Synthesis of Isoindolo[2, 1-a]quinoline Derivatives and Their Effects on N₂-Induced Hypoxia

Abstract

A variety of isoindolo[2, 1-a]quinoline derivatives as well as the following related heterocycles have been prepared : 11b, 12-dihydro-5H-isoindolo[2, 1-b][2]benzazepine-7, 13-dione (8a), 7, 8, 14, 14a-tetrahydroisoindolo[2, 1-c][3]benzazocine, -5, 13-dione(8b), 6a, 7-dihydroisoquinolino[2, 3-a]quinoline-5, 12-dione(12), 2, 3, 3a, 4-tetrahydropyrrolo[1, 2-a]quinoline-1, 5-dione (14), and pyrido[2', 3' : 3, 4]pyrrolo[1, 2-a]quinoline-5, 11(5H)-dione(17). The key synthetic step involves an intramolecular Friedel-Crafts reaction of acid chlorides such as isoindole-1-acetyl chlorides (4), the acids (3) of which were prepared starting with 2-arylisoindole-1, 3(2H)-diones (2-arylphthalimides)(1). The protective effects of isoindolo[2, 1-a]quinoline derivatives (19 and 20) against N₂-induced hypoxia were examined. Among them, 6-(diethylaminomethyl)isoindolo[2, 1-a]quinoline-5, 11(5H)-dione (19b) showed the most potency.