[Synthesis of pyronaridine related compounds and comparison of antimalarial activities].

The paper reports the synthesis of pyronaridine (I) related compounds II-V for exploring whether the antimalarial activity of pyronaridine is by virtue of a nitrogen atom at position 1 in the ring and a pair of pyrrolidinyl Mannich base side chains in its structure. The condensation of 2-methoxy-6,9-dichloroacridine or 4,7-dichloro-1,5-naphthyridine with 4-hydroxy-3,5-bis-(pyrrolidinyl-1'-methyl) aniline yielded the related compound II, 1-deazapyronaridine, or V, 5-azabispyroquine, respectively. 2-Methoxy-7,10-dichlorobenzo (b) 1,5-naphthyridine or 4,7-dichloro-1,5-naphthyridine was condensed with 4-diethylamino-1-methylbutylamine to obtain the related compound III, azacrin, or IV, 5-azachloroquine, respectively. The results of in vivo tests against Plasmodium berghei chloroquine-resistant ANKA strain, drug-sensitive P. berghei N line and drug-resistant P. yoelii nigeriensis line showed that all the related compounds II-V were less effective than pyronaridine (I). It suggests that the nitrogen atom at position 1 and pyrrolidinyl Mannich base side chains on the structure of pyronaridine play an important and indispensable role for antimalarial activity of pyronaridine. The pyrrolidinyl Mannich bases impart increased activity to the corresponding compounds.