Synthesis of functionalized benzoxazoles and their binding affinities to Aβ42 fibrils

Abstract

Functionalized benzoxazole derivatives were designed and synthesized based on the structural features of PIB and FDDNP, which show excellent binding affinities to aggregated Aβ42 fibrils. All the synthesized compounds were evaluated by competitive binding assay against aggregated Aβ42 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 (Ki = 0.47 and 0.61 nM, respectively) to PIB (Ki = 0.77 nM).