DE2426040C2 - Dibenzo [b, f] oxepine or thiepine derivatives, processes for their preparation and preparations containing them - Google Patents

Description

10

in which R ¹ —R ³ and X have the meaning given above, R ⁴ 'represents hydrogen or lower alkyl and R ⁶ ' —R * have the same meaning as R ⁶ —R ⁸ , although the hydroxy groups present may be protected, alkylated , or that one

e) for the preparation of an N-oxide of a compound of the general formula I in which R ⁴ and R ⁵ are different from hydrogen, a compound of the general formula VII

(VID

in which R'-R ³ and X have the meaning already given, R ⁴ "and R ⁵ " have the same meaning as R ⁴ and R ⁵ , but are not hydrogen, and R * -R ⁸ 'have the same meaning as R ⁶ -R ⁸ , however, hydroxyl groups present may be protected, oxidized or that one

f) for the preparation of a compound of the general formula I in which R ^{4 is} hydrogen and R ^{5 is} alkanoyloxy-lower alkyl, a compound of the general formula VIH

in which R ¹ - Ä ³ and X have the above meanings, R ⁵ '"means hydroxyalkyl, and R6- _ R8' have the same meaning as R ⁶ - R ⁸ , although any hydroxy groups present may be protected, alkanoylated, or

g) a base of the general formula 1 or an N-oxide thereof is converted into a corresponding acid addition salt, protected hydroxyl groups R ⁶ '-R ⁸ ' which may be present being converted into hydroxyl groups after one of the process alternatives a) -f) has been carried out

(vm)

7. The method according to claim 6, characterized in that a compound of the general formula II, IV, V, VI, VII, VIII or I or an N-oxide of a compound of the general formula I is used in which R ⁶ ', R ⁷ 'and R ⁸ ' or R ⁶ , R? and R ^{8 have} meanings other than lower alkylsulfonyl and optionally protected hydroxy.

8. Preparations having an effect on the nervous system, containing a compound according to one of the Claims 1 to 5 and a customary solid or liquid carrier and / or excipient

The invention relates to tricyclic compounds of the general formula

R ⁴

R ¹ R ² R ³

Cs = C-CH ₂ -N

R ^s

(D

so

55

in which X is oxygen or sulfur, R ¹ and R ^{2 are} hydrogen or lower alkyl, R ^{3 is} hydrogen or together with R ^{2 is} an additional bond and R ⁴ and R ^{5 are} hydrogen, lower alkyl, hydroxy-lower alkyl, alkanoyloxy-lower alkyl or together represent a saturated, 5- or 6-membered, optionally an oxygen atom, sulfur atom or a further nitrogen atom containing heterocycle which can be substituted by lower alkyl, hydroxy-lower alkyl or alkanoyloxy-lower alkyl, and in which furthermore R ^{6 is} lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, di- (lower alkyl) -sulfamoyl, hydroxy, halogen, trifluoromethyl, nitro, amino or di- (lower alkyl) -amino and R 'and R ⁸ each represent individually hydrogen or a substituent listed ^{under R 6} ,

as well as N-oxides of compounds of the general formula I in which R ⁴ and R ⁵ are different from hydrogen, and acid addition salts of the compounds mentioned.

The term "lower alkyl" (alone or in combinations, such as "lower alkoxy", "lower alkylthio" etc.) refers to straight-chain or branched hydrocarbon radicals with preferably up to 7 carbon atoms, such as methyl, ethyl, isopropyl or n-hexyl " Alkanoyloxy «means straight-chain or branched alkanoyloxy groups with preferably up to 18, in particular up to 10 carbon atoms, such as acetoxy, pivot

• loyloxy, pentanoyloxy, hexanoyioxy, heptanoyloxy, Octanoyloxy, nonanoyloxy, decanoyloxy, tetradecanoyloxy, Hexadecanoyloxy and Octadecanoyloxy, The heterocyclic is of 5- or 6-membered heterocycles, the one or two nitrogen atoms or one nitrogen atom and contain an oxygen atom or a sulfur atom derived; Examples are pyrrolidino, Piperazino, Piperidino, Morpholino, Thiomorpholine, Methylpiperidino etc. The one with the heterocyclic possibly linked lower alkyl, hydroxy lower The alkyl or alkanoyloxy-lower alkyl group is preferably one with the second nitrogen atom Combine piperazine residues; Examples are N-Methylpiperazino, N-Hydroxyäthylpiperazino,

N-hydroxypropylpiperazino, N-heptanoyloxypropylpiperazino. All 4 halogen atoms come into consideration as halogen atoms, i. H. Fluorine, chlorine, bromine and iodine. Chlorine is preferred.

It has been found that the compounds of general formula I according to the invention and their N-oxides and the salts of these compounds, which are new compounds, are distinguished by strong neuroleptic properties. They can therefore be used, for example, for the treatment of schizophrenia and also as tranquilizers. It is of particular advantage that no or only slight cataleptic side effects occur, so that no or only insignificant motor disorders are observed. A preferred group of the compounds according to the invention are those in which R ^{1 represents} hydrogen. Preference is also given to those of the compounds according to the invention in which R ² and R ³ together represent an additional bond. Another preferred subgroup of the compounds according to the invention is that in which X represents sulfur. Preference is also given to those of the compounds according to the invention in which R ⁴ and R ⁵ both represent lower alkyl, in particular methyl. An additional preferred subgroup of the compounds according to the invention is that in which R ^{e is} methylthio or chlorine, and R ⁷ and R ^{8 are} hydrogen. Furthermore, those compounds are preferred in which R ^{6 is} chlorine, R ^{7 is} hydrogen and R ^{8 is} methoxythio. A preferred group of the compounds according to the invention is that in which R ^{1 is} hydrogen, R ² and R ³ together form an additional bond, R ^{4 is} hydrogen or lower alkyl, R ^{5 is} lower alkyl, hydroxy-lower alkyl or alkanoyloxy-lower alkyl or R ⁴ and R ⁵ together represent a saturated, 5- or 6-membered heterocycle which may contain an oxygen atom or a further nitrogen atom and which may be substituted by hydroxy-lower alkyl or alkanoyloxy-lower alkyl, R * lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl , Di (lower alkyl) sulfamoyl, halogen, trifluoromethyl, nitro, amino or di (lower alkyl) amino and one of the substituents R ⁷ and R ^{8 is} hydrogen and the other is lower alkyl, lower alkoxy or halogen, nine preferred A subgroup of these compounds is that in which R ^{1 is} hydrogen, R ² and R ³ together form an additional bond, R ^{4 is} hydrogen, methyl or ethyl, R ^{5 is} methyl, Ethyl, hydroxyethyl or acetoxyethyl or R ⁴ and R ⁵ together the piperidine, pyrrolidine. Morpholine, N-Hydroxyäthylpiperazin- or N-Acetoxyäthylpiperazinrest represent R ⁶ methyl, methoxy, methylthio, methylsulfonyl, dimethylsulfamoyl, chlorine. Trifluoromethyl, nitro, amino or dimethylamine, R ^{7 is} hydrogen, methyl or chlorine and R ^{8 is} hydrogen, methyl or methoxy.
Preferred compounds are
N _I N-Dimethyl-3- [8- (methylthip) -dibenzo [b, F | -

thiepin-10-yl] -2-propynylamine, N.N-Dimethyl-S-i.e-chloro-dibenzoss.fJthiepin-

10-yl) -2-propynylamine and
NN-dimethyl-S-ie-chloro-S-methoxy-dibenzo-

[b, f] thiepin-10-yl) -2-propynylamine and their acid addition salts. The tricyclic compounds of the general formula I and their N-oxides and the salts of these compounds are prepared according to the invention by a process which is characterized in that
a) a compound of the general formula

R ² R ³ _y ^c = ^CH R ⁶ '

(Π)

in which R ¹ -R ³ and X have the meaning given above and R ⁶ * - R ⁸ 'have the same meaning as R ⁶ -R ⁸ , although any hydroxyl groups present may be protected,

with formaldehyde and a compound of the general formula

HN

in which R ⁴ and R ^{5 have} the meaning given above,
implements, or that one
b) a compound of the general formula

R ^7-

R ¹ R ² R ³

in which R ¹ -R ³ and X have the meaning given above, Y represents a leaving group and R ⁶ '-R ⁸ ' have the same meaning as R ⁶ - R ⁸ , although any hydroxyl groups present may be protected,
with a compound of the general formula

R ⁴

HN

in Jer R ⁴ and R '' have the meaning given above,
implements, or that one

ι ") for the production of a compound of the general alkyl represents, a compound of the general

Formula I, in which R ² and R ³ together represent an additional formula bond, a compound of the general

Formula ρ = ρ pu MH pi "

, _ _r R 'R ² R ^{3 C} - ^{C CH 2 NH R}

_R <\ ^ y— χ _A R ⁶

(V)

* ^ C = C-CH ₂ -N

R ⁵

(VIl)

10

15th

in the R ¹ , R ⁴ . R ⁵ and X have the meaning given above and R ⁶ '-R ⁸ ' have the same meaning as R ⁶ -R ⁸ , although any hydroxyl groups present may be protected,

dehydrated, or that one
d) to establish a connection of the general

Formula I in which R ^{4 is} hydrogen or lower alkyl and R ^{5 is} lower alkyl, a compound of the general formula

= C-CH ₂ -NHR ⁴ 'R ⁶

20th

25th

30th

35

in which R ¹ -R ³ and X have the meaning given above, R ⁴ 'represents hydrogen or lower alkyl and R *' - R ⁸ 'have the same meaning as R ⁶ - R ⁸ , although any hydroxyl groups present may be protected,

alkylated, or that one
e) for the production of an N-oxide of a compound

of the general formula I. in which R ⁴ and R ⁵ are different from hydrogen, a compound of the general formula

R ^r

/

55

in which R ¹ - R ³ and X have the above meaning, R * "and R ⁵ " have the same meaning as R * and R ⁵ , but are not hydrogen and R ⁶ '-R ⁸ ' have the same meaning as R ⁶ - R ⁸ , however, hydroxyl groups that are present may be protected,

oxidized or that one
f) to establish a connection of the general

Formula I, in which R * is hydrogen and R ^{5 is} aikanoyloxy-nie-

(VIID

in which R ¹ -R ¹ bid X have the above meaning, R ^v "denotes hydroxyalkyl, and R ⁶ '- R ⁸ ' have the same meaning as R ⁶ -R", although any hydroxyl groups present may be protected,
alkanoylated, or that one

g) a base of the general formula I or an N-oxide thereof is converted into a corresponding acid addition salt, protected hydroxyl groups R ⁶ '-R ⁸ ' that may be present being converted into hydroxyl groups after one of the process alternatives a) -f) has been carried out.

The various embodiments of the method according to the invention are described below Preparation of the tricyclic compounds and their N-oxides r "? W. Acid addition salts explained in more detail.

Starting compounds of the general formula II. In which R ² and R ³ together represent an additional bond can, starting from the corresponding 10-ketone, by reaction with an acetylene-organometallic compound, e.g. B. Lithium acetylide. an acetylene magnesium halide or trimethylsilylethinyllithium. The lithium acetylide is preferably in liquid ammonia and / or an organic solvent such as tetrahydrofuran or benzene, or as a complex with ethylenediamine in an inert solvent such as dioxane, tetrahydrofuran or benzene at a temperature about -10 ° C and the boiling point of the reaction mixture implemented. The acetylene magnesium halide and trimethylsilylethinyllithium are preferably reacted in an organic solvent such as tetrahydrofuran or benzene at a temperature between about -10 ° C. and the boiling point of the reaction mixture. The addition product obtained is then subjected to hydrolysis, for example by reaction with aqueous ammonium chloride solution at room temperature. The 10-ethynyl-10-carbinol obtained or (if trimethylsilyl ^{s <} , hinyllithium is assumed) 10-trimethylsilylethynyl-10-carbinol, is then subjected to dehydration, for example by heating with a strong acid such as p-toluenesulfonic acid in one organic solvents such as methylene chloride, carbon tetrachloride, acetonitrile, benzene or o-, m- or p-xylene. The corresponding starting compound of the general formula II is obtained, in which R ² and R ³ together represent an additional bond, or (if trimethylsilylethinyllithium is assumed) the corresponding 10-trimethylsilylethinyl compound. The latter is subjected to a metal-catalyzed hydrolysis by z. B. is treated in aqueous acetone or in aqueous ethanol with silver nitrate and potassium cyanide. The trimethylsilyl group is split off under these conditions at room temperature, and the desired starting

Compound of the general formula II, in which R ² and R ^J together represent an additional bond.

Starting compounds of the general formula II in which R ² and R ^{3 are} both hydrogen are, for. B. by reacting a corresponding tricyclic 10-halogen compound, for example the chlorine compound, prepared with one of the above-mentioned acetylene organometallic compounds. The reaction is preferably carried out in an inert organic solvent, e.g. B. ether, benzene or tetrahydrofuran, and carried out at a temperature between about -IO ° C and the boiling point of the reaction mixture.

The inventive reaction of the starting compounds of the general formula II with formaldehyde and the compounds of the general formula III takes place in the sense of a Mannich reaction, preferably in the presence of an inert organic solvent, e.g. B. in the presence of a lower alkanol, such as Methanol or ethanol, in a cyclic ether, like L / loxail, uüci lii ciiici 'nicuefeu AikdnCäruOciSÜiirc. Z. U. 20 SOL Acetic acid, optionally mixed with water. The temperature is preferably in the range from about 0 to IOCTC. The reaction is preferably carried out by metal salts, especially copper (II) salts. like copper acetate.

The symbol Y of the starting compounds of the general formula IV preferably represents halogen or alkyl- or aryl-substituted sulfonyloxy. The sulfonyl radicals present in these substituted Alkyl or aryl groups are preferably lower groups, in particular methyl, or phenyl or p-volyl; Y represents in its meaning as "halogen" preferably chlorine or bromine.

10,11-unsaturated starting compounds of the general Formula IV can e.g. B. by reacting the corresponding, tricyclic 10-K.etons with a organometallic compound of 2-propynyl-2-tetrahydropyranyl ether, for example with the corresponding lithium or magnesium halogen compound will. The organometallic compound of ^ -propinyl ^ -tetrahydropyranyläthers carries the corresponding Metal radical (e.g. lithium radical or magnesium halogen radical) on the carbon atom in 3-position of the 2-propynyl radical. The lithium compound is preferably in liquid ammonia and / or an organic solvent such as Tetrahydrofuran, the magnesium halogen compound in an organic solvent such as tetrahydrofuran, reacted at a temperature between about -10 "C and the boiling point of the reaction mixture. The so obtained addition compound is then subjected to hydrolysis, e.g. B. by treating with aqueous ammonium chloride solution at room temperature, and the resulting tricyclic 10- [3- (2-tetrahydropyranyloxy) -1-propynyl] -10-carbinol then undergoes dehydration and hydrolysis subjected, for example by treatment with a strong acid, ϊ. B. p-Toluenesulfonic acid, in methylene chloride, Benzene or o-, m- or p-xylene, at the boiling point of the reaction mixture (with a dehydration takes place) and subsequent boiling with p-toluenesulfonic acid in aqueous ethanol (with the Dehydration product is hydrolyzed). The 10,11-unsaturated tricyclic 10- (3-hydroxy-1-propynyl) compound thus obtained can now be converted into a corresponding. 10.1! -Unsaturated reactive ester of general formula IV are converted, for example by reaction with the corresponding alkyl or aryl-substituted sulfonic acid halide, e.g. B. the chloride, or with thionyl chloride or thionyl bromide.

Another method of making the 11-10 unsaturated Starting compounds of the general formula IV are described in Example 5.

10,11 -saturated starting compounds of the general Formula IV can by reacting a corresponding tricyclic 10-halogen compound, z. B. the chlorine compound with one of the aforementioned organometallic compounds of 2-propynyl-2-tetrahydropyranyl ether getting produced. The obtained iO.II-saturated tricyclic IO- [3- (2-tetrahydropyranyloxy) -1-propynyl compound is then, as described above, hydrated and converted to the corresponding 10,11-saturated reactive Converted ester of the general formula IV.

The reaction of the compounds of the general formulas IV and III can be carried out in an inert organic gmittc !, '.vic benzo !, toluene or? ^r nimethylfnrmamid. It is preferred to work in the presence of an excess of the compound of the general formula III to be used, which serves as an acid-binding agent. However, other acid-binding agents can also be used, e.g. B. anhydrous potassium carbonate. When using highly volatile compounds of the general formula III, the reaction is expediently carried out in a closed vessel at an elevated temperature, for example at about 50 to about 175.degree. The reaction temperature is otherwise not critical; it is expediently between about -20 ° C and the boiling point of the reaction mixture, e.g. B. between room temperature and the boiling point of the reaction mixture.

The tricyclic 10-carbinols of the general Formula V can, for example, by reacting the corresponding tricyclic 10-ketone with a organometallic compound of an optionally correspondingly N-substituted 2-propynylamine prepared will. For example, the corresponding lithium or magnesium halogen compound is used, the metal radical being in the 3-position of the 2-propynylamine. Lithium compounds are preferably implemented in liquid ammonia and / or an organic solvent such as tetrahydrofuran, Magnesium halogen compounds in an organic solvent such as tetrahydrofuran at the boiling point of the reaction mixture. The addition compound obtained is then subjected to hydrolysis subject, e.g. B. by treating with aqueous ammonium chloride solution at room temperature, after which the corresponding tricyclic 10-carbinol of the general formula V is obtained.

The inventive dehydration of the starting compounds of general formula V leads to 10,11-unsaturated end products of the general formula I. The dehydration is expedient under Use of strong acids such as organic sulfonic acids, e.g. B. p-toluenesulfonic acid, methanesulfonic acid, or mineral acids, such as hydrochloric or hydrobromic acid, carried out in anhydrous or aqueous medium can be worked. The dehydration is preferably carried out in an organic Sulfonic acid, e.g. p-toluenesulfonic acid, in the presence of an inert organic solvent such as methylene chloride, Carbon tetrachloride, acetonitrile, benzene or o-, m- or p-xylene performed when using of mineral acids, these are for example in

ti

Solution used in a lower alkanol. Other common dehydration agents! can also be used, e.g. B. acetic anhydride. The temperature for the dehydration is suitably / wipe about room temperature and about 200 ⁰ C, in particular between about 50 "C and about 200 ° C.

For the alkylation according to the invention of the starting compounds of the general formula VI different methods are available.

If a tertiary amine of the general formula I is desired, the following procedure can be used, for example will:

A starting compound of the general formula VI is combined with a compound of the general formula R ⁵ 'Y', in which R ⁵ 'is lower alkyl and Y' is a leaving group, e.g. B. halogen, such as chlorine, bromine or iodine, or lower alkanesulfonyloxy, benzenesulfonyloxy, or lower alkylbenzenesulfonyloxy is implemented. Ethylene oxide can also be used as an alkylating agent ( yuab »ciiiciSciis üüi'Cii ilicuci'cS alkyl ίΰ can be substituted); this introduces an (optionally alkylated) hydroxyethyl group. The reaction is preferably carried out in an inert solvent, e.g. B. in a lower alkanol. such as ethanol, or in dimethylformamide, and carried out at a temperature of about 15 to 75 ° C. According to another procedure for the preparation of tertiary amines of the general formula I, a starting compound of the general formula VI is treated with a mixture of formaldehyde and formic acid, preferably in excess and at an elevated temperature, e.g. B. between about 50 ° C and the boiling point of the reaction mixture, implemented. Instead of formic acid, sodium borohydride can also be used in this reaction.

