title: Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure-activity relationship of the aryl region.
abstract: The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1.
authors.affiliation: Department of Medicinal Chemistry, Elan Pharmaceuticals, South San Francisco, CA 94080, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Probst
authors.forename: Simeon
authors.initials: S
authors.lastname: Bowers
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sealy
authors.forename: Brian
authors.initials: B
authors.lastname: Stupi
authors.forename: Darren
authors.initials: D
authors.lastname: Dressen
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Jagodzinska
authors.forename: Jose
authors.initials: J
authors.lastname: Aquino
authors.forename: Andrea
authors.initials: A
authors.lastname: Gailunas
authors.forename: Anh P
authors.initials: AP
authors.lastname: Truong
authors.forename: Luke
authors.initials: L
authors.lastname: Tso
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Xu
authors.forename: Roy K
authors.initials: RK
authors.lastname: Hom
authors.forename: Varghese
authors.initials: V
authors.lastname: John
authors.forename: Jay S
authors.initials: JS
authors.lastname: Tung
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pleiss
authors.forename: John A
authors.initials: JA
authors.lastname: Tucker
authors.forename: Andrei W
authors.initials: AW
authors.lastname: Konradi
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Jacek
authors.initials: J
authors.lastname: Jagodzinski
authors.forename: Gergely
authors.initials: G
authors.lastname: Toth
authors.forename: Eric
authors.initials: E
authors.lastname: Brecht
authors.forename: Nanhua
authors.initials: N
authors.lastname: Yao
authors.forename: Hu
authors.initials: H
authors.lastname: Pan
authors.forename: May
authors.initials: M
authors.lastname: Lin
authors.forename: Dean R
authors.initials: DR
authors.lastname: Artis
authors.forename: Lany
authors.initials: L
authors.lastname: Ruslim
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bova
authors.forename: Sukanto
authors.initials: S
authors.lastname: Sinha
authors.forename: Ted A
authors.initials: TA
authors.lastname: Yednock
authors.forename: Shawn
authors.initials: S
authors.lastname: Gauby
authors.forename: Wes
authors.initials: W
authors.lastname: Zmolek
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Quinn
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Sauer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D005021:Ethylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005021:Ethylamines; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human