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ABSTRACT: Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days by oral route. Trioxanes 10, 12, 14, 16, 18, 20, and 22 have shown promising antimalarial activity. Trioxanes 14 and 18, the two most active compounds of the series, provide 100% and 60% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively. In this model beta-arteether provides 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively.
Journal of Medicinal Chemistry 06/2006; 49(9):2794-803. · 5.25 Impact Factor
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ABSTRACT: [chemical reaction: see text]. An experimental protocol demonstrating the protection of the carbonyl group as 1,2,4-trioxane, the stability of the protecting group under a variety of reaction conditions, and the regeneration of the carbonyl group with Triton B in THF at room temperature is presented. The method provides a useful alternative for the protection of carbonyl compounds having acid-sensitive moieties.
Organic Letters 01/2006; 7(25):5673-6. · 5.86 Impact Factor
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Journal of Medicinal Chemistry - J MED CHEM. 01/2006; 49(9):2794-2803.
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ABSTRACT: A new series of functionalized 1,2,4-trioxanes 10-21 have been prepared and assessed for antimalarial activity in mice. Several of these trioxanes show significant activity. Trioxane 16, the most active compound of the series, has shown activity by oral route which is comparable with that of the clinically used drug, beta-arteether.
Bioorganic & Medicinal Chemistry Letters 11/2005; 15(20):4484-7. · 2.55 Impact Factor
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ABSTRACT: Trioxanes 8a-b, easily accessible in two steps from allylic alcohol 6a-b, on reductive amination with 4-aminoquinolines 4a-c furnish a new series of trioxaquines 9a-b, 10a-b, 11a-b in 32-77% yields. Dicitrate salts of these trioxaquines have been evaluated for antimalarial activity against multidrug resistant Plasmodium yoelii in mice model.
Bioorganic & Medicinal Chemistry 04/2004; 12(5):1177-82. · 2.92 Impact Factor
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ABSTRACT: Using readily available trioxanes 6a-b, a new series of amino functionalized 1,2,4-trioxanes 8a-e and 9a-e have been prepared and evaluated for antimalarial activity against multi-drug resistant Plasmodium yoelii in Swiss mice model. Several of these novel trioxanes are orally more active than the parent trioxanes 6a-b. Antimalarial activity of amino functionalized trioxane 9a, the most potent compound in the series, is very close to that of beta-arteether.
Bioorganic & Medicinal Chemistry Letters 02/2004; 14(2):459-62. · 2.55 Impact Factor