Starting compounds of general formula VI in which R ⁴ 'represents hydrogen, ie primary amines of general formula VI, can be converted into secondary amines of general formula I by treating the primary amine of general formula VI with a haloformic acid ester, e.g. B. with ethyl chloroformate or bromoformate, to form a carbamate and this is then reacted with a complex metal hydride, such as lithium aluminum hydride. reduced. Both reaction stages are preferably carried out in an inert solvent, e.g. B. ether or tetrahydrofuran, and at a temperature between about room temperature and the reflux temperature of the reaction mixture, in particular at the reflux temperature. According to another method for the preparation of secondary amines of the general formula I, είη is the primary amine of the general formula VI with chloral, preferably in an inert solvent such as chloroform or benzene, at elevated temperature, e.g. B. between about 50 ° C and the boiling point of the reaction mixture, implemented. The resulting formylamino compound is then treated with a complex metal hydride, e.g. B. lithium aluminum hydride in anhydrous ether, reduced to the secondary amine of the general formula I According to another method for the preparation of secondary amines of the general formula I, a primary amine of the general formula VI is treated with formaldehyde, preferably in an inert solvent such as benzene or toluene, and at a temperature between about room temperature and the boiling point of the reaction mixture. The resulting Schiff base is then converted into a secondary amine of the general formula I by reduction anhydrous ether or dioxane.

The oxidation according to the invention of the compounds of the general formula VII yields the corresponding N-oxides. Hydrogen peroxide or an organic peracid is preferably used as the oxidizing agent. z. B. m-chloroperbenzoic acid is used. The oxidation is advantageously carried out in an inert organic solvent, e.g. B. in a lower alkanol. such as methanol or ethanol; Ether, benzene. Chloroform or methylene chloride, and at a temperature between about - 50 ⁰ C and room temperature, for. B. between 0 ⁰ C and room temperature. After working up in the usual way with removal of the excess oxidizing agent, the corresponding N-oxide is obtained. The latter is expediently obtained in the form of an acid addition salt.

Applications of the general formula VIII is preferably carried out by heating to about 50 to 150 "C with a reactive derivative of a corresponding alkanecarboxylic acid, z. B. the corresponding acid chloride or acid anhydride. The esterification can also through Reaction with an alkanecarboxylic acid in the presence of a strongly acidic catalyst, e.g. B. sulfuric acid or p-toluenesulfonic acid or in the presence of one dehydrating agent, e.g. B. Dicyclohexylcarbodiimide or carbonylriiimidazole can be carried out. The esterification is preferred in an organic Solvents, e.g. B. benzene. Toluene or pyridine. carried out.

If a compound of the general formula I in which R ⁶ (optionally also R ⁷ and / or R ⁸ ) is hydroxy, or a corresponding N-oxide is to be prepared, a starting compound of the general formulas II. IV, V is preferably used VI, VII or VIII, in which the corresponding hydroxyl group is protected, for example by lower alkyl, benzyl or trimethylsilyl. After the abovementioned starting compounds have reacted, this protective group is split off, the alkyl group preferably by treatment with a pyridine salt, for example pyridine hydrochloride, optionally in the presence of water, or by treatment with a boron trihalide, for example boron tribromide or boron trichloride Benzyl group preferably in the manner indicated for the alkyl group or by treatment with an alkali metal, e.g. sodium in a lower alkanol, e.g. butanol, and the trimethylsilyl group preferably by acid-catalyzed hydrolysis, e.g. by treatment with aqueous alkanolic mineral acid, such as aqueous-ethanolic hydrochloric acid. It is preferred to work in an inert organic solvent, for example benzene, toluene or xylene, or a halogenated hydrocarbon, for example methylene chloride, chloroform or carbon tetrachloride. The temperature is preferably between room temperature and Boiling point of the reaction mixture, except for the Ver Use of a boron halide, the temperature expediently in the range from about - / 0 ³ C to room temperature.

Bases of the general formula I obtained form salts with both inorganic and organic salts Acids, e.g. B. with hydrohalic acid, such as hydrochloric acid, hydrobromic acid or hydriodic acid, with other mineral acids such as

Sulfuric acid, phosphoric acid or nitric acid, as well as with organic acids such as tartaric acid, citric acid, Camphorsulfonic acid, methanesulfonic acid, toluenesulfonic acid. Salicylic acid, ascorbic acid, maleic acid or mandelic acid. Preferred salts are Hydrohalides, especially the hydrochlorides and the maleates. The acid addition salts are preferred in a solvent such as ethanol, acetone or acetonitrile by treating the free base with the corresponding, non-aqueous acid prepared.

The bases of the general formula I are partly crystalline, solid substances that are in dimethyl sulfoxide, Dimethylformamide or in chlorinated hydrocarbons, such as. B. chloroform, methylene chloride, in Alkanols, such as methanol or ethanol, or in ether or benzene, are relatively soluble and in water are relatively insoluble.

The acid addition salts of the bases of the general formula I are crystalline, solid substances. They are in dimethyl oxide and dimethylformamide and in alkanols, with methanol or ethanol, and partly also readily soluble in chlorine, methylene chloride and water. They are relatively insoluble in benzene, ether, and petroleum ether.

As explained above, the inventive End products characterized by strong neuroleptic properties as well as by the additional Advantage that they have no or very little cataleptic effect. A cataleptic effect ("Wakefulness", i.e. abnormally long retention of a forced body position) applies to neuroleptic effective compounds as a troublesome side effect and testifies to motor disorders. Representative representatives were used to demonstrate the lack of or low cataleptic side vertebrae of the end products in the rat intraperitoneql verabr-chi.

The animals are considered cataleptic. who :: the homolateral Remain the extremities in a crossed position for at least ten seconds. The number of caialeptic Animals are noted every 30 minutes for 6 hours. The ED 50 is the dose at which 50% of the animals Show catalepsy.

To demonstrate the neuroleptic properties of the end products, representative representatives of the subjected to the following test:

Determination of homovanillic acid

Rats are given the 2 hours before killing Test substance injected.

Homovanillic acid is obtained from the supernatant of the brain homogenate extracted in butyl acetate and later in an aqueous solution and with potassium ferricyanide to one fluorescent dimer oxidized. From the increased concentration of homovanillic acid (HVS) one can conclude that the test substance increases the turnover of dopamine in the basal ganglia. The homovanillic acid titer in untreated rats is arbitrarily set to 100%.

The advantageous pharmacological properties of the compounds according to the invention are also evident from can be seen in the following table:

Kata homovanillic acid

leptic

effect

EO 50 dose increase

mg / kg ip mg / kg ip of the HVS. V,

HN (CH ₃ ),

SCH ₃

Cl

H H

H H

> 100 50 330

5,300

100 50 370

H N (CHj) ₂ H N (CHj) ₂ H N (C ₂ Hj) ₂ H N (CH ₃ ), H N (CH ₃ ),

Cl H OCH ₃ S. > 100 30th 320 CH ₃ H H S. 75 50 383 Cl H H S. > i00 50 250 F. H H S. 40 40 289 Cl CH ₂ H S. > 100 50 150

Cl

Cl

Cl

.100

.100

-100

50

50

JO

165

171

154

local heating

15th

16

c = i

til: Witlung

iljl

I Π> ιι DnM ^ erosion

ρ me / lu: ι p. ücrllVV

H N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ CH ₂ CHjOH

CH ₃

H N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ CH, N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ H NHCHj H NH ₂

CH ₂ CHjOCOCHj

CH ₃

H N (CHj) ₂ H N (CHj) ₂ H N (CHj) ₂ H N (CH ₃ ) J H N (CHj) ₂
O H N (CH ₃ ),
O

F. CH ₃ H S. > 100 50 158 OCH ₃ H H S. 100 50 197 Cl H H O 40 40 436 CH (CHj) ₁ H H S. 35 35 423 Cl Cl H O 75 50 331

Cl

> 100

16

N NCHjCHjOCOCHj CI

> 100

50

16

50

CF ₃
Br
J
NH,

315

348

NS, Cl H S. > 100 50 123 NS, CH ₃ H S. > 100 50 121 NO ₂ H H S. 30th 30th 339 Cl H H S. > 100 50 132 SO ₂ CH ₃ H H S. 10 244 SO ₂ N (CHj) ₂ H H S. 60 50 343 CFj H H S. 13th 13th 347 Cl H H S. > 100 50 214 Cl H H S. 50 174

305

H H S. > 100 50 280 H H O 4.5 4.5 494 H H S. > 100 50 255 H H S. 40 40 308 H H S. 80 50 152 H H S. 30th 50 293 H H S. 4th 10 330 230 284/107

t7

Confessed connections

Effect of EDSO

mg / kg Up.

Homoyanillic acid

dose

mg / kg Lp. %

increase the HVS

A)

/ ^ N-CH ₃

L J

26th

(cf. CoIL Czech, Chem. Cornmun. Vol. 33, 1968, p. 1852 £ f)

N-CHj 24

Maleate

(cf. Coll. Czech. Chem. Commun. BA 33,1968, p. 1852 ff)

297

24

324

The ED50 value for cataleptic effect represents a limiting dose for administration in the Homovanillic acid test: If this cataleptic ED50 value is exceeded in the homovanillic acid test, toxic (cataleptic) phenomena occur that falsify the end result.

The test report shows that the compounds according to the invention regularly have fewer side effects (cataleptic effect) than the known compounds A and B. The lower side effects allow higher dosages of the compounds, so that the effect in the homovanillic acid residue is much more effective.

These data show that the compounds according to the invention are compared to the previously known products A and B have significant advantages which cannot be taken as obvious.

The products according to the invention can be used as healing agents !, z. B. in the form of pharmaceutical preparations, Find use which they or their salts in a mixture with a for the enteral, z. B. oral or pharmaceutical, organic or inorganic inert carrier materials suitable for parenteral administration, e.g. B. water, gelatin, lactose, starch, Contains magnesium stearate, talc, vegetable oils, gum arabic, polyalkylene glycols or petroleum jelly. the pharmaceutical preparations can be in solid form, e.g. B. as tablets, coated tablets, suppositories. Capsules or in liquid form, e.g. B. as solutions, suspensions or emulsions. If applicable, they are sterilized and / or contain auxiliary substances, such as preservation * -. Stabilizing, wetting or emulsifying agents, salts for changing the osmotic pressure or buffer. They can also contain other therapeutically valuable substances.

Useful pharmaceutical dosage forms contain about t to 200 mg of a compound of general formula I or one of its salts. Useful organic dosage ranges are about 0.1 mg / kg per day to about 15.0 mg / kg per day, especially from about 0.1 mg / kg per day to about 7.5 mg / kg per day. Useful parenteral dosage ranges are from about 0.01 mg / kg per day to about 0.75 mg / kg per day. It can, however, the ranges mentioned above or below can be expanded, depending on the individual needs and instructions of the specialist.

The following examples illustrate the invention. Example I.

63 g of p-toluenesulfonic acid and 1800 ml of o-xylene will be heated to boiling and the water present is distilled off. This solution is mixed with 90 g of 10- [3- (dimethylamino) -1-propinyte] -8-chloro-10,11 -dihydro-dibenzo [b, f] thiepin-10-ol added. The reaction mixture is kept at the boiling point for 45 minutes, the resulting water is distilled off. The whole is cooled and poured onto 90 ml of 2N aqueous sodium hydroxide solution poured. The aqueous phase is extracted with ether. The combined organic extracts are used three times washed with water and then extracted three times with about 3N aqueous methanesulfonic acid. the aqueous phase is washed with ether and made alkaline with concentrated sodium hydroxide solution. That

The whole thing is extracted with ether and the ether extract is washed with water, dried and evaporated. Crude N, N-dimethyl-3- (8-chlorodibenzo [b, f] thiepin-10-yl) -2-propynylamine is obtained, which after recrystallization from hexane at 118 to 120 ° C melts. The maleate precipitated from ethanol melts at 178 to 180 ⁰ C,

The 10- [3- (dimethylamino) -l-propinyrj-e-chloro-lO.l 1-dihydro-diben zo [b, f] thtepin-l 0-ol used as the starting compound can be prepared as follows:

2100 ml of liquid ammonia are used with some Crystals of iron (III) nitrate and then within 10.4 g of lithium wire (0 approx. 2 mm) are added over a period of about 2 hours. After stirring for 30 minutes within 40 minutes 369 ml of dimethylamine) -1-propyne added, after which the reaction mixture is 45 minutes ten is further stirred. Now within 105 minutes a solution of 300 g of 8-chloro-10! l-dihydro-5H-dibenzo [b, f] thiepin-10-one in 1500 ml of tetrahydrofuran was added dropwise. The reaction mixture is over Left for the night. The following morning the reaction mixture with 228 g of ammonium chloride in 600 ml of water are added, the ammonia is evaporated off, 900 ml of tetrahydrofuran are added and refluxed for 2 hours. The reaction mixture is evaporated with Water diluted and extracted with ether. The essential extracts are washed with water and extracted with 3N aqueous methanesulphonic acid. Unreacted starting ketone can be extracted from the ethereal Phase to be recovered. The aqueous phase is made alkaline with concentrated sodium hydroxide solution crude 10- [3- (DimethyIamino) -1-propynyl] -8-chloro-10,1I-dihydrin-dibenzo [b, f] thiepin-10-ol which is obtained is taken up in chloroform. The chloroform phase is washed with water, dried and evaporated. The compound obtained melts after recrystallization from acetone at> 50 to 152 ° C.

Example 2

In the same way as indicated in Example 1, 10- [3- (dimethylamino) -l-propynyl] -10,11-dihydro-e-imethylthioj-dibenzofb.flthiepin-10-ol is obtained N, N-Dimethyl-3- [8- (methylthio) -dibenzo [b, f] ihiepin * 10-yI] -2-propynyiamine. The maleate melts at 145 to 146 ° C.

The starting material is obtained in analogy to Example 2 from 10,11-dihydro-e-imethylthioJ-SH-dibenzotb.fjthiepin-10-one and, after recrystallization from benzene / hexane, melts at 142 to 144.degree.

B e i s ρ i e I 3

In the same manner as indicated in Example 1, 10- [3- (dimethylamino) -1-propynyl] -10,11-dihydro-8-methyl-dibenzo [b, f] thiepin-10-ol des is obtained N, N-Dimethyl-3- (8-methyl-dibenzo [b, f] thiepin-10-yl) -2-propynylamine. The latter compound is purified by chromatography on silica gel with chloroform as the eluent. The corresponding maleate Melts at 121 to l23 ° C.

The starting material used is made in analogy to Example 1 from 10, ll-dihydro-8-methyN5H * zo [b, f] thiepin-10-on manufactured and melted after the Recrystallize from ether at 145 to 147.5 ° C.

Example 4

A solution of 5.1 g of 10-ethynyl-8-chloro-dibenzo [b, f] thiepin in 40 ml of absolute dioxane is mixed with

65 630 mg paraformaldehydej 4.5 ml of a 6 molar solution of diethylamine in dioxane and 200 mg KupfeitH) acetate added The well-closed flask was heated to 100 ° C. for 2 hours After cooling, the mixture is poured onto ice and then acidified with 3N methanesulfonic acid Extraction with ether removes the neutral products. The aqueous phase is extracted with ammonia made alkaline Extracting with ether gives N ^ J-dimethyl-3- (8-chloro-dibenzo [b, f | thiepin-10-yl) -2-propynylamine, which after recrystallization from hexane at 118 to 120 ° C. The maleate melts melts at 178 to 180 "C

The following connections are established in an analogous manner:

N, N-dimethyl-3- [8- (methylthio) -dibenzo [b, f] thiepin-10-yl] -2-propynylamine, F. 78 to 8O ⁰ C. The hydrochloride melts at 182 to 184 ° C .

N, N-Dimethyl-3- (8-diethyI-dibenzo [b, f] thiepin-10-yI) -2-propynylamine, m.p. 70-72 ° C The hydrochloride melts at 214-216 ° C

N, N-Dimethyl-3- (8-fluoro-dibenzo [b, f] thiepin-10-yl) -2-propynyiamine, m.p. 59-61 ° C The hydrochloride melts at 234 to 236 ° C.

N.N-Diethyl-S-iS-chloro-dibenzoss / lthiepin-10-yI) -2-propynylamine. The maleate melts from 146 to 148 "C

N, N-Dimethyl-3- (8-chloro-2-methyl-dibenzo [b, f] -thiepin-10-yl) -2-propynyiamine, m.p. 96-97 ° C. The hydrochloride melts at 174 to 176 ° C.

1 -p-ß-chloro-dibenzoss.fjthiepin-10-yi) -2-propynyl] -piperidine, mp 59-61 ° C. The methanesulfonate melts at 179 to 181 ° C.

4- [3- (8-chloro-dibenzotb, f] thiepin-10-yl) -2-propynyl] -morpholine, m.p. 109 ⁰ C. The methanesulfonate melts at 164 to 166 ° C.

1- [3- (8-chloro-dibenzo [b f] thiepin-10-yl) -2-propinyI] -pyrrolidine, F. 76 b to 77 ⁰ C. The methanesulfonate melts at 152 \ s 154 ° C .

N, N-Dimethyl-3- (8-fluoro-2-methyl-dibenzo [b, f] thiepin-10-yl) -propinylamin, F. 74 to 76 ° C. The hydrochloride melts at 231-234 ⁰ C .

N, N-Dimethyl-3- (8-chloro-3-methoxydibenzo [b, f] -thiepin-10-yl) -2-propynylamine, F. 102 to 104 ° C. The methanesulfonate melts at 211 to 214 ° C.

N, N-Dimethyl-3- (8-methoxy-dibenzo [b, f] thiepin-10-yl) -2-propynylamine, F. 68 to 71 ° C. The methanesulfonate melts at 132 to 135 ⁰ C.

N, N-Dimethyl-3- (8-chloro-dibenzo [b, f] oxepin-yl) -2-propynylamine, m.p. 62 to 64 ° C. The methanesulfonate melts at 127 to 129 ° C.

N.N-Dimethyl-3- (8-isopropyl-dibenzo [b, f] -thiepin-10-yl) -2-propynylamine, Boiling point 170 ° C / 0.02 mm Hg. The hydrochloride melts at 194 to 197 ° C.

N, N-Dimethyl-3- (2,8-dichloro-dibenzo [b, f] -oxepin-10-yl) -2-propynylamine, m.p. 83 to 85 ° C. The hydrochloride melts at 224 to 227 ° C.

2- | [3- (8-chloro-dibenzo [b, r] thiepin * 0 l-yl) -2-propynyl] methylamino} -älhanol, F. 87 to 90 ⁰ C. The maleate melts at 149 to 15I ° C.

2- (4- [3- (8-Chloro-dibenzo [b, f] thiepin-10-yl) -2-propynyl] -1-piperazynyl) ethanol, m.p. 111-113-C. The dihydrochloride melts at 253 to 257 ⁰ C.

N, N-Dimethy! -3- [2-chloro-8- (methyIthiQ) ~ dibenzo- [b.fjthiepin-10-y | J-2-propmyl8min,
F, too up to 103 ⁰ C
The Hydrochloric! melts at 206 to 208 ⁰ G

N, N-Dimethyl-3- [2-methyl-8- (methylthio) -dibenzossj, f] thiepin-10-yl] -2-propynylamine,
F, 80 to 82 ⁰ C,
The hydrochloride melts at 185 to 187 ° C

N, N-Dimethyl-3- (8-nitro-dibenzo [bflthiepin-10-yI] -2-propynylammine, F, Π 3 to 115 ° C
The Maleai melts at 179 to 182 ° C

N, N-dimethyl-3- (8-chloro-11-methyl-dibenzo [b, fjthiepin-10-yl) -2-propynylamine,
Bp 210 ° C / 0 ^ mmHg.
The hydrochloride melts at 240 to 243 ° C

N, N-Dimethyl-3- [3-methyi-8- (methylthio) -dibenzo [b, f] thiepin-10-yl] -2-propinyIamiri,
69 to 72 ° C
The maleate melts at 161 to 163 ° C

N, N-dimethyl-3- [8- (dimethylamino) -dibenzo [b, r | -
thiepin-10-yl] -2-propynylamine (oil).

N, N-Dimethyl-3- [8- {methylsulfonyl) dibenzo [b, f] -thiepin-10-yl] -2-propyny! Amine, mp 131-133 ° C
The hydrochloride melts at 247 to 250 "C

N, N-Dimethyl-3- [8- (dimethylsulfamoyl) -dibenzo- [b, f] thiepin-10-yI] -2-propynylamine, m.p. 112 to 114 ° C.
The hydrochloride melts at 217 to 220 ° C

N, N-Dimethyl-3- [8- (trifluoromethyl) -dibenzo- [b, f] thiepin-10-yl] -2-propynylamine,
88 to 91 ° C
The hydrochloride melts at 196 to 198 "C.

10

15th

20th

25th

30th

The 10-ethynyl-8-chloro-dibenzo [b, f] thiepin used as starting material can be prepared as follows: a

59 g of a Trimethyläthinylsilan / tetrahydrofuran mixture (corresponding to 0.44 MoI Trimethyläthinylsilan) in 300 ml of benzene with 235 ml of n-butyllithium solution in hexane corresponding to 0.4 mol) at 0 ⁰ C was slowly added dropwise After a further half-hour stirring at this temperature, a solution of 52.8 g of 8-ChIoMO ₁ I l-dihydro-5H-dibenzo [b, f] thiepin-10-one in 250 ml of benzene is added dropwise. The solution is left in the refrigerator overnight. The following morning the reaction mixture is poured onto a solution of 250 g of ammonium chloride in 1.5 l of water. A mixture of unreacted starting ketone and 8-chloro-10, 1l-dihy-

dro-10 - [(trimethylsilyl) ethinyl] dibenzo [b, r | thiepinlO-ol obtained that is directly subjected to dehydration.

For this purpose, the mixture is taken up in 500 ml of benzene and after adding 1.2 g of p-toluenesulfonic acid 2 Boiled under reflux for hours, the water formed being distilled off. By diluting with benzene and Washing neutral with water gives a mixture of unreacted starting ketone and [(8-chloro-dibenzo [b, f] thiepin-10-yl) -ethinyl] -trimethylsilane, which is immediately subjected to trimethylsilyl group cleavage.

A solution of 64 g of silver nitrate in 150 ml of water is added dropwise to the mixture, which is dissolved in 660 ml of acetone / water (10: 1), over the course of 30 minutes and the mixture is stirred for a further hour. Then a solution of 120 g of potassium cyanide in 500 ml of water and 500 ml of benzene is added and the mixture is stirred until two clear phases are formed. Extraction with benzene gives a mixture of unreacted ketone and 10äthiny1-8-chloro-dibenzo [b, r] thiepir !, which is separated by chromatography _on silica gel. The compound obtained melts after recrystallization from ether / n-pentane at 105 to 108 ° C

The following output connections are made in an analogous manner manufactured;

10-EthinyI-8- (methylthio) -dibenzo [b, f] thiepin,
F.99 to gates.

10-ethynyl-8-methyl-dibenzo [b, f] thjepine,
M.p. 94 to 96 ° C

10-Ethynyl-8-fluoro-dibenzo [b, f] thiepin.
According to the thin-layer chromatogram, the compound is a pure oil.

10-ethynyl-8-chloro-2-methyl-dibenzo [b, f] thiepin,
F. 127 to 129 "C

10-EthinyI-8-fluoro-2-methyl-dibenzo [b, f] thiepin,
M.p. 74 to 76 ° C

10-ethynyl-8-chloro-3-methoxydibenzo [b, f] thiepin,
F.103Jjis105 ° C.

10-ethynyl-8-methoxy-dibenzo [b, f] thiepin,
F. 131 to 136 ° C.

10-ethynyl-8-chloro-dibenz [b, fh? '. Epin,
F. 118 to! 20 ⁰ C.

10-Ethynyl-8-isopropyl-dibenzo [b, r] thiepin. The compound represents according to thin-layer chromatogram a pure oil.

10-ethynyl-2,8-dichlorodibenz [b, f | oxepin,
F. 134 to 137 ° C.

10-Ethynyl-2-chloro-8- (methylthio) -dibenzo [b, f] -thiepin, m.p. 100-103 ° C

10-Ethynyl-2-methyl-8- (methylthio) -dibenzo [b, f] -thiepin, mp 124-126 ° C.

10-ethynyl-8-nitro-dibenzo [b, f] thiepin,
F. 175 to 177 ° C.

10-Ethynyl-8-chloro-i 1 -methyl-dibenzo [b, f] thiepin.
According to thin-layer chromatography, the compound is a pure oil.

10-Ethynyl-3-methyl-8- (methylthio) -dibenzo [b, f] -thiepin.

The compound represents according to thin-layer chromatogram a pure oil.

10-Ethynyl-8- (methylsulfonyl) -dibenzo [b, rithiepin,
F. 140 to 143 ° C.

10-ethynyl-8- (dimethylsulfamoyl) -dibenzo [b, f] -thiepin,
F. 133 to 135 ° C.

10-Ethiny! -8- (trifluoromethyl) -dibenzo [b, f] -thiepin,
F. 63 to 65 ° C.

Example 5

A mixture of 20 ml dimethylformamide and 10 ml of methylamine at about 0 ⁰ C with a solution of 4.7 g of 3- (8-chloro-dibenzo [b, f] thiepin-10-yl) -2-propyn-1 ol mesylate in 30 ml of dimethylformamide is slowly added dropwise. After a reaction time of about one hour, the mixture is poured onto water. Extraction with ether gives N-methyl- [3- (8-chloro-dibenzofb, f] thiepin-10-yl) -2-propynylamine which, after recrystallization from ether, melts at 92 to 94 "C. The maleate melts at 104 to 106 ⁰ C.

The following can be produced in an analogous manner:

S-ie-chloro-dibenzofb.rjthiepin-ICylJ-i-propynylamine, F. des Maleates 170 to 172 ° C.

The 3- (8-Chlordibtnzo [b, f] thi used as the starting compound <ipin-10yl) -2-propyne-1-o! -mcsy! at can can be produced as follows:

A solution of 13.5 g of 10-ethynyl-8-chloro-dibenzo [b, f] thiepin in 150 ml of absolute tetrahydrofuran is treated dropwise at room temperature with 52 ml of a 1 molar ethylmagnesium bromide solution in tetrahydrofuran. After stirring for a further hour, 1.85 g of paraformaldehyde is pyrolyzed and passed into the reaction mixture as a gas. The solution, which has now been heated to approx. 50 ^° C., is stirred for a further 30 minutes and then poured into a saturated aqueous ammonium chloride solution. Extraction with benzene and subsequent chromatography on silica gel with benzene / methanol (20: 1) as the eluent gives 3- (8-chloro-dibenzo {b, r] thiepin-10-yl) -2-propyne-1-oil, which after recrystallization from ethyl acetate / petroleum ether beilll to 113 "C melts.

