DE2557946A1 - NEW BENZOCYCLOHEPTATHIOPHEN DERIVATIVES, THEIR PRODUCTION AND USE - Google Patents

Description

SANDOZ-PATENT-GMBH
Loerrach

Case 100-4287

New benzocycloheptathiophene derivatives, their preparation and use

The invention relates to new compounds of the formula I in which

R. for hydrogen, an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 4-6 carbon atoms, a Hydroxyalkylgruppe with 2-5 carbon atoms, whose hydroxyl group by at least 2 carbon atoms are separated from the nitrogen atom, an oxoalkyl group with 3-5 carbon atoms, their carbonyl group separated from the nitrogen atom by at least 1 carbon atom is an alkanoyloxyalkyl group which is an alkanoyl radical having 2-10 carbon atoms and an oxyalkyl radical with 2-5 carbon atoms, the oxygen atom of which is replaced by at least 2 carbon atoms is separated from the nitrogen atom, contains, or an alkoxycarbonylalkyl group which is a Alkoxy radical with 1-4 carbon atoms and an alkylcarbonyl radical with 3-6 carbon atoms, whose carbonyl group is separated from the nitrogen atom by at least 1 carbon atom,

609829/0860

- 2 - - 100-4287

contains, stands,

25 5/946

R ₂ denotes hydrogen, chlorine or alkyl having 1-4 carbon atoms and

R ₃ denotes hydrogen, alkyl with 1-4 carbon atoms or halogen with an atomic number of 17 to 35, where at most 2 of the substituents R, R and R denote hydrogen

and their acid addition salts and processes for them Manufacturing.

Alkyl or alkylene groups contained in the radical R. can be straight-chain or branched.

If R _{1 is} an alkyl group defined above, this preferably contains 1-4, in particular 1-3, carbon atoms and is, for example, methyl, ethyl or isopropyl. A functional group contained in the radical R is preferred separated from the nitrogen atom by 2 or 3 carbon atoms. If R. stands for a hydroxyalkyl group, this preferably contains 2 or 3 carbon atoms. Examples of preferred hydroxyalkyl groups are 2-hydroxyethyl and 3-hydroxypropyl. _{If R 1 represents} an oxoalkyl group defined above, this preferably contains a CH ₃ —CO group and represents, for example, the acetonyl or 4-oxopentyl group. If R 1 represents an alkanoyloxyalkyl group, the oxyalkyl radical bonded to the nitrogen atom preferably contains 2 or 3 Carbon atoms, the alkanoyl radical can represent, for example, an acetyl or heptanoyl group. Examples of suitable alkanoyloxyalkyl groups are acetoxyethyl or heptanoyloxyethyl. If R _{1 represents} an alkoxycarbonylalkyl group, it contains an

609 829/0868

- 3 - 100-4287

the carbonylalkyl radical bonded to nitrogen atom is preferably 3 or 4 carbon atoms. The alkoxy radical preferably represents methoxy or ethoxy. Examples of suitable alkoxycarbonylalkyl groups ethoxycarbonylethyl and ethoxycarbonylpropyl may be mentioned.

The substituent R ₁ preferably represents an alkyl group with 1-3 carbon atoms or a hydroxyalkyl group with 2-3 carbon atoms.

IU is preferably hydrogen. Another Substituent R ^ is preferably in the 2-position of the benzocycloheptathiophene skeleton arranged. If R_ is an alkyl group defined above, contains this preferably 1-2 carbon atoms and is especially methyl.

R ^ preferably denotes hydrogen. Another Substituent R- is preferably in the 6- or 7-position, especially in the 7-position of the benzocycloheptathiophene

arranged skeleton and preferably represents chlorine. If R- is an alkyl defined above, it preferably contains 1-2 carbon atoms and is especially methyl.

Particularly preferred compounds of the formula I are those in which R, denotes an alkyl group with 1-3 carbon atoms or a hydroxyalkyl group with 2-3 carbon atoms, the hydroxyl group of which is separated from the nitrogen atom by at least 2 carbon atoms, R denotes hydrogen and R ₃ for hydrogen or chlorine, which is preferably in the 7-position

609829/0868

- * - 100-4287

of the rig framework arranged xjsu, stands.

According to the invention one arrives at the new compounds of the formula I and their acid addition salts by

a) for the preparation of compounds of the formula Ia, in which PU ^un ^ - ^R 3 have the above meaning and R- stands for hydrogen, an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 4-6 carbon atoms, a hydroxyalkyl group with 2-5 carbon atoms, whose hydroxyl group is separated from the nitrogen atom by at least 2 carbon atoms or an oxoalkyl group having 3-5 carbon atoms whose carbonyl group is separated from the nitrogen atom by at least 1 carbon atom, compounds of the formula II in which R ₂ and R _{3 have the} above meaning and R. means hydrogen or lower alkyl, with

'I.

Compounds of the formula III in which R ^ has the above meaning owns, condenses, or

b) for the preparation of compounds of the formula Ic,

TT

wherein R ₂ and R _{3 have the} above meaning and R stands for an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 4-6 carbon atoms, a hydroxyalkyl group with 2-5 carbon atoms, the hydroxyl group of which is separated from the nitrogen atom by at least 2 carbon atoms, an oxoalkyl group with 3 - 5 carbon atoms, the carbonyl group of which is separated from the nitrogen atom by at least 1 carbon atom ^ or an alkoxycarbonylalkyl group which is an alkoxy group with 1-4 carbon atoms and a carbonylalkyl group with 3-6 carbon atoms, whose carbonyl group is separated by at least 1 carbon atom from the nitrogen atom is separated, contains, stands, compounds of the formula Ib in which R ₂ and R _{3 are as defined} above, alkylated, or

609829/0868

- 5 - 100-4287

c) for the preparation of compounds of the formula Ie in which R ₀ and R_ have the above meaning, A is an alkylene group having 2-5 carbon atoms and R _{5 is} an alkyl group having 1-9 carbon atoms. Compounds of the formula Id in which R ₂ , R ₃ and A are as defined above are acylated

and the compounds of formula I obtained, if desired converted into their acid addition salts.

The condensation reaction of compounds of the formula II with compounds of the formula III can according to per se known methods take place in the presence of a water- or alcohol-releasing agent. links of the formula II, in which R. is hydrogen, can be in the enol form or the keto form isomeric thereto can be used. Suitable agents that split off water or alcohol are, for example Lewis acids or, preferably, strong inorganic or organic acids. If the reaction is in the presence a strong inorganic or organic acid is carried out, equivalent amounts of these are preferred Acids used and the reaction at elevated temperature, preferably at temperatures between 50 and 250 °. As examples of suitable acids be mineral acids such as sulfuric acid or organic acids such as benzenesulfonic acid or p-toluenesulfonic acid called. Water or alcohol, which are formed during the reaction, can be used directly during the reaction by distillation, preferably under reduced pressure, for example a pressure between 10 and 100 Torr removed. According to an expedient embodiment for example an anhydrous salt such as the p-toluenesulfonate of a compound of formula III melted together with a compound of formula II and the mixture "

609829/0868

- 6 - 1ÜU-4287

preferably heated under reduced pressure. If R. is hydrogen, the reaction temperature is preferably between 150 and 250 °, and if R. is lower alkyl, preferably between 100 and 200 °. If the reaction is carried out in the presence of a Lewis acid, it is carried out in one under the reaction conditions inert organic solvent, for example an aromatic hydrocarbon such as benzene carried out at elevated temperature, preferably at the boiling point of the reaction mixture. The Lewis acids used are preferably titanium tetrachloride or tin tetrachloride.

The alkylation of the compounds of the formula Ib according to process variant b) can in itself lead to the alkylation secondary amines conventional methods are carried out. For example, the connections of the Formula Ib with compounds of the formula IV, in which R, has the above meaning and X represents the acid radical of a reactive ester, preferably halogen or an organic sulfonic acid radical, on per se implemented in a known manner. The reaction is preferably carried out in one under the reaction conditions inert organic solvent at temperatures between about 20 ° and the boiling point of the reaction mixture, preferably in the presence of a basic one Condensing agent, e.g. an organic amine such as triethylamine or an alkali metal carbonate, or in the presence of an excess of a compound of the formula Ib. Examples of suitable solvents are lower alcohols, halogenated hydrocarbons or dimethylformamide. Compounds of formula Ic, which do not contain any groups which can be reducible by mild catalytic hydrogenation and in which they are linked to the α-position

6 09829/0868

- 7 - 100-4287

Π557946.

"to the nitrogen atom located carbon atom of the Radical R, at least one hydrogen atom is bonded,

can

can also be obtained by reductive alkylation. The reductive alkylation, which in particular for the production of compounds of the formula Ic in which R ^ is cycloalkyl with 4-6 carbon atoms, is suitable, takes place by reductive reaction with a corresponding aldehyde or ketone. The reductive Alkylation can be carried out by catalytic hydrogenation under mild reaction conditions, preferably in the presence a palladium catalyst, for example palladium / carbon (5- or 10%) or palladium / barium sulfate. Examples of suitable solvents are lower alcohols such as ethanol or dimethylformamide. For the preparation of compounds of the formula Ic, in which R, for an alkoxycarbony1-alky! Group defined above, whose carbonyl group is separated from the nitrogen atom by 2 carbon atoms, is the alkylation preferably by addition of appropriate acrylic acid derivatives according to the method of Michael carried out. The Michael addition of acrylic acid derivatives to compounds of the formula Ib can be based on

Way in an inert organic solvent under the reaction conditions, preferably a cyclic one Ethers such as dioxane, preferably in the presence of a basic catalyst, for example an organic one Ammonium hydroxydes such as Benzyltriethylammoniumhydroxyd can be carried out. The reaction temperature can be between Room temperature and boiling point of the reaction mixture, preferably between 40 and 50 °. For the preparation of compounds of the formula Ic in which R. is a hydroxyalkyl group as defined above, whose hydroxyl group is separated from the nitrogen atom by 2 carbon atoms, can

609829/0868

- 8 - 100-4287

Compounds of the formula Ib can also be reacted with corresponding epoxides in a manner known per se.

The acylation of the compounds of the formula Id according to process variant c) can be carried out by methods known per se , for example by reaction with appropriate acid halides, preferably chlorides, or corresponding acid anhydrides. If acid anhydrides are used as acylating agents, the reaction is carried out under mild reaction conditions, for example at temperatures between -10 and 50, preferably between 0 and 10 °. When using acid halides as acylating agents the reaction is preferably in the presence of an acid-binding agent, for example one organic base such as pyridine, optionally with the addition of an inert under the reaction conditions organic solvent carried out. The pH of the reaction mixture is preferably between 5 and 14, especially between 7 and 8

The compounds of the formula I obtained according to the invention can be in the form of the free bases or their acid addition salts are present. The free bases can be converted into their acid addition salts in a manner known per se be convicted and vice versa. So the inventive Compounds of the formula I e.g. with inorganic acids such as hydrogen chloride or with organic Acids such as fumaric or maleic acid form acid addition salts. Because enamines pass through in an aqueous medium If an excess of protons can be split, the acid addition salts of the compounds are obtained of the formula I, preferably in an anhydrous medium using equivalent amounts of acid.

609829/0868

- Q-100-4287

The starting compounds can be obtained as follows:

a ¹ ) Compounds of the formula Ha, in which R ₂ and IU have the above meanings, can be obtained, for example, by converting into compounds of the formula Hb, in which Rp and R., have the above meanings and

I-R. lower alkyl means the ether groups converted into hydroxyl groups in a manner known per se. The resulting compounds of the formula Ha are generally partially in their keto form.

b ¹ ) Compounds of the formula Hb can be obtained, for example, by reducing compounds of the formula V in which R ₂ , R ₃ and R. have the above meanings. The reduction can be carried out, for example, by means of a mixture of aluminum chloride and lithium aluminum hydride in an organic solvent which is inert under the reaction conditions.

c ¹ ) Compounds of the formula V can be obtained in a manner known per se by _{brominating compounds of the formula VI in which R 2} and R are as defined above using N-bromosuccinimide, the obtained in the 9- and 10-position of the ring structure dibrominated reaction products with an alcohol of the formula R.OH, in which R has the above meaning, reacted and then splitting off hydrobromic acid.

d ¹ ) Compounds of the formula VI can be based on

60 9 8 29/0868

- 10 - 100-4287

25579A6

known manner, for example analogous to the process described in Helv.Chim.Acta 49j_ 214-234 (1966), starting from corresponding 2- [2- (2-thienyl) ethyl] benzoic acid derivatives,

If the preparation of the starting compounds is not described, these are known or per se known processes or can be produced analogously to those described here or analogously to processes known per se.

The compounds of the formula I and their physiologically acceptable acid addition salts are distinguished by interesting pharmacological properties and can therefore be used as medicinal products.

This is how the compounds show in animal experiments for neuroleptics typical properties and inhibit, for example, the spontaneous motility of mice.

Due to the aforementioned effects, the compounds can be used as Neuroleptxca and in the Psychiatry can be used to treat psychotic disorders.

The compounds of the formula I and their physiologically acceptable acid addition salts can be used as medicaments together with the usual pharmaceutical excipients be contained in pharmaceutical preparations such as tablets, capsules or solutions. These galenic Preparations can be prepared according to methods known per se.

In the following examples illustrating the invention

609829/0868

- 11 - 100-4287

explain in more detail, but are not intended to limit their scope in any way, all temperature data are given in degrees Celsius.

609829/0868

Example 1;

- 12 - lÜO-4287

-Methvl

3 g ^ iperaain in 100 ml of methanol with a

Solution of 83.0 g of p-toluenesulfonic acid monohydrate in 250 ml of methanol are added, the mixture is evaporated under reduced pressure and the evaporation residue is reduced in a water jet vacuum (approx. 15 Torr) dried at 150 ° for 1 hour. The tosylate obtained is pulverized after cooling, with 50.0 g of 10-methoxy-4H-benzo [4.5] cyclohepta [1,2-b3-thiophene mixed and heated to 160 ° for 30 minutes and then 1.5 hours under reduced pressure (approx.

on ΐβη \

15 Torr) * heated. After cooling to room temperature 250 ml of chloroform and 250 ml of 20% sodium hydroxide solution are added to the solid reaction mixture, the chloroform phase is separated off and the aqueous solution is further extracted with chloroform. The united organic Solutions are washed with water, dried over potassium carbonate and evaporated. The obtained raw Title compound is recrystallized from isopropanol, melting point 147 ° to 151 °.

The starting material is obtained as follows:

a) To a mixture of 300 ml abs. Ether, 28.9 g anhydrous Aluminum chloride and 7.2 g lithium aluminum hydride 30 g of 10-methoxy-4II-benzof4,5] cycloheptatl, 2-b] thiophen-4-one are added in portions for 20 minutes at 20-25 ° and then stirred for 1 hour at room temperature. Be on it

809829/0 8 68

- 13 - 100-4287

300 ml of ethyl acetate and then 150 ml of 25% sodium hydroxide solution are added dropwise at 20 ° with cooling, The organic phase is decanted from the greasy inorganic material and concentrated. The evaporation residue is recrystallized from methanol. The pure 10-methoxy-4H-benzo [4,5] -cyclohepta [1,2-b] thiophene is obtained in this way. M.p. 94-96 ° C.

Example 2;

10 g of 4H-Benzo [4,5] cyclohepta [1,2-b] thiophen-10 (9H) -one, 41.3 g of N-methylpiperazine and 200 ml of benzene are in the Submitted flask and filled with 78.5 g of p-toluenesulfonic acid monohydrate offset. The suspension is then concentrated in vacuo and the evaporation residue for 5 hours at 200 ° oil bath temperature in a water jet vacuum (15 torr). After cooling to about 50 °, the reaction mixture is mixed with 300 ml of 3N sodium hydroxide solution and 500 ml Benzene was added and dissolved with stirring. The organic phase is then separated off, washed with water, dried over sodium sulfate and concentrated. In this way the crude title compound (base) is obtained, which, after recrystallization from isopropanol, melts at 147-151 °.

The starting material is obtained as follows:

a) 32.75 g of 10-methoxy-4H-benzo [4,5] cyclohepta [1,2-b] -thiophene are dissolved in 300 ml of 3N hydrochloric acid and 300 ml Methanol boiled under reflux for 1 hour. It is then cooled and the product filtered off. The crystals are converted from isopropanol

609829/0868

IOC -4287

crystallized. In this way the pure 4H-benzo [4,5] cyclohepta [1,2-b] thiophen-10 (9H) -one is obtained obtained, which melts at 117 - 119 °.

Analogously to Example 1 or 2, the following compounds of the formula Ia can also be prepared by reacting corresponding Piperazine derivatives of the formula III with the corresponding 4H-benzo [4,5] cyclohepta [1,2-b] thiophene derivatives of Formula II can be obtained:

Tabel

Example No. ^R l - ⁰¹¹ ^ CH ^{3 R} 2 ^R 3 Snip. 2 A H H H HF * from 226 ° Z ⁺ 2 B -CH ₃ H 7-Cl 182-184 ° 2 C H 7-Cl 149-150 ° 2 D -CH ₂ -CH ₂ -OH H 6-Cl 165-167 ° 2 E. -CH ₂ -CH ₂ -CH ₂ -OH H 7-Cl 130-132 ° 2 F -CH ₂ -CH ₂ -OH H 7-Cl 109-111 ° 2 G -CE ₂ -CH ₂ -CH ₂ -OH H H 119-120 ° 2 H -O
^ CH ₃ H H HM ** 168-170 ° 2 I. H 7-Cl 166-167 ° 2 y -CH ₂ COCH ₃ H 7-Cl 169-170 ° 2 K H H 155-156 ° 2 L 2-CH ₃ H 114-115 °

⁺ Z = decomposition * HF = hydrogen fumarate ** HM = hydrogen maleate

609829/0868

100-4287

Example 3: 4; _ £ 4H-Benzo [4 ^ 5] cYclohepta ^ lj ^ f ^ b J_th ^ oghen-

A suspension of 8.0 g of 1- (4H-Benzo [4.5] cyclohepta - [! »ä-bithiophene-10-yD-piperazine (for preparation, see Example 1) and 2.6 g of sodium bicarbonate in 20 ml of ethanol is inert A solution of 3.3 g of isopropyl bromide in 5 ml of ethanol is added dropwise at room temperature for 30 minutes, the reaction mixture is heated to boiling temperature for 4.5 hours and evaporated under reduced pressure. The residue is dissolved in 100 ml of water and 300 ml of methylene chloride, the organic phase separated off, washed with water and saturated sodium chloride solution, dried over magnesium sulphate and evaporated. The title compound obtained is converted into its hydrogen fumarate in methanol. Mp .: decomposition from 226 ° (from methanol).

Analogously to Example 3, those mentioned in Example 2 and in Examples 2 C to 2 L as well as the following connections

of the formula Ic by alkylating corresponding 4- (4H-benzo [4,5] cyclohepta [1,2-b] thiophen-10-yl) piperazine derivatives of formula Ib can be obtained.

Example No. ^R l ^R 2 ^R 3 Stnp. 3A
3B -CH ₂ CH ₂ -CQ-OC ₂ H ₅
-CH ₂ CH ₂ CH ₂ CO-OC ₂ H ₅ H
H 7-Cl
H 110-112 °
113-115 °

60 9 829/0868

- 16 - 100-4287

Example 4: lzJ2z2hlor-4H-benzo_ [4_ _i 52cYclohep_ta [1 _X 2 ₌ bJ-

A solution of 6.0 g of 1- (7-chloro-4H-benzo [4.5] cyclohepta [1,2-b] thiophen-10 ~ yl) piperazine and 1.8 g of cyclopentanone in 75 ml of ethanol is in the presence hydrogenated by 0.5 g of 10% palladium on carbon at 50 ° and 5 atm hydrogen pressure. After the theoretical amount of hydrogen has been taken up (duration approx. 5 hours), the catalyst is filtered off, the solution is evaporated to dryness and the title compound which remains as a solid residue is crystallized from ether. M.p .: 169-170 °.

Analogously to example .4, the compounds of the formula mentioned in examples 2A and 21 in particular can also be used Ic by reductive alkylation of corresponding 4- (4H-benzo [4,5] cyclohepta [1,2 ~ b] thiophen-10-yi) piperazine derivatives of formula Ib can be obtained.

Example 5:

For the solution of 2.0 g of 4- (4H-Benzo [4.5] cyclohepta [1,2-b] -thiophen-10-yl) -1-piperazine ethanol 0.48 g of acetyl chloride is left in 20 ml of anhydrous pyridine at room temperature add dropwise, the reaction mixture is stirred for a further 6 hours at room temperature and poured into 100 ml of water. The solution obtained is extracted with benzene, and the benzene solution is washed with water over magnesium sulfate dried and evaporated. The title compound crystallizes from the residue obtained from ether / petroleum ether. M.p .: 140-141 °.

609829/0868

100-4287

Analogously to Example 5, the following compound of the formula Ie can also be prepared by acylating the corresponding Hydroxy compound of the formula Id with the corresponding Acid derivative can be obtained:

Example No. A. ^R 5 ^R 2 ^R 3 M.p. 5A -CH ₂ CH ₂ (CH ₂ ) ₅ CH ₃ H H HF * 171-17 2 °

609829/0868

100-4287

N-A-OH

R,

-A-O-CO-R,

II

609829/0868

Ha

J ⁸

III X-R

II

O

VI

609829/0868

Claims (3)

Claims .R ₁ for hydrogen, an alkyl group with 1-6 carbons; substance atoms, a cycloalkyl group with 4-6 carbon atoms, a hydroxyalkyl group with 2-5 carbon atoms, the hydroxyl group of which is separated from the nitrogen atom by at least 2 carbon atoms, or, an oxoalkyl group with 3-5 carbon atoms whose carbonyl group is separated from the nitrogen atom by at least 1 carbon atom is separated, an alkanoyloxyalkyl group which contains an alkanoyl group having 2-10 carbon atoms and an oxyalkyl group having 2-5 carbon atoms, the oxygen atom of which is separated from the nitrogen atom by at least 2 carbon atoms, or an alkoxycarbonylalkyl group which is an alkoxy group having 1-4 carbon atoms and contains an alkylcarbonyl radical with 3-6 carbon atoms, the carbonyl group of which is separated from the nitrogen atom by at least 1 carbon atom, R ₂ denotes hydrogen, chlorine or alkyl having 1-4 carbon atoms and 609829/0868 - ²¹ - ICC-4287 R ₃ denotes hydrogen, alkyl with 1-4 carbon atoms or halogen with an atomic number of 17 to 35, where at most 2 of the substituents TL, R and R Mean hydrogen and their acid addition salts, characterized in that one a) for the preparation of compounds of the formula Ia, Yes wherein R ₂ and R _{3 have the} above meaning and R _{1 stands} for hydrogen, an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 4-6 carbon atoms, a hydroxyalkyl group with 2-5 carbon atoms, - their hydroxyl group by at least 2 carbon atoms from the nitrogen atom is separated, or an oxoalkyl group with 3 - 5 carbon atoms, the carbonyl group of which is separated from the nitrogen atom by at least 1 carbon atom, is compounds of the formula II, II 603829/0868 - 22 - 100-4207 wherein R ₂ and R ^ have the above meaning and R. is hydrogen or lower alkyl, with compounds of the formula III, UN N <ί III wherein R, has the above meaning, condenses, or b) for the preparation of compounds of the formula Ic, 2. Ic wherein R ₂ and R _{3 have the} above meaning and R stands for an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 4-6 carbon atoms, a hydroxyalkyl group with 2-5 carbon atoms, the hydroxyl group of which is separated from the nitrogen atom by at least 2 carbon atoms, an oxoalkyl group with 3-5 carbon atoms whose carbonyl group is separated from the nitrogen atom by at least 1 carbon atom, or an alkoxycarbonylalkyl group which has an alkoxy group with 1-4 carbon atoms and a carbonylalkyl group with 3-6 carbon atoms whose carbonyl group is separated by at least 1 carbon atom from the nitrogen atom is separated, contains, stands, compounds of the formula Ib, 609829/0868 100-4287 Ib wherein R ₀ and R, have the above meaning, alkylated, or c) for Preparation of compounds of the formula Ie, ΓΛ -A ^ O-CO-R, Ie where R_ and R _{3 have the} above meaning, A is an alkylene group with 2-5 carbon atoms and R _{5 is} an alkyl group with 1-9 carbon atoms, compounds of the formula Id, $ 09829/0868 100-4287 -A-OH Id wherein R ₀ , R_ and A have the above meanings, acylated and if desired, the compounds of the formula I obtained are converted into their acid addition salts. 60 98 29/0868 Germany West _ 25 - 100-4287 New compounds of the formula I, wherein R, for hydrogen, an alkyl group with 1-6 carbon atoms, a cycloalkyl group having 4-6 carbon atoms, a hydroxyalkyl group having 2-5 Carbon atoms whose hydroxyl group is through at least 2 carbon atoms are separated from the nitrogen atom, an oxoalkyl group with 3-5 carbon atoms, their carboxyl group separated from the nitrogen atom by at least 1 carbon atom is an alkanoyloxyalkyl group, which an alkanoyl radical with 2-7 carbon atoms and vinen oxyalkyl radical with 2-5 carbon atoms, whose The oxygen atom is separated from the nitrogen atom by at least 2 carbon atoms, or an alkoxycarbonyialkyl group which is an alkoxy group having 1-4 carbon atoms and a Alkylcarbonyl radical with 3-6 carbon atoms, whose carbonyl group has at least 1 carbon atom is separated from the nitrogen atom, contains, stands, R ₂ denotes hydrogen, chlorine or alkyl having 1-4 carbon atoms and 609829/0 868 - 26 _ Dent · schland West 100-4287 R- hydrogen, alkyl with 1-4 carbon atoms or Halogen with an atomic number of 17 to 35 means, with at most 2 of the substituents R, R and R denotes hydrogen and their acid addition salts. 3. Medicinal products, characterized in that they contain compounds of the formula I or their acid addition salts. SANDOZ-PATENT-GMBH 3700 / US / IIO 609829/0868