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Updated: May 19, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Structure-based design, synthesis, and biological evaluation of dihydroquinazoline-derived potent β-secretase
Arun K Ghosh1, Satyendra Pandey, Sudhakar Gangarajula
1Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States. akghosh@purdue.edu
Abstract:
Structure-based design, synthesis, and biological evaluation of a series of dihydroquinazoline-derived β-secretase inhibitors incorporating thiazole and pyrazole-derived P2-ligands are described. We have identified inhibitor 4f which has shown potent enzyme inhibitory (K(i)=13 nM) and cellular (IC(50)=21 nM in neuroblastoma cells) assays. A model of 4f was created based upon the X-ray structure of 3a-bound β-secretase. The model suggested possible interactions in the active site.
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