Synthesis and Evaluation of Nifurtimox–Adamantane Adducts with Trypanocidal Activity

The synthesis and pharmacological evaluation of the C-1 substituted adamantane hydrazones 1a-d, their C-2 substituted isomers 2a-d and the C-1 substituted adamantane furanoic carboxamides 3a-c is described. The new adamantane derivatives exhibited an interesting pharmacological profile, in terms of trypanocidal activity and selectivity. Of the compounds tested, the phenylacetoxy hydrazone 1b showed the most promising profile against African trypanosomes (EC50=11 ± 0.9 nM; SI=770).