GB863451A - New sulphonyl-ureas and preparations containing them - Google Patents

Abstract

The invention comprises benzenesulphonylureas of the formula R1SO2NH,CO,NR2R3 and salts thereof, wherein R1 is a phenyl radical bearing one or two alkyl, alkoxy or halogen substituents e.g. methyl, ethyl, methoxy or chloro, R2 is an aliphatic hydrocarbon radical of 1-4 carbon atoms, an alicyclic hydrocarbon radical of 5-7 carbon atoms or a benzyl or phenethyl radical and R3 is an aliphatic hydrocarbon radical of 1-4 carbon atoms, R2 and R3 together containing at least 3 carbon atoms, or R2 and R3 together with the nitrogen atom form a saturated heterocyclic ring system comprising at most 7 carbon atoms. The products are made by known methods for the production of sulphonyl ureas for example benzenesulphonylcarbamic esters or halides or benzenesulphonyl isocyanates or compounds convertible to benzenesulphonyl isocyanates under the reaction conditions are treated with amines HNR2R3 or benzenesulphonamides are reacted with N:N-di-substituted carbamic halides or urethanes or other compounds yielding the residue -NHCONR2R3. Also benzenesulphonyl-isourea ethers and benzenesulphonyl-thioureas may be converted into the desired benzenesulphonyl ureas by hydrolyses or oxidation. The compounds are used pharmaceutically as anti-diabetic agents (see Group VI). Many products are exemplified in which R1 is a p-methylphenyl, p-chlorophenyl, p-ethylphenyl, p-methoxyphenyl or m-chloro-p-methyl-phenyl radical and NR2R3 is a pyrrolidino, diethylamino, piperidino, methylcyclohexylamino, methylethylamino, hexamethyleneamino, dipropylamino, dibutylamino, methylbenzylamino, ethylpropylamino, ethylbutylamino, ethylcyclohexylamino or 1 : 1-dimethyl-trimethyleneimino radical. 4-Chlorobenzenesulphonyl isocyanate and 3-chloro-4-methyl-benzenesulphonyl isocyanate used as intermediates are made by treating the corresponding benzenesulphonamides with phosgene. N-Benzenesulphonyl - N1 - acetyl - ureas such as N- pmethyl, p-ethyl- and p-chlorobenzenesulphonyl-N1-acetyl ureas are made by treating the corresponding benzenesulphonylureas with acetic anhydride and sulphuric acid. Methyl p-methoxybenzenesulphonylcarbamate is made by the action of methyl chloroformate on p-methoxybenzenesulphonamide.ALSO:Preparations for oral treatment of diabetes comprise compounds of the formula R1SO2NHCONR2R3 or salts thereof, wherein R1 is a phenyl radical bearing one or two alkyl, alkoxy or halogen substituents, e.g. methyl, ethyl, methoxy or chloro, R2 is an aliphatic hydrocarbon radical of 1-4 carbon atoms, an alicyclic hydrocarbon radical of 5-7 carbon atoms or a benzyl or phenethyl radical and R3 is an aliphatic hydrocarbon radical of 1-4 carbon atoms, R2 and R3 together containing at least 3 carbon atoms, or R2 and R3 together with the nitrogen atom form a saturated heterocyclic ring (see Group IV (b)) in admixture or conjunction with a pharmaceutically suitable carrier. The preparations may take the form of pills, capsules, cachets, mixtures, solutions, powders or more particularly tablets in which the active constituent, e.g. N - p - tolylsulphonyl - N1 : N1-tetramethylene urea, is admixed with such diluents as starch, lactose, talc, tragacanth and magnesium stearate.