Synthesis of Functionalized Benzoxazoles and Their Binding Affinities to A￥a42 Fibrils

摘要

Functionalized benzoxazole derivatives were designed and synthesized based on the structural features of PIB and FDDNP, which show excellent binding affinities to aggregated Aモ42 fibrils. All the synthesized compounds were evaluated by competitive binding assay against aggregated Aモ42 fibrils using [125I]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).