title: Iminoheterocycles as gamma-secretase modulators.
abstract: The synthesis of a novel series of iminoheterocycles and their structure-activity relationship (SAR) as modulators of gamma-secretase activity will be detailed. Encouraging SAR generated from a monocyclic core led to a structurally unique bicyclic core. Selected compounds exhibit good potency as gamma-secretase modulators, excellent rat pharmacokinetics, and lowering of Abeta42 levels in various in vivo models.
authors: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, United States. john.caldwell@merck.com
authors: John P
authors: JP
authors: Caldwell
authors: Chad E
authors: CE
authors: Bennett
authors: Troy M
authors: TM
authors: McCracken
authors: Robert D
authors: RD
authors: Mazzola
authors: Thomas
authors: T
authors: Bara
authors: Alexei
authors: A
authors: Buevich
authors: Duane A
authors: DA
authors: Burnett
authors: Inhou
authors: I
authors: Chu
authors: Mary
authors: M
authors: Cohen-Williams
authors: Hubert
authors: H
authors: Josein
authors: Lynn
authors: L
authors: Hyde
authors: Julie
authors: J
authors: Lee
authors: Brian
authors: B
authors: McKittrick
authors: Lixin
authors: L
authors: Song
authors: Giuseppe
authors: G
authors: Terracina
authors: Johannes
authors: J
authors: Voigt
authors: Lili
authors: L
authors: Zhang
authors: Zhaoning
authors: Z
authors: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007097:Imines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007097:Imines; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases