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-10023538-B2
Publication Date
2018-07-17
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, compositions, and methods useful for treating infectious diseases, specifically focusing on 3-aryl quinoline compounds, their synthesis, pharmaceutical compositions thereof, and their application in treating infectious diseases such as malaria. The compounds are effective against malaria including malarial strains that have developed resistance to current drugs.
The background highlights the ongoing challenge of malaria, which remains one of the deadliest diseases worldwide, especially impacting sub-Saharan Africa. The problem addressed is the emergence of Plasmodium parasites resistant to multiple drugs including quinolines like chloroquine, quinine, and mefloquine; antifolates like pyrimethamine and sulfadoxine; and the respiratory combination of atovaquone and proguanil.
This invention solves the need for effective treatments against these drug-resistant malaria strains by providing 3-aryl quinolines that have demonstrated antimalarial efficacy. The disclosure includes methods for synthesizing these compounds, pharmaceutical compositions containing them, and methods of treatment, specifically targeting parasitic infections caused by resistant Plasmodium strains.
Claims Coverage
The patent includes one independent compound claim, one composition claim, and one method claim for treating parasitic infections.
Compound with specific 3-aryl quinoline structure
A compound with the structure of Formula (II), where substituents such as R1 and X1-X5 define the specific chemical nature of the 3-aryl quinoline core and its derivatives.
Pharmaceutical composition comprising the compound
A pharmaceutical composition comprising an effective amount of the compound of Formula (II), inclusive of pharmaceutically acceptable carriers or vehicles.
Method of treating parasitic infection using the pharmaceutical composition
A method of treating a parasitic infection in a subject by administering a therapeutically effective amount of the pharmaceutical composition containing the compound of Formula (II), where administration routes include oral, subcutaneous, intravenous, or intramuscular.
The claims cover novel 3-aryl quinoline compounds, their pharmaceutical formulations, and therapeutic methods of administration for treating parasitic infections, particularly drug-resistant malaria strains.
Stated Advantages
Compounds exhibit enhanced intrinsic antiplasmodial activity against multidrug-resistant Plasmodium strains compared to existing antimalarials.
Compound 1 demonstrates superior in vivo potency with a lower effective dose than chloroquine and cures malaria in the tested mouse model.
The proarrhythmic risk of Compound 1 is lower than other antimalarial agents, indicating improved cardiac safety.
Documented Applications
Treatment of malaria infections including strains resistant to quinine, mefloquine, chloroquine, or atovaquone.
Treatment of parasitic diseases caused by Plasmodium species such as P. falciparum, P. vivax, P. ovale, P. knowlesi, P. malariae, P. yoelii, and P. berghei.
Treatment or prevention of other parasitic diseases like toxoplasmosis, amebiasis, giardiasis, leishmaniasis, trypanosomiasis, coccidiosis, and schistosomiasis.
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