DD247898A5 - NEW HETEROAROMATIC AMINE DERIVATIVES, MEDICAMENTS CONTAINING THESE COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF - Google Patents

Abstract

The present invention relates to novel heteroaromatic amine derivatives of general formula I in which A is a formula group and B is a methylene, carbonyl or thiocarbonyl group or A is a formula group and B is a methylene group, wherein the carbon atom marked with x in each case with the phenyl nucleus E is a straight-chain alkylene group optionally substituted by an alkyl group, G is a straight-chain alkylene group optionally substituted by an alkyl group, R ind 1 is a hydrogen, fluorine, chlorine or bromine atom, trifluoromethyl, nitro, amino, alkylamino , Dialkylamino, alkyl, alkylmercapto, hydroxy, alkoxy or phenylalkoxy, R ind 2 is a hydrogen, chlorine or bromine atom, a hydroxy, alkoxy, phenylalkoxy or alkyl group or R ind 1 and R ind 2 together an alkylenedioxy group, R ind 3 represents a hydrogen atom, an alkenyl group, an alkyl or phenylalkyl group, and has one bonded through a carbon or nitrogen atom NEN 5- or 6-membered heteroaromatic ring, which contains an oxygen, sulfur or nitrogen atom, two nitrogen atoms or a nitrogen atom and an oxygen or sulfur atom, and may be fused to the addition of a phenyl ring, in which case the bond via the Phenyl nucleus, or an imidazo (1,2-a) pyridyl group in which the carbon skeleton of the radicals mentioned above is replaced by a halogen atom, an alkyl, hydroxy, alkoxy, phenylalkoxy, phenyl, dimethoxyphenyl, nitro, amino -, acetylamino, carbamoylamino, N-alkyl-carbamoylamino, hydroxymethyl, mercapto, alkylmercapto, alkylsulfinyl, alkylsulfonyl, alkylsulfonyloxy, alkylsulfonylamino, alkoxycarbonylmethoxy, carboxymethoxy or alkoxymethyl mono- or disubstituted or by a Methylene or ethylenedioxy may be substituted and at the same time an optionally present imino group in the above-mentioned heteroaromatic radicals may be substituted by an alkyl, phenylalkyl or phenyl group, their N-oxides and their acid addition salts with inorganic or organic acids which have valuable pharmacological properties, in particular a heart rate-lowering effect. The new compounds can be prepared by methods known per se. formula

Description

Field of application of the invention

The invention relates to a process for the preparation of novel heteroaromatic amine derivatives having valuable pharmacological properties, in particular having a long-lasting heart rate lowering effect and a detrimental effect on the 02 requirement of the heart.

The compounds prepared according to the invention are used as medicaments, for example for the treatment of sinustadycardia and ischemic heart diseases.

Characteristic of the known technical solutions

In GB-PS 1 548844 u.a. the compound of the formula

OCH,

OCH

and their physiologically acceptable acid addition salts, which have valuable pharmacological properties, namely, in addition to a mild hypertensive effect, in particular a selective heart rate-lowering effect.

Object of the invention

The aim of the invention is the provision of new compounds with valuable pharmacological properties, which can be used in particular for the treatment of sinustadycardia and ischemic heart disease.

Explanation of the essence of the invention

The invention has for its object to find new compounds with the desired properties and processes for their preparation.

According to the invention, new heteroaromatic amine derivatives of the general formula

¹ HENG- Het

manufactured,

their N-oxides, their acid addition salts, in particular their physiologically acceptable acid addition salts with inorganic or organic acids.

The new compounds have valuable pharmacological properties, in particular a long-lasting heart rate lowering effect and a depressing effect on the O ₂ requirement of the heart.

In the above general formula I means

A is a -CH ₂ -CH ₂ -, - CH = CH or -CHz-CO group

and B is a methylene, carbonyl or thiocarbonyl group or

9 ^H

Aine-CO-CO or -CH-CO- group and B a methylene group, χ

wherein the carbon atom indicated by χ is in each case linked to the phenyl nucleus, E is a straight-chain alkylene group which is optionally substituted by an alkyl group having 1 to 3 carbon atoms and has 2 to

4 carbon atoms,

G is an optionally substituted by an alkyl group having 1 to 3 carbon atoms, straight-chain alkylene group having 1 to

5 carbon atoms,

Ri represents a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl, nitro, amino, alkylamino, dialkylamino, alkyl, alkylmercapto, hydroxy, alkoxy or phenylalkoxy group, each alkyl part in each case being 1 to 3 Contain carbon atoms

R ₂ ei η hydrogen, chlorine or bromine, a hydroxy, alkoxy, phenylalkoxy or alkyl group, each alkyl portion may each contain 1 to 3 carbon atoms, or

R _{3 is} a hydrogen atom, an alkenyl group having 3 to 5 carbon atoms, an alkyl or phenylalkyl group, wherein the alkyl moiety may each contain 1 to 3 carbon atoms, and

Het a 5- or 6-membered heteroaromatic ring bonded via a carbon or nitrogen atom, which contains an oxygen, sulfur or nitrogen atom, two nitrogen atoms or a nitrogen atom and an oxygen or sulfur atom, and to which additionally a phenyl ring may be fused, wherein in this case also the bond via the phenyl nucleus can take place, or an imidazo [1,2-a] pyridyl group, in which the carbon skeleton of the abovementioned radicals is represented by a halogen atom, an alkyl, hydroxyl, alkoxy, phenylalkoxy, phenyl , Dimethoxyphenyl, nitro, amino, acetylamino, carbamoylamino, N-alkylcarbamoylamino, hydroxymethyl, mercapto, alkylmercapto, alkylsulfinyl, alkylsulfonyl, alkylsulfonyloxy, alkylsulfonylamino, alkoxycarbonylmethoxy, carboxymethoxy or Alkoxymethyl group mono- or disubstituted or may be substituted by a methylene or ethylenedioxy group and at the same time an optionally present Iminog group in the above-mentioned heteroaromatic radicals may be substituted by an alkyl, phenylalkyl or phenyl group, wherein the above-mentioned alkyl moieties may each contain 1 to 3 carbon atoms.

For the meanings mentioned in the definition of the radicals at the outset, for example, R _{1 is} that of the hydrogen, fluorine, chlorine or bromine atom, the methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, hydroxy, methoxy , Ethoxy, n-propoxy, isopropoxy, methylthio, ethylthio, isopropylthio, nitro, amino, methylamino, ethylamino, n-propylamino, isopropylamino, dimethylamino, diethylamino, di-, n-pyrolamino, diisopropylamino, methyl-ethylamino, methyl-n-propylamino, methyl-isopropylamino, ethyl-n-propylamino, benzyloxy, 1-phenylethoxy, 1-phenylpropoxy, 2-phenylethoxy or 3-phenylpropoxy group,

for R ₂ those of the hydrogen, chlorine or bromine atom, the methyl, ethyl, n-propyl, isopropyl, hydroxy, methoxy, ethoxy, n-propoxy, isopropoxy, benzyloxy, 1- Phenylethoxy, 2-phenylethoxy, 2-phenylpropoxy or 3-phenylpropoxy group or together with Ri that of the methylenedioxy or ethylenedioxy group,

for R _3, those of the hydrogen atom, the methyl, ethyl, n-propyl, isopropyl, benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 1-methyl-i-phenylethyl, 3 Phenylpropyl, allyl, n-butene (2) -yl or n-pentene (2) -yl group and for E the ethylene, n-propylene, n-butylene, 1-methylethylene, 2-ethyl-ethylene, 1-propyl-ethylene, 1-methyl-n-propylene, 2-methyl-n-propylene, 1-ethyl-n-propylene, 3-ethyl-n-propylene, 2-propyl-n-propylene or 2-methyl-n-butylene, for G, the methylene, ethylidene, n-propylidene, n-butylidene, 2-methyl-propylidene, ethylene, 1-methyl -ethylene, 2-ethylethyleri-, 1-propyl-ethylene, 2-methyl-ethylene, n-propylene, n-butylene, n-pentylene, 1-methyl-n-propylene, 3-methyl n-propylene, 1-methyl-n-butylene, 1-methyl-n-pentylene, 1-ethyl-n-propylene, 2-ethyl-n-propylene or 1-ethyl-n-butylene and for Het that of the pyrrolyl-2, pyrrolyl-3, N-methyl-pyrrolyl-2-, N-methyl-pyrrolyl-3-, 1 ^ -dimethyl-pyrrolyl-S-, 2,5-dimethylpyrrolyl-3 , Furyl 2-, furyl-3, 5-methyl-furyl-2-, 2-methyl-furyl-3, 5-nitro-furyl-2-, 5-methoxymethyl-furyl-2, benzo [b] furyl 2-, benzo [b] furyl-3-, 7-methyl-benzo (b) furyl-3, 2-methoxy-benzo [b] furyl-3, 3-methoxy-benzo [b] furyl-2 , 4-methoxy-benzo [b] furyl-3, 5-methoxy-benzo [b] furyl-3, 6-methoxy-benzo [b] furyl-3, 7-methoxy-benzo [b] furyl 3, 5-Methoxy-3-phenyl-benzo [b] furyl-2-, 3-methyl-5-methoxy-benzo [b] furyl-2, thienyl-2, thienyl-3, 5-methyl -thienyl-2-, 2-methyl-thienyl-3, 3-methyl-thienyl-2-, 2,5-dimethyl-thienyl-3, 4,5,6,7-tetrahydrobenzo [b] thienyl -3-, 4,5,6,7-tetrahydro-benzo [b] thienyl-2-, 5-chlorothienyl-2-, 5-bromo-thienyl-2-, 5-phenyl-thienyl-2-, 2-phenyl-thienyl-3, benzo [b] thienyl-2-, benzo [b] thienyl-3, 2,5-dimethyl-benzo [b] thienyl-3, 5-methyl-benzo [b] thienyl-3-, 6-methylbenzo [b] thienyl-3, 5-chloro-benzo [b] thienyl-2-, 5-bromo-benzo [b] thienyl-3, 6-hydroxybenzo [b] thienyl-3-, 7-hydroxybenzo [b] thienyl-3, 5-hydroxybenzo [b] thienyl-2-, 6-hydroxybenzo [b] thienyl-2-, 7-hydroxybenzo [b] thