Novel anilinophthalimide derivatives as potential probes for β-amyloid plaque in the brain

Article abstract of DOI:10.1016/j.bmc.2009.12.023

A group of novel 4,5-dianilinophthalimide derivatives has been synthesized in this study for potential use as β-amyloid (Aβ) plaque probes. Staining of hippocampus tissue sections from Alzheimer's disease (AD) brain with the representative compound 9 indicated selective labeling of it to Aβ plaques. The binding affinity of radioiodinated [¹²⁵I]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). [¹²⁵I]9 possessed the optimal lipophilicity with Log P 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 [¹²³I]9 may have potential as an in vivo SPECT probe for detecting amyloid plaques in the brain.