Studies on 3-substituted 1,2-benzisoxazole derivatives. 6. Syntheses of 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives and their anticonvulsant activities

Abstract

Several 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives were synthesized from 3-(bromomethyl)-1,2-benzisoxazole by the reaction with sodium bisulfite followed by chlorination and amination. Some of them displayed marked anticonvulsant activity in mice. The introduction of a halogen atom to the 5 position of the benzisoxazole ring caused increased activity and neurotoxicity; the substitution of a sulfamoyl group caused decreased activity. The activity of monoalkylated compounds might be the result of biotransformation. Among these compounds, 3-(sulfamoylmethyl)-1,2-benzisoxazole (1a) was thought to be the most promising as an anticonvulsant from the ratio of NTD50 and ED50.

Zonisamide: Pharmacology and Clinical Efficacy in Epilepsy

“…A continuous random screening for anticonvulsant activity had been in progress for many years at the research laboratories of Dainippon Pharmaceutical Co., Ltd. ZNS was discovered by serendipity in 1974 during routine testing of 1,2-benzisoxazole derivatives which were synthesized for the management of psychiatric diseases (49,101). Among the derivatives tested, some compounds including ZNS, were found to have a potent anticonvulsant activity in experimental animals.…”

METAL-LIGAND STABILITY CONSTANTS OF Pr(III) , Nd(III) AND Sm(III) METAL IONS COMPLEXES WITH SOME SUBSTITUTED ISOXAZOLINE pH-METRICALLY

“…diketone and its ketoenol form is also important pharmacophores of HIV-1 intergrease inhibiters 15 . Isoxazolines possess medicinal activities such as anti inflammatory 16 , anticonvulasant 17 , antibiotic 18 ,antitubercular 19 , antifungal 20 and anxiolytic activity 21 . Palaskar 22 has studied the effect of ionic strength in aqueous medium at 30 0 C. In view of the analytical application of isoxazoline and confirmation of dissosiable hydroxyl group (-OH), it is nessesery to know the physio-chemical properties such as proton-ligand and metal-ligand stability constant.…”

Zonisamide Attenuates MPTP Neurotoxicity in Marmosets

“…Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) was synthesized in Japan in 1972 and is widely used as an anticonvulsant drug throughout the world (1). It has a long elimination half-life (mean t 1/2 = 63 h) and easily crosses the blood-brain barrier (2).…”