FI69064C - PROCEDURE FOR THE FRAMEWORK OF PHARMACOLOGICAL VEHICLES CARBOSTYRIL AND OXIDOLDERIVAT - Google Patents

Description

775fe ^ 71 rRl ADVERTISEMENT 69064

Jglja (Ί1) UTLÄGGNINGSSKRLFT ......

• * p \ S (45>; i :: - ~: v :; 1 ** * (51) Kv.lk. * / Lm.Cl.4 C 07 D 227- / 087, 401/12, 405 / 12 »417/12 * FINLAND (21) Patenttlhakemu * - Patentansöknlng 790507 (22) Application date— Ansökningsdag 15.02.79 (FI) (23) Starting date - Glltlghetsdag 15.02.79 (41) Tullut | outside German - Bllvlt offentllg 1 8.08.79

Patent * and National Board of Registration (44) Date of sighting | - 30.08.85

Patent * och registerstyrelsen v 'Ansökan utlagd och utl.skriften publlcerad (32) (33) (31) Claim claimed privilege - Begärd priorltet 17.02.78 O9.i2.78 Federal Republic of Germany-Förbunds-republiken Tyskland (DE) P 2806721.2, P 28533 (71) Dr. Karl Thomae Gesellschaft mit Besch rank "ter Haftung, Biberach an der Riss, Federal Republic of Germany, Germany (DE) (72) Erich Muller, Biberach, Josef Nickl, Biberach, Josef Roch, Biberach, Berthold Narr, Biberach , Walter Haarmann, Biberach, Johannes Maximilian Weisenberger, Biberach, Federal Republic of Germany-Förbundsrepubl iken Tyskland (DE) (74) Leitzinger Oy (54)

The present invention relates to a process for the preparation of carbostyril and oxindole derivatives of the general formula I which have valuable pharmacological properties. In addition to the positive inotropic effect, they have antithrombotic properties in particular.

* // C 07 D 215/22, 209/34, (C 07 D 401/12, 215: 22, 213: 70), (C 07 D 401/12, 215: 22, 213: 71), (C 07 C 401/12, 215: 22, 239: 38) (C 07 D 401/12, 215: 22, 235: 28), (C 07 D 401/12, 215: 22, 215: 36) '(C 07 C 401/12, 215: 22, 239: 88), (C 07 D 401/12, 215: 22, 249 * 12) '(C 07 D 405/12, 215: 22, 307: 38), ( C 07 D 417/12, 215: 22, 277: 70) '2

In the above general formula I 69064 W is an optionally methyl-substituted vinylene group, a methylene or ethylene group, m is a number 0, 1 or 2, D is a straight-chain or branched alkylene group having 2 to 6 carbon atoms, a straight-chain or branched hydroxyalkylene group having 3 to 6 carbon atom or xylylene group, R1 is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, R2 is a cycloalkyl group having 3 to 6 carbon atoms, an aryl group having 6 to 10 carbon atoms, an aralkyl group having 7 to 11 carbon atoms, one nitrogen atom and / or one oxygen or sulfur atom or a heteroaryl group having two nitrogen atoms having 4 to 9 carbon atoms, or these atoms contain a heteroaralkyl group having 5 to 10 carbon atoms, wherein the above-mentioned aromatic rings may be monosubstituted by an alkyl group having 1 to 4 carbon atoms, hydroxy, methoxy- , amino, acetylamino, nitro, carboxyl, cyclohexyl, phenyl or halogen, and in addition the above-mentioned monosubstituted phenyl the groups may be mono- or di-substituted by 1-4-carbon-alkyl groups and / or halogen atoms (in which case the substituents on the phenyl ring may be identical or different), 1,2,4-triazolyl, triphenylmethyl-, 4,5-bis- a (p-chlorophenyl) oxazol-2-yl, N-methylcyclohexylaminocarbonylmethyl or aminoiminomethyl group or also an alkyl group having 1 to 6 carbon atoms, when either m is a number 1 or D is a straight-chain or branched hydroxyalkylene group having 3 - 6 carbon atoms or a xylylene group, R3 and which may be the same or different, are hydrogen or halogen atoms, alkyl groups having 1 to 4 carbon atoms, amino, acetylamino or nitro groups.

The term "halogen atom" mentioned in the definitions of the groups R 2, R 1 and R 4 means in particular a fluorine, chlorine, bromine or iodine atom; the meanings given in the definitions of the groups D, R 1, R 2, R 2 and R 2 are thus: D is ethylene, n-propylene, n-butylene, n-pentylene, n-hexylene, 1-methylethylene -, 2-methyl-ethylene, 1-methyl-n-propylene, 2-methyl-n-propylene, 3-methyl-n-propylene, 1-methyl-n-butylene, 2-methyl-n -butylene, 3-methyl-n-butylene, 4-methyl-n-butylene, 1-methyl-n-pentylene, 2-methyl-n-pentylene, 3-methyl-n-pentylene, 4 -methyl-n-pentylene, 5-methyl-n-pentylene, 1,1-dimethylethylene, 1,2-dimethylethylene, 2,2-dimethylethylene, 1,1-dimethyl-n-propylene , 2,2-dimethyl-n-propylene, 3,3-dimethyl-n-propylene-, 11,69064 3 1,2-dimethyl-n-propylene, 1,3-dimethyl-n-propylene, 1,1- dimethyl-iv-butylene, 2,2-dimethyl-n-butylene, 3,3-dimethyl-n-butylene, 4,4-dimethyl-n-butylene, 1,2-dimethyl -n-butylene, 1,3-dimethyl-n-butylene, 1,4-dimethyl-n-butylene, 2,3-dimethyl-n-butylene, 1-ethylethylene, 2-ethylethylene -, 1-ethyl-n-propylene, 2-ethyl-n-propylene, 3-ethyl-n-propylene, 1-ethyl-n-butylene, 2-ethyl-n-butylene, 3 -ethyl-n-butylene-, 4-ethyl-n-butylene-, 1-methyl-2-ethyl-ethylene-, 1-methyl-2-ethyl-n-propylene-, 1-methyl-3-ethyl-n -propylene, 1-methyl-2-propyl-ethylene, 1-propylethylene, 1-butylethylene, 1-propyl-n-propylene, 2-hydroxy-n-propylene, 2-hydroxy -n-butylene, 3-hydroxy-n-butylene, 2-hydroxy-n-pentylene, 3-hydroxy-n-pentylene, 4-hydroxy-n-pentylene, 2-hydroxy-n-hexylene- , A 3-hydroxy-n-hexylene, 1-methyl-2-hydroxy-n-propylene, 2-hydroxy-2-methyl-n-propylene, p-xylylene, o-xylylene or m-xylylene group, is a hydrogen atom, a methyl, ethyl, propyl or isopropyl group, R2 is a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, naphthyl, naphthylmethyl, cyclohexylphenyl, biphenyl, -, N-methyl-cyclohexylaminocarbonylmethyl -, aminoiminomethyl, pyridyl, pyridylmethyl, fufuryl, benzimidazolyl, benzthiazolyl, pyrimidyl, quinolyl, quinazolin-4-on-yl, 4,5-bis- (p- chlorophenyl) oxazol-2-yl, pyridyl oxide, methylphenyl, dimethylphenyl, tert-butylphenyl, methyl-tert-butylphenyl, methylpyridyl, methoxyphenyl, dimethoxyphenyl, methoxypyridyl, hydroxyphenyl , dihydroxyphenyl, fluorophenyl, difluorophenyl, trifluorophenyl, 1,2,4-trazolyl, fluoropyridyl, chlorophenyl, dichlorophenyl, trichlorophenyl, chloropyridyl, bromophenyl, dibromophenyl, ciminophenyl, acetylaminophenyl, aminopyridyl, acetylaminopyridyl, nitrophenyl, carboxyphenyl, hydroxy-dichlorophenyl, hydroxy-dibromophenyl, amino-dichlorophenyl, amino-dibromophenyl, hydroxy-dipert-tert-butyltert-butyltert-butyltert-butyltert , methoxy-fluorophenyl, methoxy-chlorophenyl, methoxy-bromophenyl, fluoromethylphenyl, chloromethylphenyl or bromo- a methylphenyl group, «69064 R3 and R4 * which may be the same or different, are hydrogen, fluorine, chlorine, bromine or iodine atoms, methyl, ethyl, propyl, isopropyl, butyl, tert. butyl, nitro, amino or acetylamino groups.

In particular, the invention provides compounds of general formula I in which W, D and m have the same meaning as above, 1 * 2 is cyclohexyl, benzyl, naphthyl, pyridyl, pyrimidyl, 1,2,4-triazolyl, pyridyl oxide, furfuryl, triphenylmethyl, quinolyl, benzimidazolyl, benzthiazolyl, quinazolin-4-one-yl, 4,5-bis- (p-chlorophenyl) oxazol-2-yl, N-methyl- a cyclohexylaminocarbonylmethyl or aminoiminomethyl group, a phenyl group optionally substituted by a carboxyl, hydroxy, methoxy, amino, acetylamino, nitro, cyclohexyl or phenyl group, a halogen atom and / or an alkyl group having 1 to 4 carbon atoms; a disubstituted phenyl group, a hydroxyphenyl, halophenyl or aminophenyl group substituted by two halogen atoms or two alkyl groups having 1 to 4 carbon atoms, is a hydrogen, chlorine or bromine atom, a methyl, amino, acetylamino or nitro group and is a hydrogen atom.

Preferred are those compounds of general formula I in which W is an optionally methyl-substituted vinylene group or an ethylene group, m is O, 1 or 2, D is an alkylene group having 2 to 5 carbon atoms or a hydroxyalkylene group having 3 to 5 carbon atoms, R 1 is a hydrogen atom, R 2 is cyclohexyl, phenyl, benzyl, naphthyl, biphenylyl, cyclohexylphenyl, pyridyl, methylphenyl, methoxyphenyl, fluorophenyl, chlorophenyl, dichlorophenyl, trichlorophenyl, bromophenyl, bromophenyl, bromophenyl, -, amino-hydrobromophenyl or hydroxy-di-tert-butylphenyl group, R3 and R3 are each a hydrogen atom.

Particularly preferred compounds of the above general formula I are those compounds in which 5 69064 W is an ethylene, vinylene or 2-methylvinylene group, m is 0, 1 or 2,

R 1, and are each a hydrogen atom, R 2 is cyclohexyl, phenyl, benzyl, naphthyl (2) -, 2-methoxyphenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 4 -amino-3,5-dibromophenyl, 4-hydroxy-3,5-di-tert-butylphenyl or pyridyl (2) and D is ethylene, n-propylene, n-butylene or 2- hydroxy-n-propylene moiety.

The novel compounds of the general formula I are obtained according to the invention by the following methods: a) A hydroxy compound of the general formula II R1 in which R1, R1, R1 and W are as defined above, or a salt thereof with inorganic or tertiary organic bases is reacted with a compound of the general formula III Z - D - DOm - R2 (III) wherein D, R2 and m are as defined above and Z is a nucleophilically exchangeable group such as a halogen atom or a sulfonic acid ester group, for example chlorine, bromine, iodine atom, p-toluenesulfonyloxy or methanesulfonyloxy -group.

The reaction is conveniently carried out in a suitable solvent such as dioxane, tetrahydrofuran, chloroform or toluene, but most preferably in an anhydrous aprotic solvent, such as acetone, dimethylformamide or dimethyl sulphoxide, optionally in the presence of alkali metal such as sodium carbonate, sodium carbonate, sodium carbonate, and the boiling point of the solvent used, for example at temperatures between 0 and 100 ° C, but preferably at temperatures between D and 50 ° C. However, the reaction can also be carried out without a solvent.

(b) For the preparation of compounds of general formula I in which m is the number 1 or 2:

Oxidation of a compound of general formula IV R3 ", 1 | '1 · - ° · D - SOn - r2 UV) I R4 R1 wherein R1 - R1, D and W have the same meaning as above, and n is the number 0 or 1.

The oxidation is best carried out in a solvent such as water, water / pyridine, ethanol, methanol, acetone, glacial acetic acid, formic acid, dilute sulfuric acid or trifluoroacetic acid, suitably at temperatures between -80 and + 100 ° C.

For the preparation of compounds of general formula I in which m is 1, the oxidation is conveniently carried out using an equivalent oxidant used, for example hydrogen peroxide in glacial acetic acid or formic acid at 0 to 20 ° C or acetone at 0 to 60 ° C, peracid such as perforic acid in glacial acetic acid or trifluoroacetic acid At 0-50 ° C, sodium metaperiodate in aqueous methanol or ethanol at 15-25 ° C, N-bromo-7,69064 succinimide in ethanol, tert-butyl hypochlorite in methanol at -80 to -30 ° C, iodobenzene dichloride in aqueous pyridine 0 - at 50 ° C, with nitric acid in glacial acetic acid at 0 to 20 ° C, with chromic acid in glacial acetic acid or acetone at 0 to 20 ° C and with sulfuryl chloride in methylene chloride at - 70 ° C, the resulting thioether-chlorine complex being suitably hydrolysed with aqueous ethanol .

For the preparation of compounds of general formula I in which m is the number 2, the oxidation is conveniently carried out using one or two equivalents or more of an oxidizing agent, for example hydrogen peroxide in glacial acetic acid or formic acid at 20-100 ° C or acetone at 0-60 ° C, peracid such as perforic acid or m-chloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid or chloroform at temperatures between 0 and 50 ° C, nitric acid in glacial acetic acid at 0-20 ° C, chromic acid or potassium permanganate in glacial acetic acid, water / sulfuric acid or acetone at 0-20 ° C. Thus, in the compound of the general formula IV above, n represents a number of zero, then the reaction is preferably carried out using two equivalents or more of the oxidant in question and, correspondingly, at least one equivalent if n is the number 1.

c) For the preparation of a compound of general formula I wherein m is O:

A compound of general formula V * 30 I R4 R1 wherein V R3 * D and W are as defined above may be reacted with a compound of general formula VI Y - r2 (VI) 69064 8 R2 is as defined above and one of X or Y compounds of general formulas V and VI have a mercapto group and the second group X or Y is a nucleophilically exchangeable group such as a halogen atom or a sulphonic acid ester group, for example a chlorine, bromine or iodine atom, a p-toluenesulphonyloxy or metahisulfonyloxy group, or X together with a group D with the adjacent hydroxy group is an epoxide group and Y is a mercapto group.

The reaction is conveniently carried out in a suitable solvent such as dioxane, tetrahydrofuran, chloroform or toluene, but most preferably in an anhydrous aprotic solvent such as acetone, dimethylformamide or dimethyl sulphoxide at room temperature with , for example at temperatures between 0 and 100 ° C, but preferably at temperatures between 10 and 50 ° C. However, the reaction can also be carried out without a solvent.

d) For the preparation of a carbostyril of general formula I in which R 1 is not a hydrogen atom:

Compound of general formula VII "il H- O - D - SO - R- (VII)

Λ • 'M

I * 4

B

wherein R 2 to R 4, D, W and m are as defined above, or an alkali salt thereof is reacted with a compound of general formula VIII Z to R x (VIII) wherein R 1 is as defined above and Z is a nucleophilically exchangeable group, such as halogenol 9,69064 ml or a sulfonic acid ester group, for example a chlorine, bromine or iodine atom, a p-toluenesulfonyloxy or methanesulfonyloxy group.

The alkylation is conveniently carried out in an aprotic solvent such as acetone, dimethylformamide or dimethylsulphoxide in the presence of an inorganic base such as potassium carbonate, sodium hydroxide, sodium hydride or potassium hydroxide, preferably in the presence of a temperature of 50 ° C or and 25 ° C. Suitable alkylating agents are, in particular, alkyl halides, such as methyl iodide or isopropyl bromide, or dialkyl sulphates, such as dimethyl or diethyl sulphate.

e) For the preparation of a carbostyril of general formula I, wherein VJ is a vinylene group,:

Dehydrating 3,4-dihydrocarbostyril of general formula IX R3 and Q1j - D - SOm - R2 (IX) R1 wherein - R4, D and m have the same meaning as above.

The dehydration is carried out in the presence of a dehydrating agent, for example an oxidant such as 2,3-dichloro-5,6-dicyanobenzoquinone, chloranil or a noble metal catalyst such as palladium / carbon, preferably in an inert solvent such as dioxane or mesitylene at elevated temperatures, for example between 100 200 ° C, but preferably at the boiling point of the solvent used.

f) for the preparation of a carbostyril of general formula I in which W is an ethylene group and m is O or 2;

Hydrogenation of carbostyril of general formula X 6 69064 R3 f X X - 0 - D - SOm - R2 <X)

I R

R 1 where - R 1, D and m have the same meaning as above.

The hydrogenation is carried out in a suitable solvent such as ethanol, ethyl acetate, glacial acetic acid or dioxane with catalytically activated hydrogen, for example hydrogen in the presence of a hydrogenation catalyst such as palladium / carbon, olatin, Raney nickel, Raney cobalt or Dirhenium heptasulfide. C, preferably, however, at room temperature, and at a hydrogen pressure of 1-5 bar.

The compounds of the general formulas II to X used as starting materials are partly known from the literature or can be prepared by methods known per se. For example, 6-, 7- or 8-hydroxy-3,4-dihydrocarbostyril of general formula II is obtained by acylation of the corresponding aniline derivative with the corresponding 8-halocarboxylic acid derivative and subsequent cyclization by the method of Friedel-Crafts (see J. chem. Soc. 1955, 743-744, Chem. Pharm. Bull 1961, 970-975 and Ber. Atsch. Chem. Ges. 60, 858 (1927)) or 5-hydroxy-3,4-dihydrocarbostyril of general formula II is obtained by cyclization of the corresponding 2 - (8-cyanoethyl) -cyclohexanediol-1,3-derivative, followed by aromatization with, for example, N-bromo-succinimide (see Chem. And Ind. 1970, 1435). The preparation of the corresponding hydroxycarbostril of general formula II is known from the literature (see, for example, J. Amer. Chem. Soc. T2. 346 (1950) and ibid J76 / 2402 (1954) or J.Org. Chem. 33, 1089 (1968)). and ibid 36, 3493 (1971)). J. chem. 1961, 223 further describes the preparation of 5-hydroxyindole.

The starting compounds of the general formulas IV, V, VII, IX and X are obtained by alkylation of the corresponding hydroxy derivative and, if appropriate, subsequent oxidation.

As already mentioned above, those prepared according to the invention are

II

11 69064 new compounds of general formula I have valuable pharmacological properties. In addition to the positive inotropic effect, it has antithrombotic properties.

For example, the biological properties of the following compounds were blocked: A = 6- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril, B = 6- (4-phenylsulfinylbutoxy) -3,4-dihydrocarbostryl, C = 6- (4-phenylsulfonylbutoxy) -3,4-dihydrocarbostryl, D = 6- [4- (2-pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril, E = 6- / 4- (2-pyridylsulfonyl) -butoxy / -3,4-dihydrocarbostryl , F = 6- [4- (2-pyridylsulfonyl) -butoxy] -3,4-dihydrocarbostyril, G = 6- (2-phenylsulfinyl-ethoxy) -3,4-dihydrocarbostryl, H = 6- (4-benzylsulfinyl- butoxy) -3,4-dihydrocarbostryl, I = 6- [4- (4-chlorophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril, K = 6- (4-cyclohexylsulfinyl-butoxy) -3,4-dihydrocarbostyril, L = 6- [4- (2-naphthylsulfinyl) -butoxy] -3,4-dihydrocarbostryl, M = 6- [4- (2-methoxyphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril, N = 6- (4- phenylsulfinyl-butoxy) -carbostyril, O = 6- [4- (4-hydroxy-3,5-di-tert-butyl-phenylsulfinyl) -butoxy] -carbostyril, P = 6- / 4- ( 3,4-Dichlorophenylsulfinyl) -butoxy / carbostryl, Q = 4-methyl-6- (4-phenylsulfinyl-butoxy) -carbostyril, 12 69064 R = 6- [4- (3,4-dichlorophenylsulfonyl) -butoxy] - 3,4-dihydrocarbostyril, S = 6- [4- (2,5-dichlorophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril, T = 6- / 4- (2-pyridylsulfonyl) -butoxy N-carbostyril U = 6- [4- (3,4-dichlorophenylsulfinyl) -butoxy] -3,4-dihydrocarbocitrile 1. Determination of platelet aggregation by the Born and Cross method (J. Physiol. 170/397 (1964)): _

Platelet aggregation was measured in platelet-rich plasma from healthy subjects. In this case, the decrease in optical density after the addition of adenosine diphosphate (ADP) or collagen was measured photometrically. The accumulation rate was calculated from the slope angle of the density curve. "Optical density" (O.D.) was calculated from the point on the curve where light transmittance was highest. The EC ^ values in the table refer to the optical density.

Collagen doses were chosen to be as low as possible, however, so that the accumulation was irreversible. Accumulation was triggered by adding about 0.01 ml of collagen solution to about 1 ml of high-flake plasma. (Fa. Hormonchemie, commercial collagen from Miinschen). ADP doses were chosen so that only the first step of the Bron curve was obtained. The amount of ADP required was about 1.10 ® mol / L. Fa. Commercial ADP from Boehringer-Mannheim.

The dose of compound that inhibited platelet aggregation (EC5Q) by 50% of 69064 was determined graphically.

Compound EC50 ΙΟ-6 moles / 1 __Collagen_ADP__ A 50> 100 B 4 20 C 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 O 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 prolongation of bleeding time;

Esihuomautus:

Both humans and warm-blooded organisms have an important mechanism to protect them from blood loss in the event of injury. This system is made up of platelets (platelets) which, due to their adhesion properties, quickly "clog" the damaged blood vessel, causing primary hemostasis. The primary haemostasis system, which consists essentially of platelets, and the coagulation system complement each other with the common goal of effectively protecting the body from blood loss.

14 69064

In many diseases, the clotting process and platelet aggregation can begin to function even when the vascular system is intact. Coumarin or separin is known to impair the coagulation system and this can be easily measured by known coagulation assays in which the coagulation time is prolonged by the preparation (Plasmarecalcif. Time, Quick assay, thrombin time, etc.).

Because platelets first rapidly suppress bleeding when wounded, platelet function can be well determined by measuring the bleeding time when wounding is performed in a standard manner. The normal bleeding time in humans is about 1 to 3 minutes, which, however, requires efficient and sufficient platelets. Thus, when the platelet count is normal, the prolonged bleeding time indicates that the platelet function is impaired. This occurs, for example, in some congenital platelet dysfunctions. If, on the other hand, it is desired in the arterial system to prevent the tendency of drugs to platelet aggregate spontaneously, resulting in vascular occlusion, it follows that the bleeding time under the influence of the compound must be extended for platelet-mediated treatment to be successful. Thus, the platelet active agent can be expected to have prolonged bleeding and, since the plasma coagulation system has not been affected, a normal blood clotting time.

Literature: W.D. Keidel: Kurzgefasstes Lehrbuch der Physiologie, Georg Thieme Verlag Stuttgart 1967, page 31: Der Blutstillungsvorgang.

To determine the bleeding time, test compounds were applied to awake mice at 10 mg / kg p.o. After one hour, approximately 0.5 mm of the tail end of each animal was cut and blood was aspirated every 30 seconds into filter paper. The number of blood droplets thus obtained measures the bleeding time (5 animals per experiment). The following figures represent the percentage elongation compared to the control: li 69064 15

Compound Prolongation of bleeding time after 1 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 O 73 P 12 0 · 39 R 30 T 5 U 33 1

Determination of a positive inotropic effect:

Rats were anesthetized with ether and then killed by hitting the neck. After thoracic opening, the heart was removed and both atria were separated. The vestibules were transferred to a 100 ml elinaute containing 30 degrees thyrode, which was oxidized with a gas containing 95% oxygen and 5% carbon dioxide. The hallways struck spontaneously. The contractile force was measured isometrically with a atrial load of 1 g. Test compounds were tested in each of the four atria at a concentration of 1 x 10 g / ml. The change in contractile force was expressed as a percentage of the initial value. The results obtained are shown in the following table: 69064 16

Compound Increase in contractile force,% B 30 C 35 E 16 F 18 I 52 L 63 M 65 Q 58 S 83 T 32 4. Acute toxicity:

The acute toxicity of the subjects was initially determined in groups of 10 mice. The compound was administered orally at 1000 mg / kg (observation time: 14 days): 69064 17

Compound Acute toxicity per os A> 1000 mg / kg (10 animals died 0) B> 1000 mg / kg (10 animals died O) C> 1000 mg / kg (10 animals died 0) D> 1000 mg / kg (10 animals died O) D> 1000 mg / kg (10 animals died O) E> 1000 mg / kg (10 animals died 0) F> 1000 mg / kg (10 animals died O) G> 1000 mg / kg (10 animals died O ) H> 1000 mg / kg (10 animals died 0) I> 1000 mg / kg (10 animals died 0) K> 1000 mg / kg (10 animals died 0) L> 1000 mg / kg (10 animals died 0) M > 1000 mg / kg (10 animals died 0) 0> 1000 mg / kg (10 animals died 0) P> 1000 mg / kg (10 animals died O) Q> 1000 mg / kg (10 animals died O) R> 1000 mg / kg (10 animals died 0) S> 1000 mg / kg (10 animals died 0) T> 1000 mg / kg (10 animals died 0) U> 1000 mg / kg (10 animals died 0)

Based on their pharmacological properties, the new compounds of the general formula I are suitable for the prophylaxis of thromboembolic diseases such as myocardial infarction, so-called tansient ischemic attacks, Amaurosis fugax and arteriosclerosis. For this purpose, they can optionally be processed in combination with other active ingredients into customary pharmaceutical preparations, such as granules, tablets, capsules, suppositories or suspensions. The single full dose is then 50 to 100 mg 2-3 times a day and thus the daily dose is 100 to 300 mg.

The following examples further illustrate the invention:

Example 1 69064 6- [4- (2-Pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril 14.4 g (0.13 mol) of 2-mercaptopyridine and 17.9 g (0.13 mol) of potassium carbonate are mixed with 360 ml. dimethyl sulfoxide dried in a molecular sieve and 36 g (0.12 mol) of 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C, prepared from 6-hydroxycarbostyril and 1,4-dibromobutane) are added to the mixture. * -a).

It is then stirred for 15 hours at about 25 [deg.] C., after which the reaction mixture is poured into 3.6 liters of water and stirred for a further 30 minutes. The precipitated product is filtered off with suction, washed well with water, dried and recrystallized from xylene by treatment with carbon. Pale yellow crystals with a melting point of 123-124.5 ° C are obtained.

Yield: 32 g (81.2% of theory).

Example 2 6- [4- (2-Pyridylsulfinyl) -butoxy] -3,4-dihydrocarbostyril 32.8 g (0.1 mol) of 6- [4- (2-pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril is dissolved in 330 ml of glacial acetic acid and 10.2 g (0.105 mol) of 35% hydrogen peroxide are added to the solution. After stirring for 15 minutes at about 20 [deg.] C., the glacial acetic acid is distilled off at 60 [deg.] C. in vacuo, the residue is washed with ether and the crude product obtained is recrystallized twice from xylene by treatment with carbon. Colorless crystals with a melting point of 144.5 to 146 ° C are obtained.

Yield: 27.5 g (79.8% of theory).

Example 3 6- [4- (2-Pyridylsulfonyl) -butoxy] -3,4-dihydrocarbostyril 5 g (0.015 mol) of 6- [4- (2-pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril are dissolved in 50 ml. to glacial acetic acid and 4.5 g (0.045 mol) of 35% hydrogen peroxide are added to the solution. After stirring for 40 hours at about 25 [deg.] C., the glacial acetic acid is distilled off at 60 [deg.] C. in vacuo, the solid residue is washed with ether and recrystallized from charcoal by treatment with xylene. Colorless crystals are obtained, m.p. 123.8-125 ° C.

Yield: 3.8 g (70.3% of theory).

Example 4 6- (-4-Phenylsulfinylbutoxy) -3,4-dihydrocarbostyril 32.6 g (0.2 moles) of 6-hydroxy-3,4-dihydrocarbostyril / cf.

F. Mayer et al., Ber. dtsch .. chem. Ges. 60, 858 (1927) / and 27.6 g (0.2 moles) of potassium carbonate are stirred for 5 minutes in 600 ml of molecular sieve-dried dimethyl sulfoxide and then 52.2 g of 4-phenylsulfinylbutyl bromide (prepared in Example 2) are added. thiophenol and 1,4-dibromobutane followed by oxidation with hydrogen peroxide in glacial acetic acid; an oily substance which solidifies on standing in a refrigerator). Stir for 15 hours at 25 ° C and then pour the reaction mixture into 6 liters of water. After stirring for a further 30 minutes, the precipitated product is filtered off with suction and washed well with water. After drying, recrystallize from about 600 ml of xylene by treatment with carbon. White crystals are obtained, m.p. 144.5-145.5 ° C.

Yield: 49 g (71.3% of theory).

Example 5 6- (4-Phenylmercapto-butoxy) -3,4-dihydrocarbostyril '

Prepared according to Example 4 from 6-hydroxy-3,4-dihydrocarbostyril and 4- (phenylmercapto) butyl bromide (b.p. 96-103 ° C prepared from thiophenol and 1,4-dibromobutane). Melting point: 121.5 - 123 ° C.

Yield: 75.6% of theory.

Example 6 6- (4-Phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 6-hydroxy-3/4-dihydrocarbostyril and 4-phenylsulfonylbutyl bromide (prepared from 4- (phenylmercapto) butyl bromide by oxidation according to Example 3).

20

Melting point: 157.5-158 ° C, 690 64

Yield: 65.1% of theory.

Example 7 6- [4- (4-Fluorophenylmercapto) -bufoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 4-fluorothiophenol.

Melting point: 139-140 ° C,

Yield: 93.1% of theory.

Example 8 6- [4- (4-Fluorophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-fluorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril.

Melting point: 184.5 - 186 ° C,

Yield: 88% of theory.

Example 9 6- [4- (4-Methylphenyl-mercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 4-methylthiophenol.

Melting point: 120-121 ° C,

Yield: 91% of theory.

Example 10 6- [4- (4-Methylphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-methylphenyl marker) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 149.5 - 150 ° C,

Yield: 97% of theory.

li

Example 11 69064 21 6- [4- (3-Methylphenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydro-carbostyril (melting point: 147-148 ° C) and 3-methylthiophenol.

Melting point: 95-96 ° C.

Yield: 91% of theory.

Example 12 6- [4- (3-Methylphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (3-methylphenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Waxy resin,

Yield: 95% of theory.

Rf value: 0.48 (thin layer chromatogram on silica gel - eluent: benzene / ethanol / concentrated ammonia = 75/25/1).

Example 13 6- [4- (4-Chlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 4-chlorothiophenol. Melting point: 144-146 ° C,

Yield: 88% of theory.

Example 14 6- [4- (4-Chlorophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-chlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 148-149.5 ° C,

Yield: 70% of theory.

22 v · τκ 69064

Example 15 6- [4- (3,4-Dichlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 3,4-dichlorothiophenol.

Melting point: 116.5 - 118 ° C,

Yield: 87% of theory.

Example 16 6- [4- (3,4-Dichlorophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (3,4-dichlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyl and hydrogen peroxide. Melting point: 106.5 - 108 ° C,

Yield: 74% of theory.

Example 17 6- [4- (2-Methoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 2-methoxythiophenol. Melting point: 130.5 - 133 ° C,

Yield: 74% of theory.

Example 18 6- [4- (2-Roethoxyphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (2-methoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 162-163 ° C,

Yield: 62% of theory.

Example 19 6- [4- (3-Methoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril

II

23 69064

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 3-methoxythiophenol. Melting point: 93.5 - 97 ° C,

Yield: 61% of theory.

Example 20 6- [4- (3-Methoxyphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (3-methoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 147-148 ° C,

Yield: 49% of theory.

Example 21 6- [4- (4-Methoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 4-methoxythiophenol. Melting point: 130.5 - 133 ° C,

Yield: 82% of theory.

Example 22 6- [4- (4-Methoxyphenylsulfinyl) -hutoxy] -4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-methoxyphenylmercapto) -butoxy] -3,4-dihydrocatbostyril and hydrogen peroxide.

Melting point: 132-133 ° C,

Yield: 71 S of theory.

Example 23 6- [4- (3,4-Dimethoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 3,4-dimethoxythiophenol and 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (prepared from 6-hydroxycarbostyril (see F. Mayer et al., Ber. Dtsch. Chem.

Ges. 60, 858 (1927) and 4-chlorobutanol-benzenesulfonic acid ester).

24

Melting point: 117-119 ° C, 69064

Yield: 73% of theory.

Example 24 6- [4- (3,4-Dimethoxyphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril_

Prepared according to Example 2 from 6- [4- (3,4-dimethoxyphenyl mercapto) butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 145-147 ° C,

Yield: 79% of theory.

Example 25 6- [4- (3,4-Dimethoxyphenylsulfonyl) -butoxy] -3,4-dihydrocarbostyril__

Prepared according to Example 3 from 6- [4- (3,4-dimethoxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 158-160 ° C,

Yield: 62% of theory.

Example 26 6- [4- (4-Biphenylyl mercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 4-phenylthiophenol and 6- (4-bromobutoxy) -3,4-dihydrocarbostyril.

Melting point: 179.5 - 181 ° C,

Yield: 74% of theory.

Example 27 6- [4- (4-Biphenylylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-biphenylyl mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 192-192.5 ° C,

Yield: 86% of theory.

Example 28 6 9 0 6 4 25 6- [4- (2-Naphthylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 2-naphthylmethaptane and 6- (4-bromobutoxy) -3,4-dihydrocarbostyril.

Melting point: 108.5 - 109.5 ° C.

Yield: 48% of theory.

Example 29 6- [4- (2-Naphthylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (2-naphthylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 147.5 - 148.5 ° C,

Yield: 57% of theory.

Example 30 6- [5- (2-Pyridylsulfinyl) -pentoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [5- (2-pyridylmercapto) -pentoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 116-118 ° C,

Yield: 69% of theory.

Example 31 6- (2-Methylsulfinylethoxy) -3,4-dihydrocarbostyril 1.42 g (0.006 mol) of 6- (2-methylmethaptoethoxy) -3,4-dihydrocarbostyril are suspended in 12 ml of methanol and a solution is added. containing 1.71 g (0.008 mol) of sodium metaperiodate in 8 ml of water. Stir for 1.5 hours, at which time the reaction mixture is initially observed to warm clearly. It is then diluted with a small amount of water and extracted thoroughly with chloroform. The evaporation residue is recrystallized from ethyl acetate by adding a small amount of ethanol.

Melting point: 129-131.5 ° C,

Yield: 70% of theory.

_ - ΤΓ 26

Example 32 69064 6- [5- (2-Pyridylsulfonyl) -pentoxy] -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- [5- (2-pyridylmercapto) -pentoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 113.5 - 115.0 ° C,

Yield: 71% of theory.

Example 33 6- (4-Methylsulfinylbutoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (4-methylmercaptobutoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 128.5 - 130.5 ° C,

Yield: 58% of theory.

Example 34 7- (4-Phenylsulfonyl-butoxyl) -carbostyril

Prepared according to Example 3 from 7- (4-phenylmercapto-butoxy) -carbostyril and hydrogen peroxide.

Melting point: 199-201 ° C,

Yield: 85% of theory.

i

Example 35 6- (4-Cyclohexylmercaptobutoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from cyclohexyl mercaptan and 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C).

Melting point: 114-115 ° C,

Yield: 80% of theory.

27

Example 36 69064 6- (4-Cyclohexylsulfinyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (4-cyclohexyl mercapto-butoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 153-155.5 ° C,

Yield: 63% of theory.

Example 37 6- (4-Benzylmercapto-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from benzyl mercaptan and 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril.

Melting point: 77.5-78.5 ° C,

Yield: 90% of theory.

Example 38 6- (4-Benzylsulfinyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (4-benzylmercapto-butoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 141.5 - 142 ° C,

Yield: 95% of theory.

Example 39 6- [4- (2-Furylmethyl-3-mercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 2-furfuryl mercaptan and 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C). Melting point: 79-80 ° C,

Yield: 64% of theory.

i

Example 40 69064 28 6- [4- (2-Furylmethylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (2-furylmethylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 135-136 ° C,

Yield: 60% of theory.

Example 41 6- [4- (N-Oxido-2-pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril and 2-mercaptopuridine N-oxide.

Melting point: 179.5 - 181 ° C,

Yield: 65% of theory.

Example 42 6- [4- (2-Pyrimidyl-mercapto) -butoxy] -3,4-dihydrocarbostyril

The compound was prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 2-mercaptopvimidine.

Melting point: 154-156 ° C,

Yield: 79% of theory.

Example 43 6- [4- (2-Pyrimylylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (2-pyrimidylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 154-156 ° C,

Yield: 36% of theory.

Example 44 6- [4- (4-Pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril li 29 69064

To a solution of 1.3 g of 4-mercaptopyridine and 2.3 g of a 30% solution of sodium methylate in 15 ml of methanol are added 3.0 g of 6- (4-bromobutoxy) -3,4-dihydrocarbostyril and stirred for 14 hours. at room temperature. It is then diluted with 20 ml of water and the precipitated precipitate is recrystallized from ethanol.

Melting point: 128-129 ° C,

Yield: 1.6 g (49% of theory).

Example 45 6- [4- (2-Benzimidazolylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 2-mercaptobenzimidate-Sol.

Melting point: 100 - 103 ° C,

Yield: 45% of theory.

Example 46 6- [4- (2-Benzimidazolylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (2-benzimidazolylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 180-182 ° C,

Yield: 36% of theory.

Example 47 6- [4- (2-Benzthiazolyl-mercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 2-mercaptobenzthia-Sol.

Melting point: 157-158 ° C,

Yield: 70% of theory.

Example 48 6- [4- (2-Benzthiazolylsulfinyl) -butoxy] -3,4-dihydrocarbostyril Prepared according to Example 2 from 6- [4- (2-benzthiazolylmercapto-6,69064 butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. 183-184 ° C,

Yield: 69% of theory.

Example 49 6- (2-Phenylmercaptoethoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from thiophenol and 6- (2-chloroethoxy) -3,4-dihydrocarbostyril (melting point: 152.5-153.5 ° C). Melting point: 132-133.5 ° C,

Yield: 91% of theory.

Example 50 6- (2-Phenylsulfinyl-ethoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (2-phenylmercaptoethoxy) -3,4-hydrocarbostyril and hydrogen peroxide.

Melting point: 171-172 ° C,

Yield: 84% of theory.

Example 51 6- (2-Phenylsulfonyl-ethoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- (2-phenylmercaptoethoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 185-186 ° C,

Yield: 94% of theory.

Example 52 6- (3-Phenylmercappropoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (3-bromopropoxy) -3,4-dihydrocarbostyril (melting point: 111-118 ° C) and thiophenol. Melting point: 111-112 ° C,

Yield: 77% of theory.

xj 31

EsAgerkk.i_53 69064 6- (3-Phenylsulfinyl-propoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [3- (phenylmercapto) -propoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 131.5 - 133.5 ° C,

Yield: 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 are dissolved in 100 ml of dimethylformamide and 4, To 8 g of a 50% suspension of sodium hydride in paraffin oil. 12.5 ml of methyl iodide are added, followed by stirring for 3 hours at room temperature, dilution with water and extraction with chloroform. The evaporation residue is recrystallized from methanol with a little addition of activated carbon.

Melting point: 79.5 - 80.5 ° C,

Yield: 71% of theory.

Example 55 1-Methyl-6- (4-phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 1-methyl-6- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 82-82.5 ° C,

Yield: 60% of theory.

Example 56 1-Methyl-6- (4-phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 1-methyl-6- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostitrile and hydrogen peroxide.

Melting point: 108-109 ° C,

Yield: 49% of theory.

32

Example 57 69064 6- (6-Phenylmercapto-hexoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (6-bromohexoxy) -3,4-dihydrocarbostyril (melting point: 107.5-108 ° C).

Melting point: 112.5 - 113 ° C,

Yield: 34% of theory.

Example 58 6- (6-Phenylsulfinyl-hexoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (6-phenylindaptaptohexoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 119.5 - 121.5 ° C,

Yield: 35% of theory.

Example 59 6- (2-Hyaroxy-3-phenylmercaptopropoxy) -3,4-dihydrocarbostyril 2.10 g (0.03 mol) of potassium methylate are suspended in 40 ml of methanol and 4.11 g (0.04 mol) are added to the suspension. ) thiophenol to give a clear solution. With stirring, a further 4.38 g of 6- (2,3-epoxypropoxy) -3,4-dihydrocarbostyril (melting point: 125-128 ° C) are added, which dissolves with a slight heat. After about 5 minutes, the white crystal porridge begins to separate. Allow to stand overnight, then separate by suction and recrystallize from a small amount of methanol. White crystals are obtained.

Melting point: 148-149 ° C.

Yield: 73% of theory.

Example 60 6- (2-Hydroxy-3-phenylsulfinylpropoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (2-hydroxy-3-phenylmercappropoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 185-187 ° C,

Yield: 51% of theory.

33

Example 61 s r \ r \ s * - 69064 6- (2-Hydroxy-3-phenylsulfonyl-propoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- (2-hydroxy-3-phenylmercappropoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 170-172 ° C,

Yield: 54% of theory.

Example 62 7- (4-phenylmercaptobutoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 7-hydroxy-3,4-dihydrocarbostyril (N. Shigematsu et al., Chem. Pharm. Bull. 1961, 970-975) and 4-phenylmercapto-butyl bromide (b.p. 96-103 ° C).

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Melting point: 121 - 123 C,

Yield: 72% of theory.

Example 63 7- (4-Phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 7-hydroxy-3,4-dihydrocarbostyril (N. Shigematsu et al., Chem. Pharm. Bull. 1961, 970-975) and 4-phenylsulfinylbutyl bromide.

Melting point: 134-136 ° C,

Yield: 80% of theory.

Example 64 7- (4-Phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 7-hydroxy-3,4-dihydrocarbostyril (N. Shigematsu et al., Chem. Pharm. Bull. 1961, 970-975) and 4-phenylsulfonylbutyl bromide.

Melting point: 178.5-179.5 ° C,

Yield: 74% of theory.

34

Example 65 69064 8- (4-Phenylmercaptobutoxy) ~ 3,4-dihydrocarbostyril

Prepared according to Example 4 from 8-hydroxy-3,4-dihydrocarbostyril (JD Loudon et al., J. Chem. Soc. 1955, 743-744) and 4-phenylmercapto-butyl bromide (bp 0 02: 96-103 ° C) ). Melting point: 101-102 ° C,

Yield: 75% of theory.

Example 66 8- (4-Phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 8-hydroxy-3,4-dihydrocarbostyril (J. D. Loudon et al., J. Chem. Soc. 1955, 743-744) and phenylsulfinylbutyl bromide.

Colorless resin,

Yield: 60% of theory.

Rf value: 0.60 (TLC chromatograph on silica gel - eluent: benzene / ethanol / concentrated ammonia = 75/25/1).

Example 67 8- (4-Phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 8- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostrifil and betyperoxide.

Melting point: 114.5 - 115 ° C,

Yield: 60% of theory.

Example 68 6- [4- (2-Benzthiazolylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (2-benzthiazolyl-mercury) -butoxy] -3,4-dihydrocarbostyril and betyperoxide. Melting point: 146-149 ° C,

Yield: 61% of theory.

35

Example 69 69064 6- [4- (2-Quinolylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 2-mercaptoquinoline.

Melting point: 115 ° C,

Yield: 64% of theory.

-Example 70 6- [4- (2-Quinazolin-4-one-yl-mercapto) -butoxy] -3,4-dihydrycarbon-styrene_

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 2-mercaptokinazolin-4-one.

Melting point: 184.5 - 188 ° C,

Yield: 63% of theory.

Example 71 6- (4-Triphenylmethylmercapto-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) from triphenylmethyl mercaptan.

Melting point: 169-170 ° C,

Yield: 89% of theory.

Example 72 6- [2- (2-Naphthylmercapto) -ethoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-chlorobutoxy) -3,4-dihydrocarbostyril (melting point: 147-148 ° C) and 2-naphthyl mercaptan.

Melting point: 147.5 - 147.8 ° C,

Yield: 77% of theory.

Example 73 36 69064 6- [2- (2-Naphthylsulfinyl) -ethoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [2- (2-naphthylmercapto) -ethoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 186.5 - 187.5 ° C.

Yield: 88% of theory.

Example 74 6- [2- (4-Biphenylmercapto) -ethoxy] -3,4-dihydrocarbostitrile

Prepared according to Example 1 from 6- (2-chloroethoxy) -3,4-dihydrocarbostyril (melting point: 152.5-153.5 ° C) and 4-mercaptobiphenyl.

Melting point: 192-194 ° C,

Vocabulary: 92% of theory.

Example 75 6- [2- (4-Biphenylylsulfinyl) -ethoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [2- (4-biphenylyl mercapto) -ethoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 195-196 ° C,

Vocabulary: 66% of theory.

Example 76 6- [3- (2-Pyridylmercapto) -propoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (3-bromopropoxy) -3,4-dihydrocarbostitrile and 2-mercaptopyridine.

Melting point: 108-108.5 ° C,

Yield: 42% of theory.

Il

Example 77 6 9 0 6 4 37 6- (4-Phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril 1/6 g of 6- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril are dissolved in 50 ml of methanol. 0.9 g of N-bromosuccinimide are added to the solution. Stir at room temperature for 15 hours, dilute with 500 ml of 80 ° C water and first decant the oily residue, which gradually crystallizes. Recrystallize from xylene to give white crystals,

Melting point: 144-145 ° C,

Yield: 1.2 g (66% of theory).

Example 78 6- (4-Phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril 3.3 g of 6- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril are dissolved in 50 ml of methylene chloride, cooled to -70 ° C. and then a solution of 1.5 g of sulfuryl chloride in 5 ml of methylene chloride is added dropwise. After 15 hours, 20 ml of 95% ethanol are added and the mixture is warmed to room temperature by removing the cooling bath. Neutralize with aqueous soda solution, dry the methylene chloride phase over sodium sulfate, evaporate the solvent and recrystallize the residue from toluene.

Melting point: 143-145 ° C,

Yield: 2.8 g (81% of theory).

Example 79 5 - [(4-Phenylmercapto-butoxy) -3,4-dihydrocarbostyril]

Prepared according to Example 4 from 5-hydroxy-3,4-dihydrocarbostyril and 4-phenylmercaptobutyl bromide.

Melting point: 155-157 ° C,

Yield: 64% of theory.

38

Example 80 69064 5- (4-Phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 5-hydroxy-3,4-dihydrocarbostyril and 4-phenylsulfinylbutyl bromide.

Melting point: 136-138 ° C,

Yield: 64% of theory.

Example 81 5- (4-Phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 4 from 5-hydroxy-3,4-dihydrocarbostyril and 4-phenylsulfonylbutyl bromide.

Melting point: 187-189 ° C,

Yield: 73% of theory.

Example 82 6- [4- (2-Naphthylsulfonyl) -butoxy] -3,4-dihydrocarbostyril.

Prepared according to Example 3 from 6- [4- (2-naphthylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 173-175 ° C,

Yield: 95% of theory.

Example 83 6- [4- (4-Biphenylylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- [4- (4-biphenylyl mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 232-234.5 ° C,

Yield: 83% of theory.

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Example 84 69064 6- (4-Phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- (4-phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 157-158 ° C,

Yield: 88% of theory.

Example 85 6- [4- (2-Pyridylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- [4- (2-pyridylsulfinyl) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 123; 8 - 125 ° C,

Yield: 76% of theory.

Example 86 5- (4-Phenylsulfonyl-butoxy) -carbostyril 1.8 g of 5- (4-phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril are dissolved in 45 ml of dioxane, 1.87 g of 2,3-dichloro are added to the solution. -5,6-dicyano-benzoquinone and heated at reflux for 2.5 hours in an oil bath. Filter while hot and wash with hot dioxane the insoluble residue formed during the reaction, dilute the combined filtrate with 100 ml of chloroform and shake several times with a total of 150 ml of 2N sodium hydroxide. Dry the chloroform extract over sodium sulfate and filter in the presence of activated carbon, then evaporate and add ethyl acetate until white crystals separate.

Melting point: 182-183 ° C,

Yield: 850 mg (47% of theory).

Example 87 5 -. (4-Phenylmercapto-butoxy) -carbostyril

Prepared according to Example 86 from 5- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyano-benzoquinone * o 69064

Melting point: 185 - 187υΟ,

Yield: 40% of theory.

Example 88 5- (4-Phenylsulfinyl-butoxy) -carbostyril 0.56 g of 5- (4-phenylmercapto-butoxy) -carbostyril are dissolved in 8 ml of glacial acetic acid and 0.165 ml of 30% hydrogen peroxide are added to the solution, diluted with water and extracted twice. chloroform. The chloroform extract is washed with dilute sodium hydroxide solution and water, dried over magnesium sulfate and evaporated. Ethyl acetate is added to give colorless crystals,

Melting point: 155-157 ° C,

Yield: 389 mg (65% of theory).

Example 89 6- (4-Phenylmercapto-butoxy) -carbostyril

Prepared according to Example 86 from 6- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-4,5-dicyanobenzoquinone.

Melting point: 162-164 ° C,

Yield: 35% of theory.

Example 90 6- (4-Phenylsulfinyl-butoxy) -carbostyril

Prepared according to Example 86 from 6- (4-phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyano-benzoquinone. For purification, chromatograph on a silica gel column with a mixture of benzene, ethanol and concentrated ammonia = 75/25/3.

Melting point: 181-182.5 ° C,

Yield: 48% of theory.

From the first fractions of the column chromatography, 41% of the theoretical 6- (4-phenylmercapto-butoxy) -carbostyril is isolated in a yield of 15%. Melting point: 162-4 ° C.

Example 91 6- (4-Phenylsulfonyl-butoxy) -carbostyril

Prepared according to Example 86 from 6- (4-phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyano-benzoquinone. Purification is carried out by column chromatography on silica gel (grain size: 0.2 to 0.5 mm) with a mixture of chloroform, methanol and ethyl acetate = 4/1/1.

Melting point: 212-213 ° C,

Yield: 54% of theory.

Example 92 5- (4-Phenylmercapto-butoxy) -carbostyril

To a mixture of 32.3 g of 5-hydroxycarbostyril, 30 g of potassium carbonate and 650 ml of molecular sieve-dried dimethyl sulfoxide are added 49 g of 4-phenylmercaptobutyl bromide. Stir for 20 hours at 25 ° C, dilute with 3 liters of water and separate the crystallized reaction product with suction.

