NO822255L - PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE SULFIMIN DERIVATIVES. - Google Patents

Description

This invention relates to the preparation of new sulfimines with the general formula

and their salts with strong acids, especially their physiologically compatible acid addition salts.

/ The new compounds of the above general formula I exhibit valuable pharmacological properties, in particular antithrombotic effects.

In the above general formula I means

n the number 0 or 1,

A means a methylene, vinylene or ethylene group optionally substituted with one or two alkyl groups with each 1 to 3 carbon atoms,

B means a linear or branched alkylene group of 2 to 6

carbon atoms,

means an alkyl group with 1 to 3 carbon atoms optionally substituted with a phenyl group or a phenyl group, where the phenyl nucleus can in each case be substituted with an alkyl group with 1 to 4 carbon atoms, a halogen atom, an alkoxy group with 1 to 3 carbon atoms, a cyclohexyl, phenyl - or halophenyl group; an alkyl group of 4 to 7 carbon atoms; a cycloalkyl group of 3 to 7 carbon atoms;

one with alkyl groups of 1 to 4 carbon atoms, alkoxy groups of 1 to 3 carbon atoms and/or halogen atoms di- or tri-substituted phenyl or disubstituted hydroxy or aminophenyl group, where the substituents on the phenyl nucleus may be the same or different; a naphthyl group or a pyridyl group optionally substituted by an alkoxy group with 1 to 3 carbon atoms, and

1*2 means a hydrogen atom or an acyl residue of an organic carboxylic acid, of an organic or inorganic sulphonic acid or of a carboxylic acid derivative. When it comes to the expression "an acyl residue" which is used in the definition of the residue, this is in particular an acyl residue of an aliphatic saturated or unsaturated alkanoic acid which may optionally be substituted, of an optionally substituted aromatic carboxylic acid where a -CH= CH group, one or two -CH groups can each be replaced by an oxygen, sulfur or nitrogen atom, by a carboxylic acid ester, by an optionally substituted carbamic acid, by an aliphatic or aromatic sulphonic acid or a hydroxysulphonyl group. Among halogen atoms mentioned under the definition of the radical R^, a fluorine, chlorine or bromine atom shall be understood in particular. ;' Among the meanings given at the beginning of the definition of the residues A, B, R^ and R£, e.g. in consideration ; for A the meaning of a methylene-, methylmethylene-, dimethylmethylene-, diethylmethylene-, dipropylmethylene-, vinylene-, methyl-vinylene- or ethylene group, ; for B the meaning of an ethylene-, n-propylene-, n-butylene-, n-pentylene-, n-hexylene-, 1-methyl-ethylene-, 2-methyl-ethylene-, 1-methyl-n-propylene-, 2-methyl-n-propylene-, 3-methyl-n-propylene- , 1- methyl-n-butylene-, 2-methyl-n-butylene-, 3-methyl-n-butylene-, 4-methyl-n-butylene-, 1-methyl-n-pentylene-, 2-methyl- n-pentylene-, 3-methyl-n-pentylene-, 4-methyl-n-pentylene-, 5-methyl-n-pentylene-, 1,1-dimethyl-ethylene-, 1,2-dimethyl-ethylene-, 2,2-dimethyl-ethylene-, 1,1-dimethyl-n-propylene-, 2,2-dimethyl-n-propylene-, 3,3-dimethyl-n-propylene-, 1,2-dimethyl-n- propylene-, 1,3-dimethyl-n-propylene-, 1,1-dimethyl-n-butylene-, 2,2-dimethyl-n-butylene-, 3,3-dimethyl-n-butylene-, 4,4 -dimethyl-n-butylene-, 1,2-dimethyl-n-butylene-, 1,3-dimethyl-n-butylene-, 1,4-dimethyl-n-butylene-, 2,3-dimethyl-n-butylene -, 1-ethyl-ethylene-, 2-ethyl-1-ethylene-, 1-ethyl-n-propylene-, 2- ethyl-n-propylene-, 3-ethyl-n-propylene-, 1-ethy l-n-butylene-, 2- ethyl-n-butylene-, 3-ethyl-n-butylene-, 4-ethyl-n-butylene-, l-methyl-2-ethyl-ethylene-, l-methyl-2-ethyl -n-propylene-, 1-methyl-3-ethyl-n-propylene-, 1-methyl-2-propyl-ethylene-, 1-propyl-1-ethylene-, . 1-butyl-1-ethylene- or 1-propy1-n-propylene group, for the R meaning a methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl-, tert.butyl-, pentyl-, neopentyl-, tert.pentyl-hexyl-, heptyl-, benzyl-, 1-phenylethyl-, 2-phenylethyl-, 1-phenylpropyl-, 3-phenylpropyl-, fluorobenzyl-, chlorobenzyl-, bromobenzyl-, methylbenzy1-, isopropylbenzyl-, methoxybenzy1- , ethoxybenzy1-, ;cycloprcpyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cycloheptyl-, phenyl-, fluorophenyl-, chlorophenyl-, bromophenyl-, methylphenyl-, dimethylphenyl-, isopropylphenyl-, tert.butylphenyl-, : methoxyphenyl-, ethoxyphenyl-, propoxyphenyl-, cyclohexylphenyl-, biphenylyl-, fluorophenyl-phenyl-, chlorophenyl-phenyl-, difluorophenyl-, dichlorophenyl-, dibromophenyl-, dimethoxyphenyl-, methoxychlorophenyl-, methoxy-bromophenyl-, methyl-tert.buty1-phenyl- , methyl-chlorophenyl-, methylbromophenyl-, tert.butyl-bromophenyl-, dichloroaminophenyl-, dibromo-aminophenyl-, dimethyl-aminophenyl-, dichloro-hydroxyphenyl-, dibromo-hydroxyphenyl-, dimethyl1-hydroxyphenyl-, di-tert. buty 1-hydroxyphenyl-, trimethoxy-phenyl-, naphthyl, methoxynaphthyl or pyridyl group and; for the R2 meaning a hydrogen atom, a formyl-, acetyl-, propionyl-, pivaloyl-, pentanoyl-, hexanoyl-, heptanoyl-, octanoyl-, nonanoyl-, methoxyacetyl-, methoxypropionyl-, pinanoyl-, benzoyl-, fluorobenzoyl-, chlorobenzoyl-, bromobenzoyl-, cyanobenzoyl-, methylbenzoyl-, ethylbenzoyl-, isopropylbenzoyl-, tert.butylbenzoyl-, difluorobenzoyl-, dichlorobenzoyl -, dimethylbenzoyl-, trimethylbenzoyl-, naphthoyl-, pyridinoyl-, thenoyl-, acetoxy-benzoyl-, hydroxysulfonyl-, methylsulfonyl-, ethylsulfonyl-, camphor-sulfonyl-, phenylsulfonyl-, methylphenyl-sulfonyl-, fluorophenylsulfonyl-, chlorophenylsulfonyl-, bromophenylsulfonyl, pentamethylphenylsulfonyl, naphthylsulfonyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, benzyloxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, phenylaminocarbonyl or chlorophenylaminocarbonyl group. ;Preferred compounds of the general formula I are;those where;n means the number 0 or 1,;A means a dimethylmethylene, vinylene or ethylene group,;B means a linear alkylene group of 3 to 5 carbon atoms, ;means an alkyl group of 1 to 6 carbon atoms, a benzyl, phenylethyl, cyclohexyl, naphthyl, methoxy-naphthyl or pyridyl group; an optionally with an alkyl group of 1 to 4 carbon atoms, a methoxy, cyclohexyl, phenyl or fluorophenyl group, a fluorine-, chlorine- or bromate-substituted phenyl group; a disubstituted phenyl group with alkyl groups with 1 to 4 carbon atoms, methoxy groups, chlorine and/or bromine atoms, where the substituents on the phenyl nucleus may be the same or different; or one with two chlorine or bromine atoms, two methoxy groups or two alkyl groups each having 1 to 4 carbon atoms. substituted aminophenyl, hydroxyphenyl or methoxyphenyl group and ;1*2 means a hydrogen atom, an alkanoyl group with 1 to 8 carbon atoms optionally substituted with a methoxy group;

a benzoyl or phenylsulfonyl group optionally substituted with a halogen atom, a cyano group or an alkyl group with 1 to 4 carbon atoms; an alkoxycarbonyl group having a total of 2 to 4 carbon atoms; one optionally with a chlorophenyl group,

with one or two methyl groups substituted aminocarbonyl group; a naphthoyl, pinanoyl, camphorsulfonyl, pentamethylphenylsulfonyl, pyridinoyl or thenoyl group,

and their salts with strong acids.

Particularly preferred compounds of the above general formula I are those wherein

n means the number 1,

A means a dimethylmethylene, vinylene or ethylene group,

B means an n-butylene group,

R 2 represents a methyl or methoxynaphthyl group; a phenyl group optionally substituted with a methoxy group, a fluorine or chlorine atom; a phenyl group substituted with two chlorine or bromine atoms; a methyl-bromophenyl-, 4-amino-3,5-dibromo-phenyl or di-tert.buty1-hydroxy-phenyl group and

R2 means a hydrogen atom, an alkanoyl group with 1 to 3 carbon atoms or a benzoyl or phenylsulfonyl group optionally substituted with an alkyl group with 1 to 4 carbon atoms. and their physiologically compatible salts and strong acids.

According to the invention, the new compounds are prepared as follows: a) For the preparation of a compound with the general formula I where n means the number 1, and R2 means a hydrogen atom:

Reaction of a sulfoxide with the general formula

where A, B and R are as stated at the outset, with hydrogen azide possibly formed in the reaction mixture.

The reaction is suitably carried out in a solvent or a solvent mixture such as methylene chloride, dimethylformamide or tetrahydrofuran at temperatures between 0 and 40°C, preferably at temperatures between 10 and 35°C. It is particularly advantageous to carry out the reaction with an alkali azide, e.g. sodium azide, and using polyphosphoric acid as solvent. b) For the preparation of a compound of the general formula I where a hydrogen atom means:

Reaction of a sulfoxide with the general formula

where A, B, n and R are as initially indicated, with a compound of the general formula

where X means a carbonyl or sulfonyl group, and R^ means an aryl group disubstituted in the o-position such as a 2,4,6-trimethylphenyl or 2,4,6-triisopropylphenyl group or also a hydroxy group, when X means a sulfonyl group.

The reaction is conveniently carried out in a solvent or solvent mixture such as methylene chloride, chloroform, dimethylformamide, tetrahydrofuran or dioxane, at temperatures between 0 and 50°C, preferably at temperatures between 5 and 40°C. The reaction is particularly advantageously carried out by using a compound of the general formula III without prior isolation, resp. is produced in the reaction mixture. c) For the preparation of a compound of the general formula I where n means the number 1: Oxidation of a mercapto compound of the general formula

where A, B, R 2 and R 2 are as indicated at the outset.

The oxidation is preferably carried out in a solvent or a solvent mixture, e.g. in water, water/pyridine, methanol, ethanol, acetone, formic acid, glacial acetic acid, trifluoroacetic acid or dilute sulfuric acid, depending on the oxidizing agent used, at temperatures between -80 and 1C0°C. The reaction is particularly advantageously carried out with an equivalent of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid or formic acid at 0 to 20°C or in acetone at 0 to 60°C, with a peracid such as permauric acid in glacial acetic acid or trifluoroacetic acid at 0 to 50°C, or with sodium metaperiodate in aqueous methanol or ethanol at 15 to 25°C. d) For the preparation of a compound of the general formula I where R 2 does not mean a hydrogen atom: Acylation of a compound of the general formula where n, A, B and R 1 are as indicated at the outset. The reaction is conveniently carried out in a solvent or solvent mixture such as water, methylene chloride, chloroform, ether, tetrahydrofuran, dioxane or dimethylformamide, with a suitable acylating agent, e.g. with an acid in the presence of an acid-activating or water-attracting agent such as thionyl chloride, with its anhydrides such as acetic anhydride, with its esters such as p-toluenesulfonic acid ethyl ester or carboxylic acid diethyl ester, with its halides such as acetyl chloride, ethyl chloroformate or p-toluenesulfonic acid chloride, or with a suitable isocyanate, since these can optionally also serve as a solvent, optionally in the presence of an inorganic or tertiary organic base such as sodium hydroxide, potassium carbonate, triethylamine or pyridine, the latter being . at the same time can also serve as a solvent, at temperatures between -25 and 100°C, preferably at temperatures between -10 and 80°C. e) Reaction of a hydroxy compound with the general one formula

where A is as initially indicated, or its salts with inorganic or tertiary organic bases, with a compound of the general formula

where n, R 1 , R 2 and B are as indicated at the outset, and Z means a nucleophilic replaceable group such as a halogen atom or a sulphonic acid ester residue, e.g. a chlorine, bromine or iodine atom, a p-toluenesulfonyloxy or methanesulfonyloxy group.

The reaction is conveniently carried out in a suitable solvent or a solvent mixture such as dioxane, tetrahydrofuran, chloroform or toluene, preferably in an anhydrous, aprotic solvent such as acetone, dimethylformamide or dimethylsulfoxide, optionally in the presence of an alkali base such as sodium carbonate, potassium carbonate or sodium hydroxide, at temperatures between Q°C and the boiling temperature of the solvent used, e.g. at temperatures between 0 and 100°C, preferably at temperatures between 10 and 50°C. However, the reaction can also be carried out without a solvent. f) For the preparation of a compound of the general formula I where n means the number 0:

Reaction of a thioether with the general formula

where A, B and R are, as indicated at the outset, with an amide of the general formula

where Hal means a chlorine or bromine atom, and R^<1> has the meanings given for R2 at the beginning with the exception of hydrogen, or with its alkali salt and possibly subsequent hydrolysis.

The reaction is preferably carried out with an alkali salt of a compound of the general formula IX, e.g. the sodium salt, optionally in the presence of an inorganic base such as an alkali base, in a solvent or a solvent mixture such

such as methanol, methanol/water or ethanol, suitably at temperatures between 0 and 80°C, preferably at temperatures between 5 and 50°C.

The optionally subsequent hydrolysis is carried out in the presence of an acid or base/preferably in the presence of a base such as caustic soda, in a solvent or a solvent mixture such as water, methanol, water/methanol or tetrahydrofuran/water, at temperatures up to used solvent boiling temperature.

The prepared compounds of the general formula I can optionally then be transferred to their salts with strong acids. Suitable acids are e.g. hydrochloric acid, sulfuric acid or mesitylene sulphonic acid.

The compounds with the general formulas II to IX used as starting materials are partly known from the literature or can be prepared by usual methods.

The compounds with the general formulas II or IIa used as starting materials are e.g. described in EP-A1-0.003.771

and German patent application P 30 42 632.5 of 12 November 1980 or can be produced according to the methods described in EP-A1-0.003.771.

The compounds of the general formula III used as starting materials are preferably obtained by reacting a suitable O-carbonyl or O-sulphonyl-acethydroxamic acid ester with sulfuric acid and subsequent extraction after addition of a base.

The mercapto compounds with the general formula IV used as starting materials are obtained, for example by reaction of a suitable thioether with a chloramine or with O-mesitylenesulfonyl-hydroxylamine.

A compound with the general formula V used as a starting material gives, for example, by oxidation of a suitable mercapto compound, which is obtained by reaction of a suitable thioether with a chloramine and subsequent hydrolysis, or by reaction of a suitable mercapto or sulfinyl compound with O-mesitylenesulfony1-hydroxylamine.

A compound with the general formula VII used as starting material gives, for example, by reaction of a suitable sulfinyl compound, which is obtained by oxidation of a suitable thioether, with a suitable O-mesitylenesulfonyl-hydroxylamine and optionally subsequent acylation.

A compound with the general formula VIII used as starting material gives, for example, by conversion of a suitable hydroxy- or mercapto compound with an appropriate halide in the presence of a base.

A compound with the general formula IX used as starting material gives, for example, by reacting an appropriate amide with a hypohalide.

As mentioned at the beginning, they show new connections

with the general formula I valuable pharmacological properties, especially antithrombotic effects. The compounds increase the synthesis of the aggregation-inhibiting prostaglandin

(prostacyclin). Moreover, the connections with represent

the general formula I, where n means the number 0, valuable intermediates for the preparation of the new compounds with the general formula I where n means the number 1.

Furthermore, the compounds of the general formula I exhibit an inhibitory effect on tumor metastasis formation, and this is due to the following properties of the compounds produced: 1. They are inhibitors of platelet phosphodiesterase, which is known to inhibit tumor metastasis formation (H. Gastpar, Thrombosis Research 5, 277-289 (1974) and K. V. Honn,

Science 212, 1270-1272 (1981)).

2. The compounds cause a strong prolongation of the bleeding time, i.e. they inhibit the primary hemostasis, the first attachment of platelets to damaged vessels during the formation of a pure platelet thrombus, already at a very low dosage. For the compounds of formula I, this can not only be explained by a limitation of platelet function, but also by an elevated prostacyclin release from the endothelial cells in the vessels. A confirmation is the absence of bleeding time extension

when prostacyclin synthesis in the endothelial cells is interrupted by prior administration of cyclooxygenase inhibitors. The compounds thus represent a hitherto unknown, optimal combination of two principles of action, namely elevated cAMP level by stimulating the formation (prostacyclin) and simultaneous inhibition of the breakdown (PDE inhibition). The thus achieved increase in prostacyclin activity resp. prostacyclin synthesis in the vessel wall is, according to Honn (K. v. Honn, Science 212, 1270-1272

(1981)) likewise cause inhibition of tumor metastasis formation.

As examples were the compounds

A = 6-(4-methylsulfoximino-butoxy)-3,4-dihydrocarbostyryl mesitylene sulfonate,

B = 6-(4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyryl,

C = 6-[4-(4-fluorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl,

D = 6-[4-(4-chlorophenylsulfoximino)-butoxy]-3,4-dihydro- .

carbostyril,

E =(6-[4-(N-acety1-3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyri 1,

F = 6-[4-(N-p-toluenesulfonyl-3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl,

G = 6-[4-(4-fluorophenylsulfoximino)-butoxy]-carbostyryl,

H = 6-[4-(4-chlorophenylsulfoximino)-butoxy]-carbostyryl,

I ■=' 6-[4-(3-methyl-4-bromophenylsulfoximino)-butoxy]-carbostyril,

K = 6-[ A -(4-tert.but<y>lphen<y>1-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl,

L = 6-[4-(4-cyclohexylphenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl,

M = 6-[4-(4-tert.butylphenyl-sulfoximino)-butoxy]-carbostyryl,

N = 6-(4-cyclohexy1-sulfoximino-butoxy)-carbostyryl,

0 = 6-[4-(N-butyryl-3,4-dichlorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril,

P = 5-[4-(N-acety1-4-chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolin-2-one,

Q = 6-[4-(N-(4-tert.butylbenzoyl)-3,4-dimethoxyphenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl, and

R 6-[4-(3,4-dimethoxyphenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl

examined for its biological properties as follows:

1. PDE inhibition:

Principle:

cAMP is hydrolyzed to AMP by phosphodiesterase (PDE) from various sources, including platelets. This hydrolysis is inhibited concentration-dependently by PDE inhibitors.

Method:

As phosphodiesterase, 10,000 x g of the top layer from human platelets that have been frozen with water and thawed again is used. 0.3 ml of a mixture containing 0.1 mol/l trishydroxyaminomethane (pH 7.4), 3 mmol/1 magnesium chloride, 1 mmol/1 AMP, 1 nmol/1 H-cAMP (specific activity approx. 10 MBq /pmol), PDE and the test compound resp. water for the controls, are incubated in

15 minutes at 37°C.

The incubation is stopped by adding 0.5 ml zinc sulphate (0.266 mol/l) and 0.5 ml barium hydroxide (0.226 mol/l), the precipitate is centrifuged off, and the activity of the unreacted<3>"H-cAMP that is back in On the basis of the comparison between the test compound and the control compound, the concentration for a 50% inhibitory effect (IC<-q) for the compound in question was calculated:

The inhibitory effect on the formation of tumor metastasis can also be determined according to Gastpar et al. (see Thrombosis Research 5, 277-289 (1974)) as an effect that prevents tumor cell embolism. Here, the test compound is added before the tumor cell transplantation, and the survival rate for the test animals, e.g. rats, is determined compared to the controls. 2. Determination of the prolongation of the bleeding time:

Advance notice:

The human organism and also the organism of other warm-blooded animals is in possession of an ingenious mechanism which

should protect it from blood loss in case of injuries. This system consists of the platelets (thrombocytes), which, with the help of their adhesive properties, will quickly plug a cardiac defect and thus bring about the primary hemostasis. In addition to this purely cellular blood status mechanism, the body also has a blood coagulation system. In this system, plasma factors (egg white substances) are brought into an active form, so that the liquid plasma fibrinogen can finally be transferred to a fibrin coagulum. The system of the primary hemostasis, which is mainly regulated by the platelets, but also by

the prostacyclin activity in the vessel walls and the coagulation system complement each other with a view to the same goal, namely to protect the body against blood loss.

In many diseases, coagulation processes or clumping of platelets can also occur in an intact vascular system. A weakening of the blood coagulation system by means of coumarin or heparin is known and can be easily measured using known blood coagulation methods, which show a prolongation under the influence of the preparation (plasma recalcif. time, Quick determination, thrombin time, etc.).

In the event of an injury, the first, rapid blood position occurs by the platelets adhering and aggregating on the vessel wall, and by applying a standardized injury one can thus easily. determine the function of the platelets or the prostacyclin activity in the vessel wall by measuring the bleeding time. The normal bleeding time in humans is approx.

1 to 3 minutes, but presupposes that platelets are present in active form and in sufficient numbers. With a normal platelet count, an extended bleeding time thus shows that there is a disturbed function of the platelets and/or an increased prostacyclin activity in the vessel wall. This occurs e.g. in some congenital platelet function disorders. If, on the other hand, by means of drugs one wants to prevent the tendency to spontaneous clumping of the platelets, which leads to vessel blockages in the arterial system, in a successful therapy which is effective against the platelets or the vessel wall, the bleeding time must be prolonged under the influence of the compounds.

With an antithrombotic active compound, one therefore expects an extension of the bleeding time, and since the plasmatic coagulation system is not affected, a normal blood coagulation time.

Literature: W.D. Keidel: Kurzgefa3tes Lehrbuch der

Physiologie, Georg Thi.eme Verlag Stuttgart 1967, page 31: Der Blutstillungsvorgang.

To determine the bleeding time, the test compounds are administered to awake mice at a dose of 2.5 mg/kg p.o. After 1 hour approx. was cut off from the tip of the tail of each animal. 0.5 mm, and that blood. that came out was gently wiped off at 30 second intervals using a filter paper. The number of blood drops thus obtained gave a measure of the bleeding time (5 animals per experiment). The following figures represent percentage elongation compared to controls:

2. • Acute toxicity:

The acute toxicity of the test compounds was determined approximately in groups of 10 mice each after oral administration of a single dose (observation time: 14 days):

The new compounds produced according to the invention

is, due to its above-mentioned pharmacological properties, suitable for the prevention of thromboembolic disorders such as myocardial infarction, cerebral infarction, so-called transient ischemic attacks, Amaurosis fugax, for the prevention of arteriosclerosis and for metastasis prevention.

The dosage necessary to achieve one suitable effect is suitably 2 to 4 times a day 0.1 to 4 mg/kg body weight, preferably 0.2 to 3 mg/kg body weight. The prepared compounds of the general formula I and their physiologically compatible acid addition salts with strong acids, optionally in combination with other active substances, together with one or more inert, common carrier materials and/or foot thinners, e.g. corn starch, milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, non-ionic surfactants such as polyoxyethylene fatty acid esters, water/polyethylene glycol, propylene glycol , cetylstearyl alcohol, carboxymethyl-cellulose or fatty substances such as hard fat or suitable mixtures thereof, can be incorporated into usual galenic preparations such as tablets, dragées, capsules, powders,

. suspensions, drops, ampoules, juices or suppositories.

The following examples shall serve to further illustrate the invention: Example 1

6-(4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril

3.4 g (0.01 mol) of 6-(4-phenylsulfinyl-butoxy)-3,4-dihydrocarbostyril is stirred at 45°C in 50 ml of polyphosphoric acid. After practically everything has dissolved, 0.98 g (0.015 mol) of sodium azide are added in small portions over the course of 30 minutes. A slight evolution of nitrogen gas occurs. The beige-coloured, creamy mass is stirred for 3 hours at 45-50°G and then 150 g of ice is added. The cloudy solution formed is adjusted to pH 8 with concentrated ammonia and the precipitated, resinous product is extracted with chloroform. The oily evaporation residue is recrystallized from ethyl acetate.

You get white crystals.

Melting point: 127-129°C

Yield: 1.6 g (44.6% of the theoretical).

Example- 2

6- [ 4-( 3, 4-dichlorophenylsulfoximino)-butoxy]- 3x4- dihydrocarbostyril

24.0 g (0.84 mol) 0-mesitylenesulfonyl-acethydroxamic acid ethyl ester is dissolved in 3.5 ml of dioxane and 17 ml of 90% sulfuric acid is added dropwise at 20-23°C during 20 minutes under

good stirring. The mixture is stirred for a further 10 minutes at the same temperature, then poured into 300 ml of ice water and the O-mesitylenesulfonyl hydroxylamine formed is extracted with 100 ml of methylene chloride, washed twice more with ice water and dried over magnesium sulphate. 12.4 g (0.03 mol) of 6-[4-(3,4-dichlorophenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril are introduced into the resulting solution and stirred for 18 hours at room temperature. The barely stirrable crystal slurry is diluted with 120 ml of ethyl acetate, and then the crystalline 6-[4-(3,4-dichlorophenyl-sulfoximino)-butoxy]-3,4-dihydro-carbostyryl-mesitylenesulfonate is filtered off with suction. To obtain the free base, suspend in 60 ml of methanol and stir with 17 ml of 2N caustic soda, whereby everything dissolves. After a short time, a white precipitate of 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril falls out.

Melting point: 160-161°C,

Yield: 10.4 g (81.1% of theoretical).

Example 3

6- [ 4-( 4- tert. buty1phenylsulfoximino)-butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(4-tert.butyl-phenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and 0-mesitylene-sulfonylhydroxylamine.

Melting point: 201-203°C.

Yield: 44% of the theoretical.

Example 4

6-[ 4-( 3, 5- di- tert. butyl- 4- hydroxy- phenylsulfoximino)-butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(3,5-di-tert-butyl-4-hydroxyphenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and Q-mesitylenesulfonylhydroxylamine.

Melting point: 110-112°C

Yield: 52% of the theoretical.

Example 5

6-[ 4-( 4- cyclohexylphenylsulfoximino)- butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(4-cyclohexyl-phenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 17 4-17 6°C.

Yield: 65% of the theoretical.'

Example 6

6-[ 4-( 4- biphenylylsulfoximino)- butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(4-biphenylyl-sulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylene-sulfonylhydroxylamine.

Melting point: 184-186°C.

Yield: 64% of the theoretical.

Example 7

6-[4-(naphthyl-(2)-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl: Prepared analogously to example 2 from 6-[4-(naphthy1-2-sulfiny1)-butoxy]-3,4- dihydrocarbostyril and O-mesitylenesulfony1-hydroxylamine.

Melting point: 151-152°C.

Yield: 71% of the theoretical.

Example 8

6-[ 4-( 4- fluorophenylsulfoximino)-butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 1 from 6-[4-(4-fluorophenyl-sulfinyl)-butoxy]-3,4-dihydrocarbostyril and sodium azide in polyphosphoric acid.

Melting point: 170-173°C.

Yield: 7 8% of the theoretical.

Example' 9

6-[ 4-( 4- chlorophenylsulfoximino)- butoxy]- 3, 4- dihydrocarbostyryl

Prepared analogously to example 2 from 6-[4-(4-chlorophenyl-sulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylene-sulfonylhydroxylamine.

Melting point: 150-151°C.

Yield: 60% of the theoretical.

Example 10

6-[ 4-( 3- methyl- 4- bromo- phenylsulfoximino)- butoxy]- 3, 4- dihydrocarbostyril

; Prepared analogously to example 2 from 6-[4-(S-meth<y>1^-bromophenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 150-152°C,

Yield: 60% of the theoretical.

Example 11

6-[ 4-( 3, 5- dibromo- 4- aminophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(3,4-dibromo-4-aminophenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 110-113°C,

Yield: 55% of the theoretical.

Example 12

6-(4-phenylsulfoximino-butoxy)-carbostyryl

Prepared analogously to example 2 from 6-(4-phenylsulfinyl-butoxy)-carbostyril and 0-mesitylenesulfonylhydroxylamine. Melting point: 161-162°C.

Yield: 60% of the theoretical.

Example 13

6- [ 4-( 4- tert. butylphenylsulfoximino)- butoxy]- carbostyryl

Prepared analogously to example 1 from 6-[4-(4-tert.butyl-phenylsulfinyl)-butoxy]-carbostyryl and sodium azide in polyphosphoric acid.

Melting point: 208-210°C,

Yield: 45% of the theoretical.

Example 14

6-[ 4-( 3, 5- di- tert. butyl- 4- hydroxy- phenylsulfoximino)-butoxy]- carbostyryl

Prepared analogously to example 2 from 6-[4-(3,4-di-tert-butyl-4-hydroxy-phenylsulfinyl)-butoxy]-carbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 205-207°C.

Yield: 59% of the theoretical.

Example 15

6- L4-(4-cyclohexylphenylsulfoximino)-butoxy]-carbostyryl

Prepared analogously to example 1 from 6-[4-(4-cyclohexyl-phenylsulfinyl)-butoxy]-carbostyril and sodium azide in polyphosphoric acid.

Melting point: 195-197°C,

Yield: 52% of the theoretical.

Example 16

6-[ 4-( 4-biphenylylsulfoximino)-butoxy]- carbostyryl

Prepared analogously to example 2 from 6-[4-(4-biphenylyl-sulfinyl)-butoxy]-carbostyril and O-mesitylenesulfonylhydroxylami Melting point: 2 3 6-2 3 8°C.

Yield: 76% of the theoretical.

Example 17

6-(4-cyclohexylsulfoxyminobutoxy)- carbostyryl

Prepared analogously to example 1 from 6-(4-cyclohexyl-sulfinyl-butoxy-carbostyryl and sodium azide in polyphosphoric acid. Melting point: 145-147°C.

Yield: 47% of the theoretical.

Example 18

6- [ 4-( 4- fluorophenylsulfoximino)-butoxy]- carbostyryl

Prepared analogously to example 2 from 6-[4-(4-fluorophenyl-sulfinyl)-butoxy]-carbostyryl and O-mesitylenesulfonyl hydroxylami Melting point: 177-179°C.

Yield: 70% of the theoretical.

Example- 19

6-[4-(4-chlorophenylsulfoximinc)-butoxy]-carbostyryl

Prepared analogously to example 2 from 6-[4-(4-chlorophenyl-sulfinyl)-butoxy]-carbostyryl and O-mesitylenesulfonylhydroxylamj Melting point: 201-203°C. Yield: 7 9% of the theoretical.

Example 20

6-[4-(4-bromophenylsulfoximine)-butoxy]-carbostyryl

Prepared analogously to example 2. from 6-[4-(4-bromophenylsulfinyl)-butoxy]-carbostyril and O-mesitylenesulfonyl-hydroxylamine.

Melting point: 211-213°C,

Yield: 63% of the theoretical.

Example 21

6-[4-(-3-,4-dichlorophenylsulfoximino)-butoxy]-carbostyril Prepared analogously to example 2 from 6-[4-(3,4-dichloro-phenylsulfinyl)-butoxy]-carbostyril and O-mesitylenesulfonyl- hydroxylamine.

Melting point: 214-216°C.

Yield: 73% of the theoretical.

Example 22

6-[ 4-( 3- methyl- 4- bromophenylsulfoximino)- butoxy]- carbostyryl

Prepared analogously to example 1 from 6-[4-(3-methyl-4-bromophenylsulfinyl)-butoxy]-carbostyril and sodium azide in polyphosphoric acid.

Melting point: 193-194°C,

Yield: 54% of the theoretical.

Example 2 3

6-[4-(2'-Fluoro-4-biphenylylsulfoximino)-butoxy]-carbostyryl

Prepared analogously to example 2 from 6-[4-(2'-fluoro-4-biphenylylsulfinyl)-butoxy]-carbostyril and 0-mesitylenesulfonyl-hydroxylamine.

Melting point: 191-193°C.

Yield: 74% of the theoretical.

Example 24

6-[4-(3,5-dibromo-4-aminophenylsulfoximino)-butoxy]-carbostyril Prepared analogously to example 2 from 6-[4-(3,5-dibromo-4-aminophenylsulfinyl)-butoxy]-carbostyril and O -mesitylenesulfonyl-hydroxylamine .

Melting point: 130-135°C.

Yield: 51% of the theoretical.

Example 2 5

3/ 3- dimethyl- 5-[ 4-( 4- methylphenylsulfoximino)-butoxy]- indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(4-methylphenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 146-147°C.

Yield: 84% of the theoretical.

Example 2 6

3, 3- dimethyl- 5-[ 4-( 4- tert. butylphenylsulfoximino)-butoxy]-indolin-one- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(4-tert.butylphenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 195-197°C.

Yield: 85% of the theoretical.

Example 27

3, 3- dimethyl- 5-[ 4-( 2- methyl- 4- tert. buty1-phenylsulfoximino)-butoxy]- indolinone- 2•

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(2-methyl-4-tert.butylsulfinyl)-butoxy]-indolinone-2 and 0-mesitylenesulfonylhydroxylamine.

Melting point: 149-150°C

Yield: 26% of the theoretical.

Example 28

3, 3- dimethyl- 5-[ 4-( 3, 5- di- tert.but y1- 4- hydroxyphenylsulfoximino)-butoxy]- indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(3,5-di-tert.butyl1-4-hydroxyphenylsulfoximino)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Vitreous substance. R^ value: 0.25 (silica gel plate, developer: ethyl acetate/methylene chloride 1:1),

Yield: 42% of the theoretical.

Example 2 9

3, 3- dimethyl- 5-(4- cyclohexylphenylsulfoximinobutoxy)-indolinone- 2

Prepared analogously to example 1 from 3,3-dimethyl-5-(4-cyclohexylphenylsulfinyl-butoxy)-indolinone-2 and sodium azide in polyphosphoric acid.

Melting point: 162-163°C

Yield: 39% of the theoretical.

Example 30

3, 3- dimethyl- 5-[ 4-( 2- naphthylsulfoximino)- butoxy]- indolinone-2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(2-naphthylsulfinyl)-butoxy]-indolinone-2 and O-mesitylene-sulfonylhydroxylamine.

Melting point: 120-121°C.

Yield: 6 4% of the theoretical.

Example 31

3, 3- dimethyl- 5-( 4- cyclohexylsulfoximino- butoxy)- indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-(4-cyclohexylsulfinyl-butoxy)-indolinone-2 and O-mesitylene-sulfonylhydroxylamine.

Melting point: 108-109°C.

Yield: 77% of the theoretical.

Example 32

3, 3- dimethyl- 5-( 4- benzyl sulfox imino-butoxy)- indolinone-2

Prepared analogously to example 2 from 3,3-dimethyl-5-(4-benzylsulfinyl-butoxy)-indolinone-2 and O-mesitylenesulfonyl-1-hydroxylamine.

Melting point: 98-99°C,

Yield: 82% of the theoretical.

Example 33

• 3/ 3- dimethyl- 5-[ 4-( 4- fluorophenylsulfoximino)-butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(4-fluorophenylsulfinyl)-butoxy]-indolino-2 and 0-mesitylenesulfonylhydroxylamine.

Melting point: 101-102°C.

Yield: 90% of the theoretical.

Example 34 3,3-dimethyl-5-[4-(4-chlorophenylsulfoximino)-butoxy]-indolinone-2

/Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(4-chlorophenylsulfinyl)-butoxy]-indolinone-2 and 0-mesitylenesulfonylhydroxylamine. ■

Melting point: 136-137°C.

Yield: 76% of the theoretical.

Example 35

3, 3- dimethyl- 5-[ 4-( 4- bromophenylsulfoximino)- butoxy]- indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-. (4-bromophenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylene-sulfonylhydroxylamine.

Melting point: 160-161°C.

Yield: 88% of the theoretical.

Example 36

3, 3- dimethyl- 5-[ 4-( 3, 4- dichlorophenylsulfoximino)-butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(3,4-dichlorophenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 147-148°C.

Yield: 68% of the theoretical.

Example 37

3, 3- dimethyl- 5-[ 4-( 2, 5- dichlorophenylsulfoximino)- butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(2,5-dichlorophenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

R^ value: 0.3 (silica gel plate, developer:

ethyl acetate/methylene chloride 1:1).

Yield: 18% of the theoretical.

Example 3 8

3, 3- dimethyl- 5-[ 4-( 3- methyl- 4- bromo- phenylsulfoximino)-butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(3-methyl-4-bromo-phenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 131-132°C,

Yield: 84% of the theoretical.

■ Example 3 9

3, 3- dimethyl- 5-[ 4-( 2'- fluoro- 4- biphenylylsulfoximino)- butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(2'-fluoro-4-biphenylylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 177-178°C.

Yield: 90% of the theoretical.

Example 40

3, 3- dimethyl- 5-[ 4-( 3, 5- dibrom- 4- aminophenylsulfoximino)-butoxy]- indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(3,5-dibromo-4-aminophenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 202-204°C.

Yield: 76% of the theoretical.

Example 41

3, 3- dimethyl- 5-[ 4-( 4- methoxyphenylsulfoximino)-butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(4-methoxyphenylsulfinyl)-butoxy]-indolinone and O-mesitylene-sulfonylhydroxylamine.

Melting point: 140-141°C.

Yield: 71% of the theoretical.

Example 42. 3 , 3- dimethyl- 5- [ 4- ( 2- m. ethoxy enylsulfoximino) - butoxy] indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(2-methoxyphenylsulfinyl)-butoxy]-indolinone-2pg O-mesitylenesulfonylhydroxylamine.

Colorless, resinous substance. R^ value: 0.35

(silica gel, developer: ethylene chloride/ethanol = 9:1). Yield: 52% of the theoretical.

Example 43

3, 3- dimethyl- 5-[ 4-( 3, 4- dimethoxyphenylsulfoximino)-butoxy]-indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(3,4-dimethoxy-phenylsulfinyl)-butoxy]-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 108-109°C.

Yield: 79% of the theoretical.

Example 44

3 , 3- dimethyl- 5- [ 4- ( 6- methox y.- naphth- 2- yl- sulf oximi n o) - butoxy] - indolinone- 2

Prepared analogously to example 2 from 3,3-dimethyl-5-[4-(6-methoxy-naphth-2-yl-sulfinyl)-butoxy]-indolinone-2 and 0-mesitylenesulfonylhydroxylamine.

Melting point: 174-175°C.

Yield: 88% of the theoretical.

Example 4 5

6-(4-methylsulfoximinobutoxy)-3,4-dihydrocarbostyryl mesitylene sulfonate

Prepared analogously to example 2 from 6-(4-methylsulfinyl-butoxy)-3,4-dihydrocarbostyril and O-mesitylenesulfonyl-hydroxylamine.

Melting point: 130-133°C,

Yield: 87% of the theoretical.

Example 46 3. 3-dimethyl-5-(4-phenylsulfoximino-butoxy)-indolinone-2

Prepared analogously to example 2 from 3,3-dimethyl-5-(4-phenylsulfinyl-butoxy)-indolinone-2 and O-mesitylenesulfonyl-hydroxylamine.

Melting point: 111-112°C.

Yield: 86% of the theoretical.

Example 47

6-[ 4-( N-acetyl-3, 4-dichlorophenylsulfoximino)-butoxy]-3. 4- dihydrocarbostyril

(In a mixture of 70 ml of glacial acetic acid and 70 ml of acetic anhydride, 1.40 g of 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril are suspended and stirred for 2.5 hours. To the solution formed Place under vigorous stirring 300 ml of ice water After 10 minutes, white crystals begin to form

stand out. After 1 hour, suction is applied, the mixture is washed with water and recrystallized from 140 ml of ethanol while adding a little activated charcoal. You get a white, crystalline

fabric, which is dried in an air circulation cabinet at 80°C. Melting point: 150-152°C.

Yield: 12.9 g (84% of the theoretical).

Example 4 8

6-[ 4-( N- carbamoyl-3,4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

1.49 g (0.0035 mol) of 6-[4-(3,4-dichloro-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl are dissolved in 70 ml of glacial acetic acid and 2.8 g (0.035 mol) of potassium cyanate are added and stir for 3 hours at room temperature. 40 ml of water is then added while stirring, whereby the first precipitated oil crystallizes through. The mixture is filtered off with suction, recrystallized from 65 ml of ethanol and the white, crystalline substance is dried in an air circulation cabinet at 50°C.

Melting point: 14 8-150°C,

Yield: 1.2 g (73% of the theoretical).

Example 4 9

6-[ 4-( N- butyryl- 3, 4- dichlorophen y1sulfoximino)-butox y]-3, 4- dihydrocarbostyril

3.0 g (0.007 mol) of 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl is suspended in 15 ml of pyridine and 0.9 g (1.2 x 0.007 mol) of n- butyric acid chloride.

During heating to 40°C, a pale yellow solution is formed.

After standing for a further 90 minutes, the mixture is evaporated to dryness in a water jet vacuum in a rotary evaporator, the residue is taken up in methylene chloride and decanted twice with 0.5N hydrochloric acid and once with water. After drying over magnesium sulfate, the solvent is distilled off in a rotary evaporator and the residue is recrystallized from 15 ml of ethanol. Colorless crystals are obtained.

Melting point: 133-135°C,

Yield: 2.4 g (69% of theoretical).

Example 50

6-[ 4-( N- pivaloyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril1

Prepared analogously to Example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and pivalic acid chloride.

Melting point: 158-160°C.

Yield: 81% of the theoretical.

Example 51

6-[ 4-( N-(2-Methoxyacetyl)-3, 4- dichlorophenylsulfoximini)-butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and 2-methoxyacetyl chloride.

Melting point: 103-105°C,

Yield: 50% of the theoretical.

Example 52 6-[4-(N-benzoyl-3,4-dichlorophenysulfoximini)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and benzoyl chloride.

Melting point: 100-111°C

Yield: 68% of the theoretical.

Example 5 3

6-[ 4-( N-( 4- methoxybenzoyl)- 3, 4- dichlorophenylsulfoximino)-butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and 4-methoxy-benzoyl chloride.

Melting point: 186-188°C.

Yield: 70% of the theoretical.

Example 5 4

6- [ 4- ( N- nicotinoyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydro carbostyryl

Prepared analogously to Example 49 from 6-[4-(3,4-dichlorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril and nicotinic acid chloride hydrochloride.

Melting point: 101-103°C.

Yield: 94% of the theoretical.

Example 55

6- [ 4-(N-( 4- methylphenylsulfonyl)-3, 4- dichlorophenylsulfoximino)-butoxy] -3, 4- dihydrocarbostyri. l

Prepared analogously to example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and p-toluenesulfochloride.

Melting point: 154-156°C.

Yield: 84% of the theoretical.

Example 56

6-[ 4-( N-( 2- acetoxy- phenylacetyl)- 3, 4- dichlorophenylsulfoximino)- butoxy]- 3, 4- dihydrocarbostyril

Prepared from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyri1 and 0-acety1-D,L-mandelic acid chloride analogously to example 49. After purification over a silica gel column with ethylene chloride, the compound is obtained which does not -crystallizing, vitreous resin.

R^-value: 0.2 (silica gel plate, ethylene chloride),

Yield: 50% of the theoretical.

Example 57

5-[ 4-( N- acetyl- 3, 4-dichlorophenylsulfoximino)- butoxy]- 3, 3- dimethyl 1- indolinone- 2 ■

Prepared analogously to example 47 from 5-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and acetic anhydride.

Melting point: 145-146°c.

Yield: 6 4% of the theoretical.

Example 58

5-[ 4-( N- butyryl- 3, 4- dichlorophenylsulfoximine o)- butoxy]- 3, 3- dimethyl- indolinone- 2

Prepared analogously to example 4 9 from 5-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and butyric acid chloride.

Melting point: 120-122°C.

Yield: 81% of the theoretical.

Example 5 9

5-[ 4-( N-( 2- methoxy-acetyl)- 3, 4- dichlorophenylsulfoximino)-butoxy]- indolinone- 2

Prepared analogously to Example 49 from 3,3-dimethyl-5-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-indolinone-2 and 2-methoxyacetyl chloride.

Melting point: 126-128°C.

Yield: 72% of the theoretical.

Example 60

5-[ 4-( N- ethoxycarbonyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 3- dimethyl- indolinone- 2

Prepared analogously to example 49 from 5-[4-(4-Chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and .chloro-carbonic acid ethyl ester.

Melting point: 102-104°C,

Yield: 7 9% of the theoretical.

Example or' 61

5-[ 4-( N- acety1- 4- chlorophenylsulfoximincQ - butoxy]- 3, 3- diroetyl-indolinone- 2

Prepared analogously to example 47 from 5-[4-(4-chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and acetic anhydride.

Melting point: 138-140°C.

Yield: 75% of the theoretical.

Example 62

5- [ 4-( N- butyry1- 4- chlorophenylsulfoximino)- butoxy]- 3, 3- dimethyl-indolinone- 2

Prepared analogously to example 49 from 5-[4-(4-chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and butyric acid chloride.

Melting point: 166-168°C.

Yield: 38% of the theoretical.

Example 6 3

5-[ 4-( N- pivaloy1- 4- chlorophenylsulfoximino)- butoxy]- 3, 3-dimethyl- indolinone-2

Prepared analogously to example 49 from 5-[4-(4-chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and pivalic acid chloride.

Melting point: 95-97°C.

Yield: 76% of the theoretical.

Example 64

5-[ 4-( N- capryl-4- chlorophenylsulfoximino)- butoxy]- 3, 3- dimethyl-indolinone-2

Prepared analogously to example 49 from 5-[4-(4-chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and caprylic acid chloride. Resin.

R^ value: 0.5 (silica gel plate, ethyl acetate/methylene chloride = 1:1). Yield: 95% of the theoretical.

Example- 65

5-[ 4-( N- carbamoyl- 4- chlorophenylsulfoximino)- butoxy]-3, 3- dimethyl- indolinone- 2

Prepared analogously to example 48 from 5-[4-(4-chlorophenyl-sulfoximino.)-butoxy]-3,3-dimethyl-indolinone-2 and potassium cyanate.

Colorless resin.

R^-value: 0.4 (silica gel plate, ethylene chloride/ethanol =9:1), Yield: 75% of the theoretical.

Example 6 6

5- [ 4-( N-dimethylaminocarbonyl-4-chlorophenylsulfoximino)-butoxy]-3. 3- dimethyl- indolinone- 2

Prepared analogously to example 49 from 5-[4-(4-chlorophenyl-sulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and dimethyl-carbamyl chloride.

Melting point: 170-172°C,

Yield: 64% of the theoretical.

Example 67

6-[4-(N-acety1-3,4-dimethoxyphenylsulfoximino)-butoxy]-3. 4- dihydrocarbostyril

Prepared analogously to Example 47 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and acetic anhydride.

Melting point: 8 9-92°C.

Yield: 60% of the theoretical.

Example 6 8

6-[ 4-( N- butyry1- 3, 4- dimethoxyphenylsulfoximini)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 4 9 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and butyric acid chloride. Glassy, colorless resin. R^ value: 0.35 (silica gel plate, ethylene chloride/ethanol =9:1).

Yield: 41% of the theoretical.

■ Example 6 9 ■ 6- [ 4-( N- benzoyl- 3, 4- dimethoxyphenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl and benzoyl-. chloride.

Melting point: 7 8-80°C.

Yield: 50% of the theoretical.

Example 70

6- [ 4-( N-( 4- chlorobenzoyl)- 3, 4- dimethoxyphenylsulfoximino)-butoxy]- 3, 4- dihydrocarbostyril■

Prepared analogously to example 49 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl and 4-chloro-benzoyl chloride.

Melting point: 134-137°C.

Yield: 61% of the theoretical.

Example 71

6-[ 4-( N-( 4- tert. butylbenzoyl)-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,4- dihydrocarbostyryl

Prepared analogously to example 49 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and

4-tert.Buty1-benzoyl chloride.

Melting point: 98-101°C.

Yield: 87% of the theoretical.

Example 7 2 6-[4-(N-nicotinoyl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and nicotinic acid chloride hydrochloride.

Melting point: 90-93°C,

Yield: 75% of the theoretical.

Example 7 3

6-[ 4-( N- pmtamethylphenylsulfonyl- 3, 4- dimethoxyphenylsulfoximino)-butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 4 9 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl and penta-

methylbenzene sulfonic acid chloride.

Melting point: 186-188°C.

Yield: 75% of the theoretical.

Example 7 4

5-[ 4-( N- acetyl- 3, 4- dimethoxyphenylsulfoximino)- butoxy]-3, 3- dimethylindolin- 2- one

Prepared analogously to example 47 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethylindolin-2-one and acetic anhydride.

Glassy resin.

R^-value: C.3 (silica gel plate, ethylene chloride/ethanol = 9:1), Yield: 99% of the theoretical.

Example- 7 5

5-[ 4-( N- butyryl- 3, 4- dimethoxyphenyls ulfoximino)- butoxy]-3, 3- dimethylindolin- 2- one

Prepared analogously to example 49 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethylindolin-2-one and butyric acid chloride. Resin.

R^ value: 0.35 (silica gel plate, ethyl acetate/methylene chloride = 1:1), Yield: 92% of the theoretical.

Example 7 6

5-[ 4-( N- piavl oy1- 3, 4- dimethoxyphenylsulfoximino)- butoxy]-3, 3- dimethyl- indolinone- 2

Prepared analogously to example 49 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and pivalic acid chloride. Resin.

Rf value: 0.45 (silica gel plate, ethyl acetate/methylene chloride = 1:1), Yield: 88% of the theoretical.

Example 7 7

5-[ 4-( N- carbamoyl- 3, 4- dimethoxyphenylsulfoximino)- butoxy]-3, 3- dimethyl- indolinone- 2

Prepared analogously to example 48 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and potassium cyanate. Resin.

Rf value: 0.25 (silica gel plate, ethylene chloride/ethanol = 9:1), Yield: 75% of the theoretical.

Example 7 8

5- [ 4-( N- dimethylaminocarbonyl-3, 4- dimethoxyphenylsulfoximino)-butoxy]- 3, 3- dimethylin doTinon- 2

Prepared analogously to Example 49 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and dimethylcarbamyl chloride. Resin.

Rf value: 0.3 (silica gel plate, ethylene chloride/ethanol = 9:1), Yield: 98% of the theoretical.

Example 7 9 5- [ 4-( N -( 4- chlorobenzoyl)- 3, 4- dimethoxyphenylsulfoximino)- butoxy]- 3, 3- dimethyl indolinone- 2

Prepared analogously to Example 49 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and 4-chloro-benzoyl chloride.

Melting point: 174-177°C,

Yield: 74% of the theoretical.

Example 80

5-[4-(N-nicotinoyl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3. 3-dimethyl-indolinone-2

Prepared analogously to Example 49 from 5-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,3-dimethyl-indolinone-2 and nicotinic acid chloride hydrochloride. Resin.

R^ value: 0.25 (silica gel plate, ethylene chloride/ethanol = 9:1), Yield: 76% of the theoretical.

Example number 81

6 - [4-(2-naphthoyl)-3,4-dimethoxyphenylsulfoximino)-butoxy]-3. 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and 2-naphthoic acid chloride. Resin.

R^-value: 0.45 (silica gel plate, ethyl acetate/methylene chloride = 1:1), Yield: 93% of the theoretical.

Example 82

6- [ 4-( N -(1- naphthoyl)- 3,4-dimethoxyphenylsulfoximino)-butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dimethoxy phenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl and 1-naphthoic acid chloride. Resin.

R^ value: 0.3 (silica gel plate, ethyl acetate/methylene chloride = 1:1), Yield: 83% of the theoretical.

Example 8 3

6-[ 4-( N-( 2- thienoyl)- 3, 4- dimethoxyphenyl sulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(3,4-dimethoxy-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and thiophene-2-carboxylic acid chloride. Resin.

Rf value: 0.3 (silica gel plate, ethyl acetate/methylene chloride = 1:1), Yield: 88% of the theoretical.

Example 84

6-[ 4-( 3, 4- dimethoxyphenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(3,4-dimethoxy-phenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 154-156°C.

Yield: 64% of the theoretical..

Example 85

6- [ 4-( N- benzoyl- 4- fluorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(4-fluorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril and benzoyl chloride. Melting point: 64-68°C.

Yield: 87% of the theoretical.

Example 86

6- [ 4-( N-( 4- chlorobenzoyl)- 4- fluorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(4-fluorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyryl and 4-chloro-benzoyl chloride.

Melting point: 134-138°C,

Yield: 78% of the theoretical.

Example 87

6- [ 4- ( 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydro-carbostyril

145.5 g of p-toluenesulfonic acid are dissolved while stirring

in 350 ml of dimethylformamide and stir in 70.1 g of 6-[4-(3,4-dichloro-phenylsulfinyl)-butoxy]-3,4-dihydrocarbostyril. 106.7 g of O-mesitylenesulfonyl hydroxamic acid ethyl ester is then added. The reaction is slightly exothermic, and by occasional cooling it is ensured that the temperature of the reaction mixture does not exceed 20°C. After 46 hours, add 350 ml of water with good stirring until the first slight cloudiness appears.

After addition of a suspension of seed crystals, crystallization of a large proportion of the product begins within 30 minutes under further stirring. For completion, a further 300 ml of water is stirred in. The mixture is stirred for a further 30 minutes, then the crystals of the formed 0-mesitylene sulphonic acid salt are filtered off and washed with water.

The still water-moist filter cake is suspended in 500 ml of methanol

and stir in 100 ml of 2N caustic soda, all at once. The compound dissolves after a short time, but then crystallization of the free sulfoximine follows. The mixture is stirred for a further 1/2 hour at room temperature, filtered off with suction and washed with ice-cold methanol. It is dried in an air circulation cabinet at 80°C. Melting point: 160-162°C.

Yield: 61.7 g (84.9% of the theoretical).

Example 88

6-[ 4-( 3, 4- dichlorophenyl- N-( 4- toluenesulfonyl)- sulfoximino)-butoxy]- 3, 4- dihydrocarbostyril

200 mg 6-[4-(3,4-dichlorophenyl-N-(4-toluenesulfonyl)sulfimino)butoxy]-3,4-dihydrocarbostyril [prepared from 6-[4-(3,4-dichloro-phenylmercapto)- butoxy]-3,4-dihydrocarbostyril and N-chloro-4-toluenesulfonamide sodium (chloramine T)] are suspended in methanol, 0.35 ml of 2N caustic soda and 0.06 ml of hydrogen peroxide solution (397.4 mg/ml) are added and heated to boiling under reflux cooling for 4 hours. At the beginning of boiling, a clear solution is formed, and after an hour crystals precipitate. After further heating, the crystals are sucked off while still hot and dried in air.

Melting point: 155-157°C

Yield: 59% of the theoretical

Example 89

6- [ 3-( 3, 4-dichlorophenylsulfoximino)- propoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[3-(3,4-dichloro-phenylsulfinyl)-propoxy]-3,4-dihydrocarbostyril and O-mesitylene-sulfonylhydroxylamine.

Melting point: 144-146°C

Yield: 67% of the theoretical.

Example 90

6-[ 5-( 3, 4- dichlorophenylsulfoximino)- pentoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-[5-(3,4-dichloro-phenylsulfinyl)-pentoxy]-3,4-dihydrocarbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 154-155°C,

Yield: 29% of the theoretical.

Example 91

6-(3-ethylsulfoximinopropoxy)-3,'4-dihydrocarbostyril

Prepared analogously to example 2 from 6-(3-ethylsulfinyl-propoxy)-3,4-dihydrocarbostyril and O-mesitylenesulfonyl-1-hydroxylamine.

Melting point: 107-109°C,

Yield: 61% of the theoretical.

Example 9 2

' 6- [ 4-( N- 4- cyanobenzoyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and 4-cyano-benzoyl chloride.

Melting point: 200-202°C,

Yield: 79% of the theoretical.

Example 93

6-[ 4-( N- 2- thenoyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and

2-thiophenecarboxylic acid chloride.

Melting point:. 100-102°C

Yield: 61% of the theoretical.

Example 94

6-[ 4-( N-(+)- pinanoyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4-.- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and (+)-pinanoic acid chloride.

Melting point: 69-74°C,

Yield: 94% of the theoretical..

Example 9 5

6-[ 4-( N-(-)- pinanoyl- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl and

(-)-Pinanoic acid chloride.

Melting point: 69-74°C,

Yield: 91% of the theoretical.

Example 96

6-[ N- pentamethylphenylsulfonyl- 3, 4- dichlorophenylsulfoximino) - butoxy]— 3, 4- dihydrocarbostyril

Prepared analogously to Example '49 from 6-[4-(3,4-dichlorophenylsulfoximino)butoxy]-3,4-dihydrocarbostyril and pentamethylphenylsulfochloride.

Melting point: 149-151°C.

Yield: 83% of the theoretical.

Example 97

6-[ 4-( N- methanesulfony1- 3, 4- dichlorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl and methanesulfonyl chloride.

Melting point: 172-174°C,

Yield: 37% of the theoretical.

Example 98 6-[4-(N-acetyl-4-cyclohexylphenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to example 47 from 6-[4-(4-cyclohexylphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyryl and acetic anhydride.

Melting point: 135-136°C,

Yield: 92% of the theoretical.

Example 99 6-[4-(N-pivaloyl-4-cyclohexylphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(4-cyclohexyl-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and pivaloyl chloride.

Melting point: 170-172°C,

Yield: 95% of the theoretical.

Example 100

6-[ 4-( N- benzoyl- 4- cyclohexylphenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(4-cyclohexylphenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril and benzoyl chloride.

Melting point: 187-189°C.

Yield: 92% of the theoretical.

Example 101 6-[4-(N-acetyl-4-fluorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to example 47 from 6-[4-(4-fluorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril (R^-value: 0.60) and acetic anhydride.

R^ value: 0.65 (silica gel, developer: ethylene chloride/ ethanol = 85:15).

Yield: 54% of the theoretical.

Example■ 102

6- [ Ar - ( N- butyroyl- 4- fluoro enylsulf oximino) - butoxy] - 3, 4-dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(4-fluoro-phenylsulfoximino)-butoxy]-3.,4-dihydrocarbostyril (R^-value 0.6i and butyric acid chloride.

R^ value: 0.70 (silica gel, developer: ethylene chloride/ethanol 85:15).

Yield: 78% of the theoretical.

Example 103

6-[ 4-( N- 2- methoxyacetyl- 4- fluorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(4-fluorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril (R^-value: 0.60) and 2-methoxyacetyl chloride.

R^ value: 0.66 (silica gel, developer: ethylene chloride/ ethanol = 85/15).

Yield: 67% of the theoretical.

Example 104

6-[ 4-( N-(+)- pinanoyl- 4- fluorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared from 6-[4-(4-fluorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and (+)-pinanoic acid chloride analogously to Example 49.

Melting point: 116-120°C,

Yield: 61% of the theoretical.

Example 105

6- [. 4-(N-(-)-pinanoyl-4-fluorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(4-fluoro-phenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril and

(-)-Pinanoic acid chloride.

Melting point: 122-123°C,

Yield: 45% of the theoretical.

Example 106

6-[ 4-( N- 4- toluenesulfonyl- 4- fluorophenylsulfoximino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-[4-(4-fluorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril and 4-toluene sulfochloride.

Melting point: 67-70°C,

Yield: 57% of the theoretical.

Example 107

6- [ 4-( N-( + )- 10- camphorsulfonyl- 4- fluorophenylsulfoximino)-butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to Example 49 from 6-[4-(4-fluorophenyl-sulfoximino)-butoxy]-3,4-dihydrocarbostyril and (+)-10-camphor sulfochloride.

Melting point: 81-100°C,

Yield: 61% of the theoretical.

Example 108

6-[ 4- ( N- 4- chlorobenzoyl- 4- methylsulfoximino)- butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 49 from 6-(4-methylsulfoximino)-butoxy)-3,4-dihydrocarbostyril and 4-chlorobenzoyl chloride.

Melting point: 176-178°C,

Yield: 87% of the theoretical.

Example 109

6-( 4- n- hexylsulfoximino- butoxy)- 3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 6-(4-n-hexylsulfinyl-butoxy)-3,4-dihydrocarbostyril and O-mesitylenesulfonyl-hydroxylamine.

Melting point: 111-113°C,

Yield: 59% of the theoretical.

Example 110

6-( N- acetyl- 4- n- hexyl sulfoximino- butoxy)- 3, 4- dihydrocarbostyril

Prepared analogously to example 47 from 6-(4-n-hexyl-sulfoximino-butoxy)-3,4-dihydrocarbostyril and acetic anhydride Melting point: 119-121°C,

Yield: 90% of the theoretical.

Example 111

6-(N-benzoyl-4-n-hex'ylsulfoximino-butoxy)-3,4-dihydrocarbostyril

Prepared analogously to example 49 from 6-(4-n-hexyl-sulfoximino-butoxy)-3,4-dihydrocarbostyryl and benzoyl chloride. Melting point: 112-114°C,

Yield: 75% of the theoretical.

Example 112

6-[4-(2-phenylethylsulfoximino.)-butoxy]-3,4-dihydrocarbostyril

Prepared analogously to example 2 from 6-[4-(2-phenylethylsulfinyl)-butoxy]-3,4-dihydrocarbostyril and O-mesitylene-hydroxylamine.

Melting point: 158-159°C,

Yield: 69% of the theoretical.-

Example 113

5-(4~ phenylsulfoximinobutoxy)-3, 4- dihydrocarbostyril

Prepared analogously to example 2 from 5-(4-phenylsulfinyl-butoxy)-3,4-dihydrocarbostyril and O-mesitylenesulfonylhydroxylamine.

Melting point: 159-160°C,

Yield: 76% of the theoretical.

Example 114 5-(N-acetyl-4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril

Prepared analogously to example 47 from 5-(4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril and acetic anhydride. Melting point: 134-137°C,

Yield: 61% of the theoretical.

Example 115

7-(4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril

Prepared analogously to example 87 from 7-(4-phenylsulfinyl-butoxy)-3,4-dihydrocarbostyril,. O-mesitylenesulfonylhydroxamic acid ethyl ester and p-toluenesulfonic acid.

Melting point: 137-139°C,

Yield: 81% of the theoretical.

Example 116

7- ( N- acetyl- 4- phenylsulfoximino- butoxy)- 3, 4- dihydrocarbostyril

Prepared analogously to example 47 from 7-(4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril and acetic anhydride.

Melting point: 111-113°C,

Yield: 78% of the theoretical.

Example 117

8- ( 4-phenylsulfoximino-butoxy).- 3 , 4- dihydrocarbostyril

Prepared analogously to example 2 from 8-(4-phenylsulfinyl-butoxy)-3,4-dihydrocarbostyril and mesitylenesulfonylhydroxylamine.

Melting point: 78-80°C,

Yield: 96% of the theoretical.

Example 118

8-( N- acety1- 4- phenylsulfoximino- butoxy)- 3, 4- dihydrocarbostyril

Prepared analogously to example 47 from 8-(4-phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril and acetic anhydride Melting point: 116-118°C

Yield: 82% of the theoretical.

Example 119

6-(3-ethylsulfoximino-propoxy)-carbostyryl

Prepared analogously to example 2 from 6-(3-ethylsulfinyl-propoxy)-carbostyril and 0-mesitylenesulfonylhydroxylamine. Melting point: 166-167°C,

Yield: -80% of the theoretical.

Example 120

6-[ 4-( N- benzoyl- 4- fluorophenylsulfoximino)- butoxy]- carbostyryl

Prepared analogously to example 49 from 6-[4-(4-fluoro-phenylsulfoximino)-butoxy]-carbostyryl and benzoyl chloride. Melting point: 137-141°C,

Yield: 34% of the theoretical.

Example 121

3, 3- dimethyl- 5-[ 4-( 3, 4- dimethylphenylsulfoximino)-butoxy]-indolinone- 2

Prepared analogously to example 87 from 3,3-dimethyl-5-[4-(3,4-dimethylphenylsulfinyl)-butoxy]-indolinone-2, O-mesitylenesulfonylhydroxamic acid ethyl ester and p-toluenesulfonic acid.

Melting point: 153-154°C,

Yield: 77% of the theoretical.

Example 122

3, 3- dimethyl- 5-[ 4-( N-acety1- 3, 4- dimethylphenylsulfoximino)- butoxy] indolinone- 2

Prepared analogously to Example 47 from 3,3-dimethyl-5-[4-(3,4-dimethylphenylsulfoximino)-butoxy]-indolinone-2 and acetic anhydride.

Melting point: 150-152°C,

Yield: 78% of the theoretical.

Example 123

3, 3- dimethyl- 5-( 4- methylsulfoximino- butoxy)- indolinone- 2

Prepared according to example 2 from 3,3-dimethyl-5-(4-methylsulfinyl-butoxy)-indolinone-2 and O-mesitylenesulfonylhydroxylamine.

Melting point: 123-124°C,

Yield: 98% of the theoretical.

Example 124

3, 3- dimethyl- 5-[ 4-( N- 4- chlorophenylaminocarbonyl- methylsulfoximino)-butoxy]- indolinone- 2

Prepared from 3,3-dimethyl-5-(4-methylsulfoximino-butoxy)-indolinone-2 and 4-chlorophenyl isocyanate in absolute dioxane at room temperature for 30 minutes.

Melting point: 175-177°C,

Yield: 89% of the theoretical.

Example 125

3, 3- dimethyl- 5-[ 4-( N- 4- toluenesulfonyl- 4- methylsulfoximino)-butoxy]- indolinone- 2

Prepared analogously to example 49 from 3,3-dimethyl-5-(4-methylsulfoximino-butoxy)-indolinone-2 (R^ value: 0.45)

and 4-toluene sulfochloride.

R^-value: 0.70 (silica gel, developer: ethyl acetate/ methylene chloride = 1:1),

Yield: 63% of the theoretical.

Example 126

3 , 3- dimethyl- 5- [ 4- ( N- 4-. chlorobenzoyl- 4- methylsulfoximino) - butoxy]- indolinone- 2

Prepared analogously to Example 49 from 3,3-dimethyl-5-(4-methylsulfoximino-butoxy)-indolinone-2 and 4-chlorobenzoyl chloride.

Melting point:. 176-178°C,

Yield: 73% of the theoretical.

Example 127

6-[ 4-( N- acetyl- 3, 4- dichlorophenylsulfoximino)- butoxy]- 3, 4-dihydrocarbostyril

3,4-dichlorophenylsulfinyl-4-bromobutane is reacted analogously to example 2 with O-mesitylenesulfonylhydroxylamine to 3,4-dichlorophenylsulfoximino-4-bromobutane and then transferred analogously to example 47 with acetic anhydride to 3,4-dichlorophenyl-(N-acetyl-sulfoximino )-4-bromobutane.

Melting point: 170-173°G,

Yield: 98% of the theoretical.

163.2 mg (0.001 mol) of 6-hydroxycarbostyril, dissolved in 2 ml of dimethyl sulfoxide, is added to 448 mg (0.0013 mol) of 3,4-dichlorophenyl-(N-acetyl-sulfoximino)-4-bromobutane and 276.4 mg ( 0.002 mol of anhydrous potassium carbonate and stirred for 17 hours at room temperature. Water is then added portionwise in small portions after which the reaction product crystallizes in white needles. Melting point: 149-151°C,

Yield: 267.1 mg (62.5% of the theoretical).

Example 128

6- (4f- methylsulfimino-butoxy)-3, 4- dihydrocarbostyril-hydrogen-sulphate

0.12 g of sodium is dissolved in 25 ml of methanol, 1.3 g of 6-(4-methylmercapto-butoxy)-3,4-dihydrocarbostyril is introduced with stirring and added over the course of 40 minutes at a temperature of 17°C 0, 57 g of hydroxylamine-O-sulfonic acid. The temperature thereby rises to 22°C. Stirring is continued overnight, then the separated sodium sulphate is sucked off and, by gradual addition of ether, a resinous substance is precipitated which, after rubbing with ether, crystallizes into a somewhat hygroscopic substance. Extract and dry in a vacuum desiccator over calcium chloride. Melting point: 75-80°C,

Yield: 0.656 g (20% of the theoretical).

Example 129

6- [ 4- ( 3, 4- dichlorophenylsulfimino)- butoxy]- 3, 4- dihydrocarbostyryl mesitylene sulfonate

Prepared analogously to example 2 from 6-[4-(3,4-dichloro-phenylmercapto)-butoxy]-3,4-dihydrocarbostyril and O-mesitylene-sulfonylhydroxylamine.

Melting point: 82-83°C.

Yield: 49% of the theoretical.

Example 130

6- [ 4-( 3, 4- dimethoxyphenylsulfimino)-butoxy]- 3, 4- dihydrocarbostyryl- mesitylene sulfonate

Prepared analogously to example 2 from 6-[4-(3,4-dimethoxy-'phenylmercapto)-butoxy]-3,4-dihydrocarbostyril and O-mesitylene-sulfonylhydroxylamine.

Melting point: 140-145°C,

Yield: 83% of the theoretical.

Example 131

6-[ 4-( 2'- fluoro- 4- biphenylylsulfimino)- butoxy]- carbostyryl mesitylene sulfonate

Prepared analogously to example 2 from 6-[4-(2<1->fluoro-4-biphenylylmercapto)-butoxy]-carbostyril and O-mesitylenesulfonyl-hydroxylamine.

Melting point: 125-128°C,

Yield: 63% of the theoretical.

. Example 132

6-[ 4-( 4- tert. butylphenylsulfimino)- butoxy]- carbostyryl

Prepared analogously to example 2 from 6-[4-(4-tert.butyl-phenylmercapto)-butoxy]-carbostyril and O-mesitylenesulfonyl-hydroxylamine.

Melting point: 145-150°C,

Yield: 55% of the theoretical.

Example' 133

6-[ 4-( N- 4- toluenesulfonyl- 4- fluorophenylsulfimino)- butoxy]-3, 4- dihydrocarbostyril

0.70 g of 6-[4-(4-fluorophenylmercapto)-butoxy]-3,4-dihydrocarbostyril is suspended in 20 ml of methanol and a clear solution of 1.16 g of N-chloro-4-toluenesulfonamide sodium is added. After stirring overnight at room temperature, the methanol is distilled off. The obtained residue is chromatographed on a silica gel column with methylene chloride/ethyl acetate = 1:1. Melting point: 122-124°C,

Yield: 0.59 g (57% of theoretical).

Example 134

6-[ 4-( N- 4- toluenesulfonyl- 3, 4- dichlorophenylsulfimino)- butoxy]-3, 4- dihydrocarbostyril

Prepared analogously to Example 133 from 6-[4-(3,4-dichloro-phenylmercapto)-butoxy]-3,4-dihydrocarbostyril and N-chloro-4-toluenesulfonamide sodium.

Melting point: 150-152°C,

Yield:' 62% of the theoretical.

. Example 135

5- [ 4-( N- 4- toluenesulfonyl- 4- bromophenylsulfimino)- butoxy]-3. 3- dimethyl- indolinone- 2

Prepared analogously to Example 133 from 5-[4-(4-bromophenyl-mercapto)-butoxy]-3,3-dimethyl-indolinone-2 and N-chloro-4-toluene-sulfonamide sodium.

Melting point: 163-164°C,

Yield: 33% of the theoretical.

Example 136

6- [ 4-( N- 4- toluenesulfonyl- methoxyphenylsulfimino)- butoxy]-3. 4- dihydrocarbostyril

Prepared analogously to Example 133 from 6-[4-(3-methoxy-phenylmercapto)-butoxy]-3,4-dihydrocarbostyril and N-chloro-4-toluenesulfonamide sodium.

Melting point: 110-114°C,

Yield: 38% of the theoretical.

Example 137

6-[ 4-( N- 4- toluenesulfony1- phenylsulfimino)- butoxy]- 3, 4- dihydrocarbostyril

Prepared analogously to example 133 from 6-(4-phenylmercapto-butoxy)-3,4-dihydrocarbostyril (R^-value = 0.45) and N-chloro-4-toluenesulfonamide sodium.

Melting point: 58°C (sintering)

R^ value: 0.37 (silica gel, ethylene chloride/ethanol = 9:1), Yield: 62% of the theoretical.

Example 13. 8

6-[ 4-( N- 4- toluenesulfony1- cyclohexylsulfimino)- butoxy]- 3, 4-dihydrocarbostyril

Prepared analogously to Example 133 from 6-(4-cyclohexyl-mercapto-butoxy)-3,4-dihydrocarbostyril and N-chloro-4-toluenesulfonamide sodium.

Melting point: 162-163°C,

Yield: 53% of the theoretical.

. Example 139

6-[ 4-( N- 4- toluenesulfonyl- 3, 4- dichlorophenylsulfimino)- butoxy]-carbostyril

Prepared analogously to example 133 from 6-[4-(3,4-dichloro-phenylmercapto)-butoxy]-carbostyril (R^ value: 0.34) and N-chloro-4-toluenesulfonamide sodium.

R^ value: 0.32 (silica gel plate, ethylene chloride/ethanol = 9:1), Yield: 39% of the theoretical.

Claims (5)

1. Process for the preparation of therapeutically active sulfimine derivatives with the general formula: where n means the number 0 or 1, A means a methylene, vinylene or ethylene group optionally substituted with one or two alkyl groups with each 1 to 3 carbon atoms, B means a linear or branched alkylene group of 2 to 6 carbon atoms, means an optionally substituted alkyl with a phenyl group group with 1 to 3 carbon atoms or a phenyl group, where the phenyl nucleus can in each case be substituted with an alkyl group with 1 to 4 carbon atoms, a halogen atom, an alkoxy group with 1 to 3 carbon atoms, - a cyclohexyl, phenyl or halophenyl group; an alkyl group of 4 to 7 carbon atoms; a cycloalkyl group of 3 to 7 carbon atoms; one with alkyl groups of 1 to 4 carbon atoms, alkoxy groups of 1 to 3 carbon atoms and/or halogen atoms di- or tri-substituted phenyl or disubstituted hydroxy or aminophenyl group, where the substituents' on the phenyl nucleus may be the same or different; a naphthyl group or a pyridyl group optionally substituted by an alkoxy group with 1 to 3 carbon atoms, and R^ means a hydrogen atom or an acyl residue of an organic carboxylic acid, of an organic or inorganic sulphonic acid or of a carboxylic acid derivative, and salts thereof with strong acids, characterized by a) for the preparation of a compound of the general formula I where n means the number 1 and R2 means a hydrogen atom, a sulfoxide with the general formula is reacted where A, B and are as indicated at the outset, with possibly hydrogen azide formed in the reaction mixture, or b) to prepare a compound of the general formula I where R^ denotes a hydrogen atom, react a sulfoxide • with the general formula where A, B, n and R^ are as indicated at the outset, with a compound of the general formula where X means a carbonyl or sulfonyl group, and R^ means an aryl group disubstituted in the o-position such as a 2,4,6-trimethyl or triisopropylphenyl group or also a hydroxy group if X means a sulfonyl group, or c) for the preparation of a compound with the general formula I where n means the number 1, a mercapto compound with the general formula is oxidized where A, B, and R ? is as indicated at the outset, or d) for the preparation of a compound of the general formula I where R. y does not mean a hydrogen atom, a compound of the general formula is acylated where' n, A, B and R^ are as indicated at the outset, or) a hydroxy compound of the general formula where A is as initially indicated, or its salts with inorganic or tertiary organic bases, is reacted with a compound of the general formula where n, R^ , R- and B are as indicated at the outset, and Z means a nucleophilic leaving group, or f) for the preparation of a compound of the general formula I where n means the number 0, a thioether of the general formula is reacted where A, B and R^ are as indicated at the outset, with an amide of the general formula where Hal means a chlorine or bromine atom, and R2 1 has the meanings given for R2 at the beginning with the exception of hydrogen, or with its alkali salt, and optionally the resulting reaction product is then hydrolysed, and optionally a prepared compound of the general formula I is transferred with a strong acid to a salt, in particular a physiologically compatible salt. 2. Method according to claim 1, characterized in that compounds of formula I are prepared where n means the number 1, A means a dimethylene, vinylene or ethylene group, B means an n-butylene group, R^ means a methyl or methoxynaphthyl group, a phenyl group optionally substituted with a methoxy group, a fluorine or chlorine atom, a phenyl group substituted with two chlorine or bromine atoms, a methyl-bromophenyl-, 4-amino-3,5-dibromophenyl- or di-tert.butyl-hydroxyphenyl group, and R2' denotes a hydrogen atom, an alkanoyl group with 1 to 3 carbon atoms or a benzoyl or phenylsulfonyl group optionally substituted with an alkyl group with 1 to 4 carbon atoms. 3. Method according to claim 1, characterized in that a compound with the general formula is prepared where A means an ethylene or vinylene group, B means an n-butylene group, means a methyl-, phenyl-, 4-fluorophenyl-, 4-chlorophenyl-, .3,4-dichlorophenyl or 3-methyl-4-bromophenyl group and R2 means a hydrogen atom, an acetyl or p-toluenesulfonyl group. 4. Process according to claims 1 to 3, characterized in that 6-[4-(N-acetyl-3,4-dichlorophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril is produced. 5. Method according to claims 1 to 3, characterized in that 6-[4-(3-methyl-4-bromophenylsulfoximino)-butoxy]-carbostyril is produced.