Síntese de N-(1-Aril-1H-Pirazol) benzamidas com potencial ação tripanocida

Abstract

Chagas disease (CD) is classified as a Neglected Tropical Disease (NTD) by the World Health Organization (WHO), with an estimated prevalence of around 6 to 7 million people worldwide and approximately 10,000 deaths annually. It is caused by the protozoan Trypanosoma cruzi, primarily transmitted through contact with the feces of infected triatomine insect vectors. Current treatment is limited to only two drugs, Benznidazole (BZ)and Nifurtimox (NFX), both of which present serious adverse effects that often lead to treatment discontinuation. Moreover, these drugs show low efficacy in the chronic stage of CD. In this context, the present study proposes the synthesis of 20 N-(1-aryl-1H-pyrazole)benzamides 1(a-j) and 2(a-j), aiming to evaluate their trypanocidal further, which can show higher efficacy and lower toxicity effects. The synthetic route to obtain the final compounds involves multiple steps, including the preparation of the following intermediates: 1-aryl-1H-pyrazoles 3(a-j), 4-nitro-1-aryl-1H-pyrazoles 4(a-j), 4-amino-1-aryl-1H-pyrazoles 5(a-j), ethyl 5-amino-1-aryl-1H-pyrazole-4-carboxylates 6(a-j), and 5-amino-1-aryl-1H-pyrazoles 7(a-j). Throughout the development of this work, all intermediates 3(a-j), 4(a-j), and 5(a-j) were obtained and characterized, in addition to 5 and 7 intermediates from the series 6(a-j) and 7(a-j), respectively, totaling 42 derivatives. Among the final compounds, three were obtained, consisting of two final products from series 1(a-j) and one final product from series 2(a-j).