Abstract
Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modification introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acids / chemistry*
-
Amyloid Precursor Protein Secretases / antagonists & inhibitors*
-
Aspartic Acid Endopeptidases / antagonists & inhibitors*
-
Crystallography, X-Ray
-
Drug Design*
-
Humans
-
Models, Molecular
-
Peptide Fragments / chemical synthesis
-
Peptide Fragments / chemistry
-
Peptide Fragments / pharmacology
-
Protease Inhibitors / chemical synthesis*
-
Protease Inhibitors / chemistry
-
Protease Inhibitors / pharmacology*
-
Structure-Activity Relationship
Substances
-
Amino Acids
-
Peptide Fragments
-
Protease Inhibitors
-
Amyloid Precursor Protein Secretases
-
Aspartic Acid Endopeptidases
-
BACE1 protein, human
-
statine