N-Bridged bicyclic sulfonamides as inhibitors of gamma-secretase.
The structural modification of a series of [3.3.1] bicyclic sulfonamide based gamma-secretase inhibitors is described. Appropriate substitution on the bicyclic scaffold provides a significant increase in the metabolic stability of the compounds resulting in an improved in vivo metabolic profile.
Bowers
Simeon
S
Department of Medicinal Chemistry, Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, CA 94080, USA.
Probst
Gary D
GD
Truong
Anh P
AP
Hom
Roy K
RK
Konradi
Andrei W
AW
Sham
Hing L
HL
Garofalo
Albert W
AW
Wong
Karina
K
Goldbach
Erich
E
Quinn
Kevin P
KP
Sauer
John-Michael
JM
Wallace
William
W
Nguyen
Lan
L
Hemphill
Susanna S
SS
Bova
Michael P
MP
Basi
Guriqbal S
GS
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
D001643:Bridged Bicyclo Compounds; D011480:Protease Inhibitors; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases