A set of novel riminophenazine derivatives has been synthesized and evaluated for in vitro activity against chloroquine–sensitive (CQ-S) and chloroquine–resistant (CQ-R) strains of P. falciparum and against different species of Leishmania promastigotes. Most of the new compounds inhibited the growth of Leishmania promastigotes as well as CQ-S and CQ-R strains of P. falciparum with IC50 in submicromolar range, resulting in the best cases 1-2 orders of magnitude more potent than the parent compound clofazimine.