Synthesis and Structure−Activity Relationships of Imidazopyridine/Pyrimidine‐ and Furopyridine‐Based Anti‐infective Agents against Trypanosomiases

다국어 초록 (Multilingual Abstract)

Neglected tropical diseases remain among the most critical public health concerns in Africa and South America. The drug treatments for these diseases are limited, which invariably leads to fatal cases. Hence, there is an urgent need for new antitrypanosomal drugs. To address this issue, a large number of diverse heterocyclic compounds were prepared. Straightforward synthetic approaches tolerated pre‐functionalized structures, giving rise to a structurally diverse set of analogs. We report on a set of 57 heterocyclic compounds with selective activity potential against kinetoplastid parasites. In general, 29 and 19 compounds of the total set could be defined as active against Trypanosoma cruzi and T. brucei brucei, respectively (antitrypanosomal activities <10 μM). The present work discusses the structure−activity relationships of new fused‐ring scaffolds based on imidazopyridine/pyrimidine and furopyridine cores. This library of compounds shows significant potential for anti‐trypanosomiases drug discovery.
Attention to the neglected: In this study we modified imidazopyridine/pyrimidine and furopyridine cores at eight different positions to obtain various heterocyclic compounds as anti‐infective agents. This work explores the structure−activity relationships against various Trypanosoma subtypes. These imidazopyridine/pyrimidine‐ and furopyridine‐based compounds demonstrate high antitrypanosomal activities on parasite cultures and show significant promise for trypanosomiases drug discovery.