Abstract |
Keto-trioxanes 7a-d, easily accessible in two steps from allylic alcohols 5a-d, underwent reductive amination with substituted anilines to furnish amino-functionalized trioxanes 8a-i, 9a-i, 10a-i, and 11a-i. All these new trioxanes were assessed for their oral antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice. 2-Naphthalene-based trioxanes 9c and 9i, the most active compounds of the series, provided 100% protection to the malaria-infected mice at 24 mg/kg × 4 days, while the related trioxane 9b and phenanthrene-based trioxane 11e provided a similar level of protection at 48 mg/kg × 4 days. All other trioxanes, except 10c, 10d, and 10g, provided 100% protection at 96 mg/kg × 4 days. In this model, β- arteether provided 100% protection at 48 mg/kg × 4 days and 20% protection at 24 mg/kg × 4 days.
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Authors | Chandan Singh, Mohammad Hassam, Niraj Krishna Naikade, Ved Prakash Verma, Ajit Shankar Singh, Sunil K Puri |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 53
Issue 21
Pg. 7587-98
(Nov 11 2010)
ISSN: 1520-4804 [Electronic] United States |
PMID | 20936847
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aniline Compounds
- Antimalarials
- Heterocyclic Compounds, 2-Ring
- Ketones
- Naphthalenes
- Spiro Compounds
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Topics |
- Administration, Oral
- Aniline Compounds
(chemical synthesis, chemistry, pharmacology)
- Animals
- Antimalarials
(chemical synthesis, chemistry, pharmacology)
- Drug Resistance
- Heterocyclic Compounds, 2-Ring
(chemical synthesis, chemistry, pharmacology)
- Ketones
(chemical synthesis, chemistry, pharmacology)
- Malaria
(prevention & control)
- Mice
- Naphthalenes
(chemical synthesis, chemistry, pharmacology)
- Parasitic Sensitivity Tests
- Plasmodium yoelii
(drug effects)
- Spiro Compounds
(chemical synthesis, chemistry, pharmacology)
- Structure-Activity Relationship
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