| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1370127 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
Abstract
Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor, (−)-37, which showed in vivo reduction of amyloid beta peptides. The crystal structure of 18a showed a binding mode driven by interaction with the catalytic aspartate dyad and distribution of the biaryl amide decoration towards S1 and S3 pockets.
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Authors
Gary Tresadern, Francisca Delgado, Oscar Delgado, Harrie Gijsen, Gregor J. Macdonald, Dieder Moechars, Frederik Rombouts, Richard Alexander, John Spurlino, Michiel Van Gool, Juan Antonio Vega, Andrés A. Trabanco,