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- W2008063169 abstract "The design and application of an effective, new class of organofluorine inhibitors of amyloid fibrillogenesis are described. Based on experimental evidence a core structure containing indol-3-yl, trifluoromethyl, hydroxyl, and carboxylic acid ester functions has been designed. Several substituted derivatives of this core structure have been synthesized, using various indole derivatives. While all inhibitor candidates have shown considerable effect (20−70% inhibition) in structure−activity relationship studies (inhibitor/Aβ = 10 ratio), several compounds have demonstrated excellent activity (93−96% inhibition). Using concentration dependence studies, the activity of the most active molecules have been quantified. These inhibitors practically completely block the fibril formation of Aβ1-40, as shown by maximum inhibition values (ICmax = 98−100%). The median inhibitor concentration values (IC50 = 0.23−0.53 molinhibitor/molAβ) demonstrate favorable stoichiometry for the inhibition. The respective elimination of the functional groups from the core structure has resulted in a partial or complete loss of activity, indicating the significant role of each group. Experiments with these derivatives suggest the particular importance of the acidic hydroxyl group during peptide−inhibitor interaction." @default.
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- W2008063169 date "2006-03-25" @default.
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- W2008063169 title "Organofluorine Inhibitors of Amyloid Fibrillogenesis" @default.
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- W2008063169 doi "https://doi.org/10.1021/bi0601104" @default.
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