Tetracyclic sulfones as potent gamma-secretase inhibitors: synthesis and structure-activity relationship studies.
Complex tetracyclic sulfones were designed as gamma-secretase inhibitors and a stereoselective synthesis was achieved. Gamma-secretase activity was seen predominately in the (-) enantiomeric series. Compounds such as 2a and 2b showed remarkable in vitro and in vivo potency.
Sasikumar
T K
TK
Merck Research Laboratories, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com
Burnett
Duane A
DA
Asberom
Theodros
T
Wu
Wen-Lian
WL
Bennett
Chad
C
Cole
David
D
Xu
Ruo
R
Greenlee
William J
WJ
Clader
John
J
Zhang
Lili
L
Hyde
Lynn
L
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D015195:Drug Design; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D011480:Protease Inhibitors; D013450:Sulfones; D053829:Amyloid Precursor Protein Secretases