title: Carbamate-appended N-alkylsulfonamides as inhibitors of gamma-secretase.
abstract: 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.
authors.affiliation: Department of Discovery Chemistry, Research and Development, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA. carl.bergstrom@bms.com
authors.forename: Carl P
authors.initials: CP
authors.lastname: Bergstrom
authors.forename: Charles P
authors.initials: CP
authors.lastname: Sloan
authors.forename: Wai-Yu
authors.initials: WY
authors.lastname: Lau
authors.forename: David W
authors.initials: DW
authors.lastname: Smith
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Steven B
authors.initials: SB
authors.lastname: Hansel
authors.forename: Craig T
authors.initials: CT
authors.lastname: Polson
authors.forename: Jason A
authors.initials: JA
authors.lastname: Corsa
authors.forename: Donna M
authors.initials: DM
authors.lastname: Barten
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Felsenstein
authors.forename: Susan B
authors.initials: SB
authors.lastname: Roberts
mesh_terms: 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*
chemical_list: D016229:Amyloid beta-Peptides; D002219:Carbamates; D011480:Protease Inhibitors; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases