Indian Patents. 211560:SUBSTITUTED BENZENESULFONY-LUREAS AND -THIOUREAS, PROCESSES FOR THEIR PREPARATION, THEIR USE FOR THE PRODUCTION OF PHARMACEUTICAL PREPARATIONS AND MEDICAMENTS CONTAINING THEM

Title of Invention	SUBSTITUTED BENZENESULFONY-LUREAS AND -THIOUREAS, PROCESSES FOR THEIR PREPARATION, THEIR USE FOR THE PRODUCTION OF PHARMACEUTICAL PREPARATIONS AND MEDICAMENTS CONTAINING THEM
Abstract	Substituted benzenesulfonylureas and -thioureas of the formula I in which R (1), R(2), R(3), R(4), R(5), R(6), E, X and Y have the meanings indicated in the patent claims, exhibit outstanding effects on the cardiovascular system.

Full Text	Substituted benzenesulfonylureas and -thioureas, pro¬cesses for their preparation, their use for the produc¬tion of pharmaceutical preparations, and medicaments containing them in which: R(l) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2) is hydrogen, F, Cl, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which 1, 2, 3 or 4 carbon atoms can be replaced by heteroatoms, e.g. 0, N or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(3) is H, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by hetero¬ atoms, e.g. O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(4) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms, e.g. O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one or more of the CH2 groups can be replaced by heteroatoms, e.g. by O, S or NH; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(5) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms, e.g. O, N or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(6) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms, e.g. O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is oxygen or sulfur; X is oxygen or sulfur; Y is [CR(7)2]1_4, O, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br; and their pharmaceutically tolerable salts. The term alkyl describes, if not stated otherwise, straight-chain or branched saturated hydrocarbon radicals. The cycloalkyl radical can additionally carry an alkyl substituent. Halogen substituents which can be employed are the elements fluorine, chlorine, bromine and iodine. Aryl is the aromatic systems phenyl, thienyl, furyl, pyrrolyl, thiazolyl, naphthyl or pyridyl, which in each case can be substituted by one to three substituents such as alkyl having 1 or 2 carbon atoms, alkoxy having 1 or 2 carbon atoms, CI, Br or F; in particular phenyl, naphthyl and thienyl. Furthermore, compounds having centers of chirality, for example in the alkyl chains Y, R(3), R(4), R(5) and R(6) can occur. In this case, the invention includes both the individual antipodes per se, and a mixture of the two enantiomers in different proportions, and also the associated meso compounds or mixtures of meso compounds, the enantiomers or diastereomers. Similar sulfonylureas having hypoglycemic action are disclosed in Belgian Application BE 754454 and German Of fenlegungsschrif t 1 198 354. German Patent Applications P 43 41 655.1 (HOE 93/F 399) and P 43 44 957.3 (HOE 93/F 439) propose benzenesulfonylureas and -thioureas which, however, do not have a cyclo group corresponding to the Y-containing ring. The hypoglycemic actions of the sulfonylureas are des¬cribed therein. A prototype of such hypoglycemic sulfo¬nylureas is glibenclcunide, which is used therapeutically as an agent for the treatment of diabetes mellitus and serves in research as a much-esteemed tool for the study of so-called ATP-sensitive potassium channels. In addi¬tion to its hypoglycemic action, glibenclamide has still other actions, which up to now can still not be employed therapeutically, but which are all attributed to blockade of precisely these ATP-sensitive potassium channels* This includes, in particular, an antifibrillatory action on the heart. In the treatment of ventricular fibrillation or its preliminary stages, however, a simultaneous blood sugar fall would be undesirable or even dangerous, as it can further aggravate the condition of the patient. It was therefore the object of the present invention to synthesize compounds which have a cardiac action which is equally as good as glibenclamide but do nou affect the blood sugar or affect it distinctly less in cardioactive doses or concentrations than glibenclamide. Suitable experimental animals for the detection of such actions are, for example, mice, rats, guinea-pigs, rabbits, dogs, monkeys or pigs. The compounds I are used as pharmaceutical active com¬pounds in human and veterinary medicine. They can further be used as intermediates for the production of further pharmaceutical active compounds. Preferred compounds I are those in which: R(1) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms, R(2) is hydrogen, F, CI, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which one or more of the CH2 groups can be replaced by 0, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by a heteroatom; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms, e.g. 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is oxygen or sulfur; X is oxygen or sulfur; Y is [CR(7)2]1_3, O, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br; and their pharmaceutical^ tolerable salts. Particularly preferred compounds of the formula I are those in which: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R (2) is F, CI, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms or a CbH2b+1 group, in which one or more of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7, or 8; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (caH2a+i^ group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) are together a CbH2b group, in which one of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, f luorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is oxygen or sulfur; X is oxygen or sulfur; Y is [CR(7)2]1_3# 0, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br; and their pharmaceutically tolerable salts. Very particularly preferred compounds of the formula I are those in which: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5, or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by 0, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4), R(5) and R(6) independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is sulfur; X is oxygen; Y is [CR(7)2]1-3, 0, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br; and their pharmaceutically tolerable salts. Very especially preferred compounds of the formula I are those in which: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6,7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by 0, S or NH; b is 1, 2, 3, 4, 5, 6, 7, or 8; R(4) , R(5) and R(6) independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is sulfur; X is oxygen; Y is [CR(7)2]1-3; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br; and their pharmaceutically tolerable salts* Particularly preferred compounds of the formula I are those in which R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, S or NH; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by O, S or NH; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is sulfur; X is oxygen; Y is CR(7)2; R(7) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br; and their pharmaceutically acceptable salts. Additional particularly preferred compounds are those in which: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) and R(5) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(6) is aryl; £ is sulfur; X is oxygen; Y is CR(7)2; R(7) is hydrogen, alkyl having 1 or 2 carbon atoms, F or CI. The compounds I of the present invention are useful pharmaceuticals for the treatment of cardiac arrhythmias of all types of origin and for the prevention of sudden heart death due to arrhythmia and can therefore be used as antiarrhythmics. Examples of arrhythmic, disorders of the heart are supraventricular arrhythmias, such as atrial tachycardias, atrial flutters or paroxysmal supraventricular arrhythmias, or ventricular arrhythmias, such as ventricular extrasystoles, but in particular life-threatening ventricular tachycardias or the particu¬larly dangerous ventricular fibrillation. They are suitable in particular for those cases where arrhythmias are the consequence of a constriction of a coronary vessel, such as occur in angina pectoris or during an acute cardiac infarct or as a chronic consequence of a cardiac infarct. They are therefore particularly suitable in postinfarct patients for the prevention of sudden heart death. Further syndromes where arrhythmias of this type and/or sudden heart death due to arrhythmia play a part are, for example, cardiac insufficiency or cardiac hypertrophy as a consequence of a chronically increased blood pressure. Moreover, the compounds I can positively affect a decreased contractility of the heart. This can include a disease-related fall in cardiac contractility, for example in cardiac insufficiency, but also acute cases such as heart failure in the case of the effects of shock. Likewise, in the case of a heart transplantation, after operation has taken place the heart can resume its operational capacity more rapidly and reliably. The same applies to operations on the heart, which necessitate a temporary stopping of cardiac activity by means of cardioplegic solutions, it being possible to use the compounds both for the protection of the organs, for example during treatment with or storage thereof in physiological bath fluids, and during transfer to the recipient body. The invention furthermore relates to a process for the preparation of the compounds I which comprises (a) reacting a sulfonamide of the formula II R(l)-N=C=0 IV to give a substituted benzenesulfonylurea I a. Suitable cations M in the salts of the formula III are alkali metal and alkaline earth metal ions. Equivalently to the R(l)-substituted isocyanates IV, R(1)-substituted carbamic acid esters, R(l)-substituted carbamoyl halides or R(l)-substituted ureas can be employed. can be prepared from an aromatic benzenesulfonamide II or its salt III with an R(1)-substituted trichloroacetamide of the formula V CI3C-(CO)-NHR(l) VI in the presence of a base in an inert solvent according to Synthesis 1987, 734-735 at temperatures from 25°C to 150°C. Suitable bases are, for example, alkali metal or alkaline earth metal hydroxides, or alternatively alkoxides, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxide or potassium ethoxide. Suitable inert solvents are ethers such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether (diglyme), nitriles such as aceto-nitrile, amides such as dime thy lformamide (DMF) or N-methylpyrrolidone (NMP), hexamethylphosphoramide, sul¬foxides such as DMSO, sulfones such as sulfolane, hydro¬carbons such as benzene, toluene, xylenes. Furthermore, mixtures of these solvents with one another are also suitable, is prepared from a benzenesulfonamide II or its salt III and an R(l)-substituted isothiocyanate VI R(l)-N=C-S. VI (d) A substituted benzenesulfonylurea of the formula I a can be prepared by a conversion reaction of a benzenesul-fonylthiourea of the structure I b. The replacement of the sulfur atom by an oxygen atom in the appropriately substituted benzenesulfonylthioureas lb can be carried out, for example, with the aid of oxides or salts of heavy metals or alternatively by use of oxidants such as hydrogen peroxide, sodium peroxide or nitrous acid. A thiourea can also be desulfurized by treatment with phosgene or phosphorus pentachloride. The intermediate compounds obtained are chloroformamidines or carbodi- imides, which are converted into the corresponding substituted benzenesulfonylureas la, for example, by hydrolysis or addition of water. During desulfurization, isothioureas behave like thioureas and can accordingly also be used as starting substances for these reactions. (e) A benzenesulfonylurea I a can be prepared by reaction of an amine of the formula R(1)-NH2 with a benzenesul- fonyl isocyanate of the formula VII Likewise, an amine R(1)-NH2 can be reacted with a benzenesulfonylcarbamic acid ester, a -carbamoyl halide or a benzenesulfonylurea I a [where R(l) = H] to give a compound I a. (f) A benzenesulfonylthiourea I b can be prepared by reaction of an amine of the formula R(1)-NH2 with a benz¬ enesulfonyl isothiocyanate of the formula VIII The sulfonyl isothiocyanates are prepared by reaction of the corresponding sulfonamides with equimolar amounts of alkali metal hydroxides and carbondisulfide in an organic solvent such as DMF, DMSO or N-methylpyrrolidone. The dialkali metal salt of the sulfonyl dithiocarbamic acid thus obtained is reacted in an inert solvent with a slight excess of phosgene, or a substitute for this such as triphosgene, chloroformic acid esters (2 equivalents) or thionyl chloride. The solution of the sulfonyl isothiocyanate thus obtained can be reacted directly with the corresponding amines or ammonia. (g) A benzenesulfonylurea I a can be prepared from a benzenesulfonylurea of the formula IX a and R(3)R(4)NH by means of dehydrating agents or activation by means of carbonyl halides or formation of mixed anhydrides: The dehydrating agents employed can be all compounds suitable for the preparation of amide bonds, such as dicyclohexylcarbodiimide, carbonyldiimidazole or pro-panephosphoric anhydride. The solvents used are inert nonprotic solvents such as THF, DMF, diethyl ether, dichioromethane, as well as mixtures of these solvents. (h) A benzenesulfonylthiourea I b can be prepared from a benzenesulfonylthiourea of the formula IX b and R(3)R(4)NH by means of dehydrating agents or activation by means of carbonyl halides or formation of mixed anhydrides. The dehydrating agents employed can be all compounds suitable for the preparation of amide bonds, such as dicyclohexylcarbodiimide, carbonyldiimidazole or propane-phosphoric anhydride. The solvents used are inert nonpro¬tic solvents such as THF, DMF, diethyl ether, dichloro-methane, as well as mixtures of these solvents. The compounds I and their physiologically acceptable salts are useful therapeutics which are suitable not only as antiarrhythmics, but also in prophylaxis in disorders of the cardiovascular system, cardiac insufficiency, heart transplantation or cerebral vascular disorders in humans or mammals (for example monkeys, dogs, mice, rats, rabbits, guinea-pigs and cats). Physiologically acceptable salts of the compounds I are understood according to Remmington' s Pharmaceutical Science, 17th edition, 1985, pages 14-18 as meaning compounds of the formula X, which can be prepared from nontoxic organic and inorganic bases and benzenesulfonylureas I. Salts are preferred in this context in which M(l) in the formula X is a sodium, potassium, rubidium, calcium or magnesium ion, and also the acid addition products of basic amino acids, such as lysine or arginine. The starting compounds for the mentioned synthesis processes of the benzenesulfonylureas I are prepared by methods known per se, as are described in the literature (for example in the standard works such as Houben-Weyl, Methoden der Organischen Chemie (Methods of Organic Chemistry), Georg Thieme Verlag, Stuttgart; Organic Reactions, John Wiley & Sons, Inc., New York; and also in the patent applications indicated above), namely under reaction conditions which are known and suitable for the reactions mentioned. In this case, use can also be made of variants which are known per se but not mentioned here in more detail * If desired, the starting substances can also be formed in situ in such a way that they are not isolated from the reaction mixture, but immediately reacted further. Scheme 1 Suitably substituted carboxylic acids of the formula XI can thus be subjected to a halosulfonation according to Scheme 1 and the sulfonamide XII obtained by subsequent ammonolysis can be reacted with appropriate amines R(3)R(4)NH after activation of the carboxylic acid group to give the carboxamide of the formula II. Suitable activation methods are the preparation of the carbonyl chloride or mixed carboxylic anhydrides using formyl halides. In addition, the reagents known for amide bond preparation, such as carbonyldiimidazole, dicyclo-hexylcarbodiimide and propanephosphoric anhydride, can be used. The sulfonamides XII obtained in Scheme 1 as inter¬mediates can be reacted with appropriate isocyanates of the formula R(1)-N=C=E to give the benzenesulfonylurea-carboxylic acids of the formula IX according to Scheme 2 Scheme 2 The compounds I can have one or more chiral centers. In their preparation they can therefore be obtained as racemates or, if optically active starting substances are used, alternatively in optically active form. If the compounds have two or more chiral centers, they can be obtained in the synthesis as mixtures of racemates from which the individual isomers can be isolated in pure form, for example by recrystallizing from inert solvents* If desired, racemates obtained can be separated into their enantiomers mechanically or chemically by methods known per se. Diastereomers can thus be formed from the racemate by reaction with an optically active resolving agent. Suitable resolving agents for basic compounds are, for example, optically active acids, such as the R- or R,R- and S- or S,S-forms of tartaric acid, dibenzoyl-tartaric acid, diacetyltartaric acid, camphorsulfonic acids, mandelic acids, malic acid or lactic acid. Carbinols can further be amidated with the aid of chiral acylating reagents, for example R- or S-a-methylbenzyl isocyanate, and then separated. The various forms of the diastereomers can be separated in a known manner, for example by fractional crystallization, and the enantiomers of the formula I can be liberated from the diastereomers in a known manner. Resolution of enantiomers is further carried out by chromatography on optically active support materials. The compounds I according to the invention and their physiologically acceptable salts can be used for the production of pharmaceutical preparations. In this context, they can be brought into a suitable dose form together with at least one solid or liquid excipient or auxiliary on their own or in combination with other pharmaceuticals having cardiovascular activity, such as calcium antagonists, NO donors or ACE inhibitors. These preparations can be used as pharmaceuticals in human or veterinary medicine. Possible excipients are organic or inorganic substances which are suitable for enteral (for example oral) parenteral, for example intravenous, administration, or topical applications and do not react with the novel compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc, lanolin and petroleum jelly. In particular, tablets, coated tablets, capsules, syrups, juices or drops are used for oral administration, solutions, preferably oily or aqueous solutions, and also suspensions, emulsions or implants, are used for rectal administration, and ointments, creams, pastes, lotions, gels, sprays, foams, aerosols, solutions (for example in alcohols such as ethanol or isopropanol, acetonitrile, 1,2-propanediol or their mixtures with one another or with water) or powders are used for topical application. The novel compounds can also be lyophilized and the lyophilizates obtained used, for example, for the produc¬tion of injection preparations. In particular for topical application, liposomal preparations are also suitable, which contain stabilizers and/or wetting agents, emulsi-fiers, salts and/or auxiliaries such as lubricants, preservatives, salts for influencing the osmotic pres¬sure, buffer substances, colorants and flavorings and/or aromatic substances. If desired, they can also contain one or more further active compounds, for example one or more vi tamins. The doses which are necessary for the treatment of cardiac arrhythmias with the compounds I depend on whether the therapy is acute or prophylactic. Normally, a dose range of approximately at least 0.1 mg, preferably at least 1 mg, up to at most 100 mg, preferably up to at most 10 mg, per kg per day is adequate if prophylaxis is conducted• A dose range of 1 to 10 mg per kg per day, based on an adult of average weight 75 kg, is preferred. The dose can in this case be divided as an oral or parenteral individual dose or else in up to four indivi¬dual doses. If acute cases of cardiac arrhythmias are treated, for example in an intensive care unit, paren¬teral administration can be advantageous. A preferred dose range in critical situations can then be 10 to 100 mg and be administered, for example, as an intrave¬nous continuous infusion* According to the invention, in addition to the compounds described in the working examples, the compounds I compiled in the following Table can also be obtained: (1) 3-Sulfonylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-methylcyclopropanecarboxamide (2) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-ethylcyclopropanecarboxamide (3) 3-Sulf onylamino-N-me thy laminocarbonyl-4-me thoxy-phenyl-N-1-propylcyclopropanecarboxamide (4) 3-Sulf onylamino-N-me thy laminocarbonyl-4-me thoxy-phenyl-N-2-propylcyclopropanecarboxamide (5) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-butylcyclopropanecarboxamide (6) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-2-butylcyclopropanecarboxamide (7) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-pentylcyclopropanecarboxamide (8) 3-Sulf onylamino-N-me thylaminocarbonyl-4-me thoxy-phenyl-N-2-pentylcyclopropanecarboxamide (9) 3 -Sulf onylamino-N-me thylaminocarbonyl-4-me thoxy-phenyl-N-3-pentylcyclopropanecarboxamide (10) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-l-butyl-2-methylcyclopropanecarboxamide (11) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-butyl-3-methylcyclopropanecarboxamide (12) 3 -Sulf onylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-1-hexylcyclopropanecarboxamide (13) 3-Sulf onylamino-N-me thylaminocarbonyl-4-me thoxy-phenyl-N-2-hexylcyclopropanecarboxamide (14) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-3-hexylcyclopropanecarboxamide (15) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-heptylcyclopropanecarboxamide (16) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-2-heptylcyclopropanecarboxamide r. (17) 3-Sulfonylamino-N-methylaminocarbonyl-4-iaethoxy-phenyl -N- 3 -heptylcyclopropanecarboxamide (18) 3 -Sulf onylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-1-octylcyclopropanecarboxamide (19) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-2-octylcyclopropanecarboxamide (2 0) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-adamantylcyclopropanecarboxamide (21) 3 -Sulf onylamino-N-methylaminocarbonyl -4 -methoxy-phenyl-N-2-adamantylcyclopropanecarboxamide (22) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-dimethylcyclopropanecarboxamide (23) 3-Sul£onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N'-ethylcyclopropanecarboxamide (24) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N' -1-propylcyclopropanecarboxamide (25) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-propylcyclopropanecarboxamide (26) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl -N'-1-butylcyclopropanecarboxamide (27) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-butylcyclopropanecarboxamide (28) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-diethylcyclopropanecarboxamide (2 9) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-ethyl-N'-1-propylcyclopropanecarboxmide (3 0) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-ethyl-N'-2-propylcyclopropanecarboxamide (31) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenylpyrrolidinylcyclopropanecarboxamide (32) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenylpiperidylcyclopropanecarboxamide (33) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenylmorpholinocyclopropanecarboxamide (34) 3 -Sulf onylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-methylpiperazinylcyclopropanecarboxamide (35) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy- phenyl-4-thiomorpholinylcyclopropanecarboxamide (3 6) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy- phenyl-N-methylcyclopropanecarboxamide (37) 3 - Sul fonylamino-N-me thylaminothiocarbonyl - 4 -methoxy-phenyl-N-ethylcyclopropanecarboxamide (38) 3-Sul f onylamino-N-me thylaminothiocarbonyl-4-me thoxy-phenyl-N-1-propylcyclopropanecarboxamide (39) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-2-propylcyclopropanecarboxamide (40) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-butylcyclopropanecarboxamide (41) 3-Sul f onylamino-N-methylaminothiocarbonyl-4-me thoxy-phenyl-N-2-butylcyclopropanecarboxamide (42) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-pentylcyclopropanecarboxamide (43) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-pentylcyclopropanecarboxamide (44) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-pentylcyclopropanecarboxamide (45) 3-Sul f onylamino-N-me thylaminothiocarbonyl-4-me thoxy -phenyl-N-l-butyl-2-methylcyclopropanecarboxamide (46) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-me thoxy -phenyl-N-1-butyl-3-methylcyclopropanecarboxamide (47) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-methoxy-phenyl-N-1-hexylcyclopropanecarboxamide (48) 3 - Sul f onylamino-N-methylaminothiocarbonyl -4 -methoxy-phenyl-N-2-hexylcyclopropanecarboxamide (49) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-methoxy-phenyl-N-3-hexylcyclopropanecarboxamide (50) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-1-heptylcyclopropanecarboxamide (51) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-2-heptylcyclopropanecarboxamide (52) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-heptylcyclopropanecarboxamide (53) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-octylcyclopropanecarboxamide (54) 3-Sul f onylamino-N-me thylaminothiocarbonyl-4-me