Jay P Powers

Summary

Affiliation: Amgen Inc
Country: USA

Publications

  1. ncbi SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase
    Jay P Powers
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    J Med Chem 49:1034-46. 2006
  2. ncbi Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4
    Jay P Powers
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 16:2842-5. 2006
  3. doi Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors
    Yosup Rew
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 19:1797-801. 2009
  4. doi Discovery and optimization of benzenesulfonanilide derivatives as a novel class of 11β-HSD1 inhibitors
    Yosup Rew
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 22:3786-90. 2012
  5. doi Distinctive molecular inhibition mechanisms for selective inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1
    Hua Tu
    Department of Metabolic Disorders, Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem 16:8922-31. 2008
  6. doi Discovery of amide replacements that improve activity and metabolic stability of a bis-amide smoothened antagonist hit
    Matthew L Brown
    Amgen Inc, 1120 Veterans Blvd, South San Francisco, CA 94080, United States
    Bioorg Med Chem Lett 21:5206-9. 2011
  7. doi Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors
    Daqing Sun
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 21:405-10. 2011
  8. doi The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors
    Xuelei Yan
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 20:7071-5. 2010
  9. doi Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors
    Dustin L McMinn
    Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 19:1446-50. 2009
  10. doi Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
    Daqing Sun
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 18:3513-6. 2008

Collaborators

Detail Information

Publications15

  1. ncbi SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase
    Jay P Powers
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    J Med Chem 49:1034-46. 2006
    ..Structure-activity relationships and structural studies have identified the mechanism of action for compounds in this series, several of which possess drug-like properties, as unique, reversible, covalent inhibitors of HCV NS5b...
  2. ncbi Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated kinase-4
    Jay P Powers
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 16:2842-5. 2006
    ..High-throughput screening of a small-molecule compound library resulted in the identification of a novel series of N-acyl 2-aminobenzimidazoles that are potent inhibitors of interleukin-1 receptor-associated kinase-4...
  3. doi Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11beta-HSD1 inhibitors
    Yosup Rew
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 19:1797-801. 2009
    ..These efforts led to the discovery of piperidyl benzamide 15 which features improved properties over the cyclohexyl benzamide derivatives...
  4. doi Discovery and optimization of benzenesulfonanilide derivatives as a novel class of 11β-HSD1 inhibitors
    Yosup Rew
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 22:3786-90. 2012
    ..Optimization of this series rapidly resulted in the discovery of compounds (S)-10 and (S)-23 (11β-HSD1 SPA IC(50)=1.8 and 1.4 nM, respectively)...
  5. doi Distinctive molecular inhibition mechanisms for selective inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1
    Hua Tu
    Department of Metabolic Disorders, Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem 16:8922-31. 2008
    ..Together, the structural and kinetic analyses demonstrate two distinctive molecular inhibition mechanisms, providing valuable information for future inhibitor design...
  6. doi Discovery of amide replacements that improve activity and metabolic stability of a bis-amide smoothened antagonist hit
    Matthew L Brown
    Amgen Inc, 1120 Veterans Blvd, South San Francisco, CA 94080, United States
    Bioorg Med Chem Lett 21:5206-9. 2011
    ..Several bioisosteric replacements of the labile amide that maintained in vitro potency were identified and shown to be metabolically stable in vitro and in vivo...
  7. doi Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors
    Daqing Sun
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 21:405-10. 2011
    ..Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models...
  8. doi The synthesis and SAR of novel diarylsulfone 11β-HSD1 inhibitors
    Xuelei Yan
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 20:7071-5. 2010
    ..Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent efficacy in a non-human primate ex vivo pharmacodynamic model...
  9. doi Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors
    Dustin L McMinn
    Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 19:1446-50. 2009
    ..A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg)...
  10. doi Discovery and initial SAR of arylsulfonylpiperazine inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
    Daqing Sun
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 18:3513-6. 2008
    ..Optimization of the initial lead resulted in the discovery of compound (R)-45 (11beta-HSD1 IC(50)=3nM)...
  11. doi Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model
    Lisa D Julian
    Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, California 94080, USA
    J Med Chem 51:3953-60. 2008
    ..This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model...
  12. ncbi Crystal structures of IRAK-4 kinase in complex with inhibitors: a serine/threonine kinase with tyrosine as a gatekeeper
    Zhulun Wang
    Department of Molecular Structure, Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, California 94080, USA
    Structure 14:1835-44. 2006
    ..The pattern of phosphate ligand interactions in the activation loop bears a close resemblance to that of a tyrosine kinase. Our results provide insights into IRAK-4 function and the design of selective inhibitors...
  13. doi Rational design and binding mode duality of MDM2-p53 inhibitors
    Felix Gonzalez-Lopez de Turiso
    Department of Therapeutic Discovery, Amgen Inc, 1120 Veterans Boulevard, South San Francisco, California 94080, USA
    J Med Chem 56:4053-70. 2013
    ..A pharmacodynamic (PD) experiment in mice implanted with human SJSA-1 tumors showed p21(WAF1) mRNA induction (2.7-fold over vehicle) upon oral dosing of 27 at 300 mg/kg...
  14. doi Discovery of potent, selective, and orally bioavailable inhibitors of interleukin-1 receptor-associate kinase-4
    Zhulun Wang
    Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA Electronic address
    Bioorg Med Chem Lett 25:5546-50. 2015
    ..These efforts led to the discovery of 16, a highly potent, selective, and orally bioavailable inhibitor of IRAK-4. ..
  15. doi Design of 1-piperazinyl-4-arylphthalazines as potent Smoothened antagonists
    Brian S Lucas
    Department of Medicinal Chemistry, Amgen, S San Francisco, CA 94080, USA
    Bioorg Med Chem Lett 20:3618-22. 2010
    ..A series of 1-amino-4-arylphthalazines was developed as potent and orally bioavailable inhibitors of Smo. A representative compound from this class demonstrated significant tumor volume reduction in a mouse medulloblastoma model...