New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton
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Milhous, W. K.
Smith, K. S.
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The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of >960 mg/kg.
Source:Journal of Medicinal Chemistry, 2008, 51, 19, 6216-6219
- Amer Chemical Soc, Washington