New hydroxy-substd. di:oxo-quinoline derivs - with analgesic, antipyretic and antiphlogistic activity, for treating pain, fever, inflammation and colds

摘要

Quinolinedione derivs. (I) are new, (where R1 = H, 1-3C alkyl opt. substd. by carboxy or 2-4C alkoxycarbonyl, 4-6C alkyl, 3-6C cycloalkyl, 3-5C alkynyl, 2-3C alkyl opt. substd. in the 2-position by hydroxy, 1-3C alkoxy or alkylthio, phenyl opt. substd. by halogen or 1-3C alkoxy, or tetrahydrofurfuryl; R2 = H, or 1-3C alkyl; and R3 = H, trifluoromethyl, phenyl or 1-3C alkyl or R2+R3 = 3-5C alkylene; X = methylene opt. mono- or disubstd. by 1-3C alkyl). 8-Hydroxy-1-methyl- 7,8-dihydro-2,5(1H,6H) -quinolinedione (Ia) is specifically claimed. USE - Cpds. (I) are analgesics, antipyretics and/or antiphlogistics of the aminophenazone type. Cpd. (Ia) (below) has an LD50 of 1700 mg/kg in mice and an ED50 (mg/kg) of 19.9 after 45 mins. and 14.4 after 90 mins. against inflammatory pain induced in rats. Adult unit dosages of cpds. (I) are 25-1200 mg. In an example, aziodiisobutyronitrile (2g), carbon tetrachloride (500ml) and N-bromosuccinimide (50.2g), were added to a soln. of 1-methyl-7, 8-dihydro-2,5 (1H,6H)-quinolinedione (50g) in chloroform (500ml) and the mixt. was heated, cooled, filtered and evaporated. The residue was treated with acetone (200ml), water (180ml) and silver carbonate (50g), the mixt. was stirred and filtered and the residue was washed. Evaporation of the filtrate, distillation of the residue with toluene, chromatography and recrystallisation (ethyl acetate/ethanol) gave 8-hydroxy-1- methyl-7,8- dihydroxy-2,5(1H,6H)- quinolinedione (Ia) (11.2g); m.pt. 194-196 deg.C.