title: BACE-1 inhibitory activities of new substituted phenyl-piperazine coupled to various heterocycles: chromene, coumarin and quinoline.
abstract: The protease beta-secretase plays a central role in the synthesis of pathogenic amyloid-beta in Alzheimer's disease. Here, we report a new series of analogues based on the phenyl-piperazine scaffold coupled to various heterocyclic moieties, which demonstrate improved inhibitory activities on BACE-1 (FRET assay) compared to already known naphthyl counterparts. The obtained results suggest further structural modifications to access to more potent BACE-1 inhibitors.
authors.affiliation: Laboratoire de Chimie Biomoléculaire, Unité INSERM U-623-IBDM, Faculté des Sciences Luminy, Université de la Méditerrannée, Case 907, 13288 Marseille Cedex 09, France.
authors.forename: Cédrik
authors.initials: C
authors.lastname: Garino
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pietrancosta
authors.forename: Younes
authors.initials: Y
authors.lastname: Laras
authors.forename: Vincent
authors.initials: V
authors.lastname: Moret
authors.forename: Amandine
authors.initials: A
authors.lastname: Rolland
authors.forename: Gilles
authors.initials: G
authors.lastname: Quéléver
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kraus
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D001578:Benzopyrans / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry*; D010450:Endopeptidases / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry*
chemical_list: D001578:Benzopyrans; D003374:Coumarins; D004791:Enzyme Inhibitors; D010879:Piperazines; D011804:Quinolines; C030123:coumarin; C037219:quinoline; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; C031503:phenylpiperazine