Melting point: 185-187 ° C (from toluene),

Yield: 45.0 g (70% of theory).

Example 93 5- (4-Phenylsulfonyl-butoxy) -carbostyril

5- (4-Phenylmercapto-butoxy) -carbostyril and 4 moles of hydrogen peroxide were prepared according to Example 88 at 60 ° C and for 14 hours.

Melting point: 182-183 ° C,

Yield: 73% of theory.

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Example 94 69064 6- (4-Phenylmercapto-butoxy) -carbostyril

Prepared according to Example 92 from 6-hydroxycarbostyril and 4-phenylmercaptobutyl bromide.

Melting point: 161-163 ° C,

Yield: 78% of theory.

Example 95 6- (4-Phenylsulfinyl-butoxy) -carbostyril

Prepared according to Example 88 from 6- (4-phenylmercapto-butoxy) -carbostyril and hydrogen peroxide.

Melting point: 181-182 ° C,

Yield: 68% of theory.

Example 96 6- (4-Phenylsulfinyl-butoxy) -carbostyril-i

Prepared according to Example 92 from 6-hydroxycarbostyril and 4-phenylsulfinylbutyl bromide difeta.

Melting point: 181-182 ° C,

Yield: 71% of theory.

Example 97 7- (4-Phenylsulfinyl-butoxy) -carbostyril

Prepared according to Example 86 from 7- (4-phenylsulfinyl-butoxy) -3,4-dihydrocarbostyril.

Melting point: 193-194 ° C,

Yield: 51% of theory.

II

43

Example 98 69064 8- (4-phenylmercapto-butoxy) -carbostyril

Prepared according to Example 86 from 8- (4-phenylmercapto-butoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyanobenzoquinone.

Melting point: 119-120 ° C,

Yield: 40% of theory.

Example 99 8- (4-Phenylsulfinyl-butoxy) -carbostyril

Prepared according to Example 88 from 8- (4-phenylmercapto-butoxy) -carbostyril by oxidation with hydrogen peroxide.

Melting point: 125/5 - 126.5 ° C,

Yield: 60% of theory.

Example 100 5- (4-Phenylsulfonyl-butoxy) -carbostyril 100 mg of 5- (4-phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril, 30 mg of palladium / carbon and 1 ml of mesitylene are heated to reflux. After 3.5 hours, an additional 30 mg of palladium / carbon is added and further heated for 9 hours. After stirring while hot, the filtrate is evaporated and the residue is chromatographed on a column of silica gel with a mixture of benzene, ethanol and concentrated ammonia = 75/25/3. In addition to the unreacted starting material, 9 mg of 5- (4-phenylsulfonyl-butoxy) -carbostyril are obtained,

Melting point: 182-183 ° C.

Example 101 6- (4-Aminoiminomethylmercapto-butoxy) -3,4-dihydrocarbostyril 18 g of 6- (4-bromobutoxy) -3,4-dihydrocarbostyril and 5 g of thiourea in 250 ml of water are heated to reflux. occurred completely (approximately 4 hours). After cooling, the impure diseases are extracted with chloroform and made alkaline with ammonia. The separated crystals are filtered off and dried.

Melting point: 140-141.8 ° C,

Melting point of the hydrochloride: 208-211 ° C,

Yield: 90% of theory.

Example 102 6- (4-Phenylsulfonyl) -butoxy-3,4-dihydrocarbostyril 107 mg of 6- (4-phenylsulfonyl) -butoxycarbostyril are suspended in 15 ml of methanol, 40 mg of palladium / carbon are added and hydrogenated at 50 DEG C. for 14 hours. and at a hydrogen pressure of 2.5 bar. After filtration of the catalyst, the clear solution is evaporated to give colorless crystals.

Melting point: 153-154 ° C,

Yield: 89 mg (83% of theory).

Example 103 6- (4-, Benzyl mercapto-butoxy) -3,4-dihydrocarbostyril 2.5 g of 6- (4-mercaptobutoxy) -3,4-dihydrocarbostyril are dissolved in 25 ml of dimethyl sulfoxide and 1.4 g of potassium carbonate are added to the solution with stirring. and then 1.3 ml of benzyl chloride. Stir for 15 hours at room temperature, dilute with 200 ml of water, separate the separated oily substance and recrystallize from ethyl acetate.

Melting point: 76-78 ° C,

Yield: 2.8 g (82% of theory).

Example 104 6- (5-Phenylmercaptopentoxy) -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (5-bromopetoxy) -3,4-dihydrocarbostyril and thiophenol.

Closing point: 117-119 ° C,

Yield: 71% of theory.

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Example 105 69064 6- (5-Phenylsulfinyl-pentoxyl) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- (5-phenylmercapto-pentoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 104-109.5 ° C,

Yield: 66% of theory.

Example 106 6- (5-Phenylsulfinyl-pentoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- (5-phenylmercapto-pentoxy) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 136.5 - 137.8 ° C,

Yield: 62% of theory.

Example 107 6- [5- (2-Pyridyl-mercapto) -pentoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (5-bromopentoxy) -3,4-dihydrocarbostyril and 3-mercaptopyridine.

Melting point: 113-114.8 ° C,

Yield: 76% of theory.

Example 108 5- (2-Hydroxy-3-phenylmercapto-pronoxy) -3,4-dihydrocarbostyril

Prepared according to Example 59 from 5- (2,3-epoxy-propoxy) -3,4-dihydrocarbostyril and thiophenol.

Melting point: 135-137 ° C,

Yield: 64% of theory.

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Example 109 69064 5- (2-Hydroxy-3-phenylsulfinyl-propoxy) -3,4-dihydrocarbostyril

Prepared according to Example 2 from 5- (2-hydroxy-3-phenylmercappropoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 186-188 ° C,

Yield: 60% of theory.

Example 110 5- (2-Hydroxy-3-phenylsulfonyl-propoxy) -3,4-dihydrocarbostyril

Prepared according to Example 3 from 5- (2-hydroxy-3-phenylmercaptopropoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 168-170 ° C,

Yield: 53% of theory.

Example 111 6- [4- (4-Hydroxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril and 4-hydroxythiophenol.

Melting point: 191.5 - 193.0 ° C,

Yield: 83% of theory.

Example 112 6- [4- (4-Hydroxyphenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-hydroxyphenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 206-207.8 ° C,

Yield: 84% of theory.

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Example 113 69064 6- [4- (4-Hydroxyphenylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- [4- (4-hydroxyphenyl mercapto) butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 219-219.5 ° C,

Yield: 78% of theory.

Example 114 6- [4- (4-Acetaminophenylmercapto) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril and 4-acetaminothiophenol.

Melting point: 162.5 - 163.0 ° C,

Yield: 65% of theory.

Example 115 6- [4- (4-Acetaminophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 2 from 6- [4- (4-acetaminophenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 202.0 - 203.8 °,

Yield: 55% of theory.

Example 116 6- [4- (4-Acetaminophenylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 3 from 6- [4- (4-acetaminophenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 143.5 - 147.0 ° C,

Yield: 88% of theory.

Example 117 69064 48 6- [4- (4,5-Di-p-chloro-phenyl-oxazol-2-yl-mercapto) -butoxy] -3,4-dihydrocarbostyril_

Prepared according to Example 1 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril and 2-mercapto-4,5-di-p-chlorophenyl oxazole. Melting point: 110-115 ° C,

Yield: 70% of theory.

Example 118 6- [4- (2-Pyridylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 86 from 6- [4- (2-pyridylsulfinyl) butoxy] -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyanobenzoquinone.

Melting point: 152-154 ° C,

Yield: 48% of theory.

Example 119 6- (4-Phenylmercapto-butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 102 from 6- (4-phenylmercapto-butoxy) -carbostyril by catalytic hydrogenation of Rhenium VII sulfide over a catalyst.

Melting point: 121-122 ° C,

Yield: 67% of theory.

Example 120 8- (4-Phenylsulfonyl-butoxy) -carbostyril

Prepared according to Example 86 from 8- (4-phenylsulfonyl-butoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-disanobenzoquinone.

Melting point: 146-147 ° C,

Yield: 41% of theory.

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Example 121 69064 49 7- (4-Phenylmercapto-butoxy) -carbostyril

Prepared according to Example 86 from 7- (4-phenylmercaptobutoxy) -3,4-dihydrocarbostyril and 2,3-dichloro-5,6-dicyanobenzoquinone.

Melting point: 157.5 - 158.5 ° C,

Yield: 54% of theory.

Example 122 6- [4- (2,5-Dichlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril 54 2.21 g (0.0315 moles) of potassium methylate and 5.76 g (0.0315 moles) of methanol are dissolved in any methanol. ) 98% 2,5-dichlorothiophenol. and 8.94 g (0.03 mol) of 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) are added to the solution. The solution is heated to reflux to form a clear solution first. After about 5 minutes, so much of the crystalline reaction product separates that the reaction mixture solidifies into crystalline porridge, which can hardly be stirred.

After 1 hour, cool to room temperature, separate by suction and recrystallize from ethanol. Colorless crystals are obtained. Melting point: 133-134 ° C.

Yield: 10.60 g (89.1% of theory).

Example 123 6- [4- (2,5-Dichlorophenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril 5.55 g (0.014 mol) of 6- [4- (2,5-dichlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril suspend in 40 ml of glacial acetic acid and add 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 stir at room temperature. The suspension becomes pale and an almost clear solution is formed. After 70 hours, the white crystals have separated. Separate by suction and recrystallize from ethanol. Melting point: 185-186 ° C,

Yield: 5.43 g (94.1% of theory).

F.simfirJckj_124 50 69064 6- [4- (2,5-Dichlorophenylsulfonyl) -butoxy] -3,4-dihydrocarbostyril 2.97 g (0.0075 moles) of 6- / 4- (2,5-dichlorophenylmercapto) -butoxy / - 3,4-Dihydrocarbostyril is added to 15 ml of ice-cold formic acid and 1.49 ml of 40.08% hydrogen peroxide (0.0175 mol) are added. Stir for 2.5 hours and then dilute with three times the amount of water. The separated crystals are recrystallized from ethanol.

Melting point: 174.5 - 175.5 ° C,

Yield: 1.99 α (61.9% of theory).

Example 125 6- [4- (S-Dichlorophenylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 124 from 6- [4- (3,4-dichlorophenylmercapto) -butoxy] -3,4-dihydrocarbostyril (melting point: 116.5-118 ° C) and hydrogen peroxide.

Melting point: 172-173 ° C,

Yield: 96% of theory.

Example 126 6- [4- (4-Hydroxy-3,5-di-tert-butyl-phenylmercapto) -butoxy] -3,4-dihydrocarbostyril_

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 4-hydroxy-3,5-di-tert-butylthiophenol.

Melting point: 146-147 ° C,

Yield: 68.8% of theory.

Example 127 6- [4- (4-Hydroxy-3,5-di-tert-butyl-phenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril_______

Prepared according to Example 123, 6- [4- (4-hydroxy-3,5-di-tert-1-52,69064 miles of 6- [4- (4-pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril ( melting point: 128-133 ° C) according to Example 123 with hydrogen peroxide.

Melting point: 154 ° C,

Yield: 57% of theory.

Example 132 6- [4- (4-Pyridylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 124 from 6- [4- (4-pyridylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 179-183 ° C,

Yield: 35.9% of theory.

Example 133 6- [3- (3,4-Dichlorophenylsulfinyl) -2-hydroxy-propoxy] -3,4-dihydrocarbostyril-3.51 g (0.016 mol) of 6- (2,3-epoxy-propoxy) -3.4 -dihydrocarbostyril (melting point: 125-128 ° C) is dissolved in 35 ml of methanol and 4.29 g of 3,4-dichlorothiophenol are added to the solution. Heat at reflux for 5 hours, then cool to give crystals which are filtered off with suction and recrystallized from ethanol. Melting point: 175-176 ° C,

Yield: 2.48 g (38.9% of theory).

The 6- [3- (3,4-dichlorophenylmercapto) -2-hydroxypropoxy] -3,4-dihydrocarbocitrile thus obtained is oxidized with hydrogen peroxide according to Example 123.

Melting point: 108-110 ° C,

Yield: 75% of theory.

Example 134 6- (3-Benzylmercaptopropoxy) -3,4-dihydrocarbostyril

Prepared according to Example 122 from 6- (3-bromopropoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and benzyl mercaptan.

> ö li 53

Melting point: 97.5-99.0 ° C. 69064

Yield: 58% of theory.

Example 135 6- (3-Benzylsulfinyl-propoxy) -3,4-dihydrocarbostyril

Prepared according to Example 123 from 6- (3-benzylmercapto) -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 144.5 - 147.0 ° C,

Yield: 51% of theory.

Example 136 5- (3-tert-Butylmercapto-2-hydroxy-propoxy) -3,4-dihydrocarbostyril_

Prepared according to Example 133 from 5- (2,3-epoxy-propoxy) -3,4-dihydrocarbostyril. (melting point: 171-173 ° C) and tert-butyl mercaptan.

Melting point: 105-109 ° C,

Yield: 77.1% of theory.

Example 137 5- (3-tert-Butylsulfinyl-2-hydroxy-propoxy) -3,4-dihydrocarbostyril_

Prepared according to Example 123 from 5- (3-tert-butyl mercapto-2-hydroxy-propoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 175-177 ° C,

Yield: 52.1% of theory.

Example 138 5- (3-tert-Butylsulfonyl-2-hydroxy-propoxy) -3,4-dihydrocarbostyril_

Prepared according to Example 124 from 5- (3-tert-butyl mercapto-2-hydroxypropoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 210-212 ° C,

Yield: 37.1% of theory.

54

Example 139 69064 6- [4- (2-Pyridylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (2-pyridylsulfinyl) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 179-180 ° C,

Yield: 65.8% of theory.

Example 140 4-Methyl-6- (4-phenylmercapto-butoxy) -carbostyril 5.25 g (0.03 moles) of 4-methyl-6-hydrocarbostyril (melting point: 326-330 ° C, see RR Holmes et al. , J. Amer. Chem. Soc. 76, 2404 (1954)), 8.09 g (0.033 mol) of 4-phenylmercaptobutyl bromide and 6.22 g (0.045 mol) of potassium carbonate are stirred for 16 hours at room temperature in 70 ml of dimethyl sulfoxide, which then diluted with water and the separated crystals are recrystallized from toluene after drying.

Melting point: 148-150 ° C,

Yield: 6.2 g (61.2% of theory).

Example 141 4-Methyl-6- (4-phenylsulfinyl-butoxy) -carbostyril

Prepared according to Example 140 from 4-methyl-6-hydroxycarbostyril (melting point: 326-330 ° C) and 4-phenylsulfinylbutyl bromide.

Melting point: 167-168 ° C,

Yield: 47.3% of theory.

Example 142 4-Methyl-6- (4-phenylsulfonyl-butoxy) -carbostyril

Prepared according to Example 140 from 4-methyl-6-hydroxycarbostyril (melting point: 326-330 ° C) and 4-phenylsulfonylbutyl bromide.

li 55

Melting point: 217-219 ° C, 69064

Yield: 66.6% of theory. .

Example 143 4-Methyl-6- [4- (2-pyridylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 4-methyl-6- (4-bromobutoxy) -carbostyril (melting point: 217-219 ° C) and 2-mercaptopyridine. Melting point: 149-151 ° C,

Yield: 85.7% of theory.

Example 144 4-Methyl-6- [4- (2-pyridylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 4-methyl-6- [4- (2-pyridyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 167-169 ° C,

Yield: 61.8% of theory.

Example 145 4-Methyl-6- [4- (2-pyridylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 4-methyl-6- [4- (2-pyridyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 195-197 ° C,

Yield: 29.5% of theory.

Example 146 4-Methyl-6- [4- (2-quinolylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 4-methyl-6- (4-bromobutoxy) -carbostyril and 2-mercaptoquinoline.

Melting point: 162-163 ° C,

Yield: 81.9% of theory.

____ - · u_ 56 69064

Example 14 7 U ✓ U u “4-Methyl-6- [4- (2-quinolylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 4-methyl-6- [4- (2-quinolyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 189-190 ° C,

Yield: 47.5% of theory.

Example 148 4-Methyl-6- [4- (2-quinolylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 4-methyl-6- [4- (2-quinolyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 199-203 ° C,

Yield: 31.5% of theory.

Example 149 4-Methyl-6- [4- (4-biphenylylsulfinyl) -butoxy] -carbostyrilyl

Prepared according to Example 123 from 4-methyl-6- [4- (4-biphenylyl-mercapto) -butoxy] -carbostyril (melting point: 174-176 ° C) and hydrogen peroxide.

Melting point: 161-162 ° C,

Yield: 59% of theory.

Example 150 6- / 4- (4-Chlorophenylmercapto) -butoxy / carbositrile

Prepared according to Example 122 from 6- (4-chlorobutoxy) carbostyril (melting point: 206-208 ° C) and 4-chlorothiophenol. Melting point: 168-170 ° C,

Yield: 85% of theory.

57

Example 151 69064 6- [4- (4-Chloro-phenylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (4-chlorophenylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 157-158 ° C,

Yield: 81% of theory.

Example 152 6- [4- (4-Chloro-phenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (4-chlorophenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 197 - 199 ° C /

Yield: 99% of theory.

Example 153 6- [4- (3,4-Dichloro-phenylmethyl) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 3,4-dichlorothiophenol. Melting point: 149-152 ° C,

Yield: 60% of theory.

Example 154 6- / 4- (3,4-Dichlorophenylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (3,4-dichlorophenylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 191-196 ° C,

Yield: 87% of theory.

58

Example 155 69064 6- / 4- (3/4-Dichlorophenylsulfonyl) -butoxy / carbostyril

Prepared according to Example 124 from 6- [4- (3,4-dichlorophenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide. Melting point: 188-190 ° C,

Yield: 83% of theory.

Example 156 6- / 4- (2,5-Dichlorophenylmercapto) -butoxy / carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril and 2,5-dichlorothiophenol.

Melting point: 175-176 ° C,

Yield: 85% of theory.

Example 157 6- / 4- (2- # 5-Dichlorophenylsulfinyl) -butoxy / carbostyril

Prepared according to Example 123 from 6- [4- (2,5-dichlorophenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide. Melting point: 200 - 202 ° C /

Yield: 75% of theory.

Example 158 6- [4- (2,5-Dichlorophenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (2,5-dichlorophenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide in formic acid.

Melting point: 203-205 ° C,

Yield: 79% of theory.

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Example 159 69064 59 6- / 4- (4-Fluorophenylmercapto) -butoxy / carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) -carbonyl and 4-fluorothiophenol.

Melting point: 149-150 ° C,

Yield: 85% of theory.

Example 160 6- / 4- (4-Fluorophenylsulfinyl) -butoxy / carbostyril

Prepared according to Example 123 from 6- [4- (4-fluorophenyl mercapto) butoxy] carbostyril and hydrogen peroxide.

Melting point: 164-165 ° C.

Yield: 50% of theory.

Example 161 6- [4- (4-Fluorophenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (4-fluorophenylmercapto) · butoxy / carbostyril and hydrogen peroxide in formic acid. Melting point: 209-211 ° C,

Yield: 59% of theory.

Example 162 6- [4- (4-Hydroxy-3/5-di-tert-butyl-phenylmercapto) -butoxy] -carbostyril__

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 4-hydroxy-3,5-di-tert-butyl-thiophenol (melting point: 84.5-86 ° C). 0 ° C).

Melting point: 172-173 ° C,

Yield: 77% of theory.

60

Example 163 69064 6- [4- (4-Hydroxy-3,5-di-tert-butylphenylsulfinyl) -butoxy] -carboxyl]

Prepared according to Example 123 from 6- [4- (4-hydroxy-3,5-di-tert-butylphenylmercapto) -butoxy] -carbostyril and hydrogen peroxide. Melting point: 192-194 ° C,

Saabto: 83% of theory.

Example 164 6- / 4- (4-Hydroxy-3,5-di-tert-butylphenylsulfonyl) -butoxy] -carbostyril__

Prepared according to Example 124 from 6- [4- (4-hydroxy-3,5-di-tert-butylphenylmercapto) -butoxy] -carbostyril and hydrogen peroxide in formic acid.

Melting point: 242-244 ° C,

Yield: 92% of theory.

Example 165 6- [4- (4-Biphenylyl-mercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 4-biphenyl mercaptan. Melting point: 191-192 ° C,

Yield: 82% of theory.

Example 166 6- [4- (4-Biphenylylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (4-biphenylyl mercapto) butoxy] carbostyril and hydrogen peroxide.

Melting point: 196-197 ° C,

Yield: 80% of theory.

li 61 69064

Example 167 n 6- [4- (4-Biphenylylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (4-biphenylyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 213-215 ° C,

Yield: 73% of theory.

Example 168 6- / 4- (4-Nitrophenylmercapto) -butoxy / carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 4-nitrothiophenol. Melting point: 184-185 ° C,

Yield: 96% of theory.

Example 169 6- [4- (4-Nitrophenylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (4-nitrophenylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 183-184 ° C,

Yield: 77% of theory.

Example 170 6- [4- (4-Nitrophenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (4-nitrophenylsulfinyl) -butoxy] -4-carbostyril and hydrogen peroxide in formic acid. Melting point: 230 - 232 ° C,

Yield: 70% of theory.

Example 171 62 69064 6- / 4- (2-Quinolylmercapto) -butoxy / carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 2-mercaptoquinoline. Melting point: 132 ° C,

Yield: 99% of theory.

Example 172 6- [4- (2-Quinolylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (2-quinolylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 161-162 ° C,

Yield: 66% of theory.

Example 173 6- [4- (2-Quinolylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (2-quinolylsulfinyl) -butoxy] -carbostyril and hydrogen peroxide in formic acid. Melting point: 197-198 ° C,

Yield: 58% of theory.

Example 174 5- (4-Phenylmercapto-butoxy) -oxindole

Prepared according to Example 140 from 5-hydroxyoxindole (J. chem. Soc. 1961/2723) and 4-phenylmercaptobutyl bromide. Melting point: 131-132 ° C,

Yield: 13% of theory.

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Example .175 69064 63 5- (4-Phenylsulfinyl-butoxy) -oxindole

Prepared according to Example 123 from 5- (4-phenylmercapto-butoxy) -oxindole and hydrogen peroxide.

Melting point: 114-116 ° C,

Yield: 61% of theory.

Example 176 6- [2- (Phenylsulfinylmethyl) -benzyloxy] -3,4-dihydro-carbostyril-

A mixture of 67.1 g of phthalide, 51.3 ml of thiophenol, 35.1 g of potassium methylate and 250 ml of raethanol is heated to reflux.

The resulting 2-phenylmercaptomethylbenzoic acid (yield: 78% of theory, melting point: 108-110 ° C) is then esterified with methanol / thionyl chloride by standing at -40 ° C. After standing overnight at room temperature, 2-phenylmercaptomethyl-benzoic acid methyl ester (yield: 89% of theory, bp Q 145 ° C) is obtained, which is converted into 2-phenylmercaptomethyl-phenylcarbinol by reduction with lithium aluminum hydride in diethyl ether (97%) in diethyl ether. , melting point: 64-65 ° C).

This compound is reacted with p-toluenesulfochloride to give 2-phenylmercaptomethyl-phenylcarbinol-p-toluenesulfonic acid ester. (TLC: silica gel; eluent: chloroform / ethyl acetate = 1: 1; Rf = 0.8. Yield: 55% of theory). This ester is reacted with 6-hydroxy-3,4-dihydrocarbocitrile according to Example 140 to give 6- [2- (phenylmercaptomethyl) -benzyloxy] -3,4-dihydrocarbostyril (thin layer chromatogram: silica gel; eluent: chloroform / ethyl acetate = 1: 1). , Rf = 0.35, yield: 64% of theory).

This compound is oxidized according to Example 123 with hydrogen peroxide to 6- [2- (phenylsulfinylmethyl) -benzyloxy] -3,4-dihydrocarbostyril.

Melting point: 133-135 ° C,

Yield: 64% of theory.

64

Example 177 69064 6- [4- (Phenylmercaptomethyl) -benzyloxy] -3,4-dihydrocarbostyril p-Xylylene dichloride and thiophenol are reacted in a molar ratio of 1: 1 at room temperature in dimethyl sulfoxide in the presence of excess potassium carbonate. 4-Phenylmercaptomethylbenzyl chloride (control: thin layer chromatogram) is obtained, which is reacted without isolation according to Example 140 in the reaction solution with 6-hydroxy-3,4-dihydrocarbostyril.

Melting point: 139-141 ° C,

Yield: 52% of theory.

Example 178 6- [4- (Phenylsulfinyl) -benzyloxy] -3,4-dihydrocarbostyril

Prepared according to Example 123 from 6- [4- (phenylmercaptomethyl) -benzyloxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 179-181 ° C,

Yield: 61% of theory.

Example 179 6- (4-Cyclohexylmercapto-butoxy) -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and cyclohexyl mercaptan. Melting point: 153-159 ° C,

Yield: 89% of theory.

Example 180 6- (4-Cyclohexylsulfinyl-butoxy) -carbostyril

Prepared according to Example 123 from 6- (4-cyclohexyl mercapto-butoxy) carbostyril and hydrogen peroxide.

