title: BACE-1 inhibition by a series of psi[CH2NH] reduced amide isosteres.
abstract: A series of beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing a psi(CH2NH) reduced amide bond were synthesized. Incorporation of this reduced amide isostere as a non-cleavable peptide surrogate afforded inhibitors possessing low nanomolar potencies in both an enzymatic and cell-based assay.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. craig_coburn@merck.com
authors.forename: Craig A
authors.initials: CA
authors.lastname: Coburn
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Stachel
authors.forename: Kristen G
authors.initials: KG
authors.lastname: Jones
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Steele
authors.forename: Diane M
authors.initials: DM
authors.lastname: Rush
authors.forename: Jillian
authors.initials: J
authors.lastname: DiMuzio
authors.forename: Beth L
authors.initials: BL
authors.lastname: Pietrak
authors.forename: Ming-Tain
authors.initials: MT
authors.lastname: Lai
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.forename: Janet
authors.initials: J
authors.lastname: Lineberger
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Munshi
authors.forename: M
authors.initials: M
authors.lastname: Katharine Holloway
authors.forename: Amy
authors.initials: A
authors.lastname: Espeseth
authors.forename: Adam
authors.initials: A
authors.lastname: Simon
authors.forename: Daria
authors.initials: D
authors.lastname: Hazuda
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Graham
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
mesh_terms: D000577:Amides / Q000737:chemistry*; D053829:Amyloid Precursor Protein Secretases; D001665:Binding Sites; D010450:Endopeptidases / Q000378:metabolism*; D007118:Immunoassay; D010455:Peptides / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D010455:Peptides; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases