title: Novel phenyl(thio)ureas bearing (thio)oxothiazoline group as potential BACE-1 inhibitors: synthesis and biological evaluation.
abstract: We report the synthesis and the β-site amyloid precursor protein cleaving enzyme-1 inhibitory properties of novel phenyl(thio)ureas bearing 2-(thio)oxothiazoline derivatives. A library of analogues was prepared according to specific synthetic schemes and the inhibitory activity was monitored using a fluorescence resonance energy transfer assay. Several analogues show potent inhibitory activities ranging between 1 and 0.01 µM and the activity is related to the NH acidity of the (thio)urea motif. Our results illustrate once again the close relationship between molecular recognition, complexation of the active site in enzymatic system, and organocatalysis utilizing explicit hydrogen bonding.
authors.affiliation: Chirosciences UMR 6263, University Paul-Cézanne, Aix-Marseille III, Marseille, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Andreoli
authors.forename: Abdallah Larbi
authors.initials: AL
authors.lastname: Doukara
authors.forename: Mohammed Amine
authors.initials: MA
authors.lastname: Mehdid
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vanthuyne
authors.forename: Christian
authors.initials: C
authors.lastname: Roussel
authors.forename: Jean
authors.initials: J
authors.lastname: Dessolin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Kraus
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016367:Baculoviridae / Q000235:genetics; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D009154:Mutation; D013890:Thiourea / Q000737:chemistry*; D014508:Urea / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D014508:Urea; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D013890:Thiourea