Affiliation: Novartis Institutes for BioMedical Research
- 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 antagonistsHeinrich 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...
- 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-peptidesHeinrich 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. ..
- 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-peptidesHeinrich 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...
- Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitorsHeinrich 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...
- Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po applicationAndreas 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...
- A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic miceUlf 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...
- Signal peptide peptidase dependent cleavage of type II transmembrane substrates releases intracellular and extracellular signalsKumlesh 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...
- Dynamics of Abeta turnover and deposition in different beta-amyloid precursor protein transgenic mouse models following gamma-secretase inhibitionDorothee 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...