Human African trypanosomiasis (HAT) is caused by parasitic protozoa, <i>Trypanosoma brucei</i>, which are transmitted to humans by the bite of the tsetse fly. Current treatments for HAT include highly toxic drugs with complex and lengthy dosing regimens. A well-tolerated, orally administered drug that is effective against both early- and advanced-stage HAT is urgently needed. A recently published high-throughput screen of a kinase-targeted library from the GlaxoSmithKline screening collection identified numerous sub-micromolar <i>T. brucei</i> growth inhibitors. Among these hits, NEU-0001101, bearing a 1,2-dihydroquinazolin-2-one core structure, was selected for hit optimization studies. A two-step synthesis has been developed to enable rapid diversification and structure-activity relationship (SAR) studies. Preliminary synthesis and SAR data toward optimization of NEU-0001101 will be reported.

Design and synthesis of novel 1,2-dihydroquinazolin-2-one derivatives for the treatment of human African trypanosomiasis

251st National Meeting (2016)

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