Medicines for Malaria Venture (mmv)

William Charman

Jonathan L Vennerstrom

Hugues Matile

Jacques Chollet

Yuxiang Dong

Susan A Charman

Maniyan Padmanilayam

David J Matthews

Kamaraj Spiraghavan

Bongkoch Tarnchompoo

Chawanee Thongpanchang

Penchit Chitnumsub

Jirundon Yuvaniyama

Livia Vivas

Sanjay Babu Katiyar

Yongyuth Yuthavong

Sergio Wittlin

Sumalee Kamchonwongpaisan

Darren J Creek

Lin Zhou

Yuangqing Tang

Yuanqing Tang

Tirayut Vilaivan

The present invention relates to novel compounds that are inhibitors of wild type and mutant dihydrofolate reductase (DHFR) of, which are useful for the treatment of malaria. It also relates to processes of making and using such compounds. The antimalarial compounds of the present invention have low toxicity to a host infected with the malarial parasite, and are potent when administered in pharmaceutical compositions.

Antimalarial compounds with flexible side-chains

A means and method for treating malaria, schistosomiasis, and cancer using a spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites. The compounds of the invention unexpectedly provide a single-dose cure for malaria, as well as prophylactic activity against the same. The compounds are also active against schistosomiasis and cancer.

Dispiro 1,2,4-trioxolane antimalarials

A means and method for treating malaria, schistosomiasis, and cancer using a spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group, whereby the spirocyclohexyl ring is preferably substituted at the 4-position. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites.

Spiro and dispiro 1,2,4-trioxolane antimalarials

Spiro and dispiro 1,2,4-trixolane antimalarials

Growing community of inventors

Parkville, Australia

William Charman