Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors.


Taking advantage of the structural similarity between aspartic proteases, small-molecule peptidomimetic inhibitors that already showed activity towards Secreted Aspartic Protease 2 as anti-Candida agents and HIV protease inhibitors were exploited as potential BACE1 inhibitors. A focused library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was synthesized and assayed towards BACE1 enzyme, resulting in the identification of a thiolactam-containing hit compound possessing IC50 in the low micromolar range, and confirming the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues.

DOI: 10.1016/j.bmc.2017.03.030

Cite this paper

@article{Innocenti2017DesignAS, title={Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors.}, author={Riccardo Innocenti and Elena Lenci and Gloria Menchi and Alberto Pupi and Andrea Trabocchi}, journal={Bioorganic & medicinal chemistry}, year={2017}, volume={25 19}, pages={5077-5083} }