Abstract
This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.
MeSH terms
-
Alzheimer Disease / drug therapy
-
Alzheimer Disease / metabolism*
-
Amyloid beta-Protein Precursor / antagonists & inhibitors
-
Animals
-
Asparagine / chemistry
-
Aspartic Acid Endopeptidases / antagonists & inhibitors*
-
Combinatorial Chemistry Techniques*
-
Crystallography, X-Ray
-
Disease Models, Animal
-
Ethylamines / chemical synthesis*
-
Ethylamines / chemistry
-
Ethylamines / pharmacology*
-
Fluorine / chemistry
-
Mice
-
Molecular Structure
-
Nanotechnology
-
Structure-Activity Relationship
Substances
-
Amyloid beta-Protein Precursor
-
Ethylamines
-
Fluorine
-
Asparagine
-
Aspartic Acid Endopeptidases
-
ethylamine