Apolipoprotien (apoE) is a cholesterol and lipid-carrier lipoprotein implicated in aging, atherosclerosis, Alzheimer's Disease (AD), and other neurological and lipid-related disorders. ApoE is a major genetic risk factor for the development of AD. Studies have established that the e4 isoform of the apoE gene increases an individual's risk for developing late-onset AD. We had screened four scaffolds in apoE ELISA assays and demonstrated that specific triarylamines significantly inhibited apoE gene expression. Further structure-activity relationship study performed on the triarylamine scaffold will be presented here. We approached the SAR study by locking two optimized areas of the pharmacophore and varying the rest (Chart 1). Enhancement of efficacy, reduction of lipophilicity, and improved of chemical stability were the primary goals for this study.

Development of apoE inhibitors by structure-activity relationship (SAR) study on triarylamine compounds

243rd National Meeting (2012)

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