Alzheimer's Disease (AD) is a form of senile dementia, characterized by a progressive loss of memory and cognitive function. It has been hypothesized that formation of beta-amyloid (Abeta) plaques is key to the development and progression of the disease. Therefore, inhibition of Abeta plaque formation has emerged as an attractive way of therapeutic intervention. To investigate whether small molecules can inhibit the aggregation of Abeta, we have employed indole and aza-indole moieties as key fragments in our compound design. In this poster, we will present the Structure Activity Relationship (SAR) of our compound optimization guided by a standard Thioflavin-T (ThT) screening assay. Further characterization and optimization of our compounds, e.g. metabolic stability (human & mouse), permeability, etc., allowed the identification of small molecules with promising brain penetration.

Discovery and characterization of novel small molecule inhibitors of Abeta1-42 for the treatment of Alzheimer's disease

243rd National Meeting (2012)

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