Design of potent inhibitors of human β-secretase. Part 2

We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of β-secretase that incorporates a variety of P2 side chains that yield potent inhibitors with excellent cellular activity. A 2.2 Å crystal structure of compound 13 is shown.

We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of β-secretase that incorporate a variety of P2 side chains that yield potent inhibitors with excellent cellular activity and good selectivity against Cathepsin-D.Figure optionsDownload as PowerPoint slide