Melting point: 169-170 ° C,

Yield: 57% of theory.

65

Example 181 69064 6- [4- (4-Bromophenylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) -carbonyl (melting point: 198-199 ° C) and 4-bromothiophenol. Melting point: 156-158 ° C,

Yield: 53% of theory.

Example 182 6- [4- (4-Bromophenylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (4-bromophenylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 168-170 ° C,

Yield: 65% of theory.

Example 183 6- [4- (3-Methyl-4-bromo-phenylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 189-199 ° C) and 3-methyl-4-bromothiophenol. Melting point: 167-169 ° C,

Yield: 76% of theory.

Example 184 6- [4- (3-Methyl-4-bromo-phenylsulfanyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (3-methyl-4-bromo-phenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 169-172 ° C,

Yield: 79% of theory.

Example 185 69064 66 6- [4- (3-Methyl-4-bromo-phenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (3-methyl-4-bromo-phenylmercapto) -butoxy] -carbostyril and hydrogen peroxide. Melting point: 163-167 ° C,

Yield: 57% of theory.

Example 186 6- [4- (1,2,4-Triazol-3-yl-mercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril and 3-mercapto-1,2,4-triazole.

Melting point: 203-206 ° C.

Yield: 82% of theory.

Example 187 6- / 4- (2,4,5-Trichlorophenylmercapto) -butoxy / carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 2,4,5-trichlorothiophenol. Melting point: 177-178 ° C,

Yield: 83% of theory.

Example 188 6- [4- (2,4,5-Trichlorophenylsulfinyl) -butoxyl] -carbostyril

Prepared according to Example 123 from 6- [4- (2,4,5-trichlorophenylmercapto) -butoxy] -carbostyril and hydrogen peroxide. Melting point: 206-208 ° C,

Yield: 98% of theory.

Example 189 6- [4- (3,5-Dibromo-4-amino-phenylmercapto) -butoxy] -3,4-dihydrocarbostyril __________ · 67,69064

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 3/5-dibromo-4-amino-thiophenol.

Melting point: 90-92 ° C,

Yield: 89% of theory.

Example 190 6- [4- (3,5-Dibromo-4-amino-phenylsulfinyl) -butoxy] -3,4-dihydro-carbostyril_

Prepared according to Example 123 from 6- [4- (3,5-dibromo-4-amino-phenyl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 144-146 ° C,

Yield: 76% of theory.

Example 191 6- [4- (3,5-Dibromo-4-amino-phenylsulfonyl) -butoxy] -3,4-dihydro-carbostyril ___________

Prepared according to Example 124 from 6- [4- (3,5-dibromo-4-amino-phenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 157-159 ° C,

Yield: 87% of theory.

Example 192 6- [4- (3,5-Dibromo-4-amino-phenylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) -carbonyl (melting point: 198-199 ° C) and 3,5-dibromo-4-aminothiophenol.

Melting point: 153 - 155 ° C,

Yield: 86% of theory.

Example 193 6 9 0 6 4 68 6- [4- (3,5-Dibromo-4-amino-phenylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (3,5-dibromo-4-amino-phenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide. Melting point: 205-207 ° C.

Yield: 79% of theory.

Example 194 6- [4- (3,5-Dibromo-4-amino-phenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (3,5-dibromo-4-amino-phenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide in formic acid.

Melting point: 238-241 ° C,

Yield: 87% of theory.

Example 195 6- [4- (4-Bromo-3-methyl-phenylmercapto) -butoxy] -3,4-dihydro-carbostyril_

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 4-bromo-3-methylthiophenol.

Melting point: 104-109 ° C,

Yield: 81% of theory.

Example 196 6- [4- (4-Bromo-3-methyl-phenylsulfinyl) -butoxy] -3,4-dihydro-carbocarbonyl ______________

Prepared according to Example 123 from 6- [4- (4-bromo-3-methyl-phenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Melting point: 129-130 ° C,

Yield: 75% of theory.

li 69

Example 19 7 s r \ r \ s λ - 69064 6- [4- (2/5-Dibromo-phenylmercapto) -butoxy] -3,4-dihydrocarbostyrene

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 2,5-dibromothiophenol.

Melting point: 127 - 129 ° C /

Yield: 75% of theory.

Example 198 6- [4- (2,5-Dibromo-phenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 123 from 6- [4- (2,5-dibromo-phenyl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 182 - 184 ° C /

Yield: 84% of theory.

Example 199 6- [4- (2/5-Dibromo-phenylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 2,5-dibromothiophenol. Melting point: 178 - 185 ° C /

Yield: 67% of theory.

Example 200 6- / 4- (2,5-Dibromo-phenylsulfinyl) -butoxy / carbostyril

Prepared according to Example 123 from 6- [4- (2,5-dibromo-phenylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 187-189 ° C,

Yield: 45% of theory.

Example 201 6- [3- (3/4-Dichloro-phenylmercapto) -propoxy] -3,4-dihydrocarbostyril Prepared according to Example 122 from 6- (3-bromopropoxy) -3,4-70,69064 dihydrocarbostyril (melting point: 111) - 118 ° C) and 3,4-dichloro-thiophenol.

Melting point: 106-107 ° C,

Yield: 76% of theory.

Example 202 6- [3- (3,4-Dichloro-phenylsulfinyl) -propoxy] -3,4-dihydrocarbositrile_

Prepared according to Example 123 from 6- [3- (3,4-dichloro-phenyl-mercapto) -propoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 170-172 ° C,

Yield: 84% of theory.

Example 203 6- [4- (4-Cyclohexyl-phenylmercapto) -butoxy] -3,4-dihydrocarbostyril __________________

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 4-cyclohexylthiophenol.

Melting point: 118-120 ° C,

Yield: 68% of theory.

Example 204 6- [4- (4-Cyclohexyl-phenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril__

Prepared according to Example 123 from 6- [4- (4-cyclohexyl-phenyl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 155-157 ° C,

Yield: 65% of theory.

Example 205 6- [4- (4-Cyclohexyl-phenylsulfonyl) -butoxy] -3,4-dihydrocarbos-styril _____________

Prepared according to Example 124 from 6- [4- (4-cyclohexyl-phenyl-71,69064 mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 172-174 ° C,

Yield: 52% of theory.

Example 206 6- [4- (4-Cyclohexyl-phenylmercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 188-189 ° C) and 4-cyclohexylthiophenol. Melting point: 165-167 ° C,

Yield: 64% of theory.

Example 207 6- [4- (4-Cyclohexyl-phenylsulfinyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (4-cyclohexyl-phenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 188-190 ° C,

Yield: 64% of theory.

Example 208 6- [4- (4-Cyclohexyl-phenylsulfonyl) -butoxy] -carbostyril

Prepared according to Example 124 from 6- [4- (4-cyclohexyl-phenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 185-186 ° C,

Yield: 87% of theory.

Example 209 6- [4- (4-tert-Butyl-phenyl-mercapto) -butoxy] -3,4-dihydro-carbostyril _____

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 4-tert-butylthiophenol.

Melting point: 126 - 127 ° C /

Yield: 86% of theory.

72

Example 210 69064 6- [4- (4-tert-Butyl-phenylsulfinyl) -butoxy] -3,4-dihydrocarbostyril _____________

Prepared according to Example 123 from 6- [4- (4-tert-butyl-phenyl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 121-123 ° C,

Yield: 67% of theory.

Example 211 6- [4- (4-tert-Butyl-phenylsulfonyl) -butoxy] -3,4-dihydrocarbostyril __

Prepared according to Example 124 from 6- [4- (4-tert-butyl-phenyl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 198-200 ° C,

Yield: 83% of theory.

Example 212 6- [4- (4-tert-Butyl-phenyl-mercapto) -butoxy] -carbostyril

Prepared according to Example 122 from 6- (4-bromobutoxy) carbostyril (melting point: 198-199 ° C) and 4-tert-butylthiophenol. Melting point: 156 - 158 ° C /

Yield: 63% of theory.

Example 213 6- / 4- (4-tert-Butyl-phenylsulfanyl) -butoxy] -carbostyril

Prepared according to Example 123 from 6- [4- (4-tert-butyl-phenylmercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 164-166 ° C,

Yield: 74% of theory.

73

Example 214 69064 6- / 4- (4-tert-Butyl-phenylsulfonyl) -butoxy / carbostyril

Prepared according to Example 124 from 6- [4- (4-tert-butyl-phenyl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Melting point: 203-205 ° C,

Yield: 56% of theory.

Example 215 6- [4- (2-Quinolylsulfinyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 123 from 6- [4- (2-quinolylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 154-157 ° C,

Yield: 79% of theory.

Example 216 6- [4- (2-Quinolylsulfonyl) -butoxy] -3,4-dihydrocarbostyril

Prepared according to Example 124 from 6- [4- (2-quinolylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

Rf value: 0,50 (silica gel plate; eluent: benzene / ethanol / concentrated ammonia = 75: 25: 2),

Yield: 72% of theory.

Example 217 6- [2- (N-Methyl-N-cyclohexyl-carbamidomethylmercapto) -ethoxy] -3,4-dihydrocarbostyril __________

Prepared according to Example 122 from 6- (2-chloroethoxy) -3,4-dihydrocarbostyril (melting point: 152.5-153.5 ° C) and N-methyl-N-cyclohexylthio [4] glycolic acid amide.

Rf value: 0.46 (silica gel light plate; eluent: ethylene chloride / methanol = 95: 5).

Yield: 63% of theory.

74

Example 218 69064 6- [2- (N-Methyl-N-cyclohexyl-carbamidomethylsulfinyl) -ethoxy] -3,4-dihydrocarbostyril__

Prepared according to Example 123 from 6- [2- (N-methyl-N-cyclohexylcarbamidomethylmercapto) -ethoxy] -3,4-dihydrocarbostyril and hydrogen peroxide.

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

Melting point: 143-146 ° C,

Yield: 48% of theory.

Example 219 6- [2- (N-Methyl-N-cyclohexyl-carbamidomethylsulfonyl) -ethoxy] -3,4-dihydrocarbostyril_

Prepared according to Example 124 from 6- [2- (N-methyl-N-cyclohexyl-carbamidomethylmercapto) -ethoxy] -3,4-dihydrocarbostyril and hydrogen peroxide in formic acid.

Rf value: 0.48 (silica gel light plate; eluent: ethylene chloride / methanol = 95: 5).

Melting point: 110-111 ° C,

Yield: 45% of theory.

Example 220 6- / 2- (N-Methyl-N-cyclohexyl-carbamidomethylmercapto) -ethoxy / carbostyril ______

Prepared according to Example 122 from 6- (2-chloroethoxy) carbostyril / Rf value: 0.30 (silica gel light plate; eluent: ethylene chloride / methanol = 95: 5) / and N-methyl-N-cyclohexyl-thioglycolic acid. amide.

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

Yield: 62% of theory.

Il

Example 221 69064 75 6- [2- (N-Methyl-N-cyclohexyl-carbamidomethylsulfinyl) -ethoxy] -carbostyril_

Prepared according to Example 123 from 6- [2- (N-methyl-N-cyclohexyl-carbamidomercapto) -ethoxy] -carbostyril and hydrogen peroxide. Rf value: 0.027 (silica gel light plate; eluent: ethylene chloride / methanol = 95: 5.

Melting point: 128-130 ° C,

Yield: 65% of theory.

Example 222 6- [2- (N-Methyl-N-cyclohexyl-carbamidomethylsulfonyl) -ethoxy] -carbonyl _____________

Prepared according to Example 124 from 6- [2- (N-methyl-N-cyclohexyl-carbamidomercapto) -ethoxy] -carbostyril and hydrogen peroxide. Rf value: 0.39 (silica gel casting plate; eluent: ethylene chloride / methanol = 95: 5.

Yield: 67% of theory.

Example 223 6- [3- (3,4-Dichlorophenylsulfonyl) -propoxy] -3,4-dihydrocarbostyril

Prepared according to Example 124 from 6- [3- (3,4-dichlorophenylmercapto) -propoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 187-188 ° C,

Yield: 87% of theory.

Example 224 6- [5- (3,4-Dichlorophenylmercapto) -pentoxy] -3,4-dihydrocarbostyril

Prepared according to Example 122 from 6- (5-bromopentoxy) -3,4-dihydrocarbostyril (melting point: 97-98 ° C) and 3,4-dichlorothiophenol.

Melting point: 101-104 ° C,

Yield: 69% of theory.

76 _. ... ,,, 69064

Example 225 w 6- [5- (3/4-Dichlorophenylsulfinyl) -pentoxy] -3/4-dihydrocarbostyril

Prepared according to Example 123 from 6- [5- (3/4-dichlorophenylmercapto) -pentoxy) -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 165-166 ° C,

Yield: 74% of theory.

Example 226 6- [5- (3,4-Dichlorophenylsulfonyl) -pentoxy] -3,4-dihydrocarbostyril

Prepared according to Example 124 from 6- [5- (3,4-dichlorophenyl-mercapto) -pentoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Melting point: 176-178 ° C,

Yield: 65% of theory.

Example 227 6- [4- (2-Methyl-4-tert-butyl-phenylmercapto) -butoxy] -3,4-dihydrocarbostyril _________

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 2-methyl-4-tert. butyylitiofenolista.

Melting point: 81-85 ° C,

Yield: 91% of theory.

Example 228 6- [4- (2-Methyl-4-tert-butyl-phenylsulfinyl) -butoxy] -3,4-dihydro-carbostyril_

Prepared according to Example 123 from 6- [4- (2-methyl-4-tert-butyl-phenylmercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Resinous substance.

Rf value: 0.54 (silica gel light plate; eluent: ethylene chloride / methanol = 95: 5).

Il 77 69064

Example 229 6- [4- (3,5-Dichloro-4-hydroxy-phenylmercapto) -butoxy] -3,4-dihydro-carbostyril ____

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 3,5-dichloro-4-hydroxytiphenol using nitrogen as a shielding gas.

Melting point: 110-114 ° C,

Yield: 94% of theory.

Example 230 5-Bromo-6- (4-phenylmercaptobutoxy) -carbostyril

Prepared according to Example 122 from 5-bromo-6- (4-bromobutoxy) -carbostyril (prepared by bromination of 6- (4-bromobutoxy) -carbostyril) and thiophenol.

Melting point: 209-213 ° C,

Yield: 41% of theory.

Example 231 5-Nitro-6- (4-phenylmercaptobutoxy) -carbostyril

Prepared according to Example 122 from 5-nitro-6- (4-bromobutoxy) -cargostyril (melting point: 250 ° C, prepared by nitration of 6- (4-bromobutoxy) -3,4-dihydrocarbostyril) and thiophenol.

Melting point: 228-230 ° C,

Yield: 71% of theory.

Example 232 5-Nitro-6- (4-phenylsulfinylbutoxy) carbostyril

Prepared according to Example 123 from 5-nitro-6- (4-phenylmercaptobutoxy) -carbostyril and hydrogen peroxide.

Melting point: 192-194 ° C,

Yield: 91% of theory.

Example 233 78 69064 5-Acetamino-6- (4-phenylmercaptobutoxy) -carbostyril

Prepared according to Example 122 from 5-acetamino-6- (4-bromobutoxy) carbostyril (prepared by reduction of zinc in acetic acid with the addition of 5-nitro-6- (4-bromobutoxy) carbostyril with acetic anhydride) and thiophenol.

Melting point: 238-240 ° C,

Yield: 80% of theory.

Example 234 5-Acetamino-6- (4-phenylsulfinylbutoxy) -carbostyril

Prepared according to Example 123 from 5-acetamino-6- (4-phenyl-mercapto) -butoxy) carbostyril and hydrogen peroxide.

Melting point: 213-127 ° C,

Yield: 47% of theory.

Example 235 5-Bromo-6- (4-phenylsulfinylbutoxy) -carbostyril

Prepared according to Example 123 from 5-bromo-6- (4-phenylmercapto-butoxy) -carbostyril and hydrogen peroxide.

Melting point: 190-191 ° C.

Yield: 82% of theory.

Example 236 4-Methyl-6- [4- (2-pyridylsulfinyl) -butoxy] -carbostyril

0.170 g (0.0005 mol) of 4-methyl-6- / 4- (2-pyridylmercapto) -butoxy / carbostyril dissolved in 5 ml of glacial acetic acid and 0.107 g (0.0005 mol) of taper iodate dissolved in sodium are mixed together. To 6 ml of water and allow to stand at room temperature for 22 hours.

The light brown solution is then diluted with 20 ml of water and the reaction product is extracted with chloroform. The extract is shaken once with sodium bicarbonate solution and dried over anhydrous crude 79.69064 sodium sulfate. After evaporation, it is recrystallized from toluene. Melting point: 166-168 ° C,

Yield: 0.04 g (22.5% of theory).

Example 237 6- (4-tert-Butylphenylsulfinyl) -butoxy) -3,4-dihydrocarbostyril

Prepared according to Example 123 from 6- (4-tert-butylphenyl-mercaptobutoxy) -3,4-dihydrocarbostyril (melting point: 117-118 ° C) and hydrogen peroxide. Melting point: 126-128 ° C,

Yield: 62% of theory.

Example 238 6- [4- (3-Hydroxy-pyrid-2-ylmercapto) -butoxy-3,4-dihydrocarbostyril]

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 3-hydroxy-2-mercaptopyridine. Melting point: 211-216 ° C,

Yield: 58% of theory.

Example 239 6- [4- (1,2,4-Triazol-3-ylsulfinyl) -butoxy] -carbostyrene

Prepared according to Example 123 from 6-14- (1,2,4-triazol-3-yl-mercapto) -butoxy] -carbostyril and hydrogen peroxide.

Rf value: 0.12 (silica gel light plate, eluent: ethylene chloride / methanol = 95: 5).

Example 240 6- [4- (1,2,4-Triazol-3-yl-mercapto) -butoxy] -3,4-dihydrocarbon-styrene ________

Prepared according to Example 122 from 6- (4-bromobutoxy) 3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 3-markapto-1,2,4-80 triazole. s r \ r \ s t o 69064

Melting point: 152-154 ° C,

Yield: 82% of theory.

Example 241 6- [4- (1,2,4-Triazol-3-ylsulfinyl) -butoxy] -3,4-dihydrocarbostyril ______________

Prepared according to Example 123 from 6- [4- (1,2,4-triazol-3-yl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Rf value: 0.18 (silica gel light plate, eluent: ethylene chloride / methanol = 95: 5).

Example 242 6- [4- (1,2,4-Triazol-3-ylsulfonyl) -butoxy] -3,4-dihydrocarbos-nitrile_______

Prepared according to Example 124 from 6- [4- (1,2,4-triazol-3-yl-mercapto) -butoxy] -3,4-dihydrocarbostyril and hydrogen peroxide. Rf value: 0.22 (silica gel light plate, eluent: ethylene chloride / methanol = 95: 5),

Melting point: 217-224 ° C.

Example 243 6- [4- (2,4,5-Trichlorophenylmercapto) -butoxy] -3,4-dihydrocarbosyril_

Prepared according to Example 122 from 6- (4-bromobutoxy) -3,4-dihydrocarbostyril (melting point: 142-147 ° C) and 2,4,5-trichlorothiophenol.

Melting point: 144-145 ° C,

Yield: 87% of theory.

I!

Claims (13)

69064 81 R 4 H wherein R 1, R 2 / R 2 / D, W and m are as defined above, or an alkali salt thereof is reacted with a compound of general formula (VIII) Z to R x (VIII) wherein R 1 is as defined above and Z is a nucleophilically exchangeable group such as a halogen atom or a sulfonic acid ester group, or e) to prepare a carbostyril of general formula (I) wherein W is a vinylene group, 3,4-dihydrocarbostyril of general formula (IX) is dehydrated R 3 f T 4- O - D - SOra - R 2 (IX) I R 4 R 1 wherein R 1 - R 2, D and m are as defined above or f) 'for the preparation of 3,4-dihydrocarbostyril of general formula (I) wherein W is an ethylene group and m is the number O or 2, the carbostyril of general formula (X) is hydrogenated 69064 85 R, j | 0.D.S0m.R2 · λΎ «1 'where R1 - R4, D and m have the same meaning as above. A process for the preparation of pharmacologically valuable carbostyril or oxindole derivatives of the general formula I I R 4 R 1 in which W is an optionally substituted vinylene group, a methylene or ethylene group, m is a number 0, 1 or 2, D is a straight-chain or branched alkylene group having 2 to 6 a carbon atom, a straight-chain or branched hydroxyalkylene group having 3 to 6 carbon atoms, or a xylene group, R 1 is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, R 2 is a cycloalkyl group having 3 to 6 carbon atoms, an aryl group having 6 to 10 carbon atoms, a carbon-aralkyl group, a nitrogen atom and / or an oxygen or sulfur atom or a 4-9-carbon heteroaryl group containing two nitrogen atoms or a heteroaralkyl group having 5 to 10 carbon atoms, wherein the above-mentioned aromatic nuclei may be mono- or disubstituted by an alkyl group having 1 to 4 carbon atoms, , methoxy, amino, acetylamino, nitro, carboxyl, cyclohexyl, phenyl or halogen, or in addition, the above-mentioned monosubstituted phenyl group having alkyl groups having 1 to 4 carbon atoms and / or halogen-69064 82 atoms (wherein the substituents on the phenyl core may be the same or different), 1,2,4-triazolyl, triphenylmethyl, 4,5- (p-chlorophenyl ) -oxazol-2-yl, N-methyl-cyclohexylaminocarbonylmethyl or aminoiminomethyl group or also a 1-6-alkyl group when either m is 1 or D is a straight-chain or branched hydroxyalkylene group having 3 - 6 carbon atoms, or a xylylene group, R3 and R4, which may be identical or different, are hydrogen or halogen atoms, alkyl groups having 1 to 4 carbon atoms, amino, acetylamino or nitro groups, characterized in that a) the hydroxy compound of general formula (II) Ro w_ 0 1 * 4 R 1 wherein R 1, R 3, R 4 and W are as defined above, or its salts with inorganic or tertiary organic bases are reacted with a compound of general formula (III) Z - D - SO m - R 2 (III) wherein R, R 2 and m are as defined above and Z is a nucleophilically exchangeable group such as a halogen tower li 69064 83 or a sulphonic acid ester group and / or b) for the preparation of gaseous compounds of general formula (I) in which m is 1 or 2, oxidizing a compound of general formula (IV) R 3 w-II ry 0 - D - SOn - R 2 (iv) R 1 wherein R 1 - R 2, D and W are as defined above and m is the number O or 1, or c) for the preparation of a compound of general formula (I) wherein m is O, a compound of general formula (V) R 3 V i | -4 - O - D - X (V) λ, ΛΛ1 i R1 wherein R1, R3, R4, D and W are as defined above are reacted with a compound of general formula (VI) Y - R2 (VI) wherein R2 is the same as above and one of X or Y in the compounds of general formulas (V and VI) is a mercapto group and one of X or Y is a nucleophilically exchangeable group such as a halogen atom or a sulfonic acid ester group or X together with the hydroxy group adjacent to group D is an epoxide group and Y is a mercapto group, or 84 69064 a) for the preparation of a compound of general formula (I) having no hydrogen atom, a compound of general formula (VII) R 3 W i, - D - SO - R (VII) Process according to Claim 1a, characterized in that the reaction is carried out in a solvent at a temperature between 0 ° C and the boiling point of the solvent used, for example at a temperature between 0 ° C and 100 ° C, but preferably at a temperature between 10 and 50 ° C. Process according to Claims 1a and 2, characterized in that the reaction is carried out in the presence of a precursor. Process according to Claim Ib, characterized in that the reaction is carried out in a solvent and at temperatures between -80 ° C and + 100 ° C. Process according to Claims 1b and 4, characterized in that for the preparation of a compound of general formula (I) in which m is the number 1, the oxidation is carried out with an equivalent of the oxidant in question and preferably at temperatures between -80 ° C and + 60 ° C. Process according to Claims Ib and 4, characterized in that for the preparation of a compound of general formula (I) in which m is the number 2, the oxidation is carried out with one or two equivalents of the oxidant in question or more and preferably at temperatures between -80 ° C and +100 ° C. 86 69064 Process according to Claim 1e, characterized in that the reaction is carried out in a solvent and at temperatures between 0 ° C and the boiling point of the solvent used, for example at temperatures between 0 ° C and 100 ° C, but preferably at 10 ° C and 50 ° C. Process according to Claim 1e and 7, characterized in that the reaction is carried out in the presence of an alkali base. Process according to Claim Id, characterized in that the reaction is carried out in a solvent and at temperatures between 0 ° C and 50 ° C, but preferably at temperatures between 10 ° C and 25 ° C. Process according to Claim Id and 9, characterized in that the alkylation is carried out with an alkyl halide or dialkyl sulfate in the presence of an alkali base, an alkali metal hydride or an alkali metal alcoholate. Process according to Claim 1e, characterized in that the dehydration is carried out in the solvent at elevated temperatures, for example at temperatures between 100 ° C and 200 ° C, but most preferably at the boiling point of the solvent used. Process according to Claim 1e and 11, characterized in that the dehydration is carried out in the presence of an oxidant or a noble metal catalyst. Process according to Claim 1f, characterized in that the hydrogenation is carried out in a solvent in the presence of a hydrogenation catalyst at temperatures between 0 ° C and 50 ° C, preferably at room temperature, and at a hydrogen pressure of 1 to 5 bar. 69064 87