abbott Park Road, Abbott Park, IL 60064 3537, USA
    Bioorg Med Chem Lett 19:5444-8. 2009
    ..Interestingly, an inverse correlation between in vitro inhibition of CYP3A and elevation of LPV was observed. The compounds described in this study may be useful for enhancing the pharmacokinetics of drugs that are metabolized by CYP3A...
  25. doi request reprint Synthesis and biological characterization of B-ring amino analogues of potent benzothiadiazine hepatitis C virus polymerase inhibitors
    John T Randolph
    Global Pharmaceutical Research and Development, Abbott, 200 Abbott Park Road, Abbott Park, Illinois 60064 6217, USA
    J Med Chem 52:3174-83. 2009
    ..Compound 30 is a potent inhibitor in replicon assays, with EC(50) values of 10 and 6 nM against genotypes 1a and 1b, respectively...
  26. doi request reprint Water-soluble prodrugs of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir
    David A DeGoey
    Antiviral Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 52:2964-70. 2009
    ..A direct synthetic process for the preparation of OMP and OEP prodrugs was developed, and the improved synthetic method may be applicable to the preparation of analogous soluble prodrugs of other drug classes with limited solubility...
  27. doi request reprint Identification of proteasome gene regulation in a rat model for HIV protease inhibitor-induced hyperlipidemia
    Jeffrey F Waring
    Abbott Laboratories Global Pharmaceuticals Research and Development, 100 Abbott Park Rd, Abbott Park, IL 60064 6123, USA
    Arch Toxicol 84:263-70. 2010
    ..Our results indicate a strong correlation between proteasomal induction and lipid elevations, and have allowed us to develop a rapid screen for identifying novel PIs that do not induce the proteasome...
  28. doi request reprint 2-Pyridyl P1'-substituted symmetry-based human immunodeficiency virus protease inhibitors (A-792611 and A-790742) with potential for convenient dosing and reduced side effects
    David A DeGoey
    Antiviral Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Med Chem 52:2571-86. 2009
    ..X-ray crystallographic analyses of the new cores were used to examine differences in their binding modes. The antiviral activity of the compounds against protease inhibitor resistant strains of HIV was also determined...
  29. doi request reprint Inhibitors of hepatitis C virus polymerase: synthesis and biological characterization of unsymmetrical dialkyl-hydroxynaphthalenoyl-benzothiadiazines
    Rolf Wagner
    Global Pharmaceutical Research and Development, Abbott, Abbott Park, Illinois 60064, USA
    J Med Chem 52:1659-69. 2009
    ..It also displayed an excellent pharmacokinetic profile in rats, with a plasma elimination half-life after intravenous dosing of 4.5 h, oral bioavailability of 77%, and a peak liver concentration of 21.8 microg/mL...
  30. doi request reprint Hepatitis C NS5B polymerase inhibitors: 4,4-Dialkyl-1-hydroxy-3-oxo-3,4-dihydronaphthalene-3-yl benzothiadiazine derivatives
    Douglas K Hutchinson
    Department of Antiviral Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:3887-90. 2008
    ..A number of these compounds exhibited potent activity against genotypes 1a and 1b HCV polymerase in both enzymatic and cell culture activities. A representative compound also showed favorable pharmacokinetics in the rat...
  31. doi request reprint Liver transcriptomic changes associated with ritonavir-induced hyperlipidemia in sensitive and resistant strains of rats
    Yi Yang
    Abbott Laboratories, Abbott Park, IL, USA
    Vet J 185:75-82. 2010
    ..These findings will facilitate the discovery of novel, lipid-neutral HIV PIs and the identification of relevant biomarkers for this adverse event...
  32. doi request reprint Synthesis, antiviral activity, and conformational studies of a P3 aza-peptide analog of a potent macrocyclic tripeptide HCV protease inhibitor
    John T Randolph
    Global Pharmaceutical Research and Development, Antiviral Research, 200 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:2745-50. 2008
    ....
  33. doi request reprint Des-A-ring benzothiadiazines: inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase
    Pamela L Donner
    Antiviral Research, Global Pharmaceutical Research, and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 18:2735-8. 2008
    ..We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies...
  34. doi request reprint Non-peptide entry inhibitors of HIV-1 that target the gp41 coiled coil pocket
    Kent D Stewart
    Pharmaceutical Discovery Division, Abbott Laboratories, 100 Abbott Park Rd, R46Y, AP10, Abbott Park, IL 60064 6098, United States
    Bioorg Med Chem Lett 20:612-7. 2010
    ..Structural work on the gp41/benzamide 1 complex was determined by NMR spectroscopy using a designed model peptide system that mimics an open pocket of the fusogenic form of the protein...