thoxy-phenyl-N-2-octylcyclopropanecarboxamide (55) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-me thoxy -phenyl-N-1-adamantylcyclopropanecarboxamide (56) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-adamantylcyclopropanecarboxamide (57) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-dimethylcyclopropanecarboxamide (58) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-ethylcyclopropanecarboxamide (59) 3-Sulf onylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-1-propylcyclopropanecarboxamide (60) 3 - Sul f onylamino-N-methylaminothiocarbonyl -4 -methoxy-phenyl-N-methyl-N' -2-propylcyclopropanecarboxamide (61) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-1-butylcyclopropanecarboxamide (62) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-butylcyclopropanecarboxamide (63) 3 - Sul f ony lamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-diethylcyclopropanecarboxamide (64) 3-Sul f onylamino-N-methylaminothiocarbonyl-4-me thoxy-phenyl-N-ethyl-N'-1-propylcyclopropanecarboxamide (65) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-ethyl-N'-2-propylcyclopropanecarboxamide (66) 3 - Sul f onylamino -N-methylaminothiocarbonyl - 4 -methoxy-phenylpyrrolidinylcyclopropanecarboxamide (67) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenylpiperidylcyclopropanecarboxamide (68) 3 - Sul f onylamino -N-methylaminothiocarbonyl - 4 -methoxy-phenylmorpholinocyclopropanecarboxamide (69) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-methylpiperazinylcyclopropanecarboxamide (70) 3-Sul fonylamino-N-methylaminothiocarbonyl-4-me thoxy -phenyl-4-thiomorpholinylcyclopropanecarboxamide (71) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-methylcyclopropanecarboxamide (72) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-ethylcyclopropanecarboxamide (73) 3 -Sulfonylamino-N-methylaminothiocarbonyl-4-methyl -phenyl-N-1-propylcyclopropanecarboxamide (74) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-2-propylcyclopropanecarboxamide (75) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl- phenyl-N-1-butylcyclopropanecarboxamide (76) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl -N- 2 -butylcyclopropanecarboxamide (77) 3 - Sulf onylamino -N-me thylaminothiocarbonyl - 4 -me thyl phenyl-N-1-pentylcyclopropanecarboxamide (7 8) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-2-pentylcyclopropanecarboxamide (79) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-3-pentylcyclopropanecarboxamide (80) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-l-butyl-2-methylcyclopropanecarboxamide (81) 3 -Sulf onylamino-N-me thylaminothiocarbonyl - 4 -methyl phenyl-N-1-butyl-3-methylcyclopropanecarboxamide (82) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-1-hexylcyclopropanecarboxamide (83) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-2-hexylcyclopropanecarboxamide (84) 3 -Sulf onylamino-N-me thylaminothiocarbonyl - 4 -methyl phenyl-N-3-hexylcyclopropanecarboxamide (85) 3 -Sulf onylamino -N-methylaminothiocarbonyl - 4 -methyl ■ phenyl-N-1-heptylcyclopropanecarboxamide (86) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-2-heptylcyclopropanecarboxamide (87) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-3-heptylcyclopropanecarboxamide (88) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-1-octylcyclopropanecarboxamide (89) 3 - Sulf onylamino -N-me thylaminothiocarbonyl - 4 -methyl -phenyl-N-2-octylcyclopropanecarboxamide (90) 3-Sulf onylamino-N-me thylaminothiocarbonyl-4-methyl-phenyl-N-1-adamantylcyclopropanecarboxamide (91) 3 - Sulf onylamino -N-me thylaminothiocarbonyl -4 -me thyl phenyl-N-2-adamantylcyclopropanecarboxamide Preparation of the starting materials Preparation of 2-(3-sulfonylamino-4-methoxy-phe nyl)cyclopropane carboxylic acids The 4-substituted phenylcarboxylic acid esters are added in portions with stirring to an excess of chlorosulfonic acid. The mixture is stirred for 3 0 minutes at room temperature, then poured onto ice and the resulting sulfonyl chloride is filtered off with suction* The latter is dissolved in ammonia solution, stirred at room temperature for 30 minutes, and the solution is neutralized using 2N hydrochloric acid. The product obtained is filtered off with suction* The esters ob¬tained are stirred overnight at room temperature with an excess of lithium hydroxide in THF/water mixture. The desired acids are obtained by acidifying with 2 N HCl and extracting with ethyl acetate. Prepared according to this method: 2 - (3 -sulf onylamino-4-methoxyphenyl) cyclopropanecarboxy- late M.p. 154°C 2- (3-Sulfonylamino-4-methoxyphenyl) cyclopropanecarboxylic acid M.p. 160°C Example 1 2 - [3 - sulf onylamino-N-methylaminothiocarbonyl-4-methoxy- phenyl]-N-1-phenyl-1-butylcyclopropanecarboxamide 2 50 mg of 2- (3-sulfonylamino-4-methoxyphenyl) -N-1-phenyl-1-butylcyclopropanecarboxamide are dissolved in 3 ml of DMF, and the solution is treated with 37 mg of NaOH and stirred at 40°C for 3 0 min. 54 mg of methyl isothio-cyanate are then added and the mixture is stirred at 7 0°C for a further 2 h* After cooling and neutralizing with 2 N hydrochloric acid, the product is filtered off with suction and dried* M.p. 110°C. Pharmacological data: The therapeutic properties of the compounds I can be demonstrated using the following models: (1) Action potential duration on the papillary muscle of the guinea-pig: (a) Introduc tion ATP deficiency states, as are observed during ischemia in the cardiac muscle cell, lead to a reduction of the action potential duration. They count as one of the causes of so-called reentry arrhythmias, which can cause sudden heart death. The opening of ATP-sensitive K channels as a result of the fall of ATP counts as causal here. (b) Method To measure the action potential, a standard micro-electrode technique is employed* For this, guinea-pigs of both sexes are killed by a blow to the head, the hearts are removed, and the papillary muscles are separated out and suspended in an organ bath. The organ bath is irrigated with Ringer solution (0.9% NaCl, 0.048% KC1, 0.024% CaCl2, 0.02% NaHC03 and 0.1% glucose) and aerated with a mixture of 95% oxygen and 5% carbon dioxide at a temperature of 36°C. The muscle is stimulated by means of an electrode using square-wave impulses of 1 V and 1 ms duration and a frequency of 2 Hz. The action potential is derived and recorded by means of a glass microelectrode inserted intracellularly, which is filled with 3 mM KCl solution. The substances to be tested were added to the Ringer solution in a concentration of 2.210'5 mol per liter. The action potential is amplified using an amplifier from Hugo Sachs and shown on an oscilloscope. The duration of the action potential is determined at a degree of repolarization of 95% (APD95). Action potential reductions are produced either by-addition of a 1 /uM-strength solution of the potassium channel opener Hoe 234 (J. Kaiser, H. Gogelein, Naunyn-Schmiedebergs Arch. Pharm. 1991, 343, R 59) or by addi¬tion of 2-deoxyglucose. The action potential-reducing effect of these substances was prevented or reduced by the simultaneous addition of the test substances Test substances were added to the bath solution as stock solutions in propanediol. The values indicated relate to measurements 30 minutes after addition. Glibenclamide was used in these measurements as a standard. The test concentration in all cases is 2 x 10"6 M. (c) Results: Patent claims in which: R (1) is hydrogen, alky 1 having lf 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2) is hydrogen, F, CI, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which 1, 2, 3 or 4 carbon atoms can be replaced by heteroatoms 0, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(3) is H, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by hetero¬ atoms 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(4) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1 group in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms. 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one or more of the CH5 groups can be replaced by heteroatoms 0, S or NH; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(5) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(6) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms o, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is oxygen or sulfur; X is oxygen or sulfur; Y is [CR(7)2]1.4, O, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br; or its pharmaceutically tolerable salts. 2. A compound of the formula 1 as claimed in claim 1, wherein: R(l) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms, R(2) is hydrogen, F, CI, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which one or more of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by a heteroatom 0, S or NH; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1, 2, 3 or 4 carbon atoms are replaced by heteroatoms 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is oxygen or sulfur; X is oxygen or sulfur; Y is [CR(7)2]1_3, 0, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br. 3. A compound of the formula I as claimed in one or more of claims 1 and 2, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2) is F, CI, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms or a CbH2b+1 group, in which one or more of the CH2 groups can be replaced by 0, NH or S; b is 1, 2, 3, 4, 5, 6, 7, or 8; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (caH2a+i^ group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) are together a CbH2b group, in which one of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, f luorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is oxygen or sulfur; X is oxygen or sulfur; Y is [CR(7)2]1„3, O, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br* 4. A compound of the formula I as claimed in one or more of claims 1 to 3, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5, or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is sulfur; X is oxygen; Y is [CR(7)2]1.3, 0, S or NH; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br. 5. A compound of the formula I as claimed in one or more of claims 1 to 4, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (caH2a+1) group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by 0, S or NH; b is 1, 2, 3, 4, 5, 6, 7, or 8; R(4), R(5) and R(6) independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is sulfur; X is oxygen; Y is [CR(7)2]1.3; R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br. 6. A compound of the formula I as claimed in one or more of claims 1 to 5, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, S or NH; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by O, S or NH; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) , R(5) and R(6) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; E is sulfur; X is oxygen; Y is CR(7)2; R(7) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms, F or CI, 7. A compound of the formula I as claimed in one or more of claims 1 to 6, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl havxng 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, f luorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; or R(3) and R(4) together are a CbH2b group, in which one of the CH2 groups can be replaced by O, NH or S; b is 1, 2, 3, 4, 5, 6, 7 or 8; R(4) and R(5) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by O, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; R(6) is aryl; E is sulfur; and R(3)R(4)NH by means of dehydrating agents or activation by means of carbonyl halides or formation of mixed anhydrides. 9. The use of a compound of the formula I as claimed in one or more of claims 1 to 7 for the production of a medicament for the treatment of cardiac arrhyth¬ mias * 10. The use of a compound of the formula I as claimed in one or more of claims 1 to 7 for the production of a medicament for the prevention of sudden heart death. 11. The use of a compound of the formula X as claimed in one or more of claims 1 to 7 for the production of a medicament for the treatment of ischemic condi¬tions of the heart. 12. The use of a compound of the formula I as claimed in one or more of claims 1 to 7 for the production of a scientific tool for the inhibition of ATP-sensi- tive potassium channels. 13. The use of a compound of the formula I as claimed in one or more of claims 1 to 7 for the production of a medicament for the treatment of weakened cardiac power. 14. The use of a compound of the formula I as claimed in one or more of claims 1 to 7 for the production of a medicament for the improvement of heart function after heart transplantation. 15. A medicament comprising an effective amount of a compound of the formula I as claimed in one or more of claims 1 to 7. 16# A substituted benzene sulfonylurea or -thiourea of the formula I substantially aa herein described with reference to the accompanying drawings.

Full Text

Substituted benzenesulfonylureas and -thioureas, pro¬cesses for their preparation, their use for the produc¬tion of pharmaceutical preparations, and medicaments containing them

in which:
R(l) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;
R(2) is hydrogen, F, Cl, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which 1, 2, 3 or 4 carbon atoms can be replaced by heteroatoms, e.g.
0, N or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8; R(3) is H, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which
1, 2, 3 or 4 carbon atoms are replaced by hetero¬
atoms, e.g. O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(4) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,

5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group
in which 1, 2, 3 or 4 carbon atoms are replaced by
heteroatoms, e.g. O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one or more of
the CH2 groups can be replaced by heteroatoms, e.g.
by O, S or NH;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(5) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group
in which 1, 2, 3 or 4 carbon atoms are replaced by
heteroatoms, e.g. O, N or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(6) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, fluoroalkyl having 1, 2,
3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having
3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in
which 1, 2, 3 or 4 carbon atoms are replaced by
heteroatoms, e.g. O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is oxygen or sulfur;
X is oxygen or sulfur;
Y is [CR(7)2]1_4, O, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4
carbon atoms, F, Cl or Br;
and their pharmaceutically tolerable salts.
The term alkyl describes, if not stated otherwise, straight-chain or branched saturated hydrocarbon radicals. The cycloalkyl radical can additionally carry an alkyl substituent. Halogen substituents which can be employed are the elements fluorine, chlorine, bromine and iodine.

Aryl is the aromatic systems phenyl, thienyl, furyl, pyrrolyl, thiazolyl, naphthyl or pyridyl, which in each case can be substituted by one to three substituents such as alkyl having 1 or 2 carbon atoms, alkoxy having 1 or 2 carbon atoms, CI, Br or F; in particular phenyl, naphthyl and thienyl.
Furthermore, compounds having centers of chirality, for example in the alkyl chains Y, R(3), R(4), R(5) and R(6) can occur. In this case, the invention includes both the individual antipodes per se, and a mixture of the two enantiomers in different proportions, and also the associated meso compounds or mixtures of meso compounds, the enantiomers or diastereomers.
Similar sulfonylureas having hypoglycemic action are disclosed in Belgian Application BE 754454 and German Of fenlegungsschrif t 1 198 354. German Patent Applications P 43 41 655.1 (HOE 93/F 399) and P 43 44 957.3 (HOE 93/F 439) propose benzenesulfonylureas and -thioureas which, however, do not have a cyclo group corresponding to the Y-containing ring.
The hypoglycemic actions of the sulfonylureas are des¬cribed therein. A prototype of such hypoglycemic sulfo¬nylureas is glibenclcunide, which is used therapeutically as an agent for the treatment of diabetes mellitus and serves in research as a much-esteemed tool for the study of so-called ATP-sensitive potassium channels. In addi¬tion to its hypoglycemic action, glibenclamide has still other actions, which up to now can still not be employed therapeutically, but which are all attributed to blockade of precisely these ATP-sensitive potassium channels* This includes, in particular, an antifibrillatory action on the heart. In the treatment of ventricular fibrillation or its preliminary stages, however, a simultaneous blood sugar fall would be undesirable or even dangerous, as it can further aggravate the condition of the patient.
It was therefore the object of the present invention to

synthesize compounds which have a cardiac action which is equally as good as glibenclamide but do nou affect the blood sugar or affect it distinctly less in cardioactive doses or concentrations than glibenclamide.
Suitable experimental animals for the detection of such actions are, for example, mice, rats, guinea-pigs, rabbits, dogs, monkeys or pigs.
The compounds I are used as pharmaceutical active com¬pounds in human and veterinary medicine. They can further be used as intermediates for the production of further pharmaceutical active compounds.
Preferred compounds I are those in which:
R(1) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms,
R(2) is hydrogen, F, CI, alkyl having 1, 2, 3, 4, 5 or 6
carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6
carbon atoms, fluoroalkoxy having 1, 2, 3, 4, 5 or
6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5
or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6
carbon atoms or a CbH2b+1 group in which one or more
of the CH2 groups can be replaced by 0, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group
in which one or more of the CH2 groups are replaced
by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by a heteroatom;
b is 1, 2, 3, 4, 5, 6, 7 or 8;

R(4) , R(5) and R(6)
independently of one another are hydrogen, aryl,
alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12
carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9
or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4,
5 or 6 carbon atoms, fluorocycloalkyl having 3, 4,
5 or 6 carbon atoms or a (CaH2a+1) group in which 1,
2, 3 or 4 carbon atoms are replaced by heteroatoms,
e.g. 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is oxygen or sulfur;
X is oxygen or sulfur;
Y is [CR(7)2]1_3, O, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4
carbon atoms, F, CI or Br;
and their pharmaceutical^ tolerable salts.
Particularly preferred compounds of the formula I are
those in which:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;
R (2) is F, CI, alkyl having 1, 2, 3 or 4 carbon atoms,
alkoxy having 1, 2, 3 or 4 carbon atoms or a CbH2b+1
group, in which one or more of the CH2 groups can
be replaced by O, NH or S;
b is 1, 2, 3, 4, 5, 6, 7, or 8;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (caH2a+i^
group, in which one or more of the CH2 groups are
replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
are together a CbH2b group, in which one of the CH2
groups can be replaced by O, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;

R(4) , R(5) and R(6)
are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl
having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms,
fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms,
f luorocycloalkyl having 3, 4, 5 or 6 carbon atoms or
a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms
are replaced by 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is oxygen or sulfur;
X is oxygen or sulfur;
Y is [CR(7)2]1_3# 0, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4
carbon atoms, F, Cl or Br;
and their pharmaceutically tolerable salts.
Very particularly preferred compounds of the formula I
are those in which:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5, or 6 carbon atoms or a (CaH2a+1)
group, in which one or more of the CH2 groups are
replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by 0, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4), R(5) and R(6)
independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4,

5 or 6 carbon atoms, fluorocycloalkyl having 3, 4,
5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is sulfur;
X is oxygen;
Y is [CR(7)2]1-3, 0, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br;
and their pharmaceutically tolerable salts.
Very especially preferred compounds of the formula I are those in which:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6,7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1)
group, in which one or more of the CH2 groups are
replaced by 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by 0, S or NH;
b is 1, 2, 3, 4, 5, 6, 7, or 8;
R(4) , R(5) and R(6)
independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

E is sulfur; X is oxygen;
Y is [CR(7)2]1-3;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br; and their pharmaceutically tolerable salts*
Particularly preferred compounds of the formula I are
those in which
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1)
group, in which one or more of the CH2 groups are
replaced by O, S or NH;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by O, S or NH;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) , R(5) and R(6)
independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is sulfur; X is oxygen;
Y is CR(7)2;
R(7) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl or Br;

and their pharmaceutically acceptable salts.
Additional particularly preferred compounds are those in
which:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1)
group, in which one or more of the CH2 groups are
replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by O, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) and R(5)
independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(6) is aryl; £ is sulfur; X is oxygen; Y is CR(7)2;
R(7) is hydrogen, alkyl having 1 or 2 carbon atoms, F or CI.
The compounds I of the present invention are useful pharmaceuticals for the treatment of cardiac arrhythmias of all types of origin and for the prevention of sudden

heart death due to arrhythmia and can therefore be used as antiarrhythmics. Examples of arrhythmic, disorders of the heart are supraventricular arrhythmias, such as atrial tachycardias, atrial flutters or paroxysmal supraventricular arrhythmias, or ventricular arrhythmias, such as ventricular extrasystoles, but in particular life-threatening ventricular tachycardias or the particu¬larly dangerous ventricular fibrillation. They are suitable in particular for those cases where arrhythmias are the consequence of a constriction of a coronary vessel, such as occur in angina pectoris or during an acute cardiac infarct or as a chronic consequence of a cardiac infarct. They are therefore particularly suitable in postinfarct patients for the prevention of sudden heart death. Further syndromes where arrhythmias of this type and/or sudden heart death due to arrhythmia play a part are, for example, cardiac insufficiency or cardiac hypertrophy as a consequence of a chronically increased blood pressure.
Moreover, the compounds I can positively affect a decreased contractility of the heart. This can include a disease-related fall in cardiac contractility, for example in cardiac insufficiency, but also acute cases such as heart failure in the case of the effects of shock. Likewise, in the case of a heart transplantation, after operation has taken place the heart can resume its operational capacity more rapidly and reliably. The same applies to operations on the heart, which necessitate a temporary stopping of cardiac activity by means of cardioplegic solutions, it being possible to use the compounds both for the protection of the organs, for example during treatment with or storage thereof in physiological bath fluids, and during transfer to the recipient body.
The invention furthermore relates to a process for the preparation of the compounds I which comprises (a) reacting a sulfonamide of the formula II

R(l)-N=C=0 IV
to give a substituted benzenesulfonylurea I a.
Suitable cations M in the salts of the formula III are alkali metal and alkaline earth metal ions. Equivalently to the R(l)-substituted isocyanates IV, R(1)-substituted carbamic acid esters, R(l)-substituted carbamoyl halides or R(l)-substituted ureas can be employed.

can be prepared from an aromatic benzenesulfonamide II or its salt III with an R(1)-substituted trichloroacetamide of the formula V
CI3C-(CO)-NHR(l) VI
in the presence of a base in an inert solvent according

to Synthesis 1987, 734-735 at temperatures from 25°C to 150°C.
Suitable bases are, for example, alkali metal or alkaline earth metal hydroxides, or alternatively alkoxides, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium methoxide, sodium ethoxide, potassium methoxide or potassium ethoxide. Suitable inert solvents are ethers such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether (diglyme), nitriles such as aceto-nitrile, amides such as dime thy lformamide (DMF) or N-methylpyrrolidone (NMP), hexamethylphosphoramide, sul¬foxides such as DMSO, sulfones such as sulfolane, hydro¬carbons such as benzene, toluene, xylenes. Furthermore, mixtures of these solvents with one another are also suitable,

is prepared from a benzenesulfonamide II or its salt III and an R(l)-substituted isothiocyanate VI
R(l)-N=C-S. VI
(d) A substituted benzenesulfonylurea of the formula I a can be prepared by a conversion reaction of a benzenesul-fonylthiourea of the structure I b. The replacement of the sulfur atom by an oxygen atom in the appropriately substituted benzenesulfonylthioureas lb can be carried out, for example, with the aid of oxides or salts of heavy metals or alternatively by use of oxidants such as hydrogen peroxide, sodium peroxide or nitrous acid. A thiourea can also be desulfurized by treatment with phosgene or phosphorus pentachloride. The intermediate compounds obtained are chloroformamidines or carbodi-

imides, which are converted into the corresponding substituted benzenesulfonylureas la, for example, by hydrolysis or addition of water. During desulfurization, isothioureas behave like thioureas and can accordingly also be used as starting substances for these reactions.
(e) A benzenesulfonylurea I a can be prepared by reaction
of an amine of the formula R(1)-NH2 with a benzenesul-
fonyl isocyanate of the formula VII

Likewise, an amine R(1)-NH2 can be reacted with a benzenesulfonylcarbamic acid ester, a -carbamoyl halide or a benzenesulfonylurea I a [where R(l) = H] to give a compound I a.
(f) A benzenesulfonylthiourea I b can be prepared by
reaction of an amine of the formula R(1)-NH2 with a benz¬
enesulfonyl isothiocyanate of the formula VIII

The sulfonyl isothiocyanates are prepared by reaction of the corresponding sulfonamides with equimolar amounts of alkali metal hydroxides and carbondisulfide in an organic solvent such as DMF, DMSO or N-methylpyrrolidone. The dialkali metal salt of the sulfonyl dithiocarbamic acid thus obtained is reacted in an inert solvent with a slight excess of phosgene, or a substitute for this such as triphosgene, chloroformic acid esters (2 equivalents) or thionyl chloride. The solution of the sulfonyl isothiocyanate thus obtained can be reacted directly with

the corresponding amines or ammonia.
(g) A benzenesulfonylurea I a can be prepared from a benzenesulfonylurea of the formula IX a and R(3)R(4)NH by means of dehydrating agents or activation by means of carbonyl halides or formation of mixed anhydrides:

The dehydrating agents employed can be all compounds suitable for the preparation of amide bonds, such as dicyclohexylcarbodiimide, carbonyldiimidazole or pro-panephosphoric anhydride. The solvents used are inert nonprotic solvents such as THF, DMF, diethyl ether, dichioromethane, as well as mixtures of these solvents.
(h) A benzenesulfonylthiourea I b can be prepared from a benzenesulfonylthiourea of the formula IX b and R(3)R(4)NH by means of dehydrating agents or activation by means of carbonyl halides or formation of mixed anhydrides.

