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New Acyl Derivatives of 3-Aminofurazanes and Their Antiplasmodial Activities. | LitMetric
An -acylated furazan-3-amine of a Medicines for Malaria Venture (MMV) project has shown activity against different strains of . Seventeen new derivatives were prepared and tested in vitro for their activities against blood stages of two strains of . Several structure-activity relationships were revealed. The activity strongly depended on the nature of the acyl moiety. Only benzamides showed promising activity. The substitution pattern of their phenyl ring affected the activity and the cytotoxicity of compounds. In addition, physicochemical parameters were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability) via a PAMPA. The -(4-(3,4-diethoxyphenyl)-1,2,5-oxadiazol-3-yl)-3-(trifluoromethyl)benzamide possessed good physicochemical properties and showed high antiplasmodial activity against a chloroquine-sensitive strain (IC(NF54) = 0.019 µM) and even higher antiplasmodial activity against a multiresistant strain (IC(K) = 0.007 µM). Compared to the MMV compound, the permeability and the activity against the multiresistant strain were improved.
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