A solution of 6 g of 3- (8-chloro-dibenzo [b, r | thiepin-IO-yl) -2-propyn-1-ol in 50 ml of pyridine is mixed with 1.7 ml of methanesulfonyl chloride in 10 ml of pyridine at -10 to 0 ⁰ C added dropwise and then? Stirred for hours at this temperature. Pouring onto ice, followed by acidification with hydrochloric acid and extraction with ether gives 3- (8-chloro-dibenzo [b, f] thiepin-IO-yl) -2-propyn-1-ol mesylate, which after recrystallization from ether melts at 100 to 102 ° C.

Example 6

25th

A solution of 2 ml of ethylene oxide in 10 ml of ethanol is mixed with a solution of 0.6 g of N-methyl-3- (8-chloro-dibenzofb.f] thiepin-10-yl) -2-propynyiamine in 5 ml of ethanol and stirred for about 4 hours at room temperature. The solvent is evaporated and the residue is partitioned between water and ether. The ether phase is washed with dilute aqueous ammonia solution, dried over sodium sulfate and evaporated. 2-j [3- (8-Chloridibenzo [bf] thiepin-] 0-yl) -2-propynyl] -methylaminOf-ethanol, which melts ^{at 86 to 88 0 C after recrystallization from ether / n · pentane.}

Example 7

A solution of 5.0 g of 2- [4- [3- (8-chloro-dibenzofb, f] thicpin-IO-yl) -2-propynyl] -1-piperazinyl} -ethanol in 50 ml of acetic anhydride is heated on the steam bath for 15 minutes. After evaporation of the excess Acetic anhydride under greatly reduced pressure, the oil obtained is taken up in ether and washed with saturated potassium bicarbonate solution. Concentration of the ether phase gives [2- | 4 - [- (8-chloro-dibenzo [b, f] thiepin-10-yl) -2-propynyl] -1 -piperazinyl | -äthyl] acetate, which after recrystallization from Ethyl acetate / hexane melts at 96 to 99 ° C.

In an analogous manner one obtains [2- | [J- (8-chloro-dibenzo [b, f] thiepin-10-yl) -2-propynyl] -methylamino (-ethyl] -acetate, which melts after recrystallization from petroleum ether at 48 to 5TC.

A solution of 2 g of N, N-Dimethyl-3- (8-chloro-dibenzo [b, f] thiepin-10-yl) -2-propynylamine in 100 ml of chloroform at -50 ⁰ C with 1.2 g m -Chlorperbenzoic acid added. The reaction solution is stirred for 15 minutes at this temperature, warmed to room temperature and chromatographed on basic aluminum oxide. Chloroform / methanol (9: 1) is used as the eluent. The N, N-dimethyl-3- (8-chloro-dibenzo [b, f] thiepin-10-yl) -2-propynylamine-N-oxide obtained melts after recrystallization from ethyl acetate / petroleum ether at 68-69 ° C.

Pharmaceutical preparation forms containing representative representatives of the products according to the invention, can be produced using conventional methods.

Claims (6)

Patent claims: 1. Dibenzo [b, f] oxepine or thiepine derivatives of general formula I. like R ⁶ - R ⁸ , however, the hydroxyl groups that are present may be protected, with formaldehyde and a compound of general formula III \ R ^s 0) t5 in which X is oxygen or sulfur, R ¹ and R ^{2 are} hydrogen or lower alkyl, R ^{3 is} hydrogen or together with R ^{2 is} an additional bond and R * and R ^{5 are} hydrogen, lower alkyl, hydroxy-lower alkyl, alkanoyloxy-lower alkyl or together represent a saturated, 5- or 6-membered, optionally an oxygen atom, sulfur atom or another nitrogen atom containing heterocyclic, which can be substituted by lower alkyl, hydroxy-lower alkyl or alkanoyloxy-lower alkyl, and in which furthermore R ^{6 is} lower alkyl, lower alkoxy , lower alkylthio, lower alkylsulphonyl, di (lower alkyl) sulphamoyl, hydroxy, halogen, trifluoromethyl, nitro, amino or di (lower alkyl) amino and R ⁷ and R ⁸ each individually represent hydrogen or a substituent listed under R * , and N-oxides of compounds of the general formula I in which R ⁴ and R * are different from hydrogen, and acid addition salts of the compounds mentioned. 2. N, N-Dimethyl-3- [8- (methylthio) -dibenzo [b, f] thiepin-10-y)] -2-propynylamine and acid addition salts of this compound. 3. N ^ -Dimethyl-S-ie-chloro-dibenzopj / lthiepin-10-yl) -2-propynylamine and acid addition salts of this compound. 4. N, N-Dimethyl-3- (8-chloro-3-methoxydibenzo [b, f] thiepin-10-yl) -2-propynylamine and acid addition salts of this compound. 5. N, N-dimethyl-3- [8-trifluoromethyl-dibenzo [b, f] thiepin-IO-yl) -2-propynylamine and acid addi- so (ionic salts of this compound. 6. Process for the preparation of the compounds according to claim 1, characterized in that one in a manner known per se a) a compound of the general formula II 60 HN in which R ¹ - R ^s and X have the meaning given above and R ⁶ '- R *' have the same meaning (HD R ^s in which R ⁴ and R ^{5 have} the meaning given above, reacted, or that b) a compound of the general formula IV R ¹ R ² R ³ in which R ¹ -R ³ and X have the meaning given above, Y is a leaving group and R ⁶ ^ -R ⁸ 'have the same meaning as R ⁶ -R ⁸ , although any hydroxyl groups present may be protected with a compound of general formula III HN (QI) R ⁵ in which R ⁴ and R ^{5 are} those given above Have meaning implements, or that one c) for the preparation of a compound of the general formula I in which R ² and R ³ together represent an additional bond, a compound of the general formula V R ⁴ R ⁵ (V) in which R ¹ , R ⁴ , R ^s and X have the meaning given above and R ⁶ '-R ⁸ ' have the same meaning as R ⁶ - R ⁸ , although any hydroxyl groups present may be protected, dehydrated, or d) for the preparation of a compound of the general formula I in which R ^{4 is} hydrogen or lower alkyl and R ^! represents lower alkyl, a compound formation of the general formula VI _R7 , R * R * R ³ R ¹ R ² R ³ (VD C = C-CH ₂ -NR * '\