Piperidine-derived γ-secretase modulators
| Autor: | Gerard Martin Paul Giblin, Beverley Smith, Alan Naylor, James R. Musgrave, Adrian Hall, Rosemary Z. Sasse, Ishrut Hussain, Richard L. Elliott |
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| Rok vydání: | 2010 |
| Předmět: |
education
Clinical Biochemistry Pharmaceutical Science Acetates Biochemistry Substrate Specificity Cns penetration Mice Structure-Activity Relationship chemistry.chemical_compound Dogs Piperidines Pharmacokinetics Cell Line Tumor mental disorders Drug Discovery Animals Humans Molecular Biology Gamma secretase Amyloid beta-Peptides Organic Chemistry Peptide Fragments humanities In vitro Rats chemistry Molecular Medicine Piperidine Amyloid Precursor Protein Secretases |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:1306-1311 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2009.08.072 |
| Popis: | This Letter details the SAR of a novel series of piperidine-derived gamma-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Abeta42, increase Abeta38 and have no effect on Abeta40 levels. Furthermore, 10h demonstrated excellent pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS penetration in the mouse. |
| Databáze: | OpenAIRE |
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