Tricyclic sulfones as orally active gamma-secretase inhibitors: synthesis and structure-activity relationship studies.
Tricyclic sulfones were designed as gamma-secretase inhibitors and found to have excellent potency. Extensive SAR shows that a large number of sulfonamides at position 7 of the tricycle are very well tolerated. Compounds such as 15a and 15c showed remarkable in vivo potency.
Sasikumar
T K
TK
Merck Research Laboratories, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com
Qiang
Li
L
Burnett
Duane A
DA
Cole
David
D
Xu
Ruo
R
Li
Hongmei
H
Greenlee
William J
WJ
Clader
John
J
Zhang
Lili
L
Hyde
Lynn
L
D000284:Administration, Oral; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D051379:Mice; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D011480:Protease Inhibitors; D013449:Sulfonamides; D013450:Sulfones; D053829:Amyloid Precursor Protein Secretases