%0 Journal Article %A Jia, Jianhua %A Song, Jia %A Dai, Jiapei %A Liu, Boli %A Cui, Mengchao %D 2016 %T Optically Pure Diphenoxy Derivatives as More Flexible Probes for β‑Amyloid Plaques %U https://acs.figshare.com/articles/journal_contribution/Optically_Pure_Diphenoxy_Derivatives_as_More_Flexible_Probes_for_Amyloid_Plaques/3479312 %R 10.1021/acschemneuro.6b00155.s001 %2 https://acs.figshare.com/ndownloader/files/5489864 %K Optically Pure Diphenoxy Derivatives %K IMPY %K AD brains %K diphenoxy derivatives %K 125 I-radiolabeled enantiomers %K competition binding assay %K min %K β binding probes %K ID %K SPECT %X The highly rigid and planar scaffold with π-conjugated systems has been widely considered to be indispensable for Aβ binding probes. However, the flexible benzyloxybenzene derivative [125I]­BOB-4 represents an excellent lead candidate for targeting Aβ in AD brains. Based on that, we designed two pairs of more flexible and optically pure diphenoxy derivatives with a chiral center as novel Aβ probes. These compounds possessed high affinity (Ki = 15.8–45.0 nM) for Aβ1–42 aggregates, and (R)-enantiomers showed slightly better binding ability than (S)-enantiomers. In addition, the competition binding assay implied that the optically pure diphenoxy derivatives with more flexible geometry shared the same binding site as IMPY, a classical rigid and planar Aβ probe. For 125I-radiolabeled enantiomers, (S)-[125I]5 and (R)-[125I]5, specific plaque labeling on brain sections of Tg mice and AD patients were observed in in vitro autoradiography, persuasively proving the excellent affinity of the probes. In biodistribution, (S)-[125I]5 and (R)-[125I]5 with relatively low lipophilicity exhibited moderate initial brain uptake (4.37% and 3.72% ID/g at 2 min, respectively) and extremely fast washout from normal mice brain (brain2min/brain60min = 19.0 and 17.7, respectively). In summary, the separate enantiomers displayed similar properties in vitro and in vivo, and (S/R)-[123I]5 may be potential SPECT probes for recognizing Aβ plaques in AD brains. %I ACS Publications