The dehydrating agents employed can be all compounds suitable for the preparation of amide bonds, such as dicyclohexylcarbodiimide, carbonyldiimidazole or propane-phosphoric anhydride. The solvents used are inert nonpro¬tic solvents such as THF, DMF, diethyl ether, dichloro-methane, as well as mixtures of these solvents.
The compounds I and their physiologically acceptable salts are useful therapeutics which are suitable not only as antiarrhythmics, but also in prophylaxis in disorders

of the cardiovascular system, cardiac insufficiency, heart transplantation or cerebral vascular disorders in humans or mammals (for example monkeys, dogs, mice, rats, rabbits, guinea-pigs and cats).
Physiologically acceptable salts of the compounds I are understood according to Remmington' s Pharmaceutical Science, 17th edition, 1985, pages 14-18 as meaning compounds of the formula X,

which can be prepared from nontoxic organic and inorganic bases and benzenesulfonylureas I.
Salts are preferred in this context in which M(l) in the formula X is a sodium, potassium, rubidium, calcium or magnesium ion, and also the acid addition products of basic amino acids, such as lysine or arginine.
The starting compounds for the mentioned synthesis processes of the benzenesulfonylureas I are prepared by methods known per se, as are described in the literature (for example in the standard works such as Houben-Weyl, Methoden der Organischen Chemie (Methods of Organic Chemistry), Georg Thieme Verlag, Stuttgart; Organic Reactions, John Wiley & Sons, Inc., New York; and also in the patent applications indicated above), namely under reaction conditions which are known and suitable for the reactions mentioned. In this case, use can also be made of variants which are known per se but not mentioned here in more detail * If desired, the starting substances can also be formed in situ in such a way that they are not isolated from the reaction mixture, but immediately reacted further.

Scheme 1 Suitably substituted carboxylic acids of the formula XI can thus be subjected to a halosulfonation according to Scheme 1 and the sulfonamide XII obtained by subsequent ammonolysis can be reacted with appropriate amines R(3)R(4)NH after activation of the carboxylic acid group to give the carboxamide of the formula II.
Suitable activation methods are the preparation of the carbonyl chloride or mixed carboxylic anhydrides using formyl halides. In addition, the reagents known for amide bond preparation, such as carbonyldiimidazole, dicyclo-hexylcarbodiimide and propanephosphoric anhydride, can be used.
The sulfonamides XII obtained in Scheme 1 as inter¬mediates can be reacted with appropriate isocyanates of the formula R(1)-N=C=E to give the benzenesulfonylurea-carboxylic acids of the formula IX according to Scheme 2

Scheme 2
The compounds I can have one or more chiral centers. In

their preparation they can therefore be obtained as racemates or, if optically active starting substances are used, alternatively in optically active form. If the compounds have two or more chiral centers, they can be obtained in the synthesis as mixtures of racemates from which the individual isomers can be isolated in pure form, for example by recrystallizing from inert solvents* If desired, racemates obtained can be separated into their enantiomers mechanically or chemically by methods known per se. Diastereomers can thus be formed from the racemate by reaction with an optically active resolving agent. Suitable resolving agents for basic compounds are, for example, optically active acids, such as the R- or R,R- and S- or S,S-forms of tartaric acid, dibenzoyl-tartaric acid, diacetyltartaric acid, camphorsulfonic acids, mandelic acids, malic acid or lactic acid. Carbinols can further be amidated with the aid of chiral acylating reagents, for example R- or S-a-methylbenzyl isocyanate, and then separated. The various forms of the diastereomers can be separated in a known manner, for example by fractional crystallization, and the enantiomers of the formula I can be liberated from the diastereomers in a known manner.
Resolution of enantiomers is further carried out by chromatography on optically active support materials.
The compounds I according to the invention and their physiologically acceptable salts can be used for the production of pharmaceutical preparations. In this context, they can be brought into a suitable dose form together with at least one solid or liquid excipient or auxiliary on their own or in combination with other pharmaceuticals having cardiovascular activity, such as calcium antagonists, NO donors or ACE inhibitors. These preparations can be used as pharmaceuticals in human or veterinary medicine. Possible excipients are organic or inorganic substances which are suitable for enteral (for example oral) parenteral, for example intravenous, administration, or topical applications and do not react

with the novel compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc, lanolin and petroleum jelly. In particular, tablets, coated tablets, capsules, syrups, juices or drops are used for oral administration, solutions, preferably oily or aqueous solutions, and also suspensions, emulsions or implants, are used for rectal administration, and ointments, creams, pastes, lotions, gels, sprays, foams, aerosols, solutions (for example in alcohols such as ethanol or isopropanol, acetonitrile, 1,2-propanediol or their mixtures with one another or with water) or powders are used for topical application. The novel compounds can also be lyophilized and the lyophilizates obtained used, for example, for the produc¬tion of injection preparations. In particular for topical application, liposomal preparations are also suitable, which contain stabilizers and/or wetting agents, emulsi-fiers, salts and/or auxiliaries such as lubricants, preservatives, salts for influencing the osmotic pres¬sure, buffer substances, colorants and flavorings and/or aromatic substances. If desired, they can also contain one or more further active compounds, for example one or more vi tamins.
The doses which are necessary for the treatment of cardiac arrhythmias with the compounds I depend on whether the therapy is acute or prophylactic. Normally, a dose range of approximately at least 0.1 mg, preferably at least 1 mg, up to at most 100 mg, preferably up to at most 10 mg, per kg per day is adequate if prophylaxis is conducted• A dose range of 1 to 10 mg per kg per day, based on an adult of average weight 75 kg, is preferred. The dose can in this case be divided as an oral or parenteral individual dose or else in up to four indivi¬dual doses. If acute cases of cardiac arrhythmias are treated, for example in an intensive care unit, paren¬teral administration can be advantageous. A preferred dose range in critical situations can then be 10 to

100 mg and be administered, for example, as an intrave¬nous continuous infusion*
According to the invention, in addition to the compounds described in the working examples, the compounds I compiled in the following Table can also be obtained:
(1) 3-Sulfonylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-methylcyclopropanecarboxamide
(2) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-ethylcyclopropanecarboxamide
(3) 3-Sulf onylamino-N-me thy laminocarbonyl-4-me thoxy-phenyl-N-1-propylcyclopropanecarboxamide
(4) 3-Sulf onylamino-N-me thy laminocarbonyl-4-me thoxy-phenyl-N-2-propylcyclopropanecarboxamide
(5) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-butylcyclopropanecarboxamide
(6) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-2-butylcyclopropanecarboxamide
(7) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-pentylcyclopropanecarboxamide
(8) 3-Sulf onylamino-N-me thylaminocarbonyl-4-me thoxy-phenyl-N-2-pentylcyclopropanecarboxamide
(9) 3 -Sulf onylamino-N-me thylaminocarbonyl-4-me thoxy-phenyl-N-3-pentylcyclopropanecarboxamide
(10) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-l-butyl-2-methylcyclopropanecarboxamide
(11) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-butyl-3-methylcyclopropanecarboxamide
(12) 3 -Sulf onylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-1-hexylcyclopropanecarboxamide
(13) 3-Sulf onylamino-N-me thylaminocarbonyl-4-me thoxy-phenyl-N-2-hexylcyclopropanecarboxamide
(14) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-3-hexylcyclopropanecarboxamide

