Structure-activity relationships of novel -imidazoylpiperazines with potent anti- activity.

Chagas disease is caused by the parasite , and the lack of effective and safe treatments makes identifying new classes of compounds with anti- activity of paramount importance. Hit-to-lead exploration of a metabolically stable -imidazoylpiperazine was performed. Compound , a piperazine derivative active against , was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Compounds and were identified as optimized compounds with low micromolar activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.