title: BACE1 inhibitors: a head group scan on a series of amides.
abstract: A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment.
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharma Research, Grenzacherstr. 124, CH-4070 Basel, Switzerland. thomas.woltering@roche.com
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Woltering
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wostl
authors.forename: Hans
authors.initials: H
authors.lastname: Hilpert
authors.forename: Mark
authors.initials: M
authors.lastname: Rogers-Evans
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinard
authors.forename: Alexander
authors.initials: A
authors.lastname: Mayweg
authors.forename: Martin
authors.initials: M
authors.lastname: Göbel
authors.forename: David W
authors.initials: DW
authors.lastname: Banner
authors.forename: Jörg
authors.initials: J
authors.lastname: Benz
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Travagli
authors.forename: Martina
authors.initials: M
authors.lastname: Pollastrini
authors.forename: Guido
authors.initials: G
authors.lastname: Marconi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Gabellieri
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Guba
authors.forename: Harald
authors.initials: H
authors.lastname: Mauser
authors.forename: Matteo
authors.initials: M
authors.lastname: Andreini
authors.forename: Helmut
authors.initials: H
authors.lastname: Jacobsen
authors.forename: Eoin
authors.initials: E
authors.lastname: Power
authors.forename: Robert
authors.initials: R
authors.lastname: Narquizian
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000577:Amides / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human