title: Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
abstract: Structure-activity relationship (SAR) of a novel, potent and metabolically stable series of benzo [3.2.1] bicyclic sulfonamide-pyrazoles as γ-secretase inhibitors are described. Compounds that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via oral dose, as well as those with high selectivity over Notch, are highlighted.
authors: Department of Medicinal Chemistry, Elan Pharmaceuticals, 180 Oyster Point Blvd., South San Francisco, CA 94080, USA. mxcye@hotmail.com
authors: Xiaocong M
authors: XM
authors: Ye
authors: Andrei W
authors: AW
authors: Konradi
authors: Minghua
authors: M
authors: Sun
authors: Shendong
authors: S
authors: Yuan
authors: Danielle L
authors: DL
authors: Aubele
authors: Michael
authors: M
authors: Dappen
authors: Darren
authors: D
authors: Dressen
authors: Albert W
authors: AW
authors: Garofalo
authors: Jacek J
authors: JJ
authors: Jagodzinski
authors: Lee
authors: L
authors: Latimer
authors: Gary D
authors: GD
authors: Probst
authors: Hing L
authors: HL
authors: Sham
authors: David
authors: D
authors: Wone
authors: Ying-zi
authors: YZ
authors: Xu
authors: Daniel
authors: D
authors: Ness
authors: Elizabeth
authors: E
authors: Brigham
authors: Grace T
authors: GT
authors: Kwong
authors: Chris
authors: C
authors: Willtis
authors: George
authors: G
authors: Tonn
authors: Erich
authors: E
authors: Goldbach
authors: Kevin P
authors: KP
authors: Quinn
authors: Hongbin H
authors: HH
authors: Zhang
authors: John-Michael
authors: JM
authors: Sauer
authors: Michael
authors: M
authors: Bova
authors: Guriqbal S
authors: GS
authors: Basi
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011720:Pyrazoles; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases