STUDIES ON NEW ANTIMALARIALS:SYNTHESIS OF DERIVATIVES OF BENZO(g) QUINOLINE WITH DOUBLE MANNICH BASES OF AMINOPHENOL

Since 4-3, 5-bis(pyrrolidinomethyl)-4-hydroxyanilino benzo(g) quinoline(Ⅰ) reported in a previous paper exhibited satisfactory effect against Plasmodium berghei without cross-resistance to chloroquine in mice, we have synthesized a group of derivatives of benzo(g) quinoline with double Mannich bases of aminophenol, 4-3, 5-bis(alkylaminomethyl) 2- or 4-hydroxyanilino benzo(g) quinolines(Ⅱ).2-Hydroxy-3-naphthoic acid used as the starting material was first allowed to react with ammonium chloride to yield 2-amino-3-naphthoic acid, and then with acrylonitrile to give 2-(2-cyanoethyl) amino 3-naphthoic acid. This intermediate was hydrolyzed to form 3-(3-carbory-2-naphthylamino) propanoic acid followed by cyclization and hydrolysis to afford benzo(g) 1, 2, 3, 4-tetra-hydroquinoline-4-one, which was subsequently condensed with 2- or 4-hydroxyaniline and reacted with. Mannich agents to form the end products Ⅱ(see Table).Of all the compounds synthesized, compounds: Ⅰ and Ⅱ_1～3;6 showed activities against the blood schizonts in mice, and among them, compounds Ⅰ and Ⅱ₃ were the most effective, and their activities were higher than that of dabequine.