Antiprotozoal activity of highly substituted pyrazole and pyrimidine derivates.

To further extend the structure-activity relationships of previously reported antimalarial anilino-pyrazoles VI, trisubstituted pyrazoles 13-15 and pyrimidines 16 and 17 were designed and synthesized. The novel derivatives were prepared thorough a divergent, chemo-selective approach starting from N,S-acetal intermediates. Compounds 13-17 were tested for their antimalarial and antileishmanial activity and their cytotoxicity was evaluated against human fibroblast. Pyrazoles 14d,e and pyrimidine 17e were identified as novel and effective antiplasmodial agents being able to inhibit, at micromolar concentrations, chloroquine(CQ)-sensitive and CQ-resistant Plasmodium falciparum strains as well as Leishmania infatum and Leishmania tropica protozoa. Additionally, favourable pharmacokinetics and toxicity profiles were predicted for the compounds.