(15) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-heptylcyclopropanecarboxamide
(16) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-2-heptylcyclopropanecarboxamide

r.
(17) 3-Sulfonylamino-N-methylaminocarbonyl-4-iaethoxy-phenyl -N- 3 -heptylcyclopropanecarboxamide
(18) 3 -Sulf onylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-1-octylcyclopropanecarboxamide
(19) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-2-octylcyclopropanecarboxamide
(2 0) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-1-adamantylcyclopropanecarboxamide
(21) 3 -Sulf onylamino-N-methylaminocarbonyl -4 -methoxy-phenyl-N-2-adamantylcyclopropanecarboxamide
(22) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-dimethylcyclopropanecarboxamide
(23) 3-Sul£onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N'-ethylcyclopropanecarboxamide
(24) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N' -1-propylcyclopropanecarboxamide
(25) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-propylcyclopropanecarboxamide
(26) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl -N'-1-butylcyclopropanecarboxamide
(27) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-butylcyclopropanecarboxamide
(28) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-diethylcyclopropanecarboxamide
(2 9) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-ethyl-N'-1-propylcyclopropanecarboxmide (3 0) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-phenyl-N-ethyl-N'-2-propylcyclopropanecarboxamide
(31) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenylpyrrolidinylcyclopropanecarboxamide
(32) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenylpiperidylcyclopropanecarboxamide
(33) 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxy-phenylmorpholinocyclopropanecarboxamide
(34) 3 -Sulf onylamino-N-methylaminocarbonyl-4 -methoxy-phenyl-N-methylpiperazinylcyclopropanecarboxamide
(35) 3-Sulf onylamino-N-methylaminocarbonyl-4-methoxy-
phenyl-4-thiomorpholinylcyclopropanecarboxamide
(3 6) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-

phenyl-N-methylcyclopropanecarboxamide
(37) 3 - Sul fonylamino-N-me thylaminothiocarbonyl - 4 -methoxy-phenyl-N-ethylcyclopropanecarboxamide
(38) 3-Sul f onylamino-N-me thylaminothiocarbonyl-4-me thoxy-phenyl-N-1-propylcyclopropanecarboxamide
(39) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-2-propylcyclopropanecarboxamide
(40) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-butylcyclopropanecarboxamide
(41) 3-Sul f onylamino-N-methylaminothiocarbonyl-4-me thoxy-phenyl-N-2-butylcyclopropanecarboxamide
(42) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-pentylcyclopropanecarboxamide
(43) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-pentylcyclopropanecarboxamide
(44) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-pentylcyclopropanecarboxamide
(45) 3-Sul f onylamino-N-me thylaminothiocarbonyl-4-me thoxy -phenyl-N-l-butyl-2-methylcyclopropanecarboxamide
(46) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-me thoxy -phenyl-N-1-butyl-3-methylcyclopropanecarboxamide
(47) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-methoxy-phenyl-N-1-hexylcyclopropanecarboxamide
(48) 3 - Sul f onylamino-N-methylaminothiocarbonyl -4 -methoxy-phenyl-N-2-hexylcyclopropanecarboxamide
(49) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-methoxy-phenyl-N-3-hexylcyclopropanecarboxamide
(50) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-1-heptylcyclopropanecarboxamide
(51) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-2-heptylcyclopropanecarboxamide
(52) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-heptylcyclopropanecarboxamide
(53) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-octylcyclopropanecarboxamide
(54) 3-Sul f onylamino-N-me thylaminothiocarbonyl-4-me thoxy-phenyl-N-2-octylcyclopropanecarboxamide
(55) 3-Sul fonylamino-N-me thylaminothiocarbonyl-4-me thoxy -phenyl-N-1-adamantylcyclopropanecarboxamide

(56) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-adamantylcyclopropanecarboxamide
(57) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-dimethylcyclopropanecarboxamide
(58) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-ethylcyclopropanecarboxamide
(59) 3-Sulf onylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-1-propylcyclopropanecarboxamide
(60) 3 - Sul f onylamino-N-methylaminothiocarbonyl -4 -methoxy-phenyl-N-methyl-N' -2-propylcyclopropanecarboxamide
(61) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-1-butylcyclopropanecarboxamide
(62) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-butylcyclopropanecarboxamide
(63) 3 - Sul f ony lamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-diethylcyclopropanecarboxamide
(64) 3-Sul f onylamino-N-methylaminothiocarbonyl-4-me thoxy-phenyl-N-ethyl-N'-1-propylcyclopropanecarboxamide
(65) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-ethyl-N'-2-propylcyclopropanecarboxamide
(66) 3 - Sul f onylamino -N-methylaminothiocarbonyl - 4 -methoxy-phenylpyrrolidinylcyclopropanecarboxamide
(67) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenylpiperidylcyclopropanecarboxamide
(68) 3 - Sul f onylamino -N-methylaminothiocarbonyl - 4 -methoxy-phenylmorpholinocyclopropanecarboxamide
(69) 3 - Sul f onylamino-N-methylaminothiocarbonyl - 4 -methoxy-phenyl-N-methylpiperazinylcyclopropanecarboxamide
(70) 3-Sul fonylamino-N-methylaminothiocarbonyl-4-me thoxy -phenyl-4-thiomorpholinylcyclopropanecarboxamide
(71) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-methylcyclopropanecarboxamide
(72) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-ethylcyclopropanecarboxamide

(73) 3 -Sulfonylamino-N-methylaminothiocarbonyl-4-methyl -phenyl-N-1-propylcyclopropanecarboxamide
(74) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-2-propylcyclopropanecarboxamide
(75) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-

phenyl-N-1-butylcyclopropanecarboxamide
(76) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl -N- 2 -butylcyclopropanecarboxamide
(77) 3 - Sulf onylamino -N-me thylaminothiocarbonyl - 4 -me thyl phenyl-N-1-pentylcyclopropanecarboxamide
(7 8) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-2-pentylcyclopropanecarboxamide
(79) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-3-pentylcyclopropanecarboxamide
(80) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-l-butyl-2-methylcyclopropanecarboxamide
(81) 3 -Sulf onylamino-N-me thylaminothiocarbonyl - 4 -methyl phenyl-N-1-butyl-3-methylcyclopropanecarboxamide
(82) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-1-hexylcyclopropanecarboxamide
(83) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-2-hexylcyclopropanecarboxamide

(84) 3 -Sulf onylamino-N-me thylaminothiocarbonyl - 4 -methyl phenyl-N-3-hexylcyclopropanecarboxamide
(85) 3 -Sulf onylamino -N-methylaminothiocarbonyl - 4 -methyl ■ phenyl-N-1-heptylcyclopropanecarboxamide
(86) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-2-heptylcyclopropanecarboxamide
(87) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl-phenyl-N-3-heptylcyclopropanecarboxamide
(88) 3-Sulfonylamino-N-methylaminothiocarbonyl-4-methyl phenyl-N-1-octylcyclopropanecarboxamide
(89) 3 - Sulf onylamino -N-me thylaminothiocarbonyl - 4 -methyl -phenyl-N-2-octylcyclopropanecarboxamide
(90) 3-Sulf onylamino-N-me thylaminothiocarbonyl-4-methyl-phenyl-N-1-adamantylcyclopropanecarboxamide
(91) 3 - Sulf onylamino -N-me thylaminothiocarbonyl -4 -me thyl
phenyl-N-2-adamantylcyclopropanecarboxamide
Preparation of the starting materials
Preparation of 2-(3-sulfonylamino-4-methoxy-phe nyl)cyclopropane carboxylic acids

The 4-substituted phenylcarboxylic acid esters are added in portions with stirring to an excess of chlorosulfonic acid. The mixture is stirred for 3 0 minutes at room temperature, then poured onto ice and the resulting sulfonyl chloride is filtered off with suction* The latter is dissolved in ammonia solution, stirred at room temperature for 30 minutes, and the solution is neutralized using 2N hydrochloric acid. The product obtained is filtered off with suction* The esters ob¬tained are stirred overnight at room temperature with an excess of lithium hydroxide in THF/water mixture. The desired acids are obtained by acidifying with 2 N HCl and extracting with ethyl acetate. Prepared according to this method:
2 - (3 -sulf onylamino-4-methoxyphenyl) cyclopropanecarboxy-
late
M.p. 154°C
2- (3-Sulfonylamino-4-methoxyphenyl) cyclopropanecarboxylic
acid
M.p. 160°C

Example 1
2 - [3 - sulf onylamino-N-methylaminothiocarbonyl-4-methoxy-
phenyl]-N-1-phenyl-1-butylcyclopropanecarboxamide

2 50 mg of 2- (3-sulfonylamino-4-methoxyphenyl) -N-1-phenyl-1-butylcyclopropanecarboxamide are dissolved in 3 ml of DMF, and the solution is treated with 37 mg of NaOH and stirred at 40°C for 3 0 min. 54 mg of methyl isothio-cyanate are then added and the mixture is stirred at 7 0°C for a further 2 h* After cooling and neutralizing with 2 N hydrochloric acid, the product is filtered off with suction and dried* M.p. 110°C.

Pharmacological data:
The therapeutic properties of the compounds I can be demonstrated using the following models:
(1) Action potential duration on the papillary muscle of the guinea-pig:
(a) Introduc tion
ATP deficiency states, as are observed during ischemia in the cardiac muscle cell, lead to a reduction of the action potential duration. They count as one of the causes of so-called reentry arrhythmias, which can cause sudden heart death. The opening of ATP-sensitive K channels as a result of the fall of ATP counts as causal here.
(b) Method
To measure the action potential, a standard micro-electrode technique is employed* For this, guinea-pigs of both sexes are killed by a blow to the head, the hearts are removed, and the papillary muscles are separated out and suspended in an organ bath. The organ bath is irrigated with Ringer solution (0.9% NaCl, 0.048% KC1, 0.024% CaCl2, 0.02% NaHC03 and 0.1% glucose) and aerated with a mixture of 95% oxygen and 5% carbon dioxide at a temperature of 36°C. The muscle is stimulated by means of an electrode using square-wave impulses of 1 V and 1 ms duration and a frequency of 2 Hz. The action potential is derived and recorded by means of a glass microelectrode inserted intracellularly, which is filled with 3 mM KCl solution. The substances to be tested were added to the Ringer solution in a concentration of 2.2*10'5 mol per liter. The action potential is amplified using an amplifier from Hugo Sachs and shown on an oscilloscope. The duration of the action potential is determined at a degree of repolarization of 95% (APD95).

Action potential reductions are produced either by-addition of a 1 /uM-strength solution of the potassium channel opener Hoe 234 (J. Kaiser, H. Gogelein, Naunyn-Schmiedebergs Arch. Pharm. 1991, 343, R 59) or by addi¬tion of 2-deoxyglucose. The action potential-reducing effect of these substances was prevented or reduced by the simultaneous addition of the test substances* Test substances were added to the bath solution as stock solutions in propanediol. The values indicated relate to measurements 30 minutes after addition. Glibenclamide was used in these measurements as a standard. The test concentration in all cases is 2 x 10"6 M.
(c) Results:

Patent claims

in which:
R (1) is hydrogen, alky 1 having lf 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;
R(2) is hydrogen, F, CI, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which 1, 2, 3 or 4 carbon atoms can be replaced by heteroatoms
0, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(3) is H, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7,
8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3,
4, 5 or 6 carbon atoms, fluorocycloalkyl having 3,
4, 5 or 6 carbon atoms or a (CaH2a+1) group in which
1, 2, 3 or 4 carbon atoms are replaced by hetero¬
atoms 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(4) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1 group
in which 1, 2, 3 or 4 carbon atoms are replaced by
heteroatoms. 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or

R(3) and R(4)
together are a CbH2b group, in which one or more of the CH5 groups can be replaced by heteroatoms
0, S or NH;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(5) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group
in which 1, 2, 3 or 4 carbon atoms are replaced by
heteroatoms O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(6) is H, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, fluoroalkyl having 1, 2,
3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having
3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in
which 1, 2, 3 or 4 carbon atoms are replaced by
heteroatoms o, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is oxygen or sulfur;
X is oxygen or sulfur;
Y is [CR(7)2]1.4, O, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4
carbon atoms, F, CI or Br;
or its pharmaceutically tolerable salts.
2. A compound of the formula 1 as claimed in claim 1, wherein:
R(l) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms,
R(2) is hydrogen, F, CI, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or a CbH2b+1 group in which one or more of the CH2 groups can be replaced by O, NH or S;

b is 1, 2, 3, 4, 5, 6, 7 or 8; R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group
in which one or more of the CH2 groups are replaced
by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2 groups can be replaced by a heteroatom 0, S or NH; b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) , R(5) and R(6)
independently of one another are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group in which 1,
2, 3 or 4 carbon atoms are replaced by heteroatoms
0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is oxygen or sulfur;
X is oxygen or sulfur;
Y is [CR(7)2]1_3, 0, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4
carbon atoms, F, CI or Br.
3. A compound of the formula I as claimed in one or
more of claims 1 and 2, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms,
or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2) is F, CI, alkyl having 1, 2, 3 or 4 carbon atoms,
alkoxy having 1, 2, 3 or 4 carbon atoms or a CbH2b+1
group, in which one or more of the CH2 groups can
be replaced by 0, NH or S;
b is 1, 2, 3, 4, 5, 6, 7, or 8;

R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (caH2a+i^
group, in which one or more of the CH2 groups are
replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
are together a CbH2b group, in which one of the CH2
groups can be replaced by O, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) , R(5) and R(6)
are hydrogen, aryl, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, f luorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1, 2, 3 or 4 carbon atoms are replaced by 0, NH or S; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is oxygen or sulfur;
X is oxygen or sulfur;
Y is [CR(7)2]1„3, O, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4
carbon atoms, F, Cl or Br*
4. A compound of the formula I as claimed in one or more of claims 1 to 3, wherein:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5, or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are

replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by O, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) , R(5) and R(6)
independently of one another are hydrogen, aryl,
alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12
carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9
or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4,
5 or 6 carbon atoms, fluorocycloalkyl having 3, 4,
5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is sulfur;
X is oxygen;
Y is [CR(7)2]1.3, 0, S or NH;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br.
5. A compound of the formula I as claimed in one or more of claims 1 to 4, wherein:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (caH2a+1)
group, in which one or more of the CH2 groups are
replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2 groups can be replaced by 0, S or NH;

b is 1, 2, 3, 4, 5, 6, 7, or 8;
R(4), R(5) and R(6)
independently of one another are hydrogen, aryl,
alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12
carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9
or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4,
5 or 6 carbon atoms, fluorocycloalkyl having 3, 4,
5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is sulfur;
X is oxygen;
Y is [CR(7)2]1.3;
R(7) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, CI or Br.
6. A compound of the formula I as claimed in one or more of claims 1 to 5, wherein:
R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3 or 4 carbon atoms;
R(2) is methoxy or ethoxy;
R(3) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which one or more of the CH2 groups are replaced by O, S or NH; a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by O, S or NH;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) , R(5) and R(6)
independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4,

5 or 6 carbon atoms, fluorocycloalkyl having 3, 4,
5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by 0, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
E is sulfur;
X is oxygen;
Y is CR(7)2;
R(7) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms, F or CI,
7. A compound of the formula I as claimed in one or
more of claims 1 to 6, wherein: R(l) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms
or cycloalkyl having 3 or 4 carbon atoms; R(2) is methoxy or ethoxy; R(3) is hydrogen, alkyl havxng 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11 or 12 carbon atoms, cycloalkyl having 3, 4,
5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having
1, 2, 3, 4, 5 or 6 carbon atoms, f luorocycloalkyl
having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1)
group, in which one or more of the CH2 groups are
replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
or
R(3) and R(4)
together are a CbH2b group, in which one of the CH2
groups can be replaced by O, NH or S;
b is 1, 2, 3, 4, 5, 6, 7 or 8;
R(4) and R(5)
independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms or a (CaH2a+1) group, in which 1,
2, 3 or 4 carbon atoms are replaced by O, NH or S;
a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R(6) is aryl; E is sulfur;

and R(3)R(4)NH by means of dehydrating agents or activation by means of carbonyl halides or formation of mixed anhydrides.
9. The use of a compound of the formula I as claimed in
one or more of claims 1 to 7 for the production of
a medicament for the treatment of cardiac arrhyth¬
mias *
10. The use of a compound of the formula I as claimed in one or more of claims 1 to 7 for the production of a medicament for the prevention of sudden heart death.
11. The use of a compound of the formula X as claimed in one or more of claims 1 to 7 for the production of a medicament for the treatment of ischemic condi¬tions of the heart.
12. The use of a compound of the formula I as claimed in
one or more of claims 1 to 7 for the production of
a scientific tool for the inhibition of ATP-sensi-

tive potassium channels.
13. The use of a compound of the formula I as claimed in
one or more of claims 1 to 7 for the production of
a medicament for the treatment of weakened cardiac
power.
14. The use of a compound of the formula I as claimed in
one or more of claims 1 to 7 for the production of
a medicament for the improvement of heart function
after heart transplantation.
15. A medicament comprising an effective amount of a
compound of the formula I as claimed in one or more
of claims 1 to 7.
16# A substituted benzene sulfonylurea or -thiourea of
the formula I substantially aa herein described with reference to the accompanying drawings.

Documents:

242-mas-1996-abstract.pdf

242-mas-1996-claims filed.pdf

242-mas-1996-claims granted.pdf

242-mas-1996-correspondence others.pdf

242-mas-1996-correspondence po.pdf

242-mas-1996-description complete filed.pdf

242-mas-1996-description complete granted.pdf

242-mas-1996-form 1.pdf

242-mas-1996-form 19.pdf

242-mas-1996-form 26.pdf

242-mas-1996-form 3.pdf

242-mas-1996-form 4.pdf

242-mas-1996-form 5.pdf

242-mas-1996-other documents.pdf

abs-242-mas-1996.jpg

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Patent Number

211560

Indian Patent Application Number

242/MAS/1996

PG Journal Number

50/2007

Publication Date

14-Dec-2007

Grant Date

05-Nov-2007

Date of Filing

14-Feb-1996

Name of Patentee

M/S. HOECHST AKTIENGESELLSCHAFT

Applicant Address

D-65926 FRANKFURT AM MAIN,

Inventors:

#	Inventor's Name	Inventor's Address
1	DR.DIETER MANIA	GOETHESTRASSE 43, D-61462 KONIGSTEIN,
2	DR. HEINZ GOGELEIN	ZUM EISKELLER 7, D-60259 FRANKFURT,
3	DR. JOACHIM KAISER	WOOGSTRASSE 29B, D-60431 FRANKFURT,
4	DR. HEINRICH ENGLERT	STORMSTRASSE 13, D-65719 HOFHEIM,
5	DR. UWE GERLACH	IM HEIDECK 30, D-65795 HATTERSHEIM,

PCT International Classification Number

A61 K 31/395

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	195 05 910.7	1995-02-21	Germany