3,4-Fused cyclohexyl sulfones as gamma-secretase inhibitors.
The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly potent gamma-secretase inhibitors. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain A beta in transgenic mouse models and thus have potential as possible treatments for Alzheimer's disease.
Shaw
Duncan
D
Department of Medicinal Chemistry, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. Duncan_shaw@merck.com
Best
Jonathan
J
Dinnell
Kevin
K
Nadin
Alan
A
Shearman
Mark
M
Pattison
Christine
C
Peachey
James
J
Reilly
Michael
M
Williams
Brian
B
Wrigley
Jonathan
J
Harrison
Timothy
T
D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D018360:Crystallography, X-Ray; D003500:Cyclization; D010450:Endopeptidases / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D011480:Protease Inhibitors; D013450:Sulfones; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse