Compounds, compositions and associated methods comprising 3-aryl quinolines
Inventors
Riscoe, Michael K. • Winter, Rolf W. • Pou, Sovitj • Hinrichs, David J. • Kelly, Jane Xu • Li, Yuexin • Nilsen, Aaron
Assignees
Oregon Health and Science University • US Department of Veterans Affairs
Publication Number
US-9249103-B2
Publication Date
2016-02-02
Expiration Date
2033-01-14
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Abstract
Compounds, compositions and methods useful for treating infectious diseases are provided. In particular, 3-aryl quinoline compounds, their synthesis, pharmaceutical compositions thereof and methods of treating infectious diseases such as malaria, are disclosed.
Core Innovation
The invention provides compounds, pharmaceutical compositions, and methods comprising 3-aryl quinolines that are useful in the treatment of infectious diseases, particularly malaria. The disclosure includes the synthesis of these compounds, compositions containing them, and methods of treating malaria, including malarial strains that have developed resistance to currently available drugs.
Malaria remains a deadly disease worldwide, with a significant impact in sub-Saharan Africa, especially among young children and pregnant women. A major challenge is the growing resistance of Plasmodium parasites to multiple antimalarial drugs, including quinolines, antifolates, and other combinations such as atovaquone and proguanil.
The disclosed invention addresses this problem by providing 3-aryl quinoline compounds effective against malaria infections, including drug-resistant strains that have diminished response to existing treatments. The compounds have demonstrated enhanced antiparasitic activity and improved therapeutic indices, offering potential new treatments for resistant malaria.
Claims Coverage
The patent contains two independent claims directed to a compound with the structure of Formula (III) and pharmaceutical compositions containing these compounds, as well as methods of treating parasitic infections using these compositions. The claims cover the compounds themselves, their pharmaceutical formulations, and the methods of administering them for treatment.
Compound with Formula (III) structure
A compound having the specific chemical structure of Formula (III) representing 3-aryl quinolines with defined substituents.
Pharmaceutical compositions comprising the compound
Pharmaceutical compositions containing an effective amount of the compound of Formula (III) for therapeutic use.
Method of treating parasitic infections with pharmaceutical compositions
Administering a therapeutically effective amount of the pharmaceutical composition containing the Formula (III) compound to a subject to treat parasitic infections.
Administration routes and targeted parasitic infections
The methods include administering the pharmaceutical compositions orally, subcutaneously, intravenously, or intramuscularly to treat Plasmodium infections, including strains resistant to quinine, mefloquine, chloroquine, or atovaquone, specifically targeting P. falciparum and P. yoelii.
Overall, the independent claims cover novel 3-aryl quinoline compounds defined by Formula (III), pharmaceutical compositions that include these compounds in therapeutically effective amounts, and methods of treating drug-resistant parasitic infections, especially malaria, by administering these compositions via various routes.
Stated Advantages
The disclosed 3-aryl quinoline compounds exhibit enhanced in vitro and in vivo antiplasmodial activity, including efficacy against multidrug-resistant strains of Plasmodium falciparum.
The compounds show improved therapeutic indices and lower cytotoxicity relative to existing antimalarials.
Compound 1 demonstrates greater potency and cure rates in mouse models compared to chloroquine, including curing animals at significantly lower doses.
The compounds have a lower proarrhythmic risk than some current antimalarials, indicated by higher hERG channel IC50 values, suggesting improved cardiac safety.
Documented Applications
Treatment of infectious diseases caused by parasitic organisms, particularly malaria caused by Plasmodium species such as P. falciparum and P. yoelii.
Treatment of malaria infections including those by multidrug-resistant strains resistant to quinine, mefloquine, chloroquine, atovaquone, and other antimalarial drugs.
Therapeutic and prophylactic use in mammals, including humans, to inhibit or prevent parasitic infections.
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