Synthesis of isoindolo[2,1-a]quinoline derivatives and their effects on N2-induced hypoxia

A variety of isoindolo2,1-a]quinoline derivatives as well as the following related heterocycles have been prepared: 11b,12-dihydro-5H-isoindolo2,1-b]2]benzazepine-7,13-dione (8a), 7,8,14,14a-tetrahydroisoindolo2,1-c]3]benzazocine-5, 13-dione (8b), 6a,7-dihydroisoquinolino2,3-a]quinoline-5,12-dione (12), 2,3,3a-4-tetrahydropyrrolo1,2-a]quinoline-1,5-dione (14), and pyrido2',3':3,4]pyrrolo1,2-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 isoindolo2,1-a]quinoline derivatives (19 and 20) against N2-induced hypoxia were examined. Among them, 6-(diethylaminomethyl)isoindolo2,1-a]quinoline-5,11(5H)-dio ne (19b) showed the most potency.