N-(5-chloro-2-(hydroxymethyl)-N-alkyl-arylsulfonamides as gamma-secretase inhibitors.
A series of N-alkylbenzenesulfonamides were developed from a high throughput screening hit. Classic and parallel synthesis strategies were employed to produce compounds with good in vitro and in vivo gamma-secretase activity.
Parker
Michael F
MF
Department of Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. parkerm@BMS.com
Barten
Donna M
DM
Bergstrom
Carl P
CP
Bronson
Joanne J
JJ
Corsa
Jason A
JA
Deshpande
Milind S
MS
Felsenstein
Kevin M
KM
Guss
Valerie L
VL
Hansel
Steven B
SB
Johnson
Graham
G
Keavy
Daniel J
DJ
Lau
Wai Y
WY
Mock
Jeremy
J
Prasad
C V C
CV
Polson
Craig T
CT
Sloan
Charles P
CP
Smith
David W
DW
Wallace
Owen B
OB
Wang
Henry H
HH
Williams
Andrew
A
Zheng
Ming
M
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015394:Molecular Structure; D011485:Protein Binding; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases