IL36983A - N-(p-beta-(8-quinolinylcarboxamidoethyl)-benzenesulphonyl)-ureas and process for their manufacture - Google Patents

Claims (2)

1. HOE 70/F Q96K we claim is : Benzenesulphonyl urea derivatives of the formula in which X represents a hydrogen, chlorine or "bromine atom, a methoxy or methyl group, Y represents -CH(CH5)-CH2-, -CH2-CH(CH5)- or preferably R represents a) an alkyl group of 3 to 6 carbon atoms, b) a cycloalkyl group of 5 to 8 carbon atoms, which may be substituted by 1 or 2 alkyl groups of up to 3 carbon atoms in total or by a chlorine atom, c) a cycloalkenyl group of 5 to 8 carbon, atoms, which may be substituted by 1 or 2 alkyl groups of 3 carbon atoms in total, d) a bicycloalkyl or bicycloalkenyl group of 7 or 8 carbon atoms, e) a nortricyclyl group, fjg) an alkylene-imino radical of 3 to 7 carbon atoms in the ring, which may be unoaturatod or substituted by 1 or 2 methyl groups or a lower alkyl group or a methoxy group, 36983/2 . ·» Z represents a hydrogen atom or a methylene or dlmethylene group, which forms together with Y a 5- or 6- membe ed ring* and the salts thereof.

2. ) N^^*6*ohloro»quinolino-8*oarboxamido-ethyl)-benzene-sulphonyl/- *•cyclohexyl*«rea. sulphonyl^-N'·(4»methyl cyclohexyl)-urea. 8) -^5-(p»6^ohloro-quinolino-8-carboxamido-ethyl)-benzene- sulphonyl/*!*1*(3*methyl^pentamethylene)«·semicarbazide. HOE 70/F Q96K 9) 4-/ -( B-6-chloro-quinolino-8-carboxamido-ethyl)-benzene- sulphonyl/-l,l-pentamethylene-semicarbazide. 10) 4- 4-( B-6-chloro-quinolino-8-carboxamido-ethyl)-benzene- sulphony1/-1 ,1-hexamethylene-semicarbazide . 11) 4- -( B-6-chloro-quinolino-8-carboxamido-ethyl)-benzene- 8ulphonyl7~l , 1-( 3-ethy1-pentamethylene )-semicarbazide . 12) 4-/4-(β-6-bromo-quinolino-8-carboxamido-ethyl)-benzene- sulphonyl7~l , i-hexamethylene-semicarbazide . 13). A process for the manufacture of benzenesulphonyl-ureas as claimed in claim 1, which comprises introducing, optionall stepwise, into a compound containing the grouping I of the formula in which n is 0,1 or 2. a radical II of the formula and a radical III of the formula - CO - NH - R III radicals I and III being linlced by means of a NH- group contained either in radical I or in radical III, . ": optionally oxidizing the reaction products subsequently and treating them, where required, with alkaline agents or physiologically tolerable inorganic or organic acids, for salt formation. HOE 70/P 096K 14) A process for the manufacture of benzenesulphony1-ureas of the formula in which X represents a hydrogen, chlorine or "bromine atom, a methoxy or methyl group, Ϊ represents -CH(0H5)-CH2-f- -CH2-CH(CH5)- or preferably -CH2-CH2~ , R represents a) an alkyl group, of 3 to 6 carbon atoms, b) a cycloalkyl group of 5 to 8 carbon atoms, which may be substituted by 1 or 2 alkyl groups of up to 3 carbon atoms in total or by a chlorine atom, c) a cycloalkenyl group of 5 to 8 carbon atoms, which may be substituted by 1 or 2 alkyl groups of 3 carbon atoms in total, d) a bicycloalkyl or bicycloalkenyl group of 7 or 8 carbon atoms, e) a nortricyclyl group, . f) a opiro 2,fl7"heptyl grou ?. Mffaytfie cr et 'meM /en represents a hydrogen atom or a h^4^-ea- ¾-G?i^ r€-al—oLJl—c - Or oa-rbon a-e-m-e-, which forms together with Y a 5- or 6-raembered ring, and the salts thereof, as claimed in Claim 13, which comprises a) reacting a benzenesulphonyl-isocyanate , benzenesul- phonyl-carbamic acid ester, benzenesulphon 1-thiolcar- bamic acid ester, benzenesulphonyl-urea, benzenesulphonyl- HOE 70/F Q96K with an amine R-NHg or Bait thereof, or reacting a sul-phonamide of the formula or a salt thereof with a R^-substituted isocyanate, car-baDiic acid ester, thiolcarbamic acid ester, carbamic acid halide or urea; saponifying or hydrolysing a correspondingly substituted benzenesulphonyl-isourea ether, benzenesulphonyl-isourea ester, benzenesulphonyl- isothiourea ether, benzenesul" phonyl-isothiourea ether , benzenesulphonyl-parabanic acid or benzenesulphonyl- haloformic acid amidine or a compound of the formula wherein U stands for cocygon^lower-a-3rrey-i , sul hur-1pwe-κ- al½yl or halogen (preferably chlorine) ; replacing in a correspondingly substituted benzenesul- phony1-thiourea or thioamido-alk l-benzenesulphonyl- urea or -thiourea, the sulphur atom or sulphur atoms of the thio-urea and/or thio-amido group by an oxygen atom or oxygen atoms , or adding' ater to a correspondingly substituted carbodiimide ; Oxidizin a corres ondin l substituted benzenesul hin l V e) introducing the group "by acylation optionally in one or more steps, into a benzenesulphony1-urea of ■ he - formula reacting a correspondingly substituted benzenesulphonyl- halide v/ith a R-substituted urea or an alkali metal salt thereof; or reacting a correspondingly substituted benzene sulphinic acid halide or, in the presence of an acid condensation agent, even a correspondingly substituted sulphinic acid or alkali metal salt thereof with N-R-N' -hydroxy-urea ; and, where required, treating the reaction product so obtained with an alkaline agent or with a physiologically acceptable inorganic or organic acid, for salt formation. A process for the manufacture of benzenesulphonyl-ureas in which X represents a hydrogen, chlorine or bromine atom, or a methyl or methoxy group, Y represents Z represents -carbon a ome, which forms together with Ϊ a 5- or 6- an alkylene-imino radical of 3 to 7 carbon atoms in the ring, which may be unsaturated or substituted by 1 or 2. methyl groups or a lower alkyl group or a methoxy group, a pentamethylene-imino radical which is substituted by an endoalkylene group of 1 to 3 carbon atoms, a hexamethylene-imino radical which is substituted by an endoethylene group in β-ε-positbn, or a tetrahydro-isoindoline, a 4 , 7~endoalkylene-hexa-hydro- or -tetrahydro-isoindoline radical, the endoalkylene group containing 1 or 2 carbon atoms and the double bond of the tetrahydro compound being in 5,6- position, and the salts thereof, as claimed in claim 13, which comprises reacting a benzenesulphonamide of the formula or a salt thereof, with an imino-carbamic acid ester, imino-thiocarbamic acid ester or imino-urea containing as the imino group the group R-, reacting an amine of the formula RNH2 or a salt thereof with a benzenesulphonyl-isocyanate , benzensul-phonyl-carbamic acid ester, benzenesulphonyl-thiol-carbamic acid ester, benzenesulphonyl-carbamic acid halide or benzene-sulphonyl-urea, substituted in3-position by the group Z and in 4-position by the group reacting a benzenesulphochloride of the formula with a R-substituted urea, hydrolizing a benzenesulphonyl-isourea ether, ben-zenesulphonyl-isothiourea ether or benzene-sul hon 1 imino-parabahic acid derivative substituted by R, Z and replacing in a benzenesulphonylr-thiourea of the formula the sulphur atom by an oxygen atom, or introducing the radical 36933/2 v optionally step by step, into a benzene sulphonyl- urea of the formula Π 2Ν " Y 5 C) 'J- ~ NH " C0 ~ HH ~ U and, where required, treating the reaction product for salt formation with an alkaline agent or a ph siologically acceptable inorganic or organic acid. 16) Λ process for the manufacture of pharmaceutical preparations for oral administration and lowering the blood sugar level in the treatment of diabetes mellitus, which comprises bringing a benzenesulphonyl-urea of the formula specified in claim 1 or a salt thereof, optionally in admixture or conjunction with a suitable carrier, into a pharmaceutically suitable dosage unit form. 17) Pharmaceutical preparations for oral administration and lov/ering the blood sugar level in the treatment of diabetes mellitus, which comprise a content of a benzenesulphonyl-urea defined in claim 1 or a salt thereof.