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KMID : 0370220060500050326
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Yakhak Hoeji
2006 Volume.50 No. 5 p.326 ~ p.331
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Synthesis of New Benzylpiperidinyl Ether Derivatives as Amyloid-beta Aggregation Inhibitors
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Kwon Young-Ei
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Abstract
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e designed and synthesized new benzylpiperidinyl ether derivatives as beta-amyloid aggregation inhibitors for the development of novel anti-Alzheimer’s disease agents. As starting material, 4-hydroxypiperidine was used. For pro- tection of the amine group in piperidine (2), di-tert-butyl dicarbonate was reacted with 4-hydroxypiperidine in the presence of triethylamine. For introduction of benzly group, benzylbromide was treated with compound 2 in dioxane. After depro- tection of Boc group on amine in compound 3, ester (5) was synthesized by addition of ehtyl-4-chlorobutyrate. The alcohol 6 was synthesized by hydride reduction of 5 using LiAIH4 To obtain final products (7~14), the alcohol 6 was condensed with each of substituted benzoic acids. To screen beta-amyloid aggregation inhibition of the products, thioflavinT assay was performed ustin Aβ1-42 at 37℃ for 26 h incubation, in vitro. From the result of screening, compound 8, 9, 11 and 12 showed effective activity about 65~85 μM as IC50 value. Amont the prepared compounds, 4-[4-(benzyloxy)piperidino]butyl- 4-chlorobenzoate (8) was the most effective inhibitor having IC50 of 65.4 μM.
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KEYWORD
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Amyloid-beta aggregation Inhibitor, Alzheimer’s disease, piperidine derivatives, Aβ1-42
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