STUDIES ON NEW ANTIMALARIALS: SYNTHESIS OF DERIVATIVES OF BENZOb1,5-NAPHTHYRIDINE

Pyronaridine (7351) and its analogues, benzo b1, 5-naphthyridines carrying aminophenol Mannich bases, exhibited activities in both the murine blood schizonticidal test and Plasmodium yoelii-Anopheles stephensi-mouse model, while other hetrocyclic compounds, pyridoacridine and 1,5-naphthyridine compounds, carrying the same Mannich bases were only effective in the former test. Considering the indispensable role of benzob 1,5-naphthyridine ring in the above structures, a series of related new compounds Ⅱ and Ⅲ were prepared by introducing substituted aminoalkylamino, amino and phenoxy chains into the ring.2-Substituent-7-chloro-10-(substituted aminoalkylamino)-benzo b 1, 5-naphthyridines (Ⅱ_1～10) and corresponding 10-(substituted amino) benzo b 1, 5-naphthyridines (Ⅱ_1～14) (Table 1) were prepared when 2-substituent-7,10-dichlorobenzo b 1, 5-naphthyridines were condensed with substituted aminoalkylamines and amines respectively. 2-Substituent-7-chloro-10-(substituted phenoxy)benzo b 1, 5-naphthyridines (Ⅲ_1～11) (Table 2) were formed when 2-substituent-7,10-dichlorobenzo b 1, 5-naphthyridines were reacted with substituted potassium phenates.Of all compounds syntheized, compounds Ⅱ_1～10 showed activities in the above two models, and among them, compounds Ⅱ_2,6,7,10 were the most effective. Compound Ⅱ₁₁ also showed pronounced activity against the sporozoite-induced infection of P. yoelii.