Carbamate-appended N-alkylsulfonamides as inhibitors of gamma-secretase.
The synthesis and gamma-secretase inhibition data for a series of carbamate-appended N-alkylsulfonamides are described. Carbamate 54 was found to significantly reduce brain Abeta in transgenic mice. 54 was also found to possess markedly improved brain levels in transgenic mice compared to previously disclosed 1 and 2.
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
Lau
Wai-Yu
WY
Smith
David W
DW
Zheng
Ming
M
Hansel
Steven B
SB
Polson
Craig T
CT
Corsa
Jason A
JA
Barten
Donna M
DM
Felsenstein
Kevin M
KM
Roberts
Susan B
SB
D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002219:Carbamates / Q000737:chemistry*; D051379:Mice; D008822:Mice, Transgenic; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D002219:Carbamates; D011480:Protease Inhibitors; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases