1-Benzyl-3-aryl-2-thiohydantoin Derivatives as New Anti- Agents: SAR and in Vivo Efficacy.

A high throughput screening and subsequent hit validation identified compound as an inhibitor of parasite growth. Extensive structure-activity relationship optimization based on antiparasitic activity led to the highly potent compounds, 1-(4-fluorobenzyl)-3-(4-dimethylamino-3-chlorophenyl)-2-thiohydantoin () and 1-(2-chloro-4-fluorobenzyl)-3-(4-dimethylamino-3-methoxyphenyl)-2-thiohydantoin (), with a EC of 3 and 2 nM, respectively. This represents >100-fold improvement in potency compared to compound . In vivo efficacy experiments of and in an acute mouse model of Human African Trypanosomiasis showed a 100% cure rate after 4 days of oral treatment at 50 mg/kg twice per day.