Joseph L Duffy

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint HIV protease inhibitors with picomolar potency against PI-Resistant HIV-1 by extension of the P3 substituent
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:2569-72. 2003
  2. ncbi request reprint Synthesis and activity of novel HIV protease inhibitors with improved potency against multiple PI-resistant viral strains
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 12:2423-6. 2002
  3. ncbi request reprint HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1' substituent
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:3323-6. 2003
  4. ncbi request reprint Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 15:1401-5. 2005
  5. ncbi request reprint 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV
    Joseph L Duffy
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:2879-85. 2007
  6. ncbi request reprint Novel HIV-1 protease inhibitors active against multiple PI-resistant viral strains: coadministration with indinavir
    Nancy J Kevin
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:4027-30. 2003
  7. doi request reprint Aminopiperidine sulfonamide Cav2.2 channel inhibitors for the treatment of chronic pain
    Pengcheng P Shao
    Departments of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Med Chem 55:9847-55. 2012
  8. ncbi request reprint Direct observation (NMR) of the efficacy of glucagon receptor antagonists in murine liver expressing the human glucagon receptor
    Sheila M Cohen
    Department of Research Imaging, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem 14:1506-17. 2006
  9. doi request reprint Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels
    Andrew M Swensen
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
    Mol Pharmacol 81:488-97. 2012
  10. ncbi request reprint 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV
    David E Kaelin
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:5806-11. 2007

Collaborators

Detail Information

Publications20

  1. ncbi request reprint HIV protease inhibitors with picomolar potency against PI-Resistant HIV-1 by extension of the P3 substituent
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:2569-72. 2003
    ..Inhibition of multiple P450 isoforms is dependent on the regiochemistry of the pyridyl nitrogen in these compounds...
  2. ncbi request reprint Synthesis and activity of novel HIV protease inhibitors with improved potency against multiple PI-resistant viral strains
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 12:2423-6. 2002
    ..The trifluoroethyl substituent also affords a slower clearance rate in vivo (dogs); however, this may be due to more potent inhibition of at least two P450 isoforms...
  3. ncbi request reprint HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1' substituent
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:3323-6. 2003
    ..The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility...
  4. ncbi request reprint Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 15:1401-5. 2005
    ..This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice)...
  5. ncbi request reprint 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV
    Joseph L Duffy
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:2879-85. 2007
    ..The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented...
  6. ncbi request reprint Novel HIV-1 protease inhibitors active against multiple PI-resistant viral strains: coadministration with indinavir
    Nancy J Kevin
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:4027-30. 2003
    ..The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment...
  7. doi request reprint Aminopiperidine sulfonamide Cav2.2 channel inhibitors for the treatment of chronic pain
    Pengcheng P Shao
    Departments of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Med Chem 55:9847-55. 2012
    ..The discovery of metabolite 26 confounds further development of members of this aminopiperidine sulfonamide series. This discovery also suggests specific structural liabilities of this class of compounds that must be addressed...
  8. ncbi request reprint Direct observation (NMR) of the efficacy of glucagon receptor antagonists in murine liver expressing the human glucagon receptor
    Sheila M Cohen
    Department of Research Imaging, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem 14:1506-17. 2006
    ..This technique does not provide adequate quantitative precision for the comparative ranking of active compounds, but does afford physiological evidence of efficacy in the early development of a chemical series of antagonists...
  9. doi request reprint Characterization of the substituted N-triazole oxindole TROX-1, a small-molecule, state-dependent inhibitor of Ca(V)2 calcium channels
    Andrew M Swensen
    Department of Ion Channels, Merck Research Laboratories, Rahway, New Jersey, USA
    Mol Pharmacol 81:488-97. 2012
    ..2-selective inhibitor ziconotide in preclinical models of chronic pain...
  10. ncbi request reprint 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV
    David E Kaelin
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:5806-11. 2007
    ..8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated that this compound effectively reduced glucose excursion in lean mice...
  11. ncbi request reprint Discovery of potent and selective orally bioavailable beta-substituted phenylalanine derived dipeptidyl peptidase IV inhibitors
    Scott D Edmondson
    Department of Medicinal Chemistry, Merck and Co Inc, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 15:3048-52. 2005
    ....
  12. doi request reprint A potent and selective indole N-type calcium channel (Ca(v)2.2) blocker for the treatment of pain
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 21:869-73. 2011
    ..N-type calcium channels (Ca(v)2.2) have been shown to play a critical role in pain. A series of low molecular weight 2-aryl indoles were identified as potent Ca(v)2.2 blockers with good in vitro and in vivo potency...
  13. doi request reprint A novel benzazepinone sodium channel blocker with oral efficacy in a rat model of neuropathic pain
    SCOTT B HOYT
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 23:3640-5. 2013
    ..7 sodium channels. Compound 30 from this series displayed potent channel block, good selectivity versus other targets, and dose-dependent oral efficacy in a rat model of neuropathic pain...
  14. doi request reprint Imidazopyridines: a novel class of hNav1.7 channel blockers
    Clare London
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 18:1696-701. 2008
    ..Compound 4 had good efficacy (52% and 41% reversal of allodynia at 2 and 4h post-dose, respectively) in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain when dosed orally at 10mg/kg...
  15. ncbi request reprint Characterization of a new class of potent inhibitors of the voltage-gated sodium channel Nav1.7
    Brande S Williams
    Department of Ion Channels, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    Biochemistry 46:14693-703. 2007
    ..7 channel subtype, and with appropriate pharmacokinetic and drug metabolism properties, these compounds could be developed as analgesic agents...
  16. doi request reprint Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker
    Catherine Abbadie
    Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Pharmacol Exp Ther 334:545-55. 2010
    ..TROX-1 demonstrates that an orally available state-dependent Ca(v)2 channel blocker may achieve a therapeutic window suitable for the treatment of chronic pain...
  17. doi request reprint Discovery of a novel class of biphenyl pyrazole sodium channel blockers for treatment of neuropathic pain
    Sriram Tyagarajan
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 20:7479-82. 2010
    ..Compound 20 had outstanding efficacy in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain...
  18. ncbi request reprint Benzazepinone Nav1.7 blockers: potential treatments for neuropathic pain
    SCOTT B HOYT
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 17:6172-7. 2007
    ..A series of benzazepinones were synthesized and evaluated as hNa(v)1.7 sodium channel blockers. Several compounds from this series displayed good oral bioavailability and exposure and were efficacious in a rat model of neuropathic pain...
  19. doi request reprint Discovery of imidazole carboxamides as potent and selective CCK1R agonists
    Cheng Zhu
    Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co Inc, PO Box 2000, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 18:4393-6. 2008
    ..Compound 44, which was profiled extensively, showed good in vivo mouse gallbladder emptying (mGBE) and lean mouse overnight food intake (ONFI) reduction activities...
  20. ncbi request reprint A novel glucagon receptor antagonist inhibits glucagon-mediated biological effects
    Sajjad A Qureshi
    Department of Metabolic Disorder and Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey, USA
    Diabetes 53:3267-73. 2004
    ..Taken together, these data suggest that Cpd 1 is a potent glucagon receptor antagonist that has the capability to block the effects of glucagon in vivo...