Phenanthrenemethanol antimalarials

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. 

Similar side-chains can convert a non-heterocyclic nucleus into a good antimalarial. Excellent results against PI, falciparum infections were obtained, in laboratory and field, with the phenanthrene drugs WR 33063 (10,31) (Canfield and Rozman, 1974), and WR 122455 which is 3,6-f>i5(trifluoro-methyl-a,2-piperidyl-9-phenanthrenemethanol (Rinehart, Arnold, and Canfield, 1976). 

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