  35. ncbi request reprint Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-1-benzyl and N-1-[3-methylbutyl]-4-hydroxy-1,8-naphthyridon-3-yl benzothiadiazine analogs containing substituents on the aromatic ring
    Todd W Rockway
    Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064 6217, USA
    Bioorg Med Chem Lett 16:3833-8. 2006
    ..Aromatic substituents extending from position 7 of the D-ring exhibited excellent potency against both genotypes 1a and 1b...
  36. ncbi request reprint Synthesis, antiviral activity, and pharmacokinetic evaluation of P3 pyridylmethyl analogs of oximinoarylsulfonyl HIV-1 protease inhibitors
    John T Randolph
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem 14:4035-46. 2006
    ..The 3-pyridylmethyl analog 30 gave the best overall exposure (rat AUC=7.1 microg h/mL and dog AUC=4.9 microg h/mL), however, this compound was found to be a potent inhibitor of cytochrome P450 3A (Ki=2.4 nM)...
  37. ncbi request reprint Characterization of resistant HIV variants generated by in vitro passage with lopinavir/ritonavir
    Hongmei Mo
    Global Pharmaceutical Research Development, Department R47D, Abbott Laboratories, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064 6217, USA
    Antiviral Res 59:173-80. 2003
    ....
  38. ncbi request reprint Synthesis and SAR studies of potent HIV protease inhibitors containing novel dimethylphenoxyl acetates as P2 ligands
    Xiaoqi Chen
    Pharmaceutical Products Division, Abbott Laboratories, D 47D, AP52, 100 Abbott Park Road, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 13:3657-60. 2003
    ..However, the novel structural features and the high intrinsic antiviral potency of this series provides potential for the future exploration of prodrug strategies...
  39. ncbi request reprint Synthesis and antiviral activity of P1' arylsulfonamide azacyclic urea HIV protease inhibitors
    Peggy P Huang
    Abbott Laboratories, Infectious Disease Research, Dept R47D, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064 6217, USA
    Bioorg Med Chem Lett 14:4075-8. 2004
    ..Structural studies of early analogs bound in the enzyme active site were used to design more potent inhibitors. The effects of substituting the P1' benzenesulfonyl group on antiviral activity and protein binding are described...
  40. pmc Estimation of serum-free 50-percent inhibitory concentrations for human immunodeficiency virus protease inhibitors lopinavir and ritonavir
    Dean Hickman
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 48:2911-7. 2004
    ..Using this approach, we calculated the average IQs for protease inhibitor-naïve patients for LPV and RTV to be 67 and 5.6, respectively...
  41. ncbi request reprint Enantioselective synthesis of antiinfluenza compound A-315675
    David A DeGoey
    Infectious Disease Research Division, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, Illinois 60064, USA
    J Org Chem 67:5445-53. 2002
    ..Conversion of pyrrolinone 2 into 1 was accomplished in seven subsequent steps, including Michael addition of cis-1-propenylcuprate at C4 and introduction of a cyano group as a carboxylic acid equivalent at C2...
  42. pmc Complementation in cells cotransfected with a mixture of wild-type and mutant human immunodeficiency virus (HIV) influences the replication capacities and phenotypes of mutant variants in a single-cycle HIV resistance assay
    Hongmei Mo
    Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Rd, Abbott Park, IL 60064 6217, USA
    J Clin Microbiol 42:4169-74. 2004
    ..These findings suggest that the RC and susceptibility of plasma isolates from patients who are off therapy or not adherent to treatment, in which WT virus may expand to significant levels, should be interpreted with caution...
  43. pmc In vitro antiviral interaction of lopinavir with other protease inhibitors
    Akhteruzzaman Molla
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Antimicrob Agents Chemother 46:2249-53. 2002
    ..More importantly, the observed in vitro synergy between lopinavir and saquinavir provides a theoretical basis for the clinical exploration of a novel regimen of lopinavir-ritonavir and saquinavir...
  44. ncbi request reprint Design, synthesis, and structural analysis of inhibitors of influenza neuraminidase containing a 2,3-disubstituted tetrahydrofuran-5-carboxylic acid core
    Gary T Wang
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 15:125-8. 2005
    ..Both compounds 9 and 14 inhibit influenza NA A with an IC(50) of about 0.5 microM and NA B with an IC(50) of 1.0 microM...
  45. pmc Selection of resistance in protease inhibitor-experienced, human immunodeficiency virus type 1-infected subjects failing lopinavir- and ritonavir-based therapy: mutation patterns and baseline correlates
    Hongmei Mo
    Department R47D, Building AP52N, Abbott Laboratories, 200 Abbott Park Rd, Abbott Park, IL 60064 6217, USA
    J Virol 79:3329-38. 2005
    ....
  46. ncbi request reprint Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines
    John K Pratt
    Infectious Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 15:1577-82. 2005
    ..The most potent inhibitors contained small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200-400 nM against genotype 1b and 1a HCV polymerase, respectively...
