Studies on 3-substituted 1,2-benzisoxazole derivatives. 6. Syntheses of 3-(sulfamoylmethyl)-1,2-benzisoxazole derivatives and their anticonvulsant activities.
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.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004597:Electroshock; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced; D004856:Postural Balance / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D001583:Benzoxazoles