ES378917A1 - Isoindoline and benzoisothiazoline derivatives, their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

Novel isoindoline or benzisothiazoline derivatives of the formula wherein R1 is H, halogen, C 1-3 alkyl, C 1-3 alkoxy or NO 2 R2 is H, C 1-5 alkyl, phenyl or substituted phenyl R3 and R4, which may be the same or different each are H, or C 1-5 alkyl or together represent an alkylene group which may be interrupted by O, S or N, and together with the N atom to which they are attached form a heterocyclic ring and R5 is >CH 2 or >SO 2 are prepared by reacting the appropriate isoindolineacetic or benzisothiazolineacetic acid or reactive derivatives thereof with ammonia or amines of the formula or by reacting the appropriate isoindolines or benzisothiazolines with amides of the formula wherein A is a reactive atom or group such as a halogen atom or by hydrolysing the corresponding nitrile derivatives to give compounds of Formula I above in which R3 and R4 are both H or by cyclizing compounds of the Formula V wherein Y is halogen or OH to give compounds in which R5 is > CH 2 or by reacting compounds of the formula with compounds of the formula wherein B is COOH, alkoxy carbonyl or haloformyl, and C is halosulphonyl or by oxidizing compounds of Formula XV 1-Oxo-isoindoline-2-acetic acid chloride is obtained by reacting the corresponding acid with thionyl chloride. The triethylamine salt of [alpha]-(o-carboxybenzenesulphonamido)butyramide is obtained by reacting o-carboxybenzenesulphonic acid monochloride with [alpha]-aminobutyramide and triethylamine. Ethyl [alpha] - ethyl - 1 - oxo - 2 - isoindolineacetate is prepared by reacting the sodium salt of 1- oxoisoindoline with ethyl [alpha]-bromobutyrate. By a similar process ethyl 3-oxo- 1,2-benzisothiazoline- 2-acetate 1,1-dioxide and ethyl [alpha]-ethyl-3-oxo-1,2- benzoisothiazoline-2-acetate 1,1-dioxide are obtained. Pharmaceutical compositions, having tranquillizing and sedative activities and suitable for oral administration, contain one or more of the above novel compounds of Formula I and pharmaceutically acceptable carriers.