title: N-Bridged bicyclic sulfonamides as inhibitors of gamma-secretase.
abstract: The structural modification of a series of [3.3.1] bicyclic sulfonamide based gamma-secretase inhibitors is described. Appropriate substitution on the bicyclic scaffold provides a significant increase in the metabolic stability of the compounds resulting in an improved in vivo metabolic profile.
authors.affiliation: Department of Medicinal Chemistry, Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Simeon
authors.initials: S
authors.lastname: Bowers
authors.forename: Gary D
authors.initials: GD
authors.lastname: Probst
authors.forename: Anh P
authors.initials: AP
authors.lastname: Truong
authors.forename: Roy K
authors.initials: RK
authors.lastname: Hom
authors.forename: Andrei W
authors.initials: AW
authors.lastname: Konradi
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Albert W
authors.initials: AW
authors.lastname: Garofalo
authors.forename: Karina
authors.initials: K
authors.lastname: Wong
authors.forename: Erich
authors.initials: E
authors.lastname: Goldbach
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Quinn
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Sauer
authors.forename: William
authors.initials: W
authors.lastname: Wallace
authors.forename: Lan
authors.initials: L
authors.lastname: Nguyen
authors.forename: Susanna S
authors.initials: SS
authors.lastname: Hemphill
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bova
authors.forename: Guriqbal S
authors.initials: GS
authors.lastname: Basi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001643:Bridged Bicyclo Compounds; D011480:Protease Inhibitors; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases