| 摘要 |
The invention comprises 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides of the formula <FORM:0861367/IV (b)/1> and N-acyl derivatives and salts of these compounds, in which R1, R3, R5 and R6 are eac hydrogen or alkyl, R2 is hydrogen, an aliphatic hydrocarbon radical of 1-8 carbon atoms, a cycloalkyl, cycloalkenyl, phenyl or phenylalkyl radical or a monocyclic heterocyclic or heterocyclic-alkyl radical containing one oxygen, nitrogen or sulphur atom in the ring, e.g. furan, pyridine or thiophene, all these radicals being optionally substituted by halogen atoms, free, esterified or etherified hydroxyl or mercapto groups, nitro, acylamino, mono-alkyl-, di-alkyl-or N : N-alkylene-amino groups wherein the alkylene group has 4 or 5 carbon atoms and may be interrupted by a hetero-atom, carboxyl groups or alkyl groups of 1-5 carbon atoms, R4 is a halogen atom or an alkoxy, alkyl or haloalkyl group of 1-5 carbon atoms and when R2, R3, R5 and R6 are hydrogen and R4/t is chlorine, R1 may be an alkyl or acyl group. The compounds are prepared either by reacting a 2-sulphamoyl aniline of the formula <FORM:0861367/IV (b)/2> p in which R11 and R31 stand for hydrogen or alkyl with an aldehyde R2CHO or a functional derivative thereof, preferably in the presence of a mineral acid, and, if desired, alkylating or acylating the product, or by hydrogenating the 3,4-positions of the corresponding benzothiadiazine 1,1-dioxides preferably by means of a di-metal hydride such as an alkali metal borohydride, and if desired alkylating or acylating the product. The compounds are used pharmaceutically as diuretics and natriuretics. Preferred products include the 3-propyl-, 3-butyl-, 3-chloromethyl-, 3-ethoxymethyl-, 3-phenoxymethyl-, 3-benzyl-, 3-b -phenethyl-, 3-cyclohexen-31-yl-, 2-methyl- and 4-methyl-6-chloro - 7 - sulphamoyl - 3,4 - dihydro - 1,2,4-benzothiadiazine - 1,1 - dioxide, 6 - trifluoromethyl - 7 - sulphamoyl - 3,4 - dihydro - 1,2,4-benzothiadiazine-1,1-dioxide and 2-methyl-6-chloro - 7 - methylsulphamoyl - 3,4 - dihydro-1,2,4 - benzothiadiazine - 1,1 - dioxide. Many other products are specified. 2-Sulphamoyl anilines of the formula given above, which are used as starting materials are made by the reacting aniline or an N-alkyl aniline, bearing a substituent R4 in the m-position with a halogenosulphonic acid, e.g. chlorosulphonic acid and treating the resulting disulphonyl chloride chloride with ammonia or an amine.ALSO:Diuretic and natriuretic preparations comprise benzothiadiazine compounds of the formula <FORM:0861367/VI/1> or salts or N-acyl derivatives thereof, wherein R1, R3, R5 and R6 are hydrogen or alkyl, R2 is hydrogen, an aliphatic hydrocarbon radical of 1-8 carbon atoms, a cycloalkyl, cycloalkenyl, phenyl or phenylalkyl radical or a monocyclic heterocyclic or heterocyclic-alkyl radical containing one oxygen, nitrogen or sulphur atom in the ring, e.g. furan, pyridine or thiophene, all these radicals being optionally substituted by halogen atoms, free, esterified or etherified hydroxyl or mercapto groups, nitro, acyl-amino, mono-alkyl-, di-alkyl- or N : N-alkylene-amino groups, wherein the alkylene group has 4 or 5 carbon atoms and may be interrupted by a hetero atom, carboxyl groups or alkyl groups of 1-5 carbon atoms, R4 is a halogen atom or an alkoxy, alkyl or haloalkyl group of 1-5 carbon atoms, and when R2, R3, R5 and R6 are hydrogen and R4 is chlorine, R1 may be an alkyl or acyl group (see Group IV (b)), in admixture or conjunction with a pharmaceutical carrier for oral or parenteral administration. The preparations may take the form of tablets, dragees, capsules, solutions, suspensions or emulsions and may contain other therapeutic substances, for example, hypotensive agents such as Rauwolfia or Veratrum alkaloids, e.g. reserpine, rescinnamine, deserpidine, germine or protoveratrine, or hydralazine or ganglionic blockers such as chlorisondamine. An example describes the preparation of tablets containing 3 - butyl - 6 - chloro - 7 - sulphamoyl - 3,4 - dihydro - 1,2,4 - benzothiadiazine - 1,1 - dioxide. |
