DE2403060A1 - PROCESS FOR PREPARING NEW 3-CARBAMOYL-1-THIA-ISOCHROMAN-1,1-DIOXIDE DERIVATIVES - Google Patents

Description

240306C

Process for the production of new 3-carbamoyl-i-thiaiaochroraan-1, 1-dioxide derivatives

The invention relates to a method for division of new 3-carbamoyl-1-thia-isochroinane-1,1-dioxide derivatives the general formula

- (CR ⁴ R ⁵ ) - (CR ⁶ R ⁷ ) - (CR ⁸ R ⁹ ), - MH-T

worm

1 2
R and R a lower alkylreat with 1 to 4 carbon atoms,

R is a V / aaseratoffatom or a lower alkylreat with 1 to 2 carbon atoms,

4 9
R bia R are identical or different and are hydrogen atoms or lower alkyl groups with 1 to 2 carbon atoms,

R is a straight-chain or branched alkyl group with 1 to 6 carbon atoms, an aralkyl group with 7 to 10 carbon atoms or a cycloalkyl group with 3 to 6 carbon atoms and

x + y + z = 2 bia 4, preferably 3, and their acid addition salts with physiological compatible inorganic and organic acids »

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Ala example for the basic remainder

- (CR ⁴ R ⁵ ) - (CR ⁶ R ⁷ ) - (CR ⁸ R ⁹ ) -NH-R ¹⁰ in the general formula I may be mentioned the 3-n-propylaminopropyl, 3-cyclohexylaninopropyl, 4-methylamino 4-uiethylpentyl- (2) -, 4-n-propylamino-4-methylpentyl- (2) -, 4-n-butylamino-4-methylpentyl- (2) -, 4-n-hexylamino-4-inethylpentyl - (2) -, 4-Isobutyiamino-4-methylpentyl- (2) -, 4-isopropylamino-4-methylpentyl- (2), 4-sec-butylamino-4-methylpentyl- (2) -, 4-cyclohexylamino -4-methylpentyl- (2) -, 4-benzylamino-4-

methylpentyl- (2) -, 4-phenethylamino-4-ethyl-pentyl- (2) -,

and the 4-ß-phenathy lamino-4-ine thy l-pentyl (2) group.

Compounds according to the present invention are still not described in the literature. Only in the GDR patent specification No. 81 115 describes N.N-disubstituted 3-carbainoyl-i-thia-isochroman-i, 1-dioxide derivatives, which differ from the compounds of the present invention by the tertiary IT atom in the basic side chain differentiate. The compounds of the general .Formel I show compared to those in the above-mentioned GDR patent described IT.N-disubstituted 3-carbamoyl-1-thia-isochroman-i, 1-dioxide derivatives typical differences in the quality of the psychotropic effects. They are missing the central cholinergic phenomena detectable in small laboratory animals while at the same time maintaining (central) cortical ones Effect.

In the unstressed animal, prominent symptoms are sedation and ptosis,

This sedation can be reversed by external stimuli and turns into an intensified avousal reaction. Parallel to the wakefulness, an increase in locomotor activity with general central stimulation sets in. .

According to the invention, the new 3-carbamoyl-1-thia-isochroman-1,1-dioxide derivatives of the general formula I prepared by compounds of the general formula

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12 3
wherein the radicals R, R and R have the abovementioned meaning

11
and R is a halogen atom such as chlorine or bromine, a

Hydroxy or alkoxy group, with amines of the general formula

H ₂ K- (CR ⁴ R ⁵ ) _x - (CR ⁶ R ^{f /} ) _y - (CR ⁸ R ⁹ ) _z -IiH-R ¹⁰ III,

wherein the radicals R ^ to R have the abovementioned meaning own, or reacts their acid addition salts and the compounds of general formula I obtained, if they are obtained as bases, if desired with physiolo Gisch compatible inorganic or organic acids converted into their acid addition salts.

As examples of amines of the general formula III, the are produced by known processes, may be mentioned that

i-Amino-3-n-propylaminopropane (bp ^: 75-77 ⁰ C), 1-amino-3-cyclohexylaminopropane (bp ₁ , -: 116 C), 2-methylamino-4-amino-2-methylpentane (bp ₁ ^: 58-62 ⁰ C), 2-n-propylamino-4-amino-2-methylpentane (bp ₁₄ : 75-78 ⁰ C), 2-n-butylamino-4-amino-2-methylpentane (bp ₁₂ J 88-93 ⁰ C), 2-n-hexylamino-4-aiaino-2-nethylpentan (Kp i ^ ₀ 83-87 ⁰ C), 2-isobutylamino-4-amino-2-raethylpentan (Kp ₁ ^: 87 -89 ⁰ C), 2-isopropylamino-4-

amino-2-methylpentane (Kp ₁ rs 70-75 ⁰ C), 2-sec-Butylaraino-4-amino-2-methylpentane (b.p. _15: 90-94 ⁰ C), 2-cyclohexylamino-4-amino-2 -methylpentane (bp ₁ C: 135-140 ⁰ C), 2-benzylamino-4-amino-2-methylpentane (bp ₁₄ : 150-155 ⁰ C), 2-tf-Phenäthylainino-4-amino-2-methylpentane ( Kp _{0 15:} 100-105 ⁰ C) and the 2-beta-Phenäthylamino-4-amino-2-methyl pentane (boiling _{n 9:} 101-105 ⁰ C).

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The reaction of compounds of general formula II, in which R is a halogen atom, with amines of general formula III or their acid addition salts is expediently carried out in the presence of hydrogen halide acceptors, such as the amines of general formula III used for the reaction, tertiary amines, alkali solutions or alkali carbonates at temperatures from ⁰ ° C. to the boiling point of the reaction mixture in question, preferably between 0 and 25 ^° C.

The reaction mixtures are either worked up by sucking off the sparingly soluble amides and / or by concentrating the separated organic phase

The reaction of compounds of the general formula II in which R is an alkoxy group with amines of the general Formula III takes place at a higher temperature, for example at the boiling point of the reaction mixture in question. After the reaction has ended, the crude amides are obtained by suctioning off or concentrating the reaction solutions which have been sucked in clear.

The reactions of compounds of the general formula II in which R is a halogen atom or an alkoxy group, with amines of the general formula III are expedient in the presence of organic solvents, such as, for example aromatic hydrocarbons such as benzene or toluene, paraffine carbon solvents such as n-hexane, Halogenated hydrocarbons such as carbon tetrachloride or trichlorethylene, lower aliphatic ketones such as acetone or ethyl ethyl ketone, or alcohols such as ethanol or Ieopropanol or in mixtures of the same carried out with water

By reacting compounds of the general formula II, in which R denotes a hydroxyl group, with amines of the general formula III in the presence of suitable dehydrating agents Agents such as dicyclohexylcarbodiimide are also obtained in inert organic solvents the amides of the general formula I

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The crude products obtained by the process described can by recrystallization from suitable organic solvents such as ethanol, isopropanol, benzene, η-hexane, gasoline or mixtures thereof can be easily cleaned.

In some cases, a separation can be achieved by crystallization into isomeric compounds that differ in their physical properties such as solubility and Differentiate melting point

The compounds of general formula I obtained can be prepared in a manner known per se by reaction with equimolar or excess amounts of physiologically acceptable inorganic or organic acids such as hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, nitric acid, Phosphoric acid, formic acid, acetic acid, propionic acid, dichloroacetic acid, Benzilic acid, benzoic acid, succinic acid, salicylic acid, oxalic acid, malonic acid, adipic acid, maleic acid, Fumaric acid, tartaric acid, citric acid or ascorbic acid can be converted into the acid addition salts concerned.

If the amides of the general formula I are obtained during work-up as oils or lubricants which are difficult to crystallize, then so can by reacting these products in suitable organic solvents, such as ethanol or isopropanol, with physiologically compatible inorganic or organic acids, the corresponding crystalline acid addition salts can be obtained.

The hydrohalides of the basic compounds of general formula I can be prepared directly if one

11

Compounds of the general formula II, in which R ¹ denotes a halogen atom, with equimolar amounts of amines. general formula III in suitable organic solvents such as benzene, halogenated hydrocarbons or alcohols.

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-G-

Since the compounds of the general formula I have one or more asymmetric carbon atoms, they are generally obtained as racemates. These racemates can, if it is desired to be separated into their stereoisomeric forms However, the compounds of the general formula II and, if they are one or more The compounds of general formula III, including those of the general formula III, have asymmetric carbon atoms in their optically active forms be used in the reaction

The compounds of the general formula II required as starting materials can be prepared according to those in the GDR patents No. 81 116 and 81 117 described processes are produced

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Example 1:

In a suspension of 13.5 g of 3-ChlorcaTbonyl-6,7-dimethoxy-. 1-thia-isoehroman-1,1-dioxide in 150 ml of toluene is added dropwise with stirring and cooling to a solution of 9.9 g of 2-cyclohexylaraino-4-amino-2-methylpentane in 25 ml of toluene and then also with cooling .eine Solution of 2.0 g of sodium hydroxide in 50 ml of water. Stirring is continued for 2 hours at room temperature and the aqueous phase is extracted with toluene. The oil that remains after concentrating the combined, dried toluene solutions solidifies to colorless on cooling and trituration with η-hexane Crystals from PP 119-123 ⁰ C.

Crystallization from n-hexane / benzene (3: 1) gives the isomeric forms A, B and C of the 3 - ^ "4 ^t -cyclohexylamino-4- ^t ine thylpentyl- (2 *) -carbamoyl7-6,7-dime thoxy-1 -ihia-isochroman-1,1-dioxide

A: 9.4 g (40.2% of theory) of Pp .: 121-124 ⁰ C B: 3.1 g (13.2% of theory) of Pp .: 129-131 ⁰ CC: 5.3 g (22.6% of theory) of Pp ,: 153-154 ⁰ C.

Analyzes for C ₂₃ H ₃ gHgOgS (MW: 468.6)

OHUS calculates % t 58.95 7.74 5.98. 6.85

A: found % x 58.90 7.96 6.33 6.84 B: found % x 59.08 7.85 6.46 6.80 C: found % x 59.48 7.97 5.93 6, 80

Example 2:

A mixture of 9.1 g of 3-carbomethoxy-6 _# 7-dimethoxy-1-thiaisochroman-1,1-dioxide, 5.9 g of 2-methylaynino-4-amino-2-methylpentane and 40 ml of benzene is stirred into a Heated to the boil for an hour and then the solution is sucked clear

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soaked with benzene and dried (6.2 g). After recrystallization from isopropanol, 3.5 g = 29.2 % of theory colorless crystals 3- / ~ 4 ^l -methylamino-4 ^l methylpentyl- (2 ') -carbaipoyl7-6,7-dimethoxy-1-thia- isochroman-1,1-dioxide of pp .: 157-162 ⁰ C (A). The benzene mother liquor is concentrated and the residue, which has been washed out with water and dried (4.9 g), is recrystallized from Ieopropanol. 3.9 g = 32.5 % of theory of colorless crystals are obtained 3- ^ ~ * ^{4'-methylamino-4 1} -methylpentyl- (2 ') -carbamoyl? - 6,7-dimethoxy-1-thia-i80chroman- 1,1-dioxide from ppi ·: 151-153 ⁰ C

(B). η τι
Κτλ nil
ιοΛ •
• 56: Ϊ8 ^Ν 2 ° 6 S (Μ ( J: 400.5) N 8th S. Analysis for %: C. H 6.99 7th , 01 53 • 98 7.06 6.93 7th , 90 calculated % 53 , 84 7.15 6.84 , 86 A: found 53 , 55 7.28 B: found

Analogously from 9.1 g of 3-carbomethoxy-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 5.9 g of 2-methylamino-4-amino-2-methylpentane in the presence of trichlorethylene 3, 8 g (31.7 % of theory; fraction A) and 4.3 g (35.9% of theory; fraction B) 3 - ^ "4 ^l -Methylamino-4'-methylpentyl- (2 ^f ) -carbamoylZ- ö ^ -dimethoxy-i-thia-isochroman-i, 1-dioxide obtained.

