Synthesis of isoindolo[2,1-a]quinoline derivatives and their effects on N2-induced hypoxia.
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)-dio ne (19b) showed the most potency.
Ishihara
Y
Y
Chemistry Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kiyota
Y
Y
Goto
G
G
D000818:Animals; D000860:Hypoxia / Q000139:chemically induced / Q000517:prevention & control*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009584:Nitrogen / Q000037:antagonists & inhibitors; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology
D007211:Indoles; D011804:Quinolines; D009584:Nitrogen