Design, synthesis and antitrypanosomal activities of 2,6-disubstituted-4,5,7-trifluorobenzothiophenes

• Perfluorinated building blocks used in synthesis of heterocyclic scaffolds.
• SNAr substitution reactions employed to deliver 6-benzimidazol-1-ylbenzothiophenes.
• IC50 values of lead compounds were <1 μM against Trypanosoma brucei rhodesiense.

Current treatments for Human African Trypanosomiasis (HAT) are limited in their application, have undesirable dosing regimens and unsatisfactory toxicities highlighting the need for the development of a safer drug pipeline. Our medicinal chemistry programme in developing rapidly accessible and modifiable heterocyclic scaffolds led to the design and synthesis of novel substituted benzothiophenes, with 6-benzimidazol-1-ylbenzothiophene derivatives demonstrating significant antitrypanosomal activities (IC50 < 1 μM) against Trypanosoma brucei rhodesiense and no toxicity towards mammalian cells.

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