POTENTIAL ANTIMALARIALS .15. DI-MANNICH BASES OF 2-(7'-CHLOROQUINOLIN-4'-YLAMINO)PHENOL AND 2-[7'-BROMO( AND TRIFLUOROMETHYL)-1',5'-NAPHTHYRIDIN-4'-YLAMINO]PHENOL

A total of 26 di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylamino)phenol and 2-[7'-bromo(and trifluoromethyl)-1',5'-naphthyridin-4'-ylamino]phenol, such as 2-(7'-chloroquinolin-4'-ylamino)-4,6-bis(piperidin-1"-ylmethyl)phenol, together with some 3- and 5-methyl derivatives and mono-Mannich analogues, have been prepared by condensation of the 4-chloro heterocycle with the appropriate Mannich base derivatives of 2-aininophenols. In in vitro tests against Plasmodium falciparum, many of the di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylamino)phenol exhibited activity comparable to or superior to chloroquine against the chloroquine-sensitive (FCQ-27) isolate, and vastly superior activity compared with chloroquine against the chloroquine-resistant (K-1) isolate. Strong antimalarial activity was also revealed in in vivo tests against Plasmodium vinckei vinckei in mice.