SYNTHESIS OF ISOINDOLO[2,1-A]QUINOLINE DERIVATIVES AND THEIR EFFECTS ON N2-INDUCED HYPOXIA

A variety of isoindolo[2,l -a]quinoline derivatives as well as the following related heterocycles have been prepared: 1 lb, 12-dihydro-5H-isoindolo[2,1 -b~[2]benzazepine-7,13-dione (8a), 7,8,14,14a-tetrahydroisoindolo[2,l-c][3]benzazocine-5,13-dione (8b), 6a,7-dihydroisoquinolino[2,3-a]quinoline-5,12-dione (12), 2,3,3a,4-tetrahydropyrrolo[l,2-a]quinoline-l,5-dione (14), and pyrido[2 ‘,3’: 3,4]pyrrolo[l,2-a]quinoline-5,ll(5//)-dione (17). The key synthetic step involves an intramolecular Friedel-Crafts reaction of acid chlorides such as isoindole-l-acetyl chlorides (4), the acids (3) of which were prepared starting with 2-arylisoindole-l, 3(2//)-diones (2-arylphthalimides) (1). The protective effects of isoindolo[2,l-a]quinoline derivatives (19 and 20) against N2-induced hypoxia were examined. Among them, 6-(diethylaminomethyl)isoindolo[2,l-a]quinoline-5,ll(5//)-dione (19b) showed the most potency. © 1990, The Pharmaceutical Society of Japan. All rights reserved.