Bace-1 Inhibitors Part 2: Identification of Hydroxy Ethylamines (Heas) with Reduced Peptidic Character.

Abstract This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2 . Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P 1 ′ and P 2 ′ substituents, two different binding modes were observed in X-ray co-crystal structures.