A group of novel 4,5-dianilinophthalimide derivatives has been synthesized in this study for potential use as beta-amyloid (Abeta) plaque probes. Staining of hippocampus tissue sections from Alzheimer's disease (AD) brain with the representative compound 9 indicated selective labeling of it to Abeta plaques. The binding affinity of radioiodinated [(125)I]9 for AD brain homogenates was 0.21 nM (K(d)), and of other derivatives ranged from 0.9 to 19.7 nM, except for N-methyl-4,5-dianilinophthalimide (K(i)>1000 nM). [(125)I]9 possessed the optimal lipophilicity with LogP value of 2.16, and its in vivo biodistribution in normal mice exhibited excellent initial brain uptake (5.16% ID/g at 2 min after injection) and a fast washout rate (0.56% ID/g at 60 min). The encouraging results suggest that this novel derivative of [(123)I]9 may have potential as an in vivo SPECT probe for detecting amyloid plaques in the brain.
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