Synthesis of Functionalized Benzoxazoles and Their Binding Affinities to A beta 42 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 A beta 42 fibrils. All the synthesized compounds were evaluated by competitive binding assay against aggregated A beta 42 fibrils using [I-125]TZDM and displayed good in vitro binding affinities with K-i 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).