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  • Title: Multi-target-directed coumarin derivatives: hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds.
    Author: Piazzi L, Cavalli A, Colizzi F, Belluti F, Bartolini M, Mancini F, Recanatini M, Andrisano V, Rampa A.
    Journal: Bioorg Med Chem Lett; 2008 Jan 01; 18(1):423-6. PubMed ID: 17998161.
    Abstract:
    The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multifunctional compounds to combat causes and symptoms of such neurodegeneration. To this aim we designed, synthesized, and tested a series of compounds by introducing halophenylalkylamidic functions on the scaffold of AP2238, which is a dual binding site acetylcholinesterase inhibitor. The inhibitory activity was successfully extended to the beta-site amyloid precursor protein cleavage enzyme, leading to the discovery of a potent inhibitor of this enzyme (3) and affording multifunctional compounds (2, 6, 8) for the treatment of AD.
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