The memory loss, personality changes and inability to communicate which characterize the progressive degeneration of patients with Alzheimer's disease (AD) are currently incurable and the medications that are available are merely palliative. Although there are several potential treatments in the pipeline such the use of antioxidants, a vaccine against AD and statins, none have been very successful in clinical trials. Thus, there is a massive unmet clinical need for a treatment which could delay the degeneration or ideally prevent it in the first place. For our ongoing chemical biology projects, to study retinoic acid (RA) signaling pathway, we developed receptors specific agonist and antagonist using our LRD (Limited Rational Design) approach and tested their biological activity as potential therapeutic agents for diseases modulated by RA pathways. Vitamin A and it's metabolites called all trans-retinoic acid (atRA) is known as Retinoic acid alpha agonist has been shown to have a beneficial effect on mouse models of AD through the up-regulation of the a-secretase enzyme resulting in a reduction of the toxic amyloid-� load in the brains. From our initial screening we found, 5-disubstituted boron containing-1, 2, 4- oxadiazoles [Figure1 ] based retinoids are potential A�  aggregation inhibitors. We utilized a Low-throughput screen (LTS) that inhibit generic disruption of A�  aggregation. This screen utilizes fluorescence for rapid high throughput detection of aggregation inhibitors, without the need for expensive synthetic peptide. In this talk, I will discuss detail the synthesis and screening technology we used for our study.

Synthesis of 3,5-disubstituted boron containing-1,2,4-oxadiazoles are potential therapeutic agents for treatment of Alzheimer's disease

246th National Meeting (2013)

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