Example 3:

A solution of 18.2 is added dropwise to a suspension of 36.0 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide in 340 ml of toluene with stirring and ice cooling at 2 to 10 ^{° C.} g of 2-methylamino-4-amino-2-methylpentane in 60 ml of toluene and then a solution of 5.8 g of sodium hydroxide in 150 ml of water. The mixture is then stirred for 2 hours at room temperature. The deposited crystals are filtered off with suction, and the toluene phase is separated off and concentrated. After Umkrietallieation the combined crude products from isopropanol

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38.9 g of S 72.6 % of theory 3- ^ ~ 4'-methylamino 4'-methylpentyl- (2 ^l ) -carbamoyl7-6,7-dimethoxy-1-thia- are obtained. iaochroman-1,1-dioxide of m.p .; 145-151 ⁰ C,

Analysis for C ₁₈ H ₂₈ N ₂ O ₆ S (1st 7th H N S. 01 C. 7th , 06 6.99 8th, 05 calculated % : 53.98 , 18 6.79 8th, found %: 53.98

Similarly, 13.6 g of 3-chlorocarbonyl-6 _f 7-dimethoxy-1-thia-iaochroraan-i, 1-dioxide and 7 g of 2-methylamino-4-amino-2-methylpentane in the presence of isopropanol are 13.7 g (68.5 % of theory) 3- / ~ 4 * -Methylamino-4'-methylpentyl- (2) -carbamoyl7-6,7-dimethoxy-1-thia-iaochroman-1,1-dioxide - obtained #

Analog 6.3 g (63.1% of theory) of aue 6.8 g of 3-chlorocarbonyl-6,7-dimethoxyt-thia-iaochroman-1,1-dioxide in the presence of benzene at 18-25 ⁰ C for 3 - ^ ^"t 4-methylamino-4 ^t methylpentyl (2X) -carbamoyl7-6,7-dime thoxy-1-thia-iaochroaan 1,1-dioxide.

Similarly, 13.6 g of 3-chlorocarbonyl-6,7-dimethoxy-1-thia-iaochroman-i, 1-dioxide, 7.0 g of 2-methylamino-4-amino-2-methylpentane and 21 g of potassium carbonate in Presence of carbon tetrachloride and Waeaer 4.4 g (22.0 % of theory) 3- / ~ 4'-methylamino-4 ^f -methylpentyl- (2 ') -carbamoyiy-o, 7-dimethoxy-1-thiaochroman -1,1-dioxide.

Aue of 6.8 g of 3-chlorocarbony1-6,7-dimethoxy-1-thia-i8ochroman-1,1-dioxide is obtained analogously in the presence of acetone and 3.5 g of 2-methylamino-4-amino-2-methylpentane 5 , 7 g (57.1 % of theory) 3 - ^ "" 4 ^t -methylamino-4 ^t -methylpentyl- (2 ^t ) -carbamöyl7-6,7-dimethoxy-1-thia-iaochroman-i, 1-dioxide .

