Potent and selective isophthalamide S2 hydroxyethylamine inhibitors of BACE1.

The design and synthesis of a novel series of potent BACE1 hydroxyethylamine inhibitors. These inhibitors feature hydrogen bonding substituents at the C-5 position of the isophthalamide ring with improved selectivity over cathepsin D.

Design, synthesis, and crystal structure of hydroxyethyl secondary amine-based peptidomimetic inhibitors of human beta-secretase.

The design and synthesis of a novel series of potent and cell permeable peptidomimetic inhibitors of the human beta-secretase (BACE) are described. These inhibitors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the C-terminus. The crystal structure of BACE in complex with this hydroxyethyl secondary amine isostere inhibitor is also presented.

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

We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compound 13 is shown.

Design of potent inhibitors of human beta-secretase. Part 1.

We describe a novel series of potent inhibitors of human beta-secretase. These compounds possess the hydroxyethyl amine transition state isostere. A 2.