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http://dx.doi.org/10.5012/bkcs.2008.29.9.1765

Synthesis of Functionalized Benzoxazoles and Their Binding Affinities to A β42 Fibrils  

Chun, Young-Shin (Life Sciences Research Division, Korea Institute of Science and Technology)
Lim, Soo-Jeong (Department of Nuclear Medicine, Asan Medical Center)
Oh, Seung-Jun (Department of Nuclear Medicine, Asan Medical Center)
Moon, Dae-Hyuk (Department of Nuclear Medicine, Asan Medical Center)
Kim, Dong-Jin (Life Sciences Research Division, Korea Institute of Science and Technology)
Cho, Cheon-Gyu (Department of Chemistry, Hanyang University)
Yoo, Kyung-Ho (Life Sciences Research Division, Korea Institute of Science and Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.29, no.9, 2008 , pp. 1765-1768 More about this Journal
Abstract
Functionalized benzoxazole derivatives were designed and synthesized based on the structural features of PIB and FDDNP, which show excellent binding affinities to aggregated A$\beta$ 42 fibrils. All the synthesized compounds were evaluated by competitive binding assay against aggregated A$\beta$ 42 fibrils using [$^{125}$I]TZDM and displayed good in vitro binding affinities with Ki values (0.47-15.3 nM) from subnanomolar to nanomolar range. Among them, benzoxazoles 1f and 1a having malononitrile and ester moieties at C-6 exhibited superior binding affinities ($K_i$ = 0.47 and 0.61 nM, respectively) to PIB ($K_i$ = 0.77 nM).
Keywords
Alzheimer's disease; Aβ42 fibrils; Functionalized benzoxazoles; Binding affinity
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