Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer's Disease
| Autor: | Lu Chen, Carmela Molinaro, Qinghao Chen, Yanke Xu, Azzeddine Lekhal, Sarah K. Pulicare, David A. Thaisrivongs, Wenyong Chen, Steven P. Miller, Zhiguo J. Song, Lushi Tan |
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| Rok vydání: | 2016 |
| Předmět: |
Chemistry Techniques
Synthetic 010402 general chemistry Cyclic S-Oxides 01 natural sciences Biochemistry Catalysis chemistry.chemical_compound Aniline Alzheimer Disease Amide Aspartic Acid Endopeptidases Humans Physical and Theoretical Chemistry biology Molecular Structure Thiadiazines 010405 organic chemistry Organic Chemistry Combinatorial chemistry 0104 chemical sciences chemistry biology.protein Verubecestat Amyloid Precursor Protein Secretases Amyloid precursor protein secretase Copper |
| Zdroj: | Organic letters. 18(22) |
| ISSN: | 1523-7052 |
| Popis: | Verubecestat is an inhibitor of β-secretase being evaluated for the treatment of Alzheimer’s disease. The first-generation route relies on an amide coupling with a functionalized aniline, the preparation of which introduces synthetic inefficiencies. The second-generation route replaces this with a copper-catalyzed C–N coupling, allowing for more direct access to the target. Other features of the new route include a diastereoselective Mannich-type addition into an Ellman sulfinyl ketimine and a late-stage guanidinylation. |
| Databáze: | OpenAIRE |
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