1-Aryl-4-nitro-1H-imidazoles, a new promising series for the treatment of human African trypanosomiasis

by Bourdin Trunz B, Jędrysiak R, Tweats D, Brun R, Kaiser M, Suwiński J and Torreele E. European Journal of Medicinal Chemistry, February 2011, doi: 10.1016/j.ejmech.2011.01.071.

Summary: Nitroimidazoles are a well-known class of antibacterial and antiprotozoal drugs but in spite of the widespread clinical and veterinary use of these drugs, this family has been stigmatized in part due to associated genotoxicity problems. Here we report the synthesis, the anti-trypanosomal activity and a structure–activity relationship (SAR) study of a series of about fifty 1-aryl-4-nitro-1H-imidazoles, with an emphasis on selected in vivo active molecules. Compounds 4-nitro-1-{4-(trifluoromethoxy)phenyl}-1H-imidazole and 1-(3,4-dichlorophenyl)-4-nitro-1H-imidazole are promising leads for the treatment of human African trypanosomiasis (HAT or sleeping sickness), including the fatal stage 2 of the disease, for which new treatments are urgently needed.

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