Abstract
A series of transition state analogues of beta-secretases 1 and 2 (BACE1, 2) inhibitors containing fused-ring or biaryl moieties were designed computationally to probe the S2 pocket, synthesized, and tested for BACE1 and BACE2 inhibitory activity. It has been shown that unlike the biaryl analogs, the fused-ring moiety is successfully accommodated in the BACE1 binding site resulting in the ligands with excellent inhibitory activity. Ligand 5b reduced 65% of Aβ40 production in N2a cells stably transfected with Swedish human APP.
Original language | English (US) |
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Pages (from-to) | 264-274 |
Number of pages | 11 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 19 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2009 |
Externally published | Yes |
Keywords
- Alzheimer
- Aspartic protease
- BACE1
- Computer-aided molecular design
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry