Nitrogen-appended N-alkylsulfonamides as inhibitors of gamma-secretase.
The synthesis and gamma-secretase inhibition data for a series of nitrogen-appended N-alkylsulfonamides (11-47) are described. Inhibition of brain Abeta in transgenic mice was demonstrated by two of these compounds (23 and 44).
Bergstrom
Carl P
CP
Department of Discovery Chemistry, Research and Development, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA. carl.bergstrom@bms.com
Sloan
Charles P
CP
Wang
Henry H
HH
Parker
Michael F
MF
Smith
David W
DW
Zheng
Ming
M
Hansel
Steven B
SB
Polson
Craig T
CT
Barber
Lauren E
LE
Bursuker
Isia
I
Guss
Valerie L
VL
Corsa
Jason A
JA
Barten
Donna M
DM
Felsenstein
Kevin M
KM
Roberts
Susan B
SB
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000588:Amines; D016229:Amyloid beta-Peptides; D001393:Azoles; D010446:Peptide Fragments; D011480:Protease Inhibitors; D013449:Sulfonamides; C078592:amyloid beta-protein (1-40); D053829:Amyloid Precursor Protein Secretases