9-Phenanthrenemethanol halofantrine

Halofantrine, a 9-phenanthrenemethanol derivative, is a blood schizonticide and is active against Plasmodium vivax and chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum. As no parenteral preparation is available it cannot be used for severely ill patients. Oral absorption is slow and incomplete and is increased by a fatty meal. 

Halofantrine (Hf) is a new phenanthrenemethanol antimalarial that shares many physicochemical similarities with cyclosporine and has been the subject of a number of investigations in our laboratory. Hf is orally active, well tolerated, and is finding increasing use in the treatment of malaria associated with multidrug resitant strains of Plasmodium falciparum. However, Hf is extremely lipophilic (log P 8) and poorly water soluble (<10 p,g/mL), and the bioavailability of Hf after oral administration of Hf.HCl tablets is low and variable. 

Halofantrine (38,39), a member of the 9-phenanthrenemethanol class (Fig. 39.12), originally came out of a synthesis program dating to World War II, but this particular agent was not fully developed until the 1960s. Flalofantrine has one chiral center and has been separated into its enantiomers. There appears to be little difference between the enantiomers thus, the drug is used as a racemic mixture. 

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