Design, synthesis, and evaluation of tetrahydroquinoline and pyrrolidine sulfonamide carbamates as gamma-secretase inhibitors.
Gamma-secretase is a key enzyme involved in the production of beta-amyloid peptides which are believed to play a critical role in the onset and progression of Alzheimer's disease (AD). As such, inhibition of gamma-secretase has been an attractive approach to AD therapy. In this paper, the design, synthesis, and evaluation of tetrahydroquinoline and pyrrolidine sulfonamide carbamates as gamma-secretase inhibitors are described.
Guo
Tao
T
Pharmacopeia Drug Discovery, Inc., P.O. Box 5350, Princeton, NJ 08543-5350, USA. tguo@pcop.com
Gu
Huizhong
H
Hobbs
Doug W
DW
Rokosz
Laura L
LL
Stauffer
Tara M
TM
Jacob
Biji
B
Clader
John W
JW
D000544:Alzheimer Disease / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D011759:Pyrrolidines / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D002219:Carbamates; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D011804:Quinolines; D013449:Sulfonamides; C037219:quinoline; D053829:Amyloid Precursor Protein Secretases; C032519:pyrrolidine