Batten disease is a rare, autosomal recessive neurodegenerative disorder, affecting 6 to 8 of every 100,000 live births in the US. It is the most common form of a range of disorders known as neuronal ceroid lipofuscinosis (NCLs). Various genes have been identified in which mutations can lead to Batten disease. However, the common pathway underlying these genes and their resulting proteins has not yet been identified.<br/>Currently, there is no cure for Batten disease; stem cell and gene therapy have been attempted but failed to show efficacious results. Current treatment is symptomatic and supportive but does not target the underlying pathophysiology, an accelerated rate of death of neurons by apoptosis.<br/>            The small molecule flupirtine exerts neuroprotective effects in isolated neuroal cell lines and crucially, in Batten patient lymphoblasts under pro-apoptitic conditions. Flupirtine was never designed as an NCL treatment, yet indicates potential in this disease state, as such no medicinal chemistry structure-activity relationship (SAR) studies have been conducted to investigate the potential of this compound as a hit for Batten disease.<br/>            We have established a synthetic route suitable for the generation of diverse analogues of flupirtine to permit SAR determination of neuroprotective activity in a phenotypic assay. Our preliminary screening has identified candidate analogues with enhanced neuroprotective effect over flupirtine, indicating a SAR exists for the compound and confirming flupirtine as much needed viable hit compound for drug discovery in Batten disease.<br/>

Design, synthesis, and structure-activity relationships of flupirtine derivatives for the treatment of neuronal ceroid lipofuscinosis

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.