Synthesis and antiplasmodial evaluation of new N-(imidazol-2-yl)-methyl-4-aminoquinolines

In order to develop new effective antimalarial agents, we have demonstrated that the replacement of the phenolic ring of amodiaquine-like compounds with an arylpyrrole nucleus is associated with a good antimalarial activity (M. Casagrande et al., Bioorg. Med. Chem. 2008, 16, 6813 and Bioorg. Med. Chem. 2010, 18, 6625). In addition, Chibale and co-workers recently reported a new potent antimalarial 4-aminoquinoline, termed phenylequine (PQ), characterized by a phenyl ring linked to 4-aminoquinoline nucleus through a methylenic group (M. A. L. Blackie et al., Bioorg. Med. Chem. Lett. 2010, 20, 1078). To test the effect on the antimalarial activity of the presence of other heterocyclic rings linked to the 7-chloro-4-aminoquinoline nucleus instead of the phenyl ring , a set of new 7-chloro-N-((1H-imidazol-2-yl)methyl)quinolin-4-amine and 7-chloro-N-((4-aryl-1H-imidazol-2-yl)methyl)quinolin-4-amine bearing at position 5 of imidazole a diethylaminomethyl or a pyrrolidinomethyl moiety as basic head, was synthesized and tested.