IE48179B1 - Carbostyril derivatives,a process for their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

1. New carbostyril derivatives of general formula see diagramm : EP0003771,P26,F1 wherein W represents a vinylene group (optionally substituted by a methyl group) or the ethylene group, m represents the number 0, 1 or 2, D represents a straight-chained or branched alkylene group with 2 to 6 carbon atoms, whilst there must be at least 2 carbon atoms between the oxygen atom and the SOm group, or a xylylene group, R1 represents a cycloalkyl group with 3 to 6 carbon atoms ; an aryl group with 6 to 10 carbon atoms or an aralkyl group with 7 to 11 carbon atoms, whilst the above-mentioned aromatic nuclei may be monosubstituted by an alkyl group with 1 to 4 carbon atoms, by a hydroxy, methoxy, amino, acetylamino, nitro, carboxyl, cyclohexyl or phenyl group or by a halogen atom and, additionally, the above-mentioned monosubstituted phenyl groups may be mono- or disubstituted by alkyl groups with 1 to 4 carbon atoms and/or by halogen atoms (whilst the substituents of the phenyl nucleus may be identical or different) ; an N-methyl-cyclohexylamino-carbonylmethyl, amino-iminomethylene, pyridyl, pyridylmethyl, furfuryl, benzimidazolyl, benzothiazolyl, pyrimidyl, quinolyl, quinazolin-4-on-yl, 4,5-bis-(p-chlorophenyl)-oxazol-2-yl, pyridyloxide, triazolyl, methyl-pyridyl, methoxy-pyridyl, fluoropyridyl, chloropyridyl, aminopyridyl, acetylaminopyridyl or triphenyl-methyl group, or also a tert. butyl group, if m represents the number 1, and R2 and R3 , which may be identical or different, represent hydrogen or halogen atoms, alkyl groups with 1 to 4 carbon atoms, amino, acetylamino or nitro groups.

Description

This invention rela tes to new carbostyril derivatives, to process for their preparation and to pharmaceutical compositions containing them.

According to one feature of the present invention there are provided compounds of general formula I, (I) - D - SOm -R] wherein W represents a vinylene group (optionally substituted by a methyl group) or a methylene or ethylene group; m represents the number 0, 1 or 2, D represents a straight-chained or branched alkylene group with 2 to 6 carbon atoms, whilst there must be at least 2 carbon atoms between the oxygen atom and the S0m group, or a xylylene group, R^ represents a cycloalkyl group with 3 to 6 carbon atoms; an aryl group with 6 to 10 carbon atoms or an aralkyl group with 7 to 11 carbon atoms, whilst the above-mentioned aromatic nuclei may be monosubstituted by an alkyl group with 1 to 4 carbon atoms, by a hydroxy, methoxy, amino, acetylamino, nitro, carboxyl, cyclohexyl or phenyl group or by a halogen atom and, additionally, the above-mentioned mono-substituted phenyl groups may be mono- or disubstituted by alkyl groups with 1 to 4 carbon atoms and/or by halogen atoms (whilst the substituents of the phenyl nucleus may be identical or different); an N-methyl-cyclohexylamino-carbonylmethyl, amino-iminomethylene, pyridyl, pyridylmethyl, furfuryl, benzimidazolyl, benzothiazolyl, pyrimidyl, quinolyl, quinazolin-4-on-yl, 4,5-bi s-(p-chlorophenyl)-oxazol-2-y1, pyri dy1oxi de, triazolyl, methyl-pyridyl, methoxy-pyridyl, fluoropyridyl, chloropyridyl, aminopyridyl, acetylaminopyridyl or tri phenyl-methyl group, or also a tert, butyl group, if m represents the number 1, and the SO qroun. or a xylylene group; The compounds of general formula I possess interesting pharmacological properties and in particular, in general, a positive inotropic activity as well as an antithrombotic activity.

In formula I, when R], R2 and /or R3 represent a halogen atom, this may, be a fluorine, chlorine, bromine or iodine atom.

D may, for example, represent an ethylene, npropylene, n-butylene, n-pentylene, n-hexylene, 1methylethylene, 2-methylethylene, 1-methyl-n-propylene, 2-methyl-n-propylene, 3-methyl-n-propylene, 1-methyln-butylene, 2-methyl-n-butylene, 3-methyl-n-butylene, 4- methyl-n-butylene, 1-methy1-n-pentylene, 2-methyln-pentylene, 3-methyl-n-pentylene, 4-methyl-n-pentylene, - methyl-n-pentylene, 1,1-dimethylethylene, 1,2dimethylethylene, 2,2-dimethylethylene, 1,1-dimethy1n-propylene, 2,2-dimethyl-n-propylene, 3,3-dimethyln-propylene, 1,2-dimethyl-n-propylene, 1,3-dimethyln-propylene, 1,1-dimethyl-n-butylene, 2,2-dimethyl-nbutylene, 3,3-dimethyl-n-butylene, 4,4-dimethyl-nbutylene, 1,2-dimethyl-n-butylene, 1,3-dimethyl-nbutylene, 1,4-dimethyl-n-butylene, 2,3-dimethyl-nbutylene, 1-ethylethylene, 2-ethylethylene, 1-ethyl-n20 propylene, 2-ethyl-n-propylene, 3-ethyl-n-propylene, 1-ethyl-n-butylene, 2-ethyl-n-butylene, 3-ethyl-nbutylene, 4-ethyl-n-butylene, 1-methyl-2-ethyl-ethylene, 1- methyl-2-ethyl-n-propylene, 1-methyl-3-ethyl-n-propylene, l-methyl-2-propyl-ethylene, 1-propylethylene, 1butylethylene, 1-propyl-n-propylene, 2-hydroxy-npropylene, 2-hydroxy-n-butylene, 3-hydroxy-n-butylene, 2- hydroxy-n-pentylene, 3-hydroxy-n-pentylene, 4hydroxy-n-pentylene, 2-hydroxy-n-hexylene, 3-hydroxyn-hexylene, l-methyl-2-hydroxy-n-propylene, 2-hydroxy2-methyl-n-propylene, £-xylylene, o-xylylene or m-xylylene group.

Rj may, for example, represent a cyclopropyl, cyclobutyl, cyclopentyi, cyclohexyl, phenyl, benzyl, phenylethyl, naphthyl, naphthylmethyl, cyclohexylphenyl, biphenyl, triphenylmethyl, N-methylcyclohexylaminocarbonylmethyl, amino-iminomethyl, pyridyl, pyridyImethyl, furfuryl, benzimidazolyl, benzthiazolyl, pyrimidyl, 1,2,4-triazolyl, quinolyl, quinazoline-4-one-yl, 4,5bis-(£-chlorophenyl)-oxazole-2-yl, pyridyl-oxide, methyIphenyl, dimethylphenyl, tert.-butylphenyl, methyltert.-butylphenyl, methylpyridyl, methoxyphenyl, dimethoxyphenyl, methoxypyridyl, hydroxyphenyl, fluorophenyl, difluorophenyl, trifluorophenyl, fluoropyridyl, chlorophenyl, dichlorophenyl, trichlorophenyl, chloropyridyl, bromophenyl, dibromophenyl, aminophenyl, acetylaminophenyl, aminopyridyl, acetylaminopyridyl, nitrophenyl, carboxyphenyl,hydroxy-dichlorophenyl, hydroxydibromophenyl, amino-dichlorophenyl, amino-dibromophenyl, „ 48179 hydroxy-di-tert.-butylphenyl, methoxy-fluorophenyl, methoxy-chlorophenyl, methoxy-bromophenyl, fluoromethy lphenyl , chloromethylphenyl or bromomethylphenyl group.

Rg and Rg which may be the same or different, may, for example, represent a hydrogen, fluorine, chlorine, bromine or iodine atom or a methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, nitro, amino or acetylamino group.

Preferred compounds ‘according to the invention are those wherein R^ represents a cyclohexyl, benzyl, naphthyl, pyridyl, pyrimidyl, 1,2,4-triazolyl, pyridyl-oxide, furfuryl, triphenyImethyl, quinolyl, benzimidazolyl, benzthiazolyl, quinazoline-4-one-yl, 4,5-bis-(j>15 chlorophenyl)-oxa2ole-2-yl, N-methylcyclohexylaminocarbonylmethyl or amino-iminomethyl group; a phenyl group optionally substituted by a carboxyl, hydroxy, methoxy, amino, acetylamino, nitro, cyclohexyl or phenyl group; a phenyl group substituted by one or two substituents selected from halogen atoms and alkyl groups each containing from 1 to 4 carbon atoms; or a hydroxyphenyl, halophenyl or aminophenyl group substituted by two halogen atoms or by two alkyl groups each containing from 1 to 4 carbon atoms: Rg represents a hydrogen, chlorine or bromine atom or a methyl, amino, acetylamino or nitro group: and Rg represents a hydrogen atom.

Of these preferred compounds, more preferred are those wherein W represents a vinylene group (optionally substituted by a methyl group) or an ethylene group; 817H D represents an alkylene group containing from 2 to 5 carbon atoms or a hydroxyalkylene group containing from 3 to 5 carbon atoms; R.j represents a cyclohexyl, phenyl, benzyl, naphthyl, biphenyl, cyclohexylphenyl, pyridyl, methylphenyl, methoxyphenyl, fluorophenyl, chlorophenyl, dichlorophenyl, tri chlorophenyl, bromophenyl, dibromophenyl, bromomethylphenyl, amino-dibromophenyl or hydroxy-di-tert.butylphenyl group; and Rg represents a hydrogen atom.

Of these more preferred compounds, especially preferred are those wherein W represents an ethylene, vinylene or 2-methylvinylene group; D represents an ethylene, n-propylene, n-butylene or 2-hydroxy-npropylene group;and R^ represents a cyclohexyl, phenyl, benzyl, naphth-2-yl,2-methoxypheny1, 4-chlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 4-hydroxy-3,5di-tert.-butylphenyl, 4-amino-3,5-dibromophenyl or pyrid-2-yl group.

Particularly preferred compounds according to the invention are the following: 6-(4-phenylsulfinylbutoxy)-3,4-dihydrocarbostyril, 6-[4-(3,4-dichlorophenylsulfinyl)-butoxy]-3,4dihydrocarbostyril, and 6-[4-(pyrid-2-ylsulfonyl)-butoxy]carbo styril.

The compounds of general formula I may, for example, be prepared by the following processes, which processes constitute further features of the present invention: A) Reaction of a compound of formula II, R. <9 ο '3 •OH Η (II) (wherein Rg, Rg and W are as hereinbefore defined), or a salt thereof with an inorganic or tertiary organic base, with a compound of formula III, Z - D - SO - R.

(III) (wherein D, R1 and m are as hereinbefore defined) and Z represents a nucleophilically exchangeable atom or group, for example a halogen atom or a sulfonic acid ester group, e.g. a chlorine, bromine or iodine atom or a £10 toluenesulfonyloxy or methanesulfonyloxy group).

The reaction is conveniently carried out in a suitable solvent such as e.g. dioxan, tetrahydrofuran, chloroform or toluene, but preferably, however, in an anhydrous aprotic solvent such as, for example, acetone, dimethylformamide or dimethylsulfoxide. The reaction may optionally be effected in the presence of an alkali metal base, e.g. sodium carbonate, potassium carbonate or sodium hydroxide. Suitable temperatures for the reaction are generally from 0°G to the boiling temperature of the reaction mixture, for example at temperatures of from 0 to 100°C, preferred temperatures being however, from 10 to 50°C. The reaction may, if desired, by carried out in the absence of a solvent.

B) for the preparation of compounds of general formula I wherein m is 1 or 2, a compound of general formula IV wherein R-j to R^, D and W are as hereinbefore defined 5 and n represents the number 0 or 1, is oxidised.

The oxidation is preferably carried out in the presence of a solvent, e.g. water, aqueous pyridine, ethanol, methanol, acetone, formic acid, glacial acetic acid, dilute sulfuric acid or trifluoroacetic acid. Suitable temperatures are generally from - 80 to + 100°C depending on the oxidising agent used.

The oxidation is most conveniently effected with about one equivalent of an oxidising agent. Oxidation may, for example be effected 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 e.g. perform!c acid in glacial acetic acid or trifluoroacetic acid at 0 to 50°C; with sodium metaperiodate in aqueous methanol or ethanol at 15 to 25°C; with N-bromosuccinimide in ethanol; with tert.-butyl hypochlorite in methanol at -80 to -30°C; with iodobenzene dichloride in aqueous pyridine at 0 to 50°C; with nitric acid in glacial acetic acid at 0 to 20°C; with chromic acid in glacial acetic acid or in acetone at 0 to 20°C; or with sulfuryl chloride in methylene chloride at -70°C, the thioether chlorine complex thus formed being appropriately hydrolysed with aqueous ethanol.

G) for the preparation of compounds of general formula I wherein m is 0: Reaction of a compound of formula (V) R. '2 O-D-X (V) 0' 'R. “3 with a compound of Formula VI, Y - R, (VI) (wherein, in the above formulae IV and V, Rg, Rg D and W are as hereinbefore defined and either one of X and Y represents a mercapto group whilst the other of X and Y represents a nucleophilically exchangeable atom or group such as, for example, a halogen atom or a sulfonic acid ester group, e.g. a chlorine, bromine or iodine atom or a £-toluenesulfonyloxy or methanesulfonyloxy group, or alternatively, when D represents a hydroxyalkylene group containing from 3 to 6 carbon atoms, X may, together with the hydroxy group in D, represent an epoxide group, Y then representing a mercapto group).

The reaction is conveniently carried out in a suitable solvent such as e.g. dioxan, tetrahydrofuran, chloroform or toluene, but preferably, however, in an anhydrous aprotic solvent such as e.g. acetone, dimethylformamide or dimethylsulfoxide. The reaction may, if desired, be effected in the presence of an alkali metal base such as e.g, sodium carbonate, potassium carbonate or sodium hydroxide. Suitable reaction temperatures are generally from 0°C to the boiling temperature of the reaction mixture e.g, at temperatures of from Q to 100°C. Preferred temperatures are, however, from 10 to 50°C. The reaction may, if desired, be carried out in the absence of a solvent. 481 79 D) for the preparation of compounds of general formula I wherein U represents a vinylene group, a 3,4-dihydro-carbostyril of general formula VII wherein R^ to R3, D and m are as hereinbefore defined, is dehydrogenated.

Dehydrogenation may, for example be carried out in the presence of e.g. an oxidising agent such as 2,3-dichloro-5,6-dicyanobenzoquinone, chloranil or of a nobel metal catalyst such as e.g. palladium/charcoal. The dehydrogenation is preferably at elevated temperatures, e.g. at temperatures of from 100 to 200°C, most preferably at the boiling temperature of the reaction mixture.

E) for the preparation of 3,4-dihydro-carbostyril of general formula I wherein W represents an ethylene group and m is 0 or 2; a carbostyril of general formula VIII; ,;7''-'''-:. 3-D -SO — R, m i VIII wherein R-j to Rg, D and m are as hereinbefore defined, is hydrogenated.

The hydrogenation is preferably carried out in the presence of a solvent such as ethanol, ethyl acetate, glacial acetic acid or dioxan.

Hydrogenation may, for example, be effected e.g. with hydrogen in the presence of a catalyst such as e.g. palladium/charcoal, platinum, Raney nickel, Raney cobalt or dirhenium heptasulfide, preferably at a hydrogen pressure of from 1 to 5 bar. Suitable temperatures for the hydrogenation are generally from 0 to 50°C, preferred temperatures being ambient temperatures.

The compounds of general formulae II to VIII, useful as starting materials are either known from the literature or they can be obtained according to known processes.

For example a 6-, 7- or 8-hydroxy-3,4-dihydro-carbostyril of formula II can be obtained by acylation of a corresponding aniline derivative with an appropriate β-halocarboxylic acid derivative and subsequent cyclisation according to the method described by Friedel-Crafts (see J. chem. Soc. 1955, 743-744; Chem. Pharm. Bull.1961, 970 - 975 and Ber. dtsch. Chem. Ges. 60, 858 (1927)). A -hydroxy-3,4-dihydrocarbostyril of formula II can be obtained by cyclisation of a corresponding 2-(p-cyanoethyl) cyclohexane-1,3-dione derivative and subsequent aromai tisation for example with N-bromo-succinimide (see Chem. and Ind. 1970, 1435).

The preparation of the corresponding hydroxycarbostyrils of general formula II is known from the literature (see for example J. Amer. chem. Soc. 72, 346 (1950) and ibid 76, 2402 (1954) or J. Org. Chem. 33, 1089 (1968) and ibid 36, 3493 (1971)). Furthermore, the preparation of 5-hydroxyoxindole is described in J. chem. Soc. 1961, 2723.

The compounds of general formula V useful as starting materials can be obtained by alkylation of a corresponding hydroxy derivative.

As already mentioned above, the compounds of general & rmula I possess interesting pharmacological activities. Those compounds which we have tested show not only a positive inotropic activity but also antithrombotic activity. Such compounds are thus of use in the treatment of thrombo-embolic diseases such as e.g. coronary infarct, cerebral infarct, so-called transient ischaemic attacks and amaurosis fugax as well as for the treatment of arteriosclerosis. For example the following compounds were tested with regard to their biological properties: A = 6-(4-Phenylmercapto-butoxy)-3,4-dihydrocarbostyril, B = 6-(4-Phenylsul£inylbutoxy)-3,4-dihydrocarbostyril, C = 6-(4-Phenylsulfonylbutoxy)-3,4-dihydrocarbostyril, D = 6-[4-(2-Pyridylmercapto)-butoxy]-3,4dihydrocarbostyril, E = 6-[4-(2-Pyridylsulfinyl)-butoxy]-3,4dihydrocarbostyril, F = 6-[4-(2-Pyridylsulfonyl)-butoxy]-3,4dihydrocarbostyril, G = 6-(2-Phenylsulfinyl-ethoxy)-3,4-dihydrocarbostyril, H = 6-(4-Benzylsulfinyl-butoxy)-3,4-dihydrocarbostyril, I = 6-[4-(4-Chlorophenylsulfinyl)-butoxy]-3,4dihydrocarbostyril, K ·= 6-(4-Cyclohexylsulfinyl-butoxy)-3,4dihydrocarbostyril, L = 6-[4-(2-Naphthylsulfinyl)-butoxy]-3,4·· dihydrocarbostyril, M = 6-[4-(2-Methoxyphenylsulfinyl)-butoxy]-3,4dihydrocarbostyril, N = 6-(4-Phenylsulfinyl-butoxy)-carbostyril, Ο = 6-[4-(4-Hydroxy-3j,5-di-tert.-butyl-phenylsulfinyl )-butoxy]carbostyri1, P = 6-[4-(3,4-Dichlorophenylsulfinyl)-butoxy]carbostyril, Q = 4-Methyl-6-(4-phenylsulfinyl-butoxy)carbostyril, R = 6-[4-(3,4-Dichlorophenylsulfonyl)-butoxy]3.4- dihydrocarbostyril, S = 6-[4-(2,5-Dichlorophenylsulfinyl)-butoxy]20 3,4-dihydrocarbostyril, T = 6-[4-(Pyrid-2-yl-sulfonyl)-butoxy]carbostyril and U = 6-[4-(3,4-Dichlorophenylsulfinyl)-butoxy]3.4- dihydrocarbostyril. 1. Determination of the thrombocyte aggregation 15 according to the method of Bom and Cross (J. Physiol. 170, 397 (1964)): The thrombocyte aggregation was measured in the platelet-rich plasma of healthy human donors. The decrease in optical density was measured and recorded photometrically after the addition of adenosine diphosphate or collagen. From the angle of inclination of the density curve, the velocity of aggregation was estimated (Vmax). The optical density was taken as the point on the curve where the most light was transmitted (O.D.).

Small doses of collagen were chosen, but sufficient to give irreversible aggregation. To provoke maximum aggregation, about 0.01 ml of the collagen solution was added to 1 ml of platelet-rich plasma. (Commercial collagen of Messrs. Hormonchemic, Munich). The adenosine diphosphate (ADP) doses were chosen to give only the first phase of the BORN curve. The necessary amount of ADP was about 1.10 mol/1. Commercial ADP of Messrs. Boehringer Mannheim was used.

The dosage of the test compounds which provoked a 50% inhibition of the thrombocyte aggregation was determined graphically (Εϋ^θ) Compound EDg 10-6 mol/1 Collagen ADP A 50 > 100 B 4 20 z> 5 15 D 45 > 100 E 6.5 25 F 20 20 G 3.5 17 H 2.5 14 I 4 10 K 4.5 12 L 1 10 M 4 22 N 0.6 3 0 0.2 0.5 P 0.2 1.8 Q 3.6 40 R 1.5 25 S 1.0 10 T 0.1 6 u 4 15 2. Determination of the prolongation of bleeding time; Preliminary remark: The human organism as well as other warmblooded animals have an ingenious mechanism, which protects them from blood loss in case of injury.

This system consists of blood platelets (thrombocytes), which quickly seal the injured vessels by means of their adhesiveness (primary hemistasis). Beside this cellular hemostatic mechanism, the body has a blood coagulation system. In this system plasma factors (proteins) are activated whereby plasma fibrinogen is converted to a fibrin coagulum. The system of primary hemostasis, mainly due to thrombocytes, and the coagulation system complement each other, both having the aim of protecting the body effectively from blood loss.

With some diseases it is found that coagulation and thrombocyte aggregation take place also in intact blood vessels. The influence on the coagulation system of cumarine and heparine is known and can easily be measured by coagulation loss, the coagulation time being prolonged under the influence of these substances. (Plasma-recalcif. time, Quick-Test Thrombin time, etc.).

The normality of the thrombocytes can be determined by measuring the bleeding time. The normal bleeding time in human beings is in the range of 1 to 3 minutes and requires incact thrombocytes in a sufficient number. If the number of thrombocytes is normal and the bleeding time is prolonged this signifies an abnormality in the thrombocytes. This is found in some inborn errors of thrombocyte-function (v. Willebrand-disease for example). If, on the other hand it is desired to prevent spontaneous aggregation of the thrombocytes and occlusion in the arterial system by antiplateled drugs, the bleeding time should be prolonged as a consequence. Therefore, using antiplateled substances, a prolongation of the bleeding time is expected. If the plasma coagulation system is not influenced by such a substance, coagulation tests will give a normal result.

Literature: W.D. Keidel: KurzgefasstesLehrbuch der Physiologie, Georg Thieme Verlag Stuttgart 1967, page 31: the proceeding of hemostasis.

To measure the bleeding time 10 mg/kg of the test compound is administered orally to conscious mice. After 1 hour 0.5 mm of the tip of the tail of the mouse is cut off and the droplets of blood are gently removed with filter paper every 30 seconds.

The number of drops of blood give a measure of the bleeding time (5 animals/experiment).

The values in the following table represent the prolongation in % as compared to a control group: Compound Prolongation of the Heeding time in % after one hour A 145 B 102 C 26 D 76 E 152 F 91 G 5 H 29 I >300 K 12 L 15 M 27 0 73 P 12 Q 39 R 30 T 5 u 33 3. Determination of the positive inotropic activity: Rats were narcotized with ether and subsequentlykilled by a blow behind the neck. After opening the thorax the heart was removed and both auricles were isolated. The auricles were placed into an organ bath of 100 ml. The bath had been filled with a tyrode solution at a temperature of 30°C. The tyrode solution I was infused with carbogen (95% of 0% and 5% of CO^.

The spontaneous contractions of the auricles were registered isometrically. The auricles were charged with 1 g. The test compounds were tested on 4 auricles each in a concentration of 1 x 10 g/ml. The variation in the contraction force was registered in % from the starting values.

The following table give the results obtained.

Compound Increase in contraction force in % B 30 C 35 E 16 F 18 I 52 L 63 M 65 Q 58 s 83 T 82 4. Acute toxicity; The acute toxicity of the test compounds was determined in groups of 10 mice each after oral administration of a single dose of 1 000 mg/kg (observation time: 14 days).

Compound acute toxicity per os A >1 000 mg/kg (0 out of 10 animals died) B ?1 000 mg/kg (0 out of 10 animals died) C 000 mg/kg (0 out of 10 animals died) D M 000 mg/kg (0 out of 10 animals died) E ?1 000 mg/kg (0 out of 10 animals died) F 000 mg/kg (0 out of 10 animals died) G >1 000 mg/kg (0 out of 10 animals died) H 000 mg/kg (0 out of 10 animals died) I 7l 000 mg/kg (0 out of 10 animals died) K A 000 mg/kg (0 out of 10 animals died) L ?1 000 mg/kg (0 out of 10 animals died) M ?1 000 mg/kg (0 out of 10 animals died) P 7l 000 mg/kg (0 out of 10 animals died) Q >1 000 mg/kg (0 out of 10 animals died) R >1 000 mg/kg (0 out of 10 animals died) S >1 000 mg/kg (0 out of 10 animals died) u >1 000 mg/kg (0 out of 10 animals died) According to a yet further feature of the present invention there are provided pharmaceutical compositions comprising, as active ingredient, at least one compound of formula I as hereinbefore defined in association with a pharmaceutical carrier or excipient.

For pharmaceutical administration the compounds of general formula I may be incorporated into the conventional pharmaceutical preparations in either solid or liquid form, optionally in combination with other active ingredients. The compositions may, for example, be presented in a form suitable for oral, rectal or parenteral administration. Preferred forms include, for example, plain tablets, coated tablets, capsules, suppositories, suspensions and solutions e.g. for injection.

The active ingredient may be incorporated in excipients customarily employed in pharmaceutical compositions such as, for example, talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fatty substances of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents and/or preservatives.

Advantageously the compositions may be formulated as dosage units, each unit being adapted to supply a fixed dose of active ingredient. Suitable dosage units for adults contain preferably from 50 to 100 mg of active ingredient. The oral daily dosage, which may be varied according to the compound used, the subject treated and the complaint concerned, may, for example, be from 100 to 300 mg per day in adults.

The following non-limiting Examples serve to illustrate the present invention.

Example 1 6-A-(2-Pyridylmercapto)-butoxv7-3.4-dihydrocarbostyril 14.4 g (0.13 mol) of 2-mercaptopyrldine and 17-9 g (0.13 mol) of potassium carbonate were stirred in 360 ml of dimethyl5 sulfoxide, dried over a molecular sieve, and 36 g (0.12 aol) of 5-(4-bromobutoxy)-3,4-dihydrocarbostyril (m.p.: 142 - 147°C, prepared from 6-hydroxy-carbostyril and 1,4-dibromobutane) were added to this mixture. After stirring for 15 hours at approx. 25°C, the reaction mixture was poured into 3.6 1 of water and again stirred for 30 minutes. The precipitated product was suction filtered, well washed with water, dried and recrystallized from xylene by addition of charcoal. Yellow crystals of s.p. 123 - 124.5°C were obtained.

Yield: 32 g (81.2 % of theory).

Example 2 6-/5-(2-Pyrldylsulflnvl)-butoxy7-3.4-dihydrocarbostyril 32.8 g (0.1 mol) of 6-/5-(2-pyridylmercapto)-butoxx7-3,4-dihydrocarbostyril were dissolved in 330 ml of glacial acetic acid and 10.2 g (0.105 mol) of 35 % hydrogen peroxide were added.

The solution was stirred for 15 horn’s at approx. 20°C. The glacial acetic acid was distilled off at 60°C in vacuo, the residue was washed with ether and the thus obtained crude product was recrystallized twice from xylene by addition of charcoal. Colourless crystals of m.p. 144.5 - 146°C were obtained.

Yield: 27.5 g (79.8 % of theory).

Example 3 6-/5-(2-Pyrldylsulfοητί)-butoxv7-3 , 4-dihvdrocarboatyrll g (0.015 mol) of 6-/5-(2-pyridylaercapto)-butoxy7-3,4-dihydrocarbostyril were dissolved in 50 ml of glacial acetic acid and 4.5 g (0.045 mol) of 35 % hydrogen peroxide were added. After stirring for 40 hours at approx. 25°C, the glacial acetic acid was distilled off at 60°C in vacuo.

The solid residue was washed with ether and recrystallized from xylene by addition of charcoal. Colourless crystals of m.p. 123.8 - 125°C were obtained.

Yield: 3.8 g (70.3 * of theory).

Example 4 6-(4-Fhenvlsulfinvlbutoxv)-3.4-dihvdrocarbostyril 32.6 g (0.2 mol) of 6-hydroxy-3,4-dihydrocarbostyril (see F. F. Mayer et al. in Ber. dtsch. chem. Ges. 60, 858 (1927)) and 27.6 g (0.2 mol) of potassium carbonate were stirred for 5 minutes in 600 ml of dimethylsulfoxide, dried over a molecular sieve,and subsequently 52.2 g of 4-phenylsulfinylbutylbromide (0.2 mol) (prepared from thiophenole and 1,4-dibromo20 butane and subsequent oxidation with hydrogen peroxide in glacial acetic acid analogously to example 2; oily substance, solidified whilst standing in the refrigerator) were added. After stirring for 15 hours at 25°C the reaction mixture was poured into 6 1 of water. After stirring for further 30 minu25 tes the precipitated product was suction filtered and well washed with water. After drying the residue was recrystallized from 600 ml (approx.) of xylene by addition of charcoal. White crystals of m.p. 144.5 - 145.5°C were obtained.

Yield: 49 g (71.3 % of theory).

Example 5 6-(4-Phepylfflercapto-butoxv)-3.4-dlhvdro-carbostvril Prepared analogously to Example 4 from 6-hydroxy-3,4-dihydro-oarbostyril and 4-(phenylmercapto)-butylbromide (b.p. θ 02 : 96 - 103°C, prepared from thiophenol and 1.4-dibromobutane).

M.p.: 121.5 - 123°C Yield: 75.6 % of theory.

Example 6 6-(4-PhenYlsulfonvl-butoxv)-3.4-dihvdrocarboBtyrll Prepared analogously to Example 4 from 6-hydroxy-3,4-dihydro-carbostyril and 4-phenyl-sulfonyl-butylbromide (prepared from 4-(phenylmercapto)-butylbromide by oxidation analogously to Example 3).

M.p.: 157.5 - 158°C Yield: 65.1 % of theory.

Example 7 6-/5-(4-Fluorophenvlmercapto)-butoxy7-3.4-dihydrocarbostvrll Prepared analogously to Example 1 from 6-(4-bromobutoxy)20 3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 4-fluorothiophenol .

M.p.: 139 - 14O°C Yield: 93.1 % of theory.

Example β 6-/5-(4-FluorophenylaulfInyl)-butoxy7-3.4-dlhydrocarbostyrll Prepared analogously to Example 2 from 6-/5-(4-fluorophenylmercapto)-butoxj7-3,4-dihydrocarbostyril.

M.p.: 184.5 - 186°C Yield: 88 % of theory.

Example 9 6-/5- (4-Methvlphenvl-mercapto)-butoxy7-3.4-dlhydrocarbostyril Prepared analogously to Example 1 from 6-(4-chlorobutoxy)10 3,4-dihydrocarbostyril (m.p. 147 - 148°C) aind 4-methylthiophenol .

M.p.: 120 - 121°C Yield: 91 % of theory.

Example 10 6-/5- (4-Methylphenvl-sulfInyl)-butoxy7-3.4-dihydrocarbostvril Prepared analogously to Example 2 from 6-/5-(4-methylphenylmercapto)-butoxx7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 149.5 - 150°C 20 Yield: 97 % of theory.

Example 11 6-/5-(3-Methylphenylmercapto)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-chlorobutoxy)3,4-dihydrocarbostyril (m.p. 147 - 148°C) and 3-methylthiophenol M.p.: 95 - 96°C Yield: 91 % of theory.

Example 12 6-Γ4-(5-MethylphenylsulfInvl)-butoxv7-5.4-dihydrocarbostyrll Prepared analogously to Example 2 from 6-/5-(3-methylphenylsercapto)-butoxy73,4-dihydrocarboetyril and hydrogen peroxide. Wax-like resin.

Yield! 95 % of theory.

Rfvalue: 0.48 (thin-layer chromatogram on silica gel 10 eluent: benzene/ethanol/conc. ammonia = 75/25/1).

Example 15 6- /5-(4-Chlorophenylmercanto)-butoxv7-3.4-dihydrocarbostyrll Prepared analogously to Example 1 from 6-(4-chlorobutoxy)-3.4-di hydrocarbostyril (m.p. 147 - 148°C) and 4-ohlorothiophenol .

M.p.: 144 - 146°C Yield: 88 % of theory.

Example 14 6-/5-(4-Chlorophenvlsulfinvl)-butoxv7-3.4-dihydrocarbostyrll Prepared analogously to Example 2 from 6-/5-(4-chlorophenyl20 mercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 148 - 149.5°C Yield: 70 % of theory.

Example 15 6- fii- (3.4-Dlchlorophenylmercapto)-butoxy7-5.4-dlhydrocarbostyril Prepared analogously to Example 1 from 6-(4-chlorobutoxy)3,4-dihydrocarbostyril (m.p. 147 - 148°C) and 3,4-dichloro5 thiophenol .

M.p.: 116.5 - 118°C Yields 87 % of theory.

Example 16 6-/7-(3.4-PlchlorophenYlsulfInyl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/7-(3»4-dichlorophenylmercapto)-butoxx7-3»4-dihydrocarbostyril and hydrogen peroxide. M.p.: 106.5 - 108°C Yield: 74 % of theory.

Example 17 6-/7-(2-Methoxyphenylaercapto)-butoxv7-3.4-dlhydrocarbostyrll Prepared analogously to Example 1 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p. 142 - 147°C) and 2-methoxythiophenol .

M.p.: 130.5 - 133°C 20 Yield: 74 % of theory.

Example 18 6-/7-(2-MethoxyphenylsulfInyl)-hutoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/7-(2-methoxyphenylmercapto)-butox2;7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 162 - 163°C Yield: 62 % of theory.

Example 19 6-/5-(3-Methoxyphenylmercapto)-butoxy7-3.4-dihydrocarboatyg11 Prepared analogously to Example 1 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p. 142 - 147°C) and 3-methoxythiophenol.

M.p.: 93.5 - 97°C Yield: 61 % of theory. •θ Example 20 6-/5-(g-Methoxyphenylsulflnyl)-butoxv7-3.4-dlhydrocarbostyril Prepared analogously to Example 2 from 6-/5-(3-methoxyphenylmercapto)-butoxjr7-3,4-dihydrocarbostyril and hydrogen peroxide. M.p.: 147 - 148°C Yield: 49 % of theory.

Example 21 6-/5-(4-Methoxyphenylmercapto)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p. 142 - 147°C) and 4-methoxy20 thiophenol.

M.p.: 130.5 - 133°C Yield: 82 % of theory.

Example 22 6-/Ε- (4-Methoxyphenylsulflnyj)-butoxv7-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/5-(4-methoxyphenylmercapto)-butox]r7-3,4-dihydrocarbostyril and hydrogen per5 oxide.

M.p.: 132 - 133°C Yield: 71 % of theory.

Example 23 8-/1-(3,4-Dlaethoxyphenylmercapto)-butoxv7-3,4-dihydrocarbostyril Prepared analogously to Example 1 from 3,4-diaethoxythiophenol and 6-(4-chlorobutoxy)-3,4-dihydrocarbostyril /prepared from 6-hydroxy-carbostyril (see F. Mayer et al. in Ber. dtsch. chem. Ges. 60. 858 (1927) and 4-chlorobutyl benzenesulfonate7.

M.p.: 117 - 119°C Yield: 73 % of theory.

Example 24 6-/5-(3,4-Dimethoxyphenylsulfinyl)-butox/7-3,4-dihydrocarbostyrll Prepared analogously to Example 2 from 6-/5-(3,4-dimethoxyphenylmercapto)-butoxjr7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 145 - 147°C Yield: 79 % of theory.

Example 25 6-/5- (3,4-Dimethoxyphenylsulfonyl)-butox27~3,4-dihydrocarboetyrll Prepared analogously to Example 3 from 6-/5-(3,4-dimethoxyphenylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 158 - 16O°C Yield: 62 % of theory.

Example 26 6-/5-(4-Blphenylylmercapto)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 1 from 4-phenylthiophenol and 6-(4-bromobutoxy)-3,4-dihydrooarbostyril.

M.p.: 179.5 - 181°C Yield: 74 % of theory.

Example 27 6-/5-(4-BiphenylylsulfInvl)-butoxv7-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/5-(4-biphenylylmercap to)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 192 - 192.5°C.

Yield; 86 % of theory.

Example 28 6-/5-(2-Naphthylmercapto)-butoxy7-5,4-dihydrocarbostyril Prepared analogously to Example 1 from 2-naphthylmercaptane and 6-(4-bromobutoxy)-3,4-dihydrocarbostyril.

M.p.: 108.5 - 109.5°C Yield: 48 % of theory.

Example 29 6-/5-(2-Naphthylaulfinvl)-butoxy7-5.4-dlhydrocarbostyril Prepared analogously to Example 2 from 6-/5-(2-naphthylmercapto)-butoxjr7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 147-5 - 148.5°C Yield: 57 % of theory.

Example 30 6-/5-(2-Pyridylsulfinvl)-pentoxy7-3.4-dihydrocarboatyril Prepared analogously to Example 2 from 6-/5-(2-pyridylmercap10 to)-pentox/7-3,4-dihydrocarboatyril and hydrogen peroxide.

M.p.: 116 - 118°C Yield: 69 % of theory.

Example 31 6-(2-Methylsulfinvlethoxy)-5,4-dihydrocarbostvril 1.42 g (0.006 mol) of 6-(2-methylmercaptoethoxy)-3,4-dlhydrocarboatyril were suspended in 12 ml of methanol and a solution of 1.71 g (0.008 mol) of sodium metaperiodate in 8 ml of water was added. The reaction mixture was stirred for 1,5 hours, whereby at the beginning a clear heating of the reaction mixture could be observed. Subsequently the mixture was diluted with little water and exhaustively extracted with chloroform. The evaporation residue was recrystallized from ethyl acetate by addition of little ethanol.

M.p.: 129 - 131.5°C Yield: 70 % of theory.

Example 32 6-/5-(2-Pyridylsulfonyl)-pentoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 3 from 6-/5-(2-pyridylmercapto) pentox/7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 113.5 - 115.0°C Yield: 71 % of theory.

Example 33 6-(4-Methylsulfinylbutoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-(4-methylmercapto10 butoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 128.5 - 130.5°C Yield: 58 % of theory, Example 34 7-(4-PhenylBulfonyl-butoxy)-carbostyril Prepared analogously to Example 3 from 7-(4-phenylmercaptobutoxy)-carbostyril and hydrogen peroxide.

M.p. : 199 - 201°C Yield: 85 % of theory.

Example 35 2o 6-(4-Cyclohexylmercaptobutoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 1 from cyclohexylmercaptane and 6-(4-chlorobutoxy)-3,4-dihydrocarbostyril (m.p.: 147 148°C).

M.p.: 114 - 115°C Yield: 80 % of theory.

Example 56 6-(4-Cyclohexylsulfinyl-butoxy)-3.4-dlhydrocarhostyrll Prepared analogously to Example 2 from 6-(4-cyclohexylaercapto-butoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

B.p.j 153 - 155.5°C Yields 63 % of theory.

Example 37 6-(4-Benzylmercapto-butoxy)-5.4-dihvdrocarboatyrll Prepared analogously to Example 1 from benzylmercaptane and 10 6-(4-chlorobutoxy)-3,4-dihydrocarbostyril.

M.p.: 77.5 - 78.5°C Yield: 90 % of theory.

Example 38 6-(4-Benzvlsulfinyl-butoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-(4-benzylmercaptobutoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 141.5 - 142°C Yield: 95 % of theory.

Example 39 6-/5-(2-Furylmethylmercapto)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 1 from 2-furfurylmercaptane and 6-(4-bromobutoxy)-3,4-dihydrocarbostyril (m.p.: 142 - 147°C) M.p.: 79 - 80°C Yield: 64 % of theory. - 48179 Example 40 6-/7-(2-Furylmethylsulfinyl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/7-(2-furylmethylasrcapto)-butoxy/-3,4-dihydrocarbostyril and hydrogen per5 oxide.

M.p.: 135 - 136°C Yield: 60 % of theory.

Example 41 6- /7-(N-Oxido-2-pvrldvlmercapto)-hutoxy7-3.4-dihydrocarboatvril Prepared analogously to Example 1 from 6-(4-bromobutoxy)-3»4-di hydrocarbostyril and 2-mercaptopyridine-N-oxide.

M.p.: 179.5 - 181°C Yield: 65 % of theory.

Example 42 6-/7-(2-Pyrlmidyl-mercapto)-butoxv7-3,4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-ohlorohutoxy)3,4-dihydrocarbostyril (m.p.: 147 - 148°C) and 2-mercaptopyrimidine.

M.p.: 154 - 156°C Yield: 79 % of theory.

Example 43 6-/5-(2-PyrlmidvlsulflnYl)-hutoxy7“5.4-dihYdrocarboatyril Prepared analogously to Example 2 from 6-/5-(2-pyrimidylmercapto)-butox/7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 154 - 156°C Yields 36 % of theory.

Example 44 6-/5-(4-Pyrldylnercapto)-butoxv7-3.4-dlhYdrocarbostyril To a solution of 1.3 g of 4-mercaptopyridine, 2.3 g of 30 % sodium methoxide solution and of 15 ml of methanol, 3.0 g of 6-(4-bromobutoxy)-3,4-dihydrocarbostyril were added and stirred for 14 hours at room temperature. Subsequently the solution was diluted with 20 ml of water and the obtained precipitate was reorystallized from ethanol.

M.p.: 128 - 129°C Yield: 1.6 g (49 % of theory).

Example 45 6-/5-(2-Benzlmidazolylmercapto)-butoxy7-3.4-dlhvdrocarbostyrll 2o Prepared analogously to Example 1 from 6-(4-chlorobutoxy)3,4-dihydrocarbostyril (m.p.: 147 - 148°C) and 2-mercaptobenzimidazole.

M.p.: 100 - 103°C Yield: 45 % of theory.

Example 46 6-/5- (2-Benzlmldazolylsulflnyl)-butoxv7-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/5-(2-benzimidazolylEsrcapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 160 - 182°C Yield: 36 % of theory.

Example 47 6-/5-(2-Benzthlazolyl-mercapto)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-chlorobutoxy)~ i0 3,4-dihydrocarbostyril (m.p.: 147 - 146°C) and 2-mercaptobenzthiazole.

M.p.: 157 - 158°C Yield: 70 % of theory.

Example 48 6-/5-(2-Benzthlazolylsulflnyl)-butoxy7-5.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/5-(2-benzthiazolylmercapto)-butox]r7-3,4-dihydrocarbostyril and hydrogen peroxide. M.p.: 183 - 184°C Yield: 69 % of theory.

Example 49 6-(2-Phenylmercapto-ethoxy)-3.4-dlhydrocarbostyril Prepared analogously to Example 1 from thiophenol and 6-(2-chloroethoxy)-3,4-dlhydrocarbostyril (m.p.: 152.5 to 153-5°C).

M.p.: 132 - 133.5°C Yield: 91 % oi theory.

Example 50 6-(2-Phenylsulfinyl-ethoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 2 from 6-(2-phenylmercaptoethoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 171 - 172°C Yield: 84 % of theory.

Example 51 6-(2-Phenylsulfonyl-ethoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 3 from 6-(2-phenylmercaptoethoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 185 - 186°C Yield: 94 % of theory.

IS Example 52 6-(3-Phenylmercapto-propoxy)-3.4-dlhydrocarbostvril Prepared analogously to Example 1 from 6-(3-bromopropoxy)3,4-dihydrocarbostyril (m.p.: 111 - 118°C) and thiophenol . M.p.: 111 - 112°C Yield: 77 % of thoery.

Example 53 6-(3-Phenylsulflnyl-propoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/5-(phenylmercapto)ρροροχχ7-3.4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 131.5 - 133.5°C Yields 67 % of theory.

Example 54 1-Methyl-6-(4-phenylmercapto-butoxy)-3.4-dihydrocarbostyril 16.2 g of 6-(4-phenylmercapto-butoxy)-3,4-dihydrocarbostyril were dissolved in 100 ml of dimethylformamide and 4.8 g of a 50 % sodium hydride suspension in paraffin oil were added to this solution. After addition of 12.5 ml of methyl iodide the mixture was stirred for 3 hours at room temperature, dilu ted with water and extracted with chloroform. The evaporation residue was recrystallized from methanol under addition of activated charcoal.

M.p.: 79.5 - 80.5°C Yield: 71 % of theory.

Example 55 1-Methy1-6-(4-phenylsulfinyl-butoxy)-3.4-dihydrocarbo styril Prepared analogously to Example 2 from 1-methyl-6-(4-phenylmercapto-butoxy )-3, 4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 82 - 82.5°C Yield: 60 % of theory.

Example 56 1-Methvl-6-(4-phenylsulfonyl-butoxy)-3.4-dihydrocarbo styril Prepared analogously to Example 3 from 1-methyl-6-(4-phenylaercapto-butoxy)-3,4-dihydrocarbostyril and hydrogen per5 oxide.

M.p.: 108 - 109°C Yield: 49 % of theory.

Example 57 6-(6-Phenylmercapto-hexoxy)-3,4-dlhydrocarbostyrll Prepared analogously to Example 1 from 6-(6-bromohexoxy)3,4-dihydrocarbostyril (m.p.: 107.5 - 108°C) and thiophenol. M.p.: 112.5 - 113°C Yield: 34 % of theory.

Example 58 6-(6-Phenylsulfinyl-hexoxy)-3.4-dlhydrocarbostyril Prepared analogously to Example 2 from 6-(6-phenylmercaptohexoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 119.5 - 121.5°C Yield: 35 % of theory.

Example 59 6-(2-Hydroxy-3-phenylmercapto-propoxy)-5,4-dlhvdrocarboatyrll 4,11 g (0.04 mol) of thiophenol were added to a suspension of 2.10 g (0.03 mol) of potassium methoxide in 40 ml of methanol, whereby a clear solution was obtained. Then 4.38 g of 6-(2,3-epoxypropoxy)-3,4-dihydrocarbostyril (m.p. 125 - 128°C) were added whilst stirring, whereby a clear solution was obtained under self-heating. After 5 minutes th® separation of a white crystal slurry started. After standing over night the crystals were suction filtered and recrystallized from little methanol. White crystals of m.p. 148 - 149°C were obtained.

Yield: 73 % of theory.

Example 60 6-(2-Hydroxy-3-phenylsulfinylpropoxy)-g,4-dihydrocarbostyril Prepared analogously to Example 2 from 6-(2-hydroxy-3-phenylmercaptopropoxy)-3,4-dihydrocarbostyril and hydrogen peroxide. M.p.: 185 - 187°C Yield: 51 % of theory.

Example 61 6-(2-Hydroxy-5-phenylsulfonyl-propoxy)-5.4-dihydrocarbostyril Prepared analogously to Example 3 from 6-(2-hydroxy-3-phenylmercaptopropoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 170 - 172°C.

Yield: 54 % of theory.

Example 62 7-(4-Phenylaercaptobutoxy)-5,4-dihydrocarbostyrll Prepared analogously to Example 4 from 7-hydroxy-3,4-dihydrocarbostyril (N. Shigematsu et al. in Chem. Pharm. Bull. 1961. 970 - 975) and 4-phenylmercapto-butylbromide (bP*o.O2 : to 103°C).

M.p.! 121 - 123°C Yield: 72 % of theory.

Example 65 7-(4-Phenylsulflnyl-butoxv)-5.4-dihydrocarbostyrll Prepared analogously to Example 4 from 7-hydroxy-3,4-dihydrocarbostyril (N. Shigematsu et al. in Chem. Pharm. Bull. 1961. 970 - 975) and 4-phanylsulfinylbutylbromide.

M.p.: 134 - 136°C 15 Yield: 80 % of theory.

Example 64 7-(4-Phenylsulfonyl-butoxy)-5.4-dihydrocarbostyril Prepared analogously to Example 4 from 7-hydroxy-3,4-dihydrocarbostyril (N. Shigematsu et al. in Chem. Pharm. Bull. 1961. 970 - 975) and 4-phenylsulfonylbutylbromide.

M.p.: 178.5 - 179-5°C Yield: 74 % of theory.

Example 65 8-(4-Phenylmercaptobutoxv)-3.4-dlhydrocarbostyril Prepared analogously to Example 4 from 8-hydroxy-3.4-dihydrocarbostyril (J. D. Loudon et al. in J. Chem. Soc. 1955. 743 - 744) and 4-phenylmercapto-butylbromide (bp.Q Q2 96 - 103°C).

M.p.: 101 - 102°C Yield: 75 % of theory.

Example 66 ;3 8-(4-Phenylsulfinyl-butoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 4 from 8-hydroxy-3.4-dihydrocarbostyril (J. D. Loudon et al. in J. Chem. Soc. 1955. 743 - 744) and phenylsulfinylbutylbromide.

Colourless resin was obtained.

Yield: 60 % of theory.

Rf-value: 0.60 (thinlayer chromatogram on silica gel eluent: benzene/ethanol/conc. ammonia = 75/25/1).

Example 67 8-(4-Phenylsulfonyl-butoxy)-5.4-dihydrocarbostyril Prepared analogously to Example 3 from 8-(4-phenylmercaptobutoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 114.5 - 115°C Yield: 60 % of theory. 4817 Example* 68 6-/5-(2-Benzthlazolyl-sulfonyl)-butoxy7-3.4-dlhydrocarbostyrll Prepared analogously to Example 2 from 6-/5-(2-benzthiazolylmercapto)-butox/7-3.4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 146 - 149°C Yield: 61 % of theory.

Example 69 (2-Qulnolylmercapto)-butoxy7-3.4-dihydrocarbostyrll Prepared analogously to Example 1 from 6-(4-bromobutoxy)10 3,4-dihydrocarbOBtyril (m.p. 142 - 147°C) and 2-mercaptoquinoline.

M.p.: 115°C Yield: 64 % of theory.

Example 70 6-/5- (2-Quinazoline-4-one-yl-mercapto)-butoxj7-3,4-dihydrocarbostyrll Prepared analogously to Example 1 from 6-(4-bromobutoxy)-3,4~di hydrocarbostyril (m.p.: 142 - 147°C) and 2-mercaptoquinazoline4-one.

M.p.: 184.5 - 188°C Yield: 63 % of theory.

Example 71 6-(4-TrIphenvlmethylmercapto-butoxy)-5.4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-bromobutoxy)3s4-dihydrocarbostyril (m.p.: 142 - 147°C) and triphenylaethylmercaptane.

M.p.: 169 n 170°C Yield: 89 % of theory.

Example 72 6-/7-(2-Naphthylmercapto)-ethoxy7-5.4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-chlorobutoxy)3,4-dihydrocarbostyril (m.p.: 147 - 148°C) and 2-naphthylmercaptane.

M.p.: 147.5 - 147.8°C Yield: 77 % of theory.

Example 75 6-/7-(2-Naphthylsulfinvl)-ethoxy7-3.4-dihydrocarbO3tyrll Prepared analogously to Example 2 from 6- (2-naphthylmercapto)ethoxy7-3ι4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 186.5 - 187.5°C Yield: 88 % of theory.

Example 74 6-/2-(4-Biphenylylmercapto)-ethoxy7-3.4-dihydrocarbostyrll Prepared analogously to Example 1 from 6-(2-chloroethoxy)~ 3,4-dihydrocarbostyril (m.p.: 152.5 - 153.5°C) and 4-mer46 captobiphenyl.

M.p.: 192 - 194°C Yield: 92 % of theory.

Example 75 6-/5-(4-Blphanylyl-8ulfinvl)-ethoxy7-3.4-dlhvdrocarbostvril Prepared analogously to Example 2 from 6-/5-(4-biphenylylmercapto)-ethoxx7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 195 - 196°C Yield: 66 % of theory.

Example 76 6-/5-(2-Pyridylmercapto)-propoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 1 from 6~(3~bromopropoxy)3,4-dihydrocarbostyril and 2-mercaptopyridine.

M.p.: 108 - 108.5°C Yield: 42 % of theory.

Example 77 6-(4-Phenylsulfinyl-butoxy)-3.4-dihydrocarbostyril 1.6 g of 6-(4-phenylmercapto-butoxy)-3,4-dihydrocarbostyril were dissolved in 50 ml of methanol and 0.9 g of N-bromosuccininimide were added. After stirring for 15 hours at room temperature, the mixture was diluted with 500 ml of water (80°C) and decanted from the firstly oily residue, whereby after a while crystals were formed. After recrystallization from xylene white crystals of m.p. 144 to 145°C were obtained.

Yield: 1.2 g (66 % of theory).

Example 78 6-(4-Phenylsulfinyl-butoxy)-3.4-dihydrocarbostyrll 3.3 g of 6-(4-phenylmercapto-butoxy)-3,4-dihydrocarbostyril were dissolved in 50 ml of methylene chloride, cooled to -70°C and a solution of 1.5 g of sulfuryl chloride in 5 ml of methylene chloride was added dropwisely. After 15 hours 20 ml of 95 % ethanol were added and the mixture was heated to room temperature by removing of the cooling bath, neutralized with aqueous sodium carbonate solution, the methylene chloride phase was dried with sodium sulfate and the solvent was removed. The residue was recrystallized from toluene. M.p.: 143 - 145°C Yield: 2.8 g (81 % of theory).

Example 79 -(4-Phenylmercapto-butoxy)-3,4-dlhydrocarbostyril Prepared analogously to Example 4 from 5-hydroxy-3,4-dihydrocarbostyril and 4-phenylmercaptobutylbromide* M.p.: 155 - 157°C Yield: 64 % of theory.

Example 80 -(4-Phenylsulfinyl-butoxy)-3.4-dihydro carbostyril Prepared analogously to Example 4 from 5-hydroxy-3,4-dlhydro carbostyril and 4-phenylsulfinylbutylbromide, M.p. : 136 - 138°C Yield: 64 % of theory.

Example 81 -(4-Phenylsulfonyl-butoxy)-3,4-dihydrocarbostyrll Prepared analogously to Example 4 from 5-hydroxy-3,4-dihydrocarbostyril and 4-phenylsulfonylbutylbromide.

M.p.: 187 - 189°C Yield: 73 % of theory.

Example 82 6-/5-(2-Naphthylsulfonyl)-butoxv7-3.4-dihydrocarbo8tyrll Prepared analogously to Example 3 from 6-/5-(2-naphthylmer10 capto)-butoxy7-3»4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 173 - 175°C Yield: 95 % of theory.

Example 83 6-/5-(4-BlphenylYlsulfonyl)-butoxy7-3.4-dihydrocarbostyrll Prepared analogously to Example 3 from 6-/5-(4-biphenylylmercapto)-butoxy7-3.4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 232 - 234.5°C Yield: 83 % of theory.

Example 84 6-(4-Phenylsulfonyl-butoxy)-3.4-dlhydrocarbostyril Prepared analogously to Example 3 from 6-(4-phenylsulfinylbutoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p. : 157 - 158°C Yield: 88 % of theory.

Example 85 6-/7-(2-Pyrldylsulfonyl)-butoxv7-3.4-dihydrocarbostyril Prepared analogously to Example 3 from 6-/7-(2-pyridylsulfinyl)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide. M.p.: 123.8 - 125°C Yield: 76 % of theory.

Example 86 -(4-Phenylsulfonyl-butoxy)-carbostyril 1.87 g of 2,3-dichloro-5,6-dicyano benzoquinone were added to 1.8 g of 5-(4-phenylsulfonyl-butoxy)-3,4-dihydrocarbostyril, dissolved in 45 ml of dioxane . The solution was heated for 2.5 hours in an oil bath. The reaction mixture was hot filtered and the unsoluable residue, which was formed during the reaction, was washed out with hot dioxane. The com bined filtrates were diluted with 100 ml of chloroform and several times extracted with altogether 150 ml of 2N-sodium hydroxide. After drying the chloroform extracts with sodium sulfate and filtrating in the presence of activated charcoal the residue was evaporated and ethyl acetate was added until white crystals were precipitated.

M.p. : 182 - 183°C Yield: 850 mg (47 % of theory).

Example 87 -(4-Phenvlmercapto-butoxy)-carbostyril Prepared analogously to Example 86 from 5-(4-phenylmercaptobutoxy )-3, 4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyano5 benzoquinone.

M.p.: 185 - 187°C Yield: 40 % of theory.

Example 88 -(4-Phenylsulfinyl-butoxy)-carbostyril 0.165 ml of 30 % hydrogen peroxide, dissolved in 8 ml of glacial acetic acid, were added to 0.56 g of 5-(4-phenylmercapto-butoxy)-carbostyril . The mixture was diluted with water and extracted with chloroform twice. The chloroform extract was washed with diluted sodium carbonate solu15 tion , with water, dried over magnesium sulfate and evaporated. The residue was mixed with ethyl acetate and colourless crystals of m.p. 155 - 157°C were obtained.

Yield: 389 mg (65 % of theory).

Example 89 6-(4-Phenvlmercapto-butoxy)-carbostyril Prepared analogously to Example 86 from 6-(4-phenylmercaptobutoxy )-3, 4-dihydrocarbostyril and 2,3-dichloro-4,5-dicyanobenzoquinone.

M.p.: 162 - 164°C Yield: 35 % of theory.

Example 90 6-(4-Phenylsulflnyl-butoxy)-carbostyril Prepared analogously to Example 86 from 6-(4-phenylsulfinylbutoxy)-3,4-dlhydrocarbostyril and 2,3-dichloro-5,6-dicyano5 benzoquinone. For purification the mixture was chromatographed at a silica gel column with a mixture of benzene/ethanol/ cone, ammonia <* 75/25/3.

M.p.: 181 - 182.5°C Yield: 48 % of theory.

From the first fractions of the column chromatography 6-(4-phenylmercapto-butoxy)-carbostyril of m.p. 162 - 164°C were isolated in a yield of 15 % of theory.

Example 91 6-(4-Phenvlsulfonyl-butoxy)-carbostyril Prepared analogously to Example 86 from 6-(4-phenylsulfonylbutoxy)-3» 4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyanobenzoquinone. Purification was carried out by column chromatography on silica gel (corn size: 0.2 - 0.5 mm) with chloroform/methanol/ethyl acetate = 4/1/1.

M.p.: 212 - 213°C Yield: 54 % of theory.

Example 92 -(4-Phenylmercapto-butoxy)-carbostyril g of 4-phenylmercaptobutylbromide were added to a mixture of 32-3 g of 5-hydroxycarbostyril, 30 g of potassium carbonate and 650 ml of dimethylsulfoxide, dried over a molecular sieve. The mixture was stirred for 20 hours at 25°C, diluted with 3 1 of water and the crystallized reaction product was suction filtered.

M.p·.: 185 - 187°C (from toluene) Yield: 45.0 g (70 % of theory).

Example 95 - (4-Phenylsulfonyl-butoxv)-carbostyrll Prepared analogously to Example 88 from 5-(4-phenylmercaptobutoxy)-carbostyril and 4 moles of hydrogen peroxide at a temperature of 60°C and a reaction time of 14 hours.

M.p.: 182 - 183°C Yield: 73 % of theory.

Example 94 6- (4-Phenylmercapto-butoxy)-carbostyril Prepared analogously to Example 92 from 6-hydroxycarbostyril and 4-phenylmercaptobutylbromide.

M.p.; 161 - 163°C Yield: 78 % of theory.

Example 95 6-(4-Phenylsulfinyl-butoxy)-carbostyril Prepared analogously to Example 88 from 6~(4-phenylmercaptobutoxy)-carbostyril and hydrogen peroxide.

M.p.: 181 - 182°C Yield: 68 % of theory.

Example 96 6- (4-Phenylsulfinyl-butoxy)-carbostyril Prepared analogously to Example 92 from 6-hydroxycarboetyril and 4-phenylsulfinylbutylbromide.

M.p.: 181 - 182°C Yield: 71 % of theory.

Example 97 7- (4-Phenylsulfinyl-butoxy)-carbostyril Prepared analogously to Example 86 from 7-(4-phenylsulfinyl10 butoxy)-3,4-dihydrocarbostyril.

M.p.: 193 - 194°C Yield: 51 % of theory.

Example 98 8- (4-Phenylmercapto-butoxy)-carboBtyril Prepared analogously to Example 86 from 8-(4-phenylmercaptobutoxy)-3,4-dihydrocarbostyril and 2,3-dichloro-5»6-dicyanobenzoquinone.

M.p.: 119 - 120°C Yield: 40 % of theory.

Example 99 8-(4-Phenylsulfinyl-butoxy)-carbostyril Prepared analogously to Example 88 from 8-(4-phenyimercaptobutoxy)-carbostyril by oxidation with hydrogen peroxide. 8179 M.p.; 125-5 - 126.5°C Yield: 60 % of theory.

Example 100 -(4-Phenylgulfonyl-butoxy)-carboBtyril 100 mg of 5-(4-phenylsulfonyl-butoxy)-3,4-dihydrocarbostyril were refluxed with 30 mg of palladium/charcoal and 1 ml of mesitylene. After 3.5 hours further 30 mg of palladium/charcoal were added and the mixture was heated for further 9 hours. Subsequently the reaction mixture was hot filtered, the filtrate was evaporated and the residue was chromatographed at a silica gel column with a mixture of benzene/ethanol/conc. ammonia = 75/25/3. Besides the starting material, which did not change during the reaction, 9 mg of 5-(4-phenylsulfonylbutoxy)-carbostyril were obtained.

M.p.: 182 - 183°C Example 101 6-(4-Amlno-imlnomethylmercapto-butoxy)-3.4-dihydrocarbostyril g of 6-(4-bromobutoxy)-3,4-dihydrocarbostyril, 5 g of thiourea and 250 ml of water were heated up to boiling until a solution was obtained (approx. 4 hours). After cooling the impurities were extracted with chloroform and the residue was made alkaline by means of ammonia. The precipitated crystals were suction filtered and dried.

M.p.: 140 - 141.8°C M.p, of the hydrochloride: 208 - 211 °C Yield: 90 % of theory.

Example 102 6-(4-Phenylsulfonyl)-butoxy-3,4-dihydrocarbostyrll 107 mg of 6-(4-phenylsulfonyl)-butoxy-carbostyril were suspended in 15 ml of methanol, mixed with 40 mg of palladium/charcoal and hydrogenated at 50°C and at a hydrogen pressure of 2.5 bar for 14 hours. After filtering off the catalyst and evaporating the clear solution, the residue was obtained in colourless crystals.

M.p.: 153 - 154°C Yield: 89 mg (83 % of theory).

Example 103 6-(4-Benzylmercapto-butoxy)-3.4-dihydrocarbostyril 2.5 g of 6-(4-mercaptobutoxy)-3,4-dihydrocarbostyril, dissolved in 25 ml of dimethylsulfoxide, were mixed whilst stirring with 1.4 g of potassium carbonate and subsequently with 1.3 ml of benzylchloride. After stirring for 15 hours at room temperature the reaction mixture was diluted with 200 ml of water, the precipitated oily substance was separated and recrystallized from ethyl acetate.

M.p.: 76 - 78°C Yield: 2.8 g (82 % of theory).

Example 104 6-(5-Phenylmercaptopentoxy)-5.4-dlhytirocarbostyrll Prepared analogously to Example 1 from 6-(5-bromopentoxy)25 3,4-dihydro-carbostyril and thiophenol .

M.p.: 117 - 119°C Yield: 71 % of theory.

Example 105 6-(5-Phenylsulfinyl-pentoxy)-5.4-dlhvdrooarbostyrll Prepared analogously to Example 2 from 6-(5-phenylmercaptopentoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 104 - 109.5°C Yield: 66 % of theory.

Example 106 6-(5-Phenylsulfinyl-pentoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 3 from 6-(5-phenylmercapto10 pentoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 136.5 - 137.8°C Yield: 62 % of theory.

Example 107 6-/5-(2-Pyrldyl-mercapto)-pentoxy7-5.4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(5-bromopentoxy)3,4-dihydrocarbostyril and 2-mercaptopyridine.

M.p.: 113 - 114.8°C Yield: 76 % of theory.

Example 108 -(2-Hydroxy-5-phenylmercapto-propoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 59 from 5-(2,3-epoxy-propoxy)3,4-dihydrocarbostyril and thiophenol .

M.p.: 135 - 137°C Yield: 64 % of theory.

Example 109 -(2-HYdroxy-3-phenvlsulflnvl-propoxy)-5.4-dlhvdrocarbogtvrll Prepared analogously to Example 2 from 5-(2-hydroxy-3-phenyl~ mercapto-propoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 186 - 188°C Yield: 60 % of theory.

IO Example 110 - (2-HvdroxY-3-phepylsulfonyl-propoxy)-3.4-dihydrocarbostyril Prepared analogously to Example 3 from 5-(2-hydroxy-3-phenylmercapto-propoxy)-3,4-dihydrocarbostyril and hydrogen peroxide. M.p.: 168 - 170°C Yield: 53 % of theory.

Example 111 6- /7-(4-Hydroxyphenylmercapto)-butoxy7-3,4-dihydrocarbostyril Prepared analogously to Example 1 from 6-(4-bromobutoxy)~ 3,4-dihydrocarbostyril and 4-hydroxythiophenol.

M.p.: 191.5 - 193.0°C Yield: 83 % of theory.

Example 112 6-/5-(4-Hydroxyphenylsulflnyl)-butoxv7-3.4-dlhydrocarboBtyril Prepared analogously to Example 2 from 6-/5-(4-hydroxyphenylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen per5 oxide.

M.p.: 206 - 207.8°C Yield: 84 % oS theory.

Example 115 6-/5- (4-Hydroxyphenylsulfonyl)-butoxv7-3,4-dihydrocarbostyril Prepared analogously to Example 5 from 6-/5-(4-hydroxyphenylmercapto)-butoxy/-5,4-dihydrocarbostyril and hydrogen peroxide. M.p.: 219 - 219.5°C Yield: 78 % of theory.

Example 114 6-/5-(4-Acetamlnophenyl me rcapto)-butoxy7-3,4-dihvdrocarbostYrll Prepared analogously to Example 1 from 6-(4-bromobutoxy)-5(4-dihydrocarbostyril and 4-acetaminothiophenol.

M.p.: 162.5 - 163.0°C Yield: 65 % of theory.

Example 115 6-/5-(4-Acetaminophenylsulflnyl)-butoxY7-5.4-dihydrocarbostyril Prepared analogously to Example 2 from 6-/5-(4-acetaminophenylmercapto)-butox£7-3(4-dihydrocarbostyril and hydrogen peroxide. 817 9 M.p.: 202.0 - 203.8°C Yields 55 % of theory.

Example 116 6-/5- (4-Acetamlnophenylsulfonyl)-butoxy?-3.4-dihydrocarbostyrll Prepared analogously to Example 3 from 6-/5-(4-acetaminophenylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide, M.p.: 143.5 - 147.O°C Yield: 88 % of theory.

Example 117 6-/5-(4,5-Di-p-chlorophenyl-oxazole-2-yl-mercapto)-butoxy?3.4-dlhydro carbostyril Prepared analogously to Example 1 from 6-(4-bromobutoxy)-3j4-dihydrocarbostyril and 2-mercapto-4,5-di-p-chlorophenyl-oxazole. M.p. : 110 - 115°C Yield: 70 % of theory.

Example 118 6-/5- (2-Pyridylsulflnyl)-butoxy7-carbostyril Prepared analogously to Example 86 from 6-/5-(2-pyridylsulfinyl) butoxy7-3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyano2θ benzoquinone.

M.p.: 152 - 154°C Yield: 48 % of theory.

Example 119 6-(4-Phenylmercapto-butoxy)-3.4-dlhydrocarbostyrll Prepared analogoualy to Example 102 from 6-(4-phenylmercapto-butoxy)-carbostyril by catalytic hydrogenation with rhenium-VII-sulfide as catalyst.

M.p.: 121 - 122°C Yield: 67 % of theory.

Example 120 8-(4-Phenylsulfonyl-butoxy)-carboBtvril Prepared analogously to Example 86 from 8-(4-phenylsulfonylbutoxy)^, 4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyanobenzoquinone.

M.p.: 146 - 147°C Yield: 41 % of theory.

Example 121 7-(4-Phenylmercapto-butoxy)-carbostyril Prepared analogously to Example 86 from 7-(4-phenylmercaptobutoxy)-3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyanobenzoquinone.

M.p.: 157.5 - 158.5°C Yield: 54 % of theory.

Example 122 6-/5-(2,5-Dlchlorophenylmercapto)-butoxv7-3,4-dihydrocarbostyril 8.94 g (0.03 mol) of 6-(bromobutoxy)-3,4-dihydrocarbostyril (m.p.: 142 - 147°C) were added to a mixture of 2.21 g (0.0315 mol) of potassium methoxide, 5.76 g (0.0315 mol) of 98 % 2,5-dichlorothiophenol and of 54 ml of methanol.

The reaction mixture was refluxed whereby at first a clear solution was obtained. After 5 minutes so much crystalli ne reaction product was precipitated, so that the reaction mix10 ture was hardly stirrable. After one hour the mixture was cooled to room temperature, suction filtered and recrystallized from ethanol. Colourless crystals of m.p. 133 - 134°C were obtained. Yield: 10.60 g (89.1 % of theory).

Example 123 6-/5-(2,5-Dlchlorophenylsulfinvl)-butoxy7-3.4-dihydrocarbostyril .55 g (0.014 mol) of 6-/5-(2,5-dichlorophenylmercapto)-butoxy73,4-dihydrocarbostyril, suspended in 40 ml of glacial acetic acid, were mixed with 1.19 ml of a 40.06 % aqueous solution of hydrogen peroxide (0.014 mol), dissolved in 1.5 ml of glacial acetic acid, and stirred at room temperature. The suspension was being cleared and an almost clear solution was obtained. After 70 hours white crystals were precipitated which were suction filtered and recrystallized from ethanol.

M.p.: 185 - 186°C Yield: 5.43 g (94.1 % of theory).

Example 124 6-/5-(2,5-Dichlorophenylsulfonyl)-butoxy7-3.4-dihydrocarbo styril 2.97 g (0.0075 mol) of 6-/5-(2,5-dichlorophenylmercapto)-butoxy7· 3,4-dlhydrocarbostyril were added to 15 ml of ice-cooled formic acid and mixed with 1.49 ml of 40.08 % hydrogen peroxide (0.0175 mol). After stirring for 2.5 hours the mixture was diluted with three times the amount of water. The precipitated crystals were recrystallized from ethanol.

M.p.: 174.5 - 175.5°C Yield: 1.99 g (61.9 % of theory).

Example 125 6-/5-(3.4-Dichlorophenylsulfonyl)-butoxy7-3,4-dihydrocarbostyrll Prepared analogously to Example 124 from 6-/5-(3,4-dichlorophenyl mercapto)-butox/7-3,4-dihydrocarbostyril (m.p.: 116.5 - 118°C) and hydrogen peroxide.

M.p.: 172 - 173°C Yield: 96 % of theory.

Example 126 6-/5-(4-Hydroxy-3,5-di-tert.-butyl-phenylmercapto)-butoxy720 3.4-dihydrocarbostyril_ Prepared analogously to Example 122 from 6-(4-bromobutoxy)3.4- dihydrocarbostyril (m.p.: 142 - 147°C) and 4-hydroxy3.5- di-tert.-butyl thiophenol.

M.p.: 146 - 147°C Yield: 68.8 % of theory.

Example 127 6-/7-(4-Hydroxy-3,5-di-tert.-butyl-phenylsulfinyl)-butoxy73.4- dlhydrocarbostyrll Prepared analogously to Example 123 from 6-/7-(4-hydroxy5 3,5-di-tert.-butyl-phenylmercapto)-butox/7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 170 - 171°C Yield: 80.7 % of theory.

Example 128 o 6-/7-(4-Hydroxy-3,5-di-tert.-butyl-phenylsulfonyl)-butox/73.4- dlhydrocarbostyril Prepared analogously to Example 124 from 6-/7-(4-hydroxy-3.5-di tert.-butyl-phenylmercapto)-butox/7”3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 165 - 167°C Yield: 97.6 % of theory.

Example 129 6-/7- (2-Carboxyphenylmercapto)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)20 3,4-dihydrocarbostyril and 2-thiobenzoic acid.

M.p.: 176 - 179°C Yield: 57.5 % of theory. 4817 Example 130 6-/7-(2-Carboxy-phenylsulflnvl)-butoxy7-3.4-dlhydrocarbostyrll Prepared analogously to Example 123 from 6-/7-(2-carboxy-phenyl mercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 194 - 196°C Yield: 77.2 % oi theory.

Example 131 6-/7-(4-Pyrldylsulfinyl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)10 3,4-dihydrocarbostyril and 4-mercaptopyridine and subsequent oxidation of the obtained 6-/7-(4-pyridylmercapto)-butoxy73,4-dihydrocarbostyril (m.p.: 128 - 133°C) with hydrogen peroxide analogously to Example 123.

M.p.: 154°C Yield: 57 % of theory.

Example 132 6-/7-(4~Pvrldvlsulfonyl)-butoxy7-3.4-dlhydrocarbostyril Prepared analogously to Example 124 from 6-/7-(4-pyridylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.; 179 - 183°C Yield: 35-9 % of theory.

Example 133 6-/3-(3,4-Dichlorophenylsulfinyl)-2-hydroxy-propoxy7-3» 4-dihydrocarhostyril 3.51 g (0.016 mol) of 6-(2,3-epoxy-propoxy)-3,4-dihydrocarbo5 styril (m.p.: 125 - 128°C), dissolved in 35 ml of methanol, were mixed with 4.29 g of 3,4-dichlorothiophenol . The mixture was heated to boiling for 5 hours. After cooling, crystals were obtained, which were suction filtered and recrystallized from ethanol.

M.p.: 175 - 176°C Yield: 2.48 g (38.9 % of theory).

The 6-/5-(3,4-dichlorophenylmercapto)-2-hydroxy-propoxy73,4-dihydrocarbostyril thus obtained, was oxidized analogously to Example 123 with hydrogen peroxide.

M.p.: 108 - 110°C Yield: 75 % of theory.

Example 134 6-(3-Benzylmercapto-propoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(3-bromopropoxy)~ 3,4-dihydrocarbostyril (m.p.: 142 - 147DC) and benzylmercaptane.

M.p. : 97.5 - 99.0°C Yield: 58 % of theory.

Example 135 6-(3-Benzylsulflnyl-propoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 123 from 6-(3-benzylmercapto)3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 144.5 - 147.0°C Yield: 51 % of theory.

Example 136 -(3-tert.-Butylmercapto-2-hydroxy-propoxy)-3,4-dihydrocarbostyrll Prepared analogously to Example 133 from 5-(2,3-epoxy-propoxyJ5 3,4-dihydrocarbostyril (m.p.: 171 - 173°C) and tert.-butylmercaptane.

M.p.: 105 - 109°C Yield: 77.1 % of theory.

Example 137 -(3-tert.-Butylsulfinyl-2-hydroxy-propoxy)-3,4-dihydrocarbostyrll Prepared analogously to Example 123 from 6-(3-tert.-butylmercapto-2-hydroxy-propoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 175 - 177°C Yield: 52.1 % of theory.

Example 138 -(3-tert.-Butylsulfonyl-2-hydroxy-propoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 124 from 6-(3-tert.-butylmer20 capto-2-hydroxypropoxy)-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 210 - 212°C Yield: 37.1 % of theory.

Example 139 6-/5-fe-Pyrldvl-sulfonyl)-butoxv7-carbostyrll Prepared analogously to Example 124 from 6-/5-(2-pyridylsulfinyl)-butox/7-carbostyril and hydrogen peroxide.

M.p.: 179 - 180°C Yield: 65.8 % of theory.

Example 140 4-Methyl-6-(4-phenvlmercapto-butoxv)-carbostvril .25 g (0.03 mol) of 4-methyl-6-hydrocarbostyril (m.p.: 326 10 33O°C, see R. R. Holmes et al. in J. Amer. Chem. Soc. 76. 2404 (1954)), 8.09 g (0,033 mol) of 4-phenylmercaptobutylbromide and 6.22 g (0.045 mol) of potassium carbonate were stirred at room temperature for 16 hours in 70 ml dimethylsul foxide. Subsequently the mixture was diluted with water and the precipitated crystals were recrystallized from toluene after drying.

M.p.: 148 - 150°C Yield: 6.2 g (61.2 % of theory).

Example 141 4-Methyl-6-(4-phenylsulfinyl-butoxy)~carbostyril Prepared analogously to Example 140 from 4-methyl-6-hydroxycarbostyril (m.p.: 326 - 330°C) and 4-phenylsulfinylbutylbromide.

M.p. : 167 - 168°C Yield: 47.3 % of theory. 4817 Example 142 4-MethyI-6-(4-phenylsulfonyl-butoxy)-carbostyril Prepared analogously to Example 140 from 4-methyl-6-hydroxycarbostyril (m.p.: 326 - 330°C) and 4-phenylsulfonylbutyl5 bromide.

M.p.: 217 - 219°C Yield: 66.6 % of theory.

Example 143 4-Methyl-6-/5-(2-pyridylmercapto)-butoxy7-carbostyril Prepared analogously to Example 122 from 4-methyl-6-(4-bromobutoxy)-carbostyril (m.p.: 217 - 219°C) and 2-mercaptopyridine M.p.: 149 - 151°C Yield: 85.7 % of theory.

Example 144 4-Methyl-6-/5-(2-pyridylsulfinyl)-butoxv7-carbostyril Prepared analogously to Example 123 from 4-methyl-6-/5-(2-pyridylmercapto)-butorx7carbostyril and hydrogen peroxide.

M.p.: 167 - 169°C Yield: 61.8 % of theory.

Example 145 4-Methyl-6-/5-(2-pyridylsulfonyl)-butoxy7-carbostyril Prepared analogously to Example 124 from 4-methyl-6-/5-(2-pyridylmercapto)-butox^7carbostyril and hydrogen peroxide. ... 4 8 17 9 M.p.: 195 - 197°C Yield: 29.5 % of theory.

Example 146 4-Methyl-6-/7-(2-qulnolylmercapto)-butoxv7-carbostyril Prepared analogously to Example 122 from 4-methyl-6-(4-bromobutoxy)-carbostyril and 2-mercaptoquinoline.

M.p.: 162 - 163°C Yield: 81.9 % of theory.

Example 147 4-Methyl-6-/7-(2-qulnolylsulfinyl)-butoxy7-carbostyril Prepared analogously to Example 123 from 4-methyl-6-/7-(2-quinolylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 189 - 19O°C Yield: 47.5 % of theory.

Example 148 4-Methyl-6-/7-(2-qulnolylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 4-methyl-6-/7(2-quinolylmercapto)-butoxy7carbostyril and hydrogen peroxide. M.p.: 199 - 203°C Yield: 31.5 % of theory.

Example 149 4-Methyl-6-/7-(4-biphenYlylsulflnyl)-butoxy7carbostyrll Prepared analogously to Example 123 from 4-methyl-6-/7(4-biphenylylmercapto)-butoxjr7carbostyril (m.p.: 174 - 176° C) and hydrogen peroxide.

M.p.: 161 - 162°C Yield: 59 % of theory.

Example 150 6-/7- (4-Chlorophenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-chlorobutoxy) carbostyril (m.p.: 206 - 208°C) and 4-chlorothiophenol » M.p.: 168 - 170°C Yield: 85 % of theory.

Example 151 6-/7-(4-Chlorophenylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/7-(4-chlorophenylmercapto)-butoxy7carbostyril and hydrogen peroxide. M.p.: 157 - 158°C Yield: 81 % of theory.

Example 152 6-/7-(4-Chlorophenylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 6-/7-(4-chlorophenylmercaptol-butoxy/carbostyril and hydrogen peroxide.

M.p.: 197 - 199°C Yield: 99 % of theory.

Example 155 6-/5-(5,4-Dlchlorophenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)· carbostyril (m.p.: 198 - 199°C) and 3»4-dichlorothiophenol M.p.: 149 - 152°C Yield: 60 % of theory.

Example 154 6-/5-(3,4-Dichlorophenylsulfinyl)-butoxv7carbostyril Prepared analogously to Example 123 from 6-/5-(3>4-dichloro phenylmercapto)-butox^7carbostyril and hydrogen peroxide. M.p.: 191 - 196°C Yield: 87 % of theory.

Example 155 6-/5-(3,4-Dichlorophenylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 6-/5-(3,4-dichloro phenylmercapto)-butoxy7carhostyril and hydrogen peroxide. M.p.: 188 - 190°C Yield: 83 % of theory. 8179 Example 156 6-/5-(2,5-Dlchlorophenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril and 2,5-dichlorothiophenol .

M.p.: 175 - 176°C Yield: 85 % of theory.

Example 157 6-/5-(2,5-Dlchlorophenylsulfinyl)-butoxv7carbostyrll Prepared analogously to Example 123 from 6-/5-(2,5-dichloro10 phenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 200 - 202°C Yield: 75 % of theory.

Example 158 6-/5-(2.5-Dichlorophenvlsulfonvl)-butoxy7carbostvril Prepared analogously to Example 124 from 6-/5-(2,5-dichlorophenylmercapto)-butoxy7carbostyril and hydrogen peroxide in formic acid.

M.p.: 203 - 205°C Yield: 79 % of theory.

Example 159 6-/5-(4-Fluorophenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril and 4-fluorothiophenol , M.p.: 149 - 150°C Yield: 85 % of theory.

Example 160 6-/5-(4-Fluorophenylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/5-(4-fluorophenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 164 - 165°C Yield: 50 % of theory.

Example 161 6-/5-(4-Fluorophenylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 6-/5-(4-fluoro10 phenylmercapto)-butoxy/carbostyril and hydrogen peroxide in formic acid.

M.p.: 209 - 211°C Yield: 59 % of theory.

Example 162 6-/5-(4-Hydroxy-3,5-di-tert.-butyl-phenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril (m.p.: 198 - 199°C) and 4-hydroxy-3,5-di-tert. butyl-thiophenol (m.p.: 84.5 - 86.0°C).

M.p.: 172 - 173°C Yield: 77 % of theory.

Example 165 6-/7-(4-Hydroxy-3,5-di-tert.-butylphenylsulfinyl)-butoxy/carbostyril Prepared analogously to Example 123 from 6-/7-(4-hydroxy3,5-di-tert.-butylphenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 192 - 194°C Yield: 83 % of theory.

Example 164 6-/7-(4-Hydroxy-3,5-di-tert.-butylphenylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 6-/7-(4-hydroxy3,5-di-tert.-butylphenylmercapto)-butoxy/carbostyril and hydrogen peroxide in formic acid.

M.p.: 242 - 244°C Yield: 92 % of theory.

Example 165 6-/7-(4-Blphenylylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)20 carbostyril (m.p.: 198 - 199°C) and 4-biphenylmercaptane.

M.p.: 191 - 192°C Yield: 82 % of theory.

Example 166 6-/5-(4-Biphenylylsulfinyl)-butoxv7carbostyril Prepared analogously to Example 123 from 6-/5-(4-biphenylyl mercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 196 - 197°C Yield: 80 % of theory.

Example 167 6-/5-(4-Biphenylylsulfonyl)-butoxy7carbostyrll Prepared analogously to Example 124 from 6-/5-(4-biphenylyl 10 mercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 213 - 215°C Yield: 73 % of theory.

Example 168 6-/5-(4-Nitro-phenylmercapto)-butoxy7carbostvril Prepared analogously to Example 122 from 6-(4-bromobutoxy)~ carbostyril (m.p.: 198 - 199°C) and 4-nitrothiophenol .

M.p. : 184 - 185°C Yield: 96 % of theory.

Example 169 6-/5-(4-Nitro-phenylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/5-(4-nitrophenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 183 - 184°C Yield: 77 % of theory.

Example 170 6-/5-(4-Nitro-phenylaulfonyl)-butoxv7carbostyril Prepared analogously to Example 124 from 6-/5-(4-nitrophenylsulfinylj-butoxy/carbostyril and hydrogen peroxide in formic acid.

M.p.: 230 - 232°C Yield: 70 % of theory.

Example 171 6-/5-(2-Qulnolylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril (m.p.: 132°C) and 2-mercaptoquinoline.

M.p.: 132°C Yield: 99 % of theory.

Example 172 6-/5-(2-Quinolylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/5-(2-quinolylmercapto)-butox27carbostyril and hydrogen peroxide.

M.p.: 161 - 162°C Yield: 66 % of theory.

Example 173 6-/5-(2-Qulnolylsulfonyl)-butoxv7carbostyrll Prepared analogously to Example 124 from 6-/5-(2-quinolylsulfinyl)-butoxx7carbostyril and hydrogen peroxide in formic acid.

M.p.: 197 - 198°C Yield: 58 % of theory.

Example 174 -(4-Phenylmercaptp-butoxy)-axindole Prepared analogously to Example 140 from 5-hydroxyoxindole (J. Chem. Soc. 1961. 2723) and 4-phenylmercaptobutylbromide. M.p.: 131 - 132°C Yield: 13 % of theory.

Example 175 -(4-Phenylsulfinyl-butoxy)-oxindole Prepared analogously to Example 123 from 5-(4-phenylmercaptobutoxy)-oxindole and hydrogen peroxide.

M.p.: 114 - 116°C Yield: 61 % of theory.

Example 176 6-/7-(Phenvlsulfinylmethyl)-benzyloxy7-3.4-dihydro-carbostyril A mixture of 67.1 g of phthalide, 51.3 ml of thiophenol , .1 g of potassium methoxide and 250 ml of methanol was refluxed. Subsequently the obtained 2-phenylmercaptomethylbenzoic acid (yield: 78 % of theory, m.p.: 108 - 110°C) was esterified with methanol/thionylchloride whilst standing at -40°C. After standing over night at room temperature methyl.2-phenylmercaptomethyl-benzoate (yield: 89 % of theory, b.p.Q θ?: 145°C) was obtained, which was conver5 ted to the 2-phenyImercaptomethyl-phenylcarbinole (yield: % of theory, m.p.: 64 - 65°C) by means of reduction with lithiumaluminium hydride in diethyl ether.

This compound was reacted to 2-phenylmercaptomethyl-phenylmethyl-p-toluenesulfonate by addition of p-toluenesulfo10 nyl chloride. (Thin-layer chromatogram: silica gel; eluent: chloroform/ethyl acetate = 1 : 1; R^-value =0.9.

Yield: 55 % of theory). This ester was reacted to 6-/2-(phenylmercaptomethyl)-benzyloxy7-3,4-dihydrocarbostyril analogously to Example 140 with 6-hydroxy-3,4-di15 hydrocarbostyril (thin-layer chromatogram: silica gel; eluent: chloroform/ethyl acetate = 1 : 1; -value = 0.35; Yield: 64 % of theory).

This substance was analogously to Example 123 oxidized to 6-/?-i)henylsulfinyImethyl)-benzyloxy7-3,4~dihydrocarbo20 styril by means of hydrogen peroxide.

M.p.: *133 - 135°C Yield: 64 % of theory.

Example 177 6-/-4- (Phenylmercaptomethyl)-benzyloxv7-3.4-dlhydrocarbostyril p-Xylylenedichloride was reacted with thiophenol in the mol ration 1:1 in the presence of excess potassium carbonate in dimethylsulfoxide. The obtained 4-phenylmercaptomethyl-benzylchloride (control: thin-layer chromatogram) was further reacted with 6-hydroxy-3,4-dihydrocarbostyril analogously to Example 140 without isolation, M.p.: 139 - 141°C Yield: 52 % of theory. 48ί7θ Example 178 ό-/-4- (PhenylsuIflnyl)-benzyloxy7-3.4-dihydrocarbostyril Prepared analogously to Example 123 from 6-/”4-( phenylmercaptomethyl)-benzyloxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 179 - 181°C Yield: 61 % of theory.

Example 179 6-(4-Cyclohexylmercapto-butoxy)-carbostyril 10 Prepared analogously to Example 122 from 6-(4-bromobutoxy) carbostyril (m.p.: 198 - 199°C) and cyclohexylmercaptane. M.p.: 153 - 159°C Yield:- 89 % of theory.

Example 180 6-(4-Cyclohexylsulfinyl-butoxy)-carbostyril Prepared analogously to Example 123 from 6-(4-cyclohexylmercapto-butoxy)-carbostyril and hydrogen peroxide.

M.p.: 169 - 170°C Yield: 57 % of theory.

Example 151 6-/7-(4-Bromophenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy) carbostyril (m.p.: 198 - 199°C) and 4-bromothiophenol .

M.p.: 156 - 158°C Yield: 53 % of theory.

Example 182 6-/5- (4-Bromophenvlsulflnyl)-butoxv7carbostyril Prepared analogously to Example 123 from 6-/5-(4-bromophenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 168 - 170°C Yield: 65 % of theory.

Example 183 6-/5-(3-Methyl-4-bromo-phenvlmercapto)-butoxy7oarbostyrlI Prepared analogously to Example 122 from 6-(4-bromobutoxy)~ carbostyril (m.p.: 189 - 199°C) and 3-methyl-4-bromo-thiophenol .

M.p.: 167 - 169°C 15 Yields 76 % of theory.

Example 184 6-/5- (3-Methyl-4-bromo-phenvl sulfinyl)-butoxy7-carbostyril Prepared analogously to Example 123 from 6-/5-(3-methyl4-bromo-phenylmercapto)-butoxy7oarbostyril and hydrogen peroxide.

M.p.: 169 - 172°C Yield: 79 % of theory.

Example 185 6-/5-(3-Methyl-4-bromo-phenylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 6-/5-(3-methyl4-bromo-phenylmercapto)-butox27carbostyril and hydrogen peroxide.

M.p.: 163 - 167°C Yield: 57 % of theory.

Example 186 6-/5-(1,2.4-Trlazole-5-yl-mercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carhostyril and 3-mercapto-1,2,4-triazole.

M.p. : 203 - 20^0 Yield: 82 % of theory.

Example 187 6-/5- (2,4,5-Trichlorophenylmercapto)-butoxv7carbostyril Prepared analogously to Example 122 from 6-(4-broraobutoxy)~ carhostyril (m.p.: 198 - 199°C) and 2,4,5-trichlorothiophenol M.p.: 177 - 178°C Yield: 83 % of theory.

Example 188 6-/5-(2,4,3-Trichlorophenylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/5-(2,4-5-trichlorophenylmercapto)-butoxy/carbostyril and hydrogen peroxide.

M.p.: 206 - 20S°C Yield: 98 % of theory.

Example 189 6-/5- (3,5-Dibromo-4-amino-phenylmercapto)-butox/7-3,4-dihydro5 carbostyrll Prepared analogously to Example 122 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 3,5-dibromo4-amino-thiophenol.

M.p.: 90 - 92°C 10 Yield: 89 % of theory.

Example 190 6-/5-(j,5-Dibromo-4-amino-phenyl-sulfinyl)-butoxy7-3,4-dihydrocarbostyrll Prepared analogously to Example 123 from 6-/5-(3,5-dibromo15 4-amino-phenylmercapto)-butox£7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 144 - 146°C Yield: 76 % of theory.

Example 191 6-/5-(3,5-Dibromo-4-amino-phenylsulfonyl)-butoxy/-?,4-dihydrocarbostyril Prepared analogously to Example 124 from 6-/5-(3«5-dibromo4-aminophenylsulfinyl)-butoxy7-3«4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 157 - 159°C Yield: 87 % of theory. ,. 48179 Example 192 6-/5-(3.5-Dlbromo-4-amino-phenylmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril (m.p.: 198 - 199°C) and 3,5-dibromo-4-amino5 thiophenol.

M.p.: 153 - 155°C Yield: 86 % of theory.

Example 193 6-/5-(3.5-Dlbromo-4-amlno-phenylsulf inyl)-butoxv7carbostyril Prepared analogously to Example 123 from 6-/5-(3,5-dibromo4-amino-phenylmercapto)-butox/7carbostyril and hydrogen peroxide.

M.p.: 205 - 207°C Yield: 79 % of theory.

I5 Example 194 6-/5-(3,5-Dlbromo-4-amino-phenylsulfonyl)-butoxy7carbostyrll Prepared analogously to Example 124 from 6-/5-(3,5-dibromo4-amino-phenylmercapto)-butoxy7carbostyril and hydrogen peroxide in formic acid.

M.p.: 238 - 241°C Yield: 87 % of theory. 4817 Example 195 6-/5-(4-Bromo-3-methyl-phenylmercapto)-butoxjr7-3,4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)5 3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 4-bromo3-methyl-thiophenol.

M.p.: 104 - 109°C Yield: 81 % of theory.

Example 196 6-/5- (4-Bromo-3-methyl-phenylsulfinyl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 123 from 6-/5-(4-bromo-3-me•thyl-phenylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 129 - 130°C Yield: 75 % of theory.

Example 197 6-/5-(2,5-Dlbromo-phenylmercapto)-butoxv7-3.4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)20 3.4-dihydrocarbostyril (m.p.: 142 - 147°C) and 2,5-dibromothiophenol.

M.p.: 127 - 129°C Yield: 75 % of theory.

Example 198 6-/7-(2,5-1llbromo-phenylsulf Inyl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 123 from 6-/7-(2,5-dibromophenylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 182 - 184°C Yield: 84 % of theory.

Example 199 6-/7-(2,5-Dlbromo-phenylmercapto)-butoxv7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril (m.p.: 198 - 199°C) and 2,5-dibromo-thiophenol. M.p.: 178 - 185°C Yield: 67 % of theory.

Example 200 6-/7-(2,5-Dlbromo-phenylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/7-(2,5-dibromophenylmercapto)-butoxy7carbostyril and hydrogen peroxide. M.p : 187 - 189°C Yield:, 45 % of theory.

Example 201 6- /5-(3.4-Dlchloro-phenylmercapto)-propoxv7-3.4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(3-bromopropoxy)3,4-dihydrocarbostyril (m.p.: 111 - 118°C) and 3,4-dichlorothiophenol.

M.p.: 106 - 107°C Yield: 76 % of theory.

Example 202 6-/5-(3.4-Dichloro-phenylsulfinyl)-propoxv7-3.4-dlhydrocarbostyril Prepared analogously to Example 123 from 6-/5-(3,4-dichlorophenylmercapto)-propoxx7-3»4-dihydrocarboatyril and hydrogen peroxide.

M.p.: 170 - 172°C Yield: 84 % of theory.

Example 203 6-/7-(4-Cyclohexyl-phenvlmercapto)-butoxy7-3.4-dlhydrocarbostyrll Prepared analogously to Example 122 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 4-cyclohexylthiophenol.

M.p.: 118 - 120°C Yield; 68 % of theory.

Example 204 6-/7-(4-Cyclohexyl-phenylsulfinyl)-butoxy7-3,4-dlhydrocarbostyril Prepared analogously to Example 123 from 6-/7-(4-cyclohexyl20 phenylmercapto)-butox/7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 155 - 157°C Yield: 65 % of theory. . 48179 Example 205 6_/5-(4-Cyclohexyl-phenylsulfonyl)-butoxy7-3.4-dlhydrocarbostyr11 Prepared analogously to Example 124 from 6-/5-(4-cyclohexylphenylmercapto)-butox/7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 172 - 174°C Yield: 52 % of theory.

Example 206 6-/5-(4-Cyclohexyl-phenvlmercapto)-butoxy7carbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril (m.p.: 188 - 189°C) and 4-cyclohexylthiophenol. M.p.: 165 - 167°C Yield: 64 % of theory.

Example 207 6-/5-(4-Cyclohexyl-phenylsulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/5-(4-cyclohexylphenylmercapto)-butoxy7carbostyril and hydrogen peroxide. M.p.: 188 - 190°C Yield: 64 % of theory.

Example 208 6-/5-(4-Cyclohexyl-phenylsulfonyl)-butoxy7carbostyril Prepared analogously to Example 124 from 6-/5-(4-cyclohexylphenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 185 - 186°C Yield: 87 % of theory.

Example 209 6-/5-(A-tert.-Butyl-phenylmercapto)-butoxv7-5.4-dihydrocarbostyrll Prepared analogously to Example 122 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 4-tert.-butylthiophenol, M.p.: 126 - 127°C Yield: 86 % of theory.

Example 210 6-/5-(4-tert.-Butyl-phenylsulfinyl)-butoxy7-3.4-dihydrocarbostyrll Prepared analogously to Example 123 from 6-/5-(4-tert.-butylphenylrnercapto)-butoxy7-3.4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 121 - 123°C Yield: 67 % of theory.

Example 211 6-/5-(4-tert,-Butyl-phenylsulfonyl)-butoxy7-3.4-dlhydrocarbostyril Prepared analogously to Example 124 from 6-/5-(4-tert.-butyl20 phenylmercapto)-butoxy7-3>A-dihydrocarbostyril and hydrogen peroxide.

M.p.: 198 - 200°C Yield: 83 % of theory.

Example 212 6-/5-(4-tert.-Butyl-phenylmercapto)-butoxy7carbo3tyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)carbostyril (m.p.: 198 - 199 °C) and 4-tert.-butylthiophenol.

M.p.:' 156 - 158°C Yield: 63 % of theory.

Example 213 6-/5-(4-tert.- Batvl-phenylsulfinyl)-butoxv7carbostvril Prepared analogously to Example 123 from 6-/5-(4-tert.-butyl10 phenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 164 - 166°C Yield: 74 % of theory.

Example 214 6-/5-(4-tert.-Butyl-phenylsulfonyl)-butoxv7carbostyril Prepared analogously to Example 124 from 6-/5-(4-tert.-butylphenylmercapto)-butoxy7carbostyril and hydrogen peroxide.

M.p.: 203 - 205°C Yield: 56 % of theory.

Example 215 2q 6-/5-(2-Qulnolylsulfinyl)-butoxy7-5,4-dlhydrocarbostyril Prepared analogously to Example 123 from 6-/5-(2-quinolylymercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide. 481 79 M.p.: 154 - 157°C Yield: 79 % of theory.

Example 216 6-/5- (2-Qulnolylsulfonyl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 124 from 6-/5-(2-quinolylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

Rj-value: 0.50 (silica gel fluorescent plate,· eluent: benzene/ethanol/conc. ammonia = 75/25/2).

Yield: 72 % of theory.

Example 217 6-/5-(N-Methyl-N-cyclohexyl-carbamidomethylmercapto)-ethoxy73.4- dihydrocarbostyril Prepared analogously to Example 122 from 6-(2-chloroethoxy)15 3,4-dihydrocarbostyril (m.p.: 152.5 - 153.5°C) and N-methylN-cyclohexyl-thioglycolio acid amide.

Rf-value: 0.46 (silica gel fluorescent plate; eluent: ethylenechloride/methanol = 95/5).

Yield: 63 % of theory. !0 Example 215 6-/5-(N-Methyl-N-cyclohexyl-carbamidomethylsulfinyl)-ethox£73.4- dlhydrocarbostyril Prepared analogously to Example 123 from 6-/5-(N-methyl-Ncyclohexylcarbamidomethylmercapto)-ethoxy/-3,4-dihydrocarbostyril and hydrogen peroxide.

Rf-value: 0.34 (silica gel fluorescent plate; eluent: ethylene chloride/methanol = 95/5).

M.p.: 143 - 146°C Yield: 48 % of theory.

Example 219 6-/7-(N-Methyl-N-cyclohexyl-carbamidomethylsulfonyl)-ethoxy73,4-dlhydrocarbostyrll Prepared analogously to Example 124 from 6-/7-(N-methylN-cyclohexylcarbamidomethylmercapto)-ethox/7-3,4-dihydro10 carbostyrll and hydrogen peroxide in formic acid.

Revalue: 0.48 (silica gel fluorescent plate; eluent: ethylene chloride/methanol = 95/5) M.p.: 110 - 111°C Yield: 45 % of theory.

Example 220 6-/7-(N-Methyl-N-cyclohexyl-carbamidomethylmercapto)-ethoxy7carbostyrll Prepared analogously to Example 122 from 6-(2-chloroethoxy)carbostyril /Rf-value: 0.30 (silica gel fluorescent plate; eluent: ethylene chloride/methanol = 95/5/7 and N-methylN-cyclohexyl-thioglykolic acid amide.

Rf-value: 0.41 (silica gel fluorescent plate; eluent: ethylene chloride/methanol = 95/5).

Yield: 62 % of theory.

Example 221 6-/2-(N-Methyl-N-cyclohexyl-carbamldomethylsulfinyl)ethoxy7-carbostyrll Prepared analogously to Example 123 from 6-/2-(N-methyl5 N-cyclohexyl-carbamidomercapto)-ethoxy7carbostyril and hydrogen peroxide.

Rf-value: 0.027 (silica gel fluorescent plate; eluent: ethylene chloride/methanol = 95/5).

M.p.: 128 - 130°C Yield: 65 % of theory.

Example 222 6-/2- (N-Methyl-N-cyclohexyl-earbamidomethylsulfonyl)-ethoxy7carbostyrll Prepared analogously to Example 124 from 6-/2-(N-methyl-N15 cyclohexyl-carbamidomercapto)-ethoxy7carbostyril and hydrogen peroxide.

Rf-value: 0.39 (silica gel fluorescent plate; eluent: ethylene chloride/methanol = 95/5).

Yield: 67 % of theory.

Example 223 6-/3-(3,4-Dichlorophenylsulfonyl)-propox27“3,4-dihydrocarbostyril Prepared analogously to Example 124 from 6-/5-(3,4-dichlorophenylmercapto)-propoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 187 - 188°C Yield: 87 % of theory.

Example 224 6-/5-(3,4-Dichlorophenylmercapto)-pentoxy7-3,4-dihydrocarbostyrll Prepared analogously to Example 122 from 6-(5-bromopentoxy)5 3,4-dlhydrocarbostyril (m.p.: 97 - 98°C) and 3,4-dichlorothiophenol.

M.p.: 101 - 104°C Yield: 69 % of theory.

Example 225 6-/5-(3,4-Dichlorophenylsulfinyl)-pentoxy7-3,4-dihydrocarbostyril Prepared analogously to Example 123 from 6-/5-(3,4-dichlorophenylmercapto)-pentoxy7-3.4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 165 - 166°C Yield: 74 % of theory.

Example 226 6-/5-(3.4-Dlchlorophenvlsulfonyl)-pentoxy7-5.4-dihydrocarbostyril Prepared analogously to Example 124 from 6-/5-(3,4-dichloro20 phenylmercapto)-pentoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

M.p.: 176 - 178°C Yield: 65 % of theory.

Example 227 6-/5-(2-Methyl-4-tert.-buty1-phenylmercaptoJ-butoxj/5,4-dlhydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)5 3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 2-methyl4-tert.-butylthiophenol.

M.p.: 81 - 85°C Yield: 91 % of theory.

Example 228 6-/5-(2-Methyl-4-tert.-butyl-phenylsulfinyl)-butoxy7-3,4dihydrocarbostyrll Prepared analogously to Example 123 from 6-/5-(2-methyl-4tert.-butyl-phenylmercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide. Resinous substance.

R^-value: 0.54 (silica gel fluorescent plate; eluent: ethylene chloride/methanol 95/5).

Example 229 6-/5-(3,5-Dichloro-4-hydroxy-phenylmercapto)-butoxy7-3,4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 3,4-dichloro4-hydroxy-thiophenol under nitrogen as protective gas.

M.p.: 110 - 114°C Yield: 94 % of theory.

Example 230 -Bromo-6-(4-phenyImercaptobutoxy)-carbostyril Prepared analogously to Example 122 from 5-bromo-6-(4-bromobutoxy)-carbostyril (prepared by bromination of 6-(4-bromo5 butoxy)-carbostyril) and thiophenol.

M.p.: 209 - 213°C Yield: 41 % of theory.

Example 231 - Nltro-6-(4-phenyl-mercaptobutoxy)-carbostyril Prepared analogously to Example 122 from 5-nitro-6-(4-bromobutoxy)-carbostyril (m.p.: 250°C, prepared by nitration of 6- (4-bromobutoxy)-3)4-dihydrocarbostyril) and thiophenol.

M.p.: 228 - 230°C Yield: 71 % of theory.

Example 232 -Nitro-6-(4-phenylsulfinylbutoxy)-carbostyril Prepared analogously to Example 123 from 5-nitro-6-(4-phenylmercaptobutoxy)-carbostyril and hydrogen peroxide.

M.p.: 192 - 194°C Yield: 91 % of theory.

Example 235 -Acetamino-6-(4-phenylmercaptobutoxy)-carbostyril Prepared analogously to Example 122 from 5-acetamino-6-(4-bromo butoxy)-carbostyril (prepared by reduction with zinc in acetic acid of 5-nitro-6-(4-bromobutoxy)-carbostyril under addition of acetic anhydride) and thiophenol.

M.p.: 238 - 240°C Yield: 80 % of theory.

Example 234 -Acetamlno-6-(4-phenylsulflnylbutoxY)-carbostyrll Prepared analogously to Example 123 from 5-acetamino-6(4-phenylmercapto)-butoxy)-carbostyril and hydrogen peroxide. M.p.: 213 - 217°C Yield: 47 % of theory.

Example 235 -Bromo-6-(4-phenylsulfinylbutoxy)-carbo3tyril Prepared analogously to Example 123 from 5-bromo-6-(4-phenylmercaptobutoxy)-carbostyril and hydrogen peroxide.

M.p.: 190 - 191°C Yield: 82 % of theory.

Example 236 4-Methyl-6-/5-(2-pyridylsulfinyl)-butoxy7carbostyrll 0.170 g (0.0005 mol) of 4-methyl-6-/5-(2-pyridylmercapto)~ butoxy7carbostyril, dissolved in 5 ml of glacial acetic acid, and 0.107 g (0.0005 mol) of sodium metaperiodate, dissolved in 6 ml of water, were mixed and left stand at room temperature for 22 hours. Subsequently the solution was diluted with 20 ml of water and the reaction product was extracted with chloroform. The extract was shaken once with sodium bicarbonate solution and dried over water-free magnesium sulfate. After evaporating the organic phase the obtained residue was recrystallized from toluene.

M.p. ; 166 - 168°C Yield: 0.04 g (22,5 % of theory). >4-8 17 9 Example 237 6-(4-tert.-Butylsulfinyl-butoxy)-3,4-dihydrocarbostyril Prepared analogously to Example 123 from 6-(4-tert.-butylmercapto-butoxy)-3,4-dihydrocarbostyrl (m.p.: 117 - 118°C) and hydrogen peroxide.

M.p.: 126 - 128°C Yield: 62 % of theory.

Example 238 6-/5-(3-Hydroxy-pyride-2-yl)-butoxy7-3.4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 3-hydroxy2-mercapto-pyridine.

M.p.: 211 - 216°C Yield: 58 % of theory.

Example 239 6-/5-(1,2,4-Trlazole-3-yl-sulfinyl)-butoxy7carbostyril Prepared analogously to Example 123 from 6-/5-(1,2,4-triazole-3-yl-mercapto)-butoX27carbostyril and hydrogen peroxide .

Rf-value: 0.12 (silica gel fluorescent plate, eluent: ethylenechloride/methanol = 95/5).

Example 240 6-/7- (1,2,4-Triazole-3-yl-mercapto)-butoxy7-3»4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy)5 3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 3-mercapto1,2,4-triazole.

M.p.: 152 - 154°C Yield: 82 % of theory.

Example 241 6-/7-(1,2,4-Triazole-3-yl-sulfinyl)-butoxy7-3,4-dihydrocarbostyrll Prepared analogously to Example 123 from 6-/7-(1,2,4-triazole3-yl-mercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

Rf-value: 0.18 (silica gel fluorescent plate, eluent: ethylenechloride/methanol = 95/5).

Example 242 G-/4-(1,2,4-Triazole-3-yl-sulfonyl)-butoxy7-3,4-dihydrocarbostyril Prepared analogously to Example 124 from 6-/7-(1,2,4-triazole-3-yl-mercapto)-butoxy7-3,4-dihydrocarbostyril and hydrogen peroxide.

R^-value: 0.22 (silica gel fluorescent plate, eluent: ethylenechloride/methanol = 95/5).

M.p.: 217 - 224°C. Λ8179 Example 243 6-/5-(2,4,5-Trichlorophenylmercapto)-butoxx7-3,4-dihydrocarbostyril Prepared analogously to Example 122 from 6-(4-bromobutoxy) 5 3,4-dihydrocarbostyril (m.p.: 142 - 147°C) and 2,4,5-trichloro-thiophenol.

M.p.: 144 - 145°C Yield: 87 % of theory. 100 Example A Tablets containing 100 mg of 6-/5-(2-Pyridylsulfinyl)-butoxjr73.4-dihydrocarbostyril Composition: 1 tablet contains: Active ingredient 100.0 mg Lactose 80.0 mg Corn starch 34.0 mg Polyvinylpyrrolidone 4.0 mg Magnesium stearate 2.0 ag Method of preparation: 220.0 mg The active ingredient, mixed with lactose and corn starch, was homogeneously moistened with an aqueous solution of poly15 vlnylpyrrolidone. The mixture was passed through a screen of 2.0 mm mesh-size, dried at 50°C (in ahurdl^, again passed through a screen of mesh-size 1.5 mm and the lubricant was added. Then the mixture was pressed into tablets.

Weight of tablet: 220 mg Diameter: 10 mm, biplan with a facet on both sides and a notch on one side.

Example B Coated tablets containing 50 mg of 6-(4-Phenylsulfinylbutoxy)3.4-dihydrocarbostyril 1 coated tablet contains: Active ingredient Lactose Corn starch 50.0 mg 40.0 mg 17.0 mg 101 Polyvinylpyrrolidone 2.0 mg Magnesium stearate 1.0 mg 110.0 mg Method of preparation: The granulate was prepared analogously to Example A.

The mixture was pressed into coated tablets.

Weight of core: 110 mg Diameter: 8 mm, biconvex.

The cores were isolated and subsequently covered in a coating vessel according to known processes with pyrrolidone and with a coating consisting essentially of sugar up to 200 mg and subsequently coated with pure sugar syrup to 210 mg Example C Hard gelatine capsules containing 100 mg of 6-/7-(2-Pyrldylsulfinyl)-butoxv7-3.4-dihydrocarbostyril 1 capsule contains: Active ingredient 100.0 mg Com starch (dried) approx. 130.0 mg Lactose (pulverized) approx. 87.0 mg Magnesium stearate 3.0 mg 320.0 mg Method of preparation: The active ingredient and the auxiliary products were mixed, passed through a screen of 0.75 mm mesh-size and mixed homogeneously with a suitable device. The mixture was filled into hard gelatine capsules of size 1.

Content of capsule: approx. 320 mg Capsule: hard gelatine size 1 102 Example D Suppositories containing 150 mg of 6-(4-Phenylsulfinylbutoxy)3,4-dlhydrocarbostyrll________1 suppository contains: Active ingredient 150.0 mg Polyethylene glycol 1500 550.0 mg Polyethylene glycol 6000 460.0 mg Polyoxyethylene sorbitane monostearate 840.0 mg 000.0 mg Method of preparation; After melting the suppository mass>the active ingredient was homogenously dispersed therein and the melt was poured into pre-cooled moulds.

Example E Suspension containing 50 mg of 6-/5-(2-Pyridylsulfinylbutoxv7-3.4-dihydrocarbostyril per 5 ml 100 ml of suspension contain: Active ingredient 1.0 g Carboxymethyl cellulose-Na-salt 0.1 g Methyl-p-hydroxybenzoate 0.05 g Propyl-p-hydroxybenzoate 0.01 g Cane sugar 10.0 g Glycerine 5.0 g Sorbit solution 70 % 20.0 g Aroma 0.3 g Water dist. ad 100 ml 103 Method of preparation: Distilled water was heated to 70°C. Whilst stirring methylp-hydroxybenzoate and propyl-p-hydroxybenzoate as well as glycerine and carboxymethyl cellulose sodium salt were dis5 solved therein. The mixture was cooled to room temperature and whilst stirring the active ingredient was added and the whole was homogenously disperged. After adding and dissol ving the sugar, the sorbit solution and the aroma, the suspension was evacuated whilst stirring for deaeration. ml of suspension contain 50 mg of active ingredient.

Claims (5)

1. , Carbostyril derivatives of general formula wherein 5 W represents a vinylene group (optionally substituted by a methyl group) or the ethylene group, m represents the number 0, 1 or 2, D represents a straight-chained or branched alkylene group with 2 to 6 carbon atoms, whilst there must be at least 2 carbon atoms 10 between the oxygen atom and the S0 m group, or a xylylene group, represents a cyeloalkyl group with 3 to 6 carbon atoms; an aryl group with 6 to 10 carbon atoms or an aralkyl group with 105 7 to Π carbon atoms, whilst the above-mentioned aromatic nuclei may be monosubstituted by an alkyl group with 1 to 4 carbon atoms, by a hydroxy, methoxy, amino, acetylamino, nitro, carboxyl, cyclohexyl or phenyl group or by a halogen atom 5 and, additionally, the above-mentioned mono-substituted phenyl groups may be mono- or disubstituted by alkyl groups with 1 to 4 carbon atoms and/or by halogen atoms (whilst the substituents of the phenyl nucleus may be identical or different); an N-methylcyclohexylamino-carbonylmethyl, amino-iminomethylene, pyridyl, 10 pyridylmethyl, furfuryl, benzimidazolyl, benzothiazolyl, pyrimidyl, quinolyl, quinazolin-4-on-yl, 4,5-bis-(p-chlorophenyl)oxazol-2-y1, pyri dy1 oxi de, tri azolyl, methyl-pyri dy1, methoxy-pyridyl, fluoropyridyl, chloropyridyl, aminopyriclyl, acetylaminopyridyl or tri phenyl-methyl group, or also a 15 tert.butyl group, if m represents the number 1, and R 2 and R 3 , which may be identical or different, represent hydrogen or halogen atoms, alkyl groups with 1 to 4 carbon atoms, amino, acetylamino or nitro groups. 2. ,5-dichlorophenyl, 4-amino-3,5-dibromophenyl, 4-hydroxy-3,5-ditert.butylphenyl or pyridyl-(2) group and 5 D represents the ethylene, n-propylene or n-butylene group. 5. 6-(4-Phenylsulphi nylbutoxy)-3,4-di hydrocarbostyri1. 6. 6- jj-(3,4-Dichlorophenylsulphinyl)-butoxy]-3,4di hydrocarbostyri 1. 7. 6-[4-(2-Ryridylsulphonyl)-butoxy]-carbostyril. 10 8. Pharmaceutical compositions containing a compound as claimed Λ in claims 1 to 7 together with one or more inert carriers or diluents. 9. Compounds as claimed in claims 1 to 7 for the preparation of a therapeutic agent for the treatment of thrombo-embolic diseases by a non-chemical method. 15 10. Process for the preparation of carbostyril derivatives as claimed in claims 1 to 7, characterised in that A) a hydroxy compound of general formula 108 wherein Rg, Rg and W are as hereinbefore defined, or a salt thereof with inorganic or tertiary organic bases, is reacted with a compound of general formula 5 Z ~°- S V R 1 ( 111 ) wherein D, R-| and m are as hereinbefore defined and Z represents a nucleophilically exchangeable group such as a halogen atom or a sulphonic acid ester group, or B) to prepare compounds of general formula I wherein 10 m represents the number 1 or 2, a compound of general formula wherein Rl to Rg, D and W are as hereinbefore defined and 109

2. Compounds of general formula I as claimed in claim 1, 20 wherein W, D and m are defined as in claim 1, R-| represents a cyclohexyl, benzyl, naphthyl, pyridyl, pyrimidyl, 1,2,4-triazolyl, pyridyl-oxide, furfuryl, tri phenylmethyl, quinolyl, benzimidazolyl, benzothiazolyl, quinazolin-4-on-yl, 25 4,5-bis-(p-chlorophenyl)-oxazol-2-yl, N-methy1-cyclohexylaminocarbonylmethyl or ami noiminomethyl group, a phenyl group optionally substituted by a carboxyl, hydroxy, methoxy, amino, 106 acetylamino, nitro, cyclohexyl or phenyl group, a phenyl group mono- or disubstituted by halogen atoms, a hydroxyphenyl, halophenyl or aminophenyl group substituted by two halogen atoms or by two alkyl groups with 1 to 4 carbon atoms, 5 R 2 represents a hydrogen, chlorine or bromine atom, tbe methyl, amino, acetylamino or nitro group, and R 3 represents a hydrogen atom.

3. Compounds of general formula I as claimed in claim 1, wherein 10 W represents a vinylene group (optionally substituted by a methyl group) or the ethylene group, m represents the number 0, 1 or 2, D represents an alkylene group with 2 to 5 carbon atoms, whilst there must be at least 2 carbon atoms between the oxygen atom 15 and the S0 ffl group, R^ represents a cyclohexyl, phenyl, benzyl, naphthyl, biphenylyl, cyclohexylphenyl, pyridyl, methylphenyl, methoxyphenyl, fluorophenyl, chlorophenyl, dichlorophenyl, tri chiorophenyl, bromophenyl, di bromophenyl, bromomethyl-phenyl, ami nodibromophenyl 20 or hydroxy-di-tert.butyl-phenyl group, and R 2 and Rg each represent a hydrogen atom. 4. -8179 n represents the number 0 or 1, is oxidized, or C) to prepare a compound of general formula I wherein m represents the number 0, a compound of general formula 5 wherein R 2 , Rg, D and U are as hereinbefore defined, is reacted with a compound of general formula Y-R 1 (VI) wherein 10 R^ is as hereinbefore defined with one of the groups X or Y in the compounds of general formulae V and VI represents the mercapto group and the other group X or Y represents a nucieophilically exchangeable group such as a halogen atom or a sulphonic acid ester group, or 15 D) to prepare a carbostyril of general formula I wherein W represents the vinylene group, a 3,4~dihydro-carbostyril of general formula 110 wherein to R^j D and m are as hereinbefore defined, is dehydrogenated, or E) to prepare a 3,4-dihydro-carbostyril of general formula I wherein W represents the ethylene group and m represents the number 0 or 2, a carbostyril of general formula (VIII), wherein 111 R 1 to Rg, D and m are as hereinefore defined, is hydrogenated. 11. Process for the preparation of carbostyril derivatives as claimed in claim 1, substantially as hereinbefore described with reference to the Examples.

4. Compounds of general formula I as claimed in claim 1 wherein W represents the ethylene, vinylene or 2-methylvinylene group, m represents the number 1 or 2, R 2 and Rg each represent a hydrogen atom, 107 R 1 represents the cyclohexyl, phenyl, benzyl, naphthyl-(2), 2-methoxyphenyl, 4-chlorophenyl, 3,4-dichlorophenyl,

5. 12. Carbostyril derivatives when prepared by a process as claimed in either claim 10 or 11.