SYNTHESIS AND EVALUATION OF DINITROANILINES FOR TREATMENT OF CRYPTOSPORIDIOSIS

The efficacy of a series of dinitroaniline herbicide derivatives for t he treatment of Cryptosporidium parvum infections has been studied. Th e lead compounds oryzalin (compound 1) and trifluralin (compound 2) ha ve low water solubility (< 3 ppm) which was alleged to be a major cont ributor to their poor pharmacokinetic availability. Derivatives of com pounds 1 and 2 were synthesized. In these derivatives the functionalit y at the C-1 amine position or the C-4 position was substituted with g roups with various hydrophilicities to determine if a direct relation existed between water solubility and overall activity. The chlorinated precursors of these derivatives were also examined and were found to be less active in the C. parvum assays, a result in direct contrast to earlier work with Leishmania. Enhanced water solubility alone did not overcome the drug availability problem; however, several candidates w ith similar activities but with toxicities lower than those of the lea d compounds were produced.