RESUMEN
Despite the serious public health problems caused by Chagas disease in several countries, the available therapy remains with only two drugs that are poorly active during the chronic phase of the disease in addition to having severe side effects. In search of new trypanocidal agents, herein we describe the synthesis and biological evaluation of eleven new 1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine compounds containing the carbohydrazide or the 2,3-dihydro-1,3,4-oxadiazole moieties. Two of them showed promising in vitro activity against amastigote forms of T. cruzi and were evaluated in vivo in male BALB/c mice infected with T. cruzi Y strain. Our results suggest that the substitution at the C-2 position of the phenyl group connected to the carbohydrazide or to the 2,3-dihydro-1,3,4-oxadiazole moieties plays an important role in the trypanocidal activity of this class of compounds. Moreover, the compound containing the 2,3-dihydro-1,3,4-oxadiazole moiety has demonstrated more favorable structural requirements for in vivo activity than its carbohydrazide analog.