The in vitro and in vivo antimalarial activity of some Mannich bases derived from 4-[7'-bromo (and chloro)-1',5'-naphthyridin-4'-ylamino]phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol.

A series of di-Mannich bases derived from 4-[7'-bromo (and chloro)-1',5'-naphthyridin-4'-ylamino]phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol were assayed for activity against chloroquine-sensitive and chloroquine-resistant isolates of cultured Plasmodium falciparum using the inhibition of uptake of radiolabelled hypoxanthine. A number of the 4-(7'-trifluoromethylquinolinyl-amino)phenols showed statistically superior activity to chloroquine and amodiaquine against both isolates. Analysis of the antimalarial activity of some of these compounds against Plasmodium berghei in mice following oral administration again demonstrated activity equal or superior to that of the established antimalarials against a chloroquine-sensitive strain, and in some cases appreciably superior activity against a chloroquine-resistant strain.