Synthesis and anticonvulsant activity of enaminones. 4. Investigations on isoxazole derivatives.

Due to the exceptional anticonvulsant activity displayed by substituted aniline enaminones, related pyridine derivatives and phenothiazines synthesised in our laboratories, the further investigation of various aromatic heterocycles was undertaken. Condensation of cyclic 1,3-diketo esters with 3-, and 5-aminoisoxazole derivatives led to a series of potent anti-maximal electroshock (MES) analogues, three of which occurred in the 3-amino series: ethyl ester (10), orally (po) active in rats [ED(50) 68.9 mg kg(-1), TD(50) > 500 mg kg(-1), protective index (PI = TD(50)/ED(50)) > 49.