ES355824A1 - New 1,3,4-oxathiazole derivatives, their preparation, and their Pharmaceutical use - Google Patents

Abstract

Novel 5 - benzylamino - 1,3,4 - oxathiazole- 3,3-dioxides of the general formula wherein R1 is a hydrogen atom or a methyl group R2 and R3 are each a hydrogen atom, a C 1-4 alkyl group, a di-alkylarnino-C 2-5 alkyl group with a total of 2 to 8 carbon atoms in the N-alkyl groups or a dialkylamino-C 2-5 alkyl group in which the two alkyl groups contain a total of 4-8 carbon atoms and are linked via an O or S atom or a CH 2 , NH or SO 2 group to form a heterocyclic ring R4 is a hydrogen or halogen atom or a C 1-4 alkyl group and R5 is a hydrogen, or halogen atom, a C 1-4 alkyl, nitro or trifluoromethyl group, a dialkylamino group with a total of 2-8 carbon atoms, a dialkylamino group with a total of 4-8 carbon atoms, the alkyl groups of which are linked via an O or S atom or a CH 2 , NH or SO 2 group to form a heterocyclic ring, a di-alkylamino-C 2-5 alkyl group with a total of 2 to 8 carbon atoms in the N-alkyl groups or a di-alkylamino-C 2-5 alkyl group in which the two alkyl groups contain a total of 4-8 carbon atoms and are linked via an O or atom or a CH 2 , NH or SO 2 group to form a heterocyclic ring and salts thereof with organic or inorganic acids or bases are prepared (a) by cyclization of an N-x-haloalkane-sulphonyl-N1-benzyl-urea of the general formula wherein X is a chlorine, bromine or iodine atom in the presence of at least the stoichiometric amount of an alkali metal hydroxide or alkaline earth metal hydroxide or tertiary organic base in a polar organic solvent at a temperature of from 30 to 150 C.: (b) by reaction of an N-([alpha]- haloalkane-sulphonyl)-arylcarbamate of the general formula X-CHR1-SO 2 NH-COOAr, wherein Ar is an optionally substituted aromatic radical, with a benzylamine of the general formula followed by cyclization in the presence of at least the stoichiometric amount of an alkali metal hydroxide or an alkaline earth metal hydroxide or a tertiary organic base in a polar organic solvent at a temperature of from 30 to 150 C., or (c) by reaction of. a 5-amino-1,3,4- oxathiazole-3,3-dioxide of the general formula with a benzyl halide of the general formula followed optionally by salification of the product. N - Chloromethanesulphonyl - phenylcarbamate is prepared by reaction of chloromethanesulphonamide with phenyl chloroformate. N- [alpha] - Chloroethanesulphonyl - N1 -3 - chlorobenzylurea is prepared by reaction of [alpha]-chloroethanesulphochloride with ammonia, followed by reaction of the resulting [alpha]-chloroethane-sulphonamide with 3-chlorobenzyl isocyanate. Pharmaceutical compositions having tranquillizing and ataraxic properties comprise, as active ingredient, a 5-benzylamino-1,3,4-oxathiazole-3,3-dioxide of the first general formula above or a salt thereof with a physiologically acceptable, non-toxic, inorganic or-organic acid or base, in admixture with a solid or liquid diluent or carrier, and may be administered orally, parenterally or rectally.