Preparation of chemically robust new artemisinin derivatives

The resurgence of malaria, largely through emergence of drug-resistant strains of the malaria parasite, Plasmodium falciparum, has in recent times substantially increased public and private focus on the development of new treatments for the disease. However, in the absence of any vaccine, major reliance continues to be placed on chemotherapy involving both traditional, largely quinoline-based, antimalarial drugs and the newer class of antimalarial drug based on artemisinin, the remarkable peroxidic sesquiterpene isolated by the Chinese in 1972. Derivatives of this compound, artesunate and artemether, are now used in routine therapy in conjunction with a longer half-life quinoline or related antimalarial. However, problems of instability and neurotoxicity associated with the current artemisinin derivatives has resulted in a vigorous search for new, more stable derivatives with better pharmacological profiles. The Centre Nationale de la Recherche Scientifique patent describes a class of relatively readily accessible new artemisinin derivatives, which in incorporating the trifluoromethyl group, appear to be more stable than the current derivatives.