title: Synthesis and structure-activity relationship of a novel series of heterocyclic sulfonamide gamma-secretase inhibitors.
abstract: gamma-Secretase inhibitors have been shown to reduce the production of beta-amyloid, a component of the plaques that are found in brains of patients with Alzheimer's disease. A novel series of heterocyclic sulfonamide gamma-secretase inhibitors that reduce beta-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative gamma-secretase substrate.
authors.affiliation: Chemical Sciences, Wyeth Research, Princeton, NJ 08543-8000, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Pu
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Kreft
authors.forename: Suzan H
authors.initials: SH
authors.lastname: Aschmies
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Atchison
authors.forename: Joshua
authors.initials: J
authors.lastname: Berkowitz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Caggiano
authors.forename: Micheal
authors.initials: M
authors.lastname: Chlenov
authors.forename: George
authors.initials: G
authors.lastname: Diamantidis
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Harrison
authors.forename: Yun
authors.initials: Y
authors.lastname: Hu
authors.forename: Donna
authors.initials: D
authors.lastname: Huryn
authors.forename: J
authors.initials: J
authors.lastname: Steven Jacobsen
authors.forename: Mei
authors.initials: M
authors.lastname: Jin
authors.forename: Kerri
authors.initials: K
authors.lastname: Lipinski
authors.forename: Peimin
authors.initials: P
authors.lastname: Lu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Martone
authors.forename: Koi
authors.initials: K
authors.lastname: Morris
authors.forename: June
authors.initials: J
authors.lastname: Sonnenberg-Reines
authors.forename: Dave R
authors.initials: DR
authors.lastname: Riddell
authors.forename: Joan
authors.initials: J
authors.lastname: Sabalski
authors.forename: Shaiu-Ching
authors.initials: SC
authors.lastname: Sun
authors.forename: Erik
authors.initials: E
authors.lastname: Wagner
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Lynn
authors.initials: L
authors.lastname: Resnick
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D006571:Heterocyclic Compounds; D051880:Receptors, Notch; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases