P3 cap modified Phe*-Ala series BACE inhibitors
| Autor: | Jason Eric Lamar, Jon A. Erickson, Todd J. Kohn, Mccarthy James R, Hsiu-Chiung Yang, Guo Deqi, Patrick C. May, Shu-Hui Chen, David E. Timm, Yip Yvonne Yee Mai, James McGee |
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| Rok vydání: | 2003 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science Peptide Biochemistry Chemical synthesis Cell Line Drug Discovery Endopeptidases Moiety Aspartic Acid Endopeptidases Humans Protease Inhibitors Molecular Biology chemistry.chemical_classification biology Chemistry Organic Chemistry Dipeptides In vitro Bioavailability Enzyme Enzyme inhibitor Cell culture biology.protein Molecular Medicine Amyloid Precursor Protein Secretases |
| Zdroj: | Bioorganicmedicinal chemistry letters. 14(1) |
| ISSN: | 0960-894X |
| Popis: | With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC(50) |
| Databáze: | OpenAIRE |
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