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Faculty Advisor

Dr. Caitlin Karver

Abstract

Caspases are cysteine-dependent aspartic proteases whose functions are connected to different mechanisms of cell death and inflammation. As caspase-1 plays a significant role in the immune response, its activity has been of interest as a target for inhibitor development as its inhibition will reduce the levels of pro-inflammatory cytokines in inflammatory diseases, thus minimizing the symptoms that arise and serving as a possible therapeutic approach. Prior work discovered a family of potent inhibitors of caspase-1 with a common triaminopyrimidine scaffold. To further explore structure-activity relationship profiles of potential inhibitors of caspase-1, two different syntheses were attempted to create two new series of analogs for future activity studies. The syntheses presented here were conducted to investigate whether the variation of the amino groups on the pyrimidine scaffold effect the inhibition of caspase-1. The successful synthesis of the desired compounds has not yet been accomplished, but the optimizations of the reactions for further studies are reported.

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