National Center for
2VJ9: Human Bace-1 In Complex With N-((1s,2r)-3-(Cyclohexylamino)- 2-Hydroxy-1-(Phenylmethyl)propyl)-3-(Ethylamino)-5-(2-Oxo- 1-Pyrrolidinyl)benzamide
BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character
Bioorg. Med. Chem. Lett. (2008) 18 p.1017-1021
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.