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.
Kortum
Steven W
SW
Pfizer Global Research and Development, Pfizer Inc., St. Louis Laboratories, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA. steve.kortum@pfizer.com
Benson
Timothy E
TE
Bienkowski
Michael J
MJ
Emmons
Thomas L
TL
Prince
D Bryan
DB
Paddock
Donna J
DJ
Tomasselli
Alfredo G
AG
Moon
Joseph B
JB
LaBorde
Alice
A
TenBrink
Ruth E
RE
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002402:Cathepsin D / Q000037:antagonists & inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005021:Ethylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D007069:Ifosfamide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008956:Models, Chemical; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D005021:Ethylamines; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse; D002402:Cathepsin D; D007069:Ifosfamide