  47. ncbi request reprint Oximinoarylsulfonamides as potent HIV protease inhibitors
    Clinton M Yeung
    Abbott Laboratories, GPRD, D 47D, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064 3501, USA
    Bioorg Med Chem Lett 15:2275-8. 2005
    ..The synthesis and structure-activity relationships (SAR) based upon the in vitro IC50 of this series of compounds are reported...
  48. pmc In vitro selection and characterization of influenza A (A/N9) virus variants resistant to a novel neuraminidase inhibitor, A-315675
    Akhteruzzaman Molla
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Virol 76:5380-6. 2002
    ..Interestingly, this mutant still retained susceptibility to A-315675 (42-fold loss). This suggests that cross-resistance between A-315675- and oseltamivir carboxylate-selected variants in vitro is minimal...
  49. ncbi request reprint Relationship between adherence and the development of resistance in antiretroviral-naive, HIV-1-infected patients receiving lopinavir/ritonavir or nelfinavir
    Martin S King
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Infect Dis 191:2046-52. 2005
    ..Relationships between adherence to protease inhibitor (PI)-based therapy and resistance development have not been fully characterized...
  50. ncbi request reprint Synthesis and structure-activity relationships of a novel series of HIV-1 protease inhibitors encompassing ABT-378 (Lopinavir)
    Hing L Sham
    Pharmaceutical Discovery, D47B, Building AP 10, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 12:1185-7. 2002
    ..Analogues in which this group is replaced with various substituted phenyl or heteroaryl groups were synthesized and the structure-activity relationships explored...
  51. ncbi request reprint Structure-based characterization and optimization of novel hydrophobic binding interactions in a series of pyrrolidine influenza neuraminidase inhibitors
    Clarence J Maring
    Department of Infectious Disease Research and Advanced Technology, Global Pharmaceutical R and D, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    J Med Chem 48:3980-90. 2005
    ..The C-1 ethyl ester prodrugs of the substituted C-4 vinyl analogues gave compounds with excellent oral bioavailability (F > 60%) when dosed in rat...
  52. ncbi request reprint Synthesis and activity of N-acyl azacyclic urea HIV-1 protease inhibitors with high potency against multiple drug resistant viral strains
    Chen Zhao
    GPRD, Abbott Laboratories, Abbott Park, IL 60064 6123, USA
    Bioorg Med Chem Lett 15:5499-503. 2005
    ..The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains...
  53. ncbi request reprint Novel lopinavir analogues incorporating non-Aromatic P-1 side chains--synthesis and structure--activity relationships
    Hing L Sham
    Pharmaceutical Discovery, R47B, Building AP 10, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 12:3101-3. 2002
    ..A series of analogues incorporating non-aromatic side chains at the P-1 position were synthesized and the structure-activity relationships explored...
  54. ncbi request reprint Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir)
    H L Sham
    Pharmaceutical Discovery, D47B, Building AP 10, Abbott Laboratories, Abbott Park, IL 60064 6101, USA
    Bioorg Med Chem Lett 11:1351-3. 2001
    ..The HIV protease inhibitor ABT-378 (Lopinavir) is metabolized rapidly and extensively by CYP-3A4 catalyzed oxidation. Three of the major metabolites identified were synthesized and their antiviral (HIV) activities determined...
  55. ncbi request reprint An 'inside-the-box' approach to drug resistance
    Kent D Stewart
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Chem Biol 11:1327-8. 2004
    ..Drug resistance is a growing problem in medicine that demands creative solutions. In this issue, Schiffer and colleagues describe their novel approach to pinpointing hot spots of resistance, which might lead to new anti-HIV therapeutics...
  56. pmc Virtual inhibitory quotient predicts response to ritonavir boosting of indinavir-based therapy in human immunodeficiency virus-infected patients with ongoing viremia
    Nancy Shulman
    Stanford University School of Medicine, California, USA
    Antimicrob Agents Chemother 46:3907-16. 2002
    ..The virtual inhibitory quotient, which incorporates both baseline viral resistance and the level of drug exposure in plasma, was superior to either baseline resistance or drug exposure alone in predicting the virologic response...
  57. ncbi request reprint Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children
    Xavier Saez-Llorens
    Hospital del Nino, Panama City, Panama
    Pediatr Infect Dis J 22:216-24. 2003
    ..Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult...
  58. pmc Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients
    Anne Genevieve Marcelin
    Department of Virology, Pitie Salpetriere Hospital, 83 Boulevard de l hopital, 75013 Paris, France
    Antimicrob Agents Chemother 49:1720-6. 2005
    ..Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses...
  59. pmc ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia
    Frank Maldarelli
    HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, United States of America
    PLoS Pathog 3:e46. 2007
    ..These data suggest that the persistent viremia on current antiretroviral therapy is derived, at least in part, from long-lived cells that are infected prior to initiation of therapy...
  60. pmc Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy
    Sarah Palmer
    HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 1201, USA
    Proc Natl Acad Sci U S A 105:3879-84. 2008
    ..These data suggest that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years...