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By heating 6.8 g of 3-chlorocarbony1-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide and 7.0 g of 2-diethylamino-4-amino-2-methylpentane in 100 ml of anhydrous benzene and separation of the precipitated 2-methylamino-4-amino-2-methylpentane monohydrochloride is obtained analogously after recrystallization from isopropanol 5.65 g (56.5 % of theory) 3- £ "4 * -Methylamino-4 * -me thyipentyl - (2 ') - carbamoy.17-6,7-dime thoxy-1 - thiaisochroman-1,1-dioxide

The 3 - / "4 ^! - Hethylamino-4 ^f -methyipentyl- (2 ') -carbamoyl7-6,7-dimethoxy-1 thia-iaochroman-1,1-dioxide produced according to the procedures described falls as a function of the Reaction conditions in various isomeric forms, the melting ranges of which are in the range from 140 to 168 ^° C.

Example 4t

In a solution of 4.15 g of crude 3-liter ethyl-3- ^ ~ 4 ^f -methylamino- ~ 4'-methylpentyl- (2 ^l ) -carbamoylZ-ö, 7-dimethoxy-1-thiaisochroman-1 , 1-dioxide (prepared from 3-methyl-3-chlorocarboryl-6 _f 7-d: iinethoxy-1-thia-isochroman-1,1-dioxide and 2-methylamino-4-amino-2-methylpentane analogously to Example 3) in 30 ml of isopropanol are added dropwise at 50 ⁰ C. 1 ml of concentrated nitric acid · After cooling 1.9 g (39.8% of theory) of 3-iie thyl-3- / ~ 4 x -Me methylamino-4 * -me thylpentyl- (2 ") carbamoyl7-6,7-dime thoxy-1-thia-isochroman-1,1-dioxidnitrat from Pp .: 167-171 ⁰ C,

Analysis for C ₁₉ H ₃₁ N ₃ O ₉ S (MW: 477.5)

CHNS

calculated % x 47.79 6.54 8.80 6.71

found % x 47.88 6.67 8.64 6.78

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Example 5ϊ

The following compounds are obtained analogously to Examples 1 and 3:

3- ^ ~ 4'-n-Propylamino-4 '-ine thylpentyl- (2') -carbanoyl7-6,7-dimethoxy-1-thia-isochroinane-i, 1-dioxide C ₂₀ H ₃₂ Ii ₂ O ₆ S MW: 428.5 mp .: 114-116 ⁰ C

3- / f "4 ^l -n-Butylamino-4'-iaethylpentyl- (2 ') -earbamoyl7-6,7-dimethoxy-1-thia-isochroman-i, 1-dioxide C ₂₁ H ₃₄ N ₂ O ₆ S MG: 442.6 Pp .: 117-121 ⁰ C

3- / ~ 4'-n-Hexylamino-4 ^f -methylpentyl- (2 ') -carbamoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide C ₂₃ H ₃₈ N ₂ O ₆ S MG: 470.6 mp .: 88-94 ⁰ C

* -Iaobutylamino-4'-methylpentyl- (2 ') -carbanoyiy-6,7-dimethoxy-1-thia-iaochroman-1,1-dioxide C ₂₁ H ₃₄ N ₂ O ₆ S MW: 442.6 Mp. : 80 - 83 ⁰ C

3- ^ ~ 4'-Isopropylamino-4 ^t -methylpentyl- (2 ») - carbamoyl7-6,7- dimethoxy-1 -thia-ieochroman-1,1-dioxide C ₂₀ H ₃₂ N ₂ O ₆ S MG: 428.5 m.p .: 72-80 ⁰ C.

3 - ^ "'4 ^l -sec.-Butylamino-4 ^t -methylpentyl- (2') -carbaiaoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide C ₂₁ H ₃₄ N ₂ O ₆ S MW: 442.6 mp .: 95-100 ⁰ C

3- _j £ ~ 4 ^l -beta-Eh6näthylainino-4 -me ^t thylpentyl- (2 ') -carbamoyl7-6,7-dime thoxy-1 -thia-isochroman-1,1-dioxide C ₂₅ H ₃₄ N ₂ O ₆ S MG: 490.6 Fp .: 115-118 ⁰ C (A)

M.p .: 140-146 ⁰ C (B)

3 - ^ "4'-Benzylamino-4'-methylpentyl- (2 ') -carbamoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide C ₂₄ H ₃₂ N ₂ O ₆ S MW: 476 , 6 m.p .: 107-110 ⁰ C (A)

Mp .: 112-114 ⁰ C (B) Mp .: 164-166 ⁰ C (C)

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3- (3 * -Cyclohexylaminopropyl-carbamoyl) -6,7-dimethoxy-1-thiaisochroman-1,1-dioxide

C ₂₀ H ₃₀ N ₂ O ₆ S MW: 426.5 pp: 80- & 8 ⁰ C

3- (3'-n-Propylaminopropyl-carbamoyl) -6,7-dimethoxy-1-thiaiaochroman-1,1-dioxide

C ₁₇ H ₂₆ N ₂ O ₆ S MW: 386.5 Pp .: IO7 - 109 ⁰ C.

3-methylamino-4'-methylpentyl- ^ ¹ ) -carbamoyl7-6,7-dimethoxy-1-thia-iaochroman-1,1-dioxide C ₁₉ H ₃₀ N ₂ O ₆ S MW: 414.5 Pp .: 78-80 ⁰ C.

3-methyl-3- ^ ~ 4'-n-butylamino-4'-methylpentyl- (2 ') -carbaiaoyl7-6,7-dimethoxy-1-thia-iaochroman-1,1-dioxide C ₂₂ H ₃₄ N ₂ O ₆ S MW: 454.6 Pp .: 102-111 ⁰ C.

3- ^ ~ 4'-isobutylamino-4'-methylpentyl- (2 ') -carbanoyl7-6,7-dime thoxy-1-thia-ieochroman-1,1-dioxide C ₂₂ H ₃₄ N ₂ O ₆ S MG: 454.6 Pp .: 101-105 ⁰ C

3-methyl-3- (3'-cyclohexylaminepropyl-carbamoyl) -6,7-dimethoxy-1-thia-isochroman-i, 1-dioxide C ₂₁ H ₃₂ N ₂ O ₆ S MW: 440.6 pp .: 74-78 ⁰ C

3-methyl-3- (3 ^l -n-propylaminopropyl-carbamoyl) -6,7-dimethoxy-1-thia-isochroman-1,1-dioxide C ₁₈ H ₂₈ N ₂ O ₆ S MW: 400.5 pp. : 112-117 ⁰ C

Example 6:

The following salts are obtained analogously to Example 4:

3 - ^ "4'-Methylamino-4 ¹ -methylpentyl- (2 ^f ) -carbamoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide-nitrate C ₁₃ H ₂₉ N ₃ O ₉ S MW : 463.5 Pp .: 177-180 ⁰ C

3- ^ ~ 4 "-Methylamino-4'-methylpentyl- (2") - carbamoylj-ö, 7-dimethoxy-i-thia-iaochroman-1,1-dioxide hydrogen sulfate C ₁₈ H ₂₉ N ₂ O ₁₀ S ₂ MW: 498.6 Pp .: 174-185 ⁰ C

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3 ~ / * "4 '-Methylamino-4' -methy3.pentyl- (2 ') -carbamoyl7-6,7-diiae thoxy-1-thia-iaochroman-1,1-dioxide-f mnarate C ₂₂ H ₃₁ N ₂ O ₁₀ S MW: 515.6 Pp .: 217-220 ⁰ C.

3- ^ ~ "4 '-o (-Phenäthylamino-4' -methylpentyl- (2 ') -carbamoyl7-6,7-dimethoxy-1-thia-iaochroinan-i, 1-dioxide-fumarate C ₂₉ H ₃₈ U ₂ O ₁₀ S MG: 606.7 pp: 120-122 ⁰ G.

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Claims (1)

Patent claims: R ¹ and R ² R ⁴ to R ⁹ x + y + z a lower alkylreat with 1 to 4 carbon atoms a hydrogen atom or a lower alkyl rest with 1 to 2 C-atoms, are the same or different and hydrogen Atoms or lower alkyl groups with 1 to 2 Carbon atoms, a straight or branched chain alkyl group with 1 to 6 carbon atoms, an aralkyl group with 7 to 10 carbon atoms, or a cycloalkyl group with 3 to 6 carbon atoms and = 2 to 4, preferably 3, mean, and their acid addition salts with physiological Compatible inorganic and organic acids, characterized in that compounds of the general formula II, 409847/1 1 16 12 3 wherein the radicals R, R and R have the abovementioned meaning and R represents a halogen atom such as chlorine or bromine, a hydroxyl or alkoxy group, with Amines of the general formula B ₅ N - (CR ⁴ R ⁵ ) - (CR ⁶ R ⁷ ), _r - (CR ⁸ R ⁹ V - HH - R ¹⁰ III, wxy Su wherein the radicals R ^ to R and the symbols x, y and ζ have the abovementioned meaning, or their acid addition salts converts and the compounds of general formula I obtained, if ax ala Baaen obtained are desired, if they are physiologically compatible inorganic or organic acids converted into their acid addition salts 2, method according to Anapruch 1, characterized in that raan For the formation of the acid addition salts of compounds of the general formula I, physiologically compatible inorganic or organic acids such as hydrochloric acid, Hydrobromic acid, hydroiodic acid, sulfuric acid, Nitric acid, phosphoric acid, formic acid, acetic acid, Propionic acid, dichloroacetic acid, benzilic acid, benzoic acid, Succinic acid, salicylic acid, oxalic acid, malonic acid, adipic acid, maleic acid, fumaric acid, tartaric acid, citric acid or ascorbic acid is used. 3 · Process according to Claims 1 and 2, characterized in that the reactions are carried out in the presence of organic solvents or thinners or mixtures does the same with water, 4. Process according to claims 1 to 3, characterized in that the organic solvent or diluent aromatic hydrocarbons such as benzene or toluene, paraffinic hydrocarbons such as n-hexane, 409847/1116 Halogenated hydrocarbons such as carbon tetrachloride or trichlorethylene, lower aliphatic ketones such as acetone or methyl ethyl ketone or alcohols such as ethanol or isopropanol be used· 5. Process according to claims 1 to 4, characterized in that the implementation of compounds of the general Formula II, in which R is a hydroxyl group, with amines of the general formula III in the presence of more suitable ones dehydrating agents such as dicyclohexylcarbodiimide is carried out. 6. Process according to claims 1 to 5, characterized in that • ^{the reactions are carried out between 0 0} C and the boiling temperature of the respective reaction mixture. 7. The method according to claims 1 to 6, characterized in that the starting compounds, which one or more Possess asymmetric carbon atoms, can be used as racemates in the reaction. 8. The method according to claims 1 to 6, characterized in that the starting compounds, which one or more Possess asymmetric carbon atoms, are used as optically active forms in the reaction. 9. Process according to claims 1 to 6, characterized in that racemic mixtures of compounds of the general formula can be broken down into stereoisomeric forms. 10. Compounds of the general formula NH- (CR ⁴ R ⁵ ) - (CR ⁶ R ⁷ ) - (CR ⁸ R ⁹ ), - NH-R ¹⁰ λ yz It 409847/1116 • ι ■ wherein 1 2
R and R a lower alkyl radical with 1 to 4 carbon atoms R ^{v is} a hydrogen atom or a lower alkyl radical having 1 to 2 carbon atoms R ^ to r "are the same or different and are hydrogen atoms or lower alkyl groups with 1 to C atoms, R is a straight-chain or branched alkyl group with 1 to 6 carbon atoms, an aralkyl group with 7 to 10 carbon atoms or a cycloalkyl group with 3 to 6 carbon atoms and x + y + z = 2 to 4, preferably 3, and their salts with physiologically compatible inorganic or organic acids 11. 3- ^ ~ 4'-Cyclohexylamino-4'-methylpentyl- (2 ») - carbamoy ^ - 6,7-dimethoxy-1-thia-isochroman-i, 1-dioxide 12. 3- ^ ~ 4'-methylamino-4 ^l -methylpentyl- (2 ^t) -carbamoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide 13. 3- / ~ 4 ^t -n-Propylamino-4 ^l -methylpentyl- (2 ^l ) -carbamoy17-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide 14. 3 - / ^[l ~ 4-n-butylamino-4 ^l -methylpentyl- (2 ^t) -carbamoyl7-6,7-dime thoxy-1-thia-isochroman-1,1-dioxide 15. 3- ^ ~ 4 ^l -n-hexylamino-4 ^l -methylpentyl- (2 ^l ) -carbamoyl7-6,7-dimethoxy-i-thia-isochroman-1,1-dioxide 16. 3 - ^ "4'-Isobutylamino-4'-methylpentyl- (2 ^f ) -carbamoy17-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide 17. 3- ^ ~ 4 ^l -Isopropylamino-4 ^l -methylpentyl- (2 ^f ) -carbamoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide 18. 3- ^ ~ 4 ^l -sec.-Butylamino-4'-methylpentyl- (2 ^l .) -Carbamoyl7-6,7-dimethoxy-1-thia-isochroman-1,1-dioxide 409847/1116 19 · 3- ^ ~ 4 ^l -ß-phenethylamino-4 ^l -methylpentyl- (2O-earbamoyl7-6,7-dimethoxy-1-thia-ieochroman-1,1-dioxide 20. 3- ^ ~ 4 ^f -Benzylamino-4 ¹ -methylpentyl- (2 ') -carbamoyl7-6 »7-diine thoxy-1-thia-ieochroman-1,1-dioxia 21 x 3- (3 ^L -cyclohexylaminopropyl-carbamoyl) -6,7-dimethoxy-1-thia-iaochroinan-1,1-dioxide 22. 3- (3'-n-Propylaminopropyl-carbamoyl) -6,7-dimethoxy-1 thia-iaochroman-1,1-dioxide 23. 3-Methyl-3- ^ ~ 4 ^t -methylamino-4 ^f -methylpentyl- (2 ") - carbamoyl7-6,7-dimethoxy-1-thia-iochroman-1,1-dioxide 4. 3-Methyl-3 - ^ "4'-n-butylamino-4 · -methylpentyl- (2 ') -carbamoyl7-6,7-dimethoxy-1-thia-ieochroman-1,1-dioxide 25. 3-Methyl-3-£ "4'-isobutylamino-4 ¹ -methylpentyl- (2x) -carbamoyl7-6,7-dimethoxy-1-thia-iaochroman-1,1-dioxide 26, 3-Methy1-3- (3'-eyelohexylaminopropyl-carbamoyl) -6,7-d ime thoxy-1-thia-iaochroman-1,1-dioxide 27 • 3-Methy1-3- (3'-n-propylaminopropyl-carbamoyl) -6,7-dime thoxy-1-thia-iaochroman-1,1-dioxide · 3- ^ ~ 4 '- «<- Phenäthylamino-4' -methylpentyl- (2 ·) -carbamoy ^^ S ^ -dimethoxy-i-thia-iaochroman-i, 1-dioxide 29. Compounds according to Anaprüchen 10 bia 28 ale salts with physiologically compatible inorganic or organic acids. 30. Compounds according to claims 10 bia 29 as salts with Chlorwaaeratoffaäure, Bromwaaaeratoffaäure, Jodwa8seratoffäure, Sulfuric acid, nitric acid, phosphorus acid, formic acid, eaaiga acid, propionic acid, dichloresaiga acid, benzila acid, benzoic acid, succinic acid, Salicylic acid, oxalic acid, malonic acid, adipic acid, maleic acid, puma acid, tartaric acid, citric acid or Acorbic acid 409847/1116