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.

Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors / Innocenti, Riccardo; Lenci, Elena; Menchi, Gloria; Pupi, Alberto; Trabocchi, Andrea. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 25(2017), pp. 5077-5083. [10.1016/j.bmc.2017.03.030]

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

INNOCENTI, RICCARDO;LENCI, ELENA;MENCHI, GLORIA;PUPI, ALBERTO;TRABOCCHI, ANDREA
2017

Abstract

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.
25
5077
5083
Innocenti, Riccardo; Lenci, Elena; Menchi, Gloria; Pupi, Alberto; Trabocchi, Andrea
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1079675
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