Heinrich Rueeger

Summary

Affiliation: Novartis Institutes for BioMedical Research

Publications

  1. ncbi Discovery and SAR of potent, orally available and brain-penetrable 5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulen- and 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen derivatives as neuropeptide Y Y5 receptor antagonists
    Heinrich Rueeger
    Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 14:2451-7. 2004
  2. doi Discovery of cyclic sulfoxide hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid β-peptides
    Heinrich Rueeger
    Department of Global Discovery Chemistry, Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
    Bioorg Med Chem Lett 23:5300-6. 2013
  3. doi Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction of amyloid β-peptides
    Heinrich Rueeger
    Department of Global Discovery Chemistry, Institutes for Biomedical Research, Novartis Pharma AG, CH 4057 Basel, Switzerland
    J Med Chem 55:3364-86. 2012
  4. doi Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors
    Heinrich Rueeger
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, PO Box, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 21:1942-7. 2011
  5. doi Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po application
    Andreas Lerchner
    Novartis Institutes for BioMedicalResearch, Novartis Pharma AG, PO Box, CH 4002, Basel, Switzerland
    Bioorg Med Chem Lett 20:603-7. 2010
  6. pmc A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice
    Ulf Neumann
    Neuroscience, Novartis Institutes for Biomedical Research NIBR, Basel, Switzerland
    Mol Neurodegener 10:44. 2015
  7. ncbi Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals
    Kumlesh K Dev
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Eur J Pharmacol 540:10-7. 2006
  8. doi Dynamics of Abeta turnover and deposition in different beta-amyloid precursor protein transgenic mouse models following gamma-secretase inhibition
    Dorothee Abramowski
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    J Pharmacol Exp Ther 327:411-24. 2008

Collaborators

Detail Information

Publications8

  1. ncbi Discovery and SAR of potent, orally available and brain-penetrable 5,6-dihydro-4H-3-thia-1-aza-benzo[e]azulen- and 4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen derivatives as neuropeptide Y Y5 receptor antagonists
    Heinrich Rueeger
    Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 14:2451-7. 2004
    ..Both classes of compounds are capable of delivering potent and selective orally and centrally bioavailable NPY Y5 receptor antagonists...
  2. doi Discovery of cyclic sulfoxide hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid β-peptides
    Heinrich Rueeger
    Department of Global Discovery Chemistry, Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
    Bioorg Med Chem Lett 23:5300-6. 2013
    ..Herein we report SAR development in the S3 and S2' subsites of BACE1 for cyclic sulfoxide hydroxyethyl amine inhibitors, the synthetic approaches employed in this effort, and in vivo data for optimized compound such as 11d. ..
  3. doi Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction of amyloid β-peptides
    Heinrich Rueeger
    Department of Global Discovery Chemistry, Institutes for Biomedical Research, Novartis Pharma AG, CH 4057 Basel, Switzerland
    J Med Chem 55:3364-86. 2012
    ..Pharmacodynamic studies in APP51/16 transgenic mice at oral doses of 180 μmol/kg demonstrated significant reduction of brain Aβ levels...
  4. doi Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors
    Heinrich Rueeger
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, PO Box, CH 4002 Basel, Switzerland
    Bioorg Med Chem Lett 21:1942-7. 2011
    ..Inhibitors of sub-micromolar potency with an improved property profile over historic HEA inhibitors resulting in improved brain penetration are described...
  5. doi Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po application
    Andreas Lerchner
    Novartis Institutes for BioMedicalResearch, Novartis Pharma AG, PO Box, CH 4002, Basel, Switzerland
    Bioorg Med Chem Lett 20:603-7. 2010
    ..Several compounds from this series demonstrated acute reduction of Abeta in human APP-wildtype transgenic (APP51/16) mice after oral administration...
  6. pmc A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice
    Ulf Neumann
    Neuroscience, Novartis Institutes for Biomedical Research NIBR, Basel, Switzerland
    Mol Neurodegener 10:44. 2015
    ..However, failures with the first clinical BACE1 inhibitors have highlighted the need to generate compounds with appropriate efficacy and safety profiles, since long treatment periods are expected to be necessary in humans...
  7. ncbi Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signals
    Kumlesh K Dev
    Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Eur J Pharmacol 540:10-7. 2006
    ..This dual assay provides a powerful tool to pharmacologically analyze sequential cleavage events of signal peptidase and SPP and their regulation...
  8. doi Dynamics of Abeta turnover and deposition in different beta-amyloid precursor protein transgenic mouse models following gamma-secretase inhibition
    Dorothee Abramowski
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    J Pharmacol Exp Ther 327:411-24. 2008
    ..This study supports the use of APP transgenic mice as translational models to characterize Abeta-lowering therapeutics...