Naphthyl and coumarinyl biarylpiperazine derivatives as highly potent human β-secretase inhibitors. Design, synthesis, and enzymatic BACE-1 and cell assays

…, Y Laras, R Rosas, G Herbette, B Maigret…

Index: Garino, Cedrik; Tomita, Taisuke; Pietrancosta, Nicolas; Laras, Younes; Rosas, Roselyne; Herbette, Gaetan; Maigret, Bernard; Quelever, Gilles; Iwatsubo, Takeshi; Kraus, Jean-Louis Journal of Medicinal Chemistry, 2006 , vol. 49, # 14 p. 4275 - 4285

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Citation Number: 57

Abstract

Twenty novel β-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinyl series were designed for their potential use in Alzheimer's disease therapy. Enzymatic and cell-based assays have been carried out. The biological results clearly demonstrate that specific substituents located at the N4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between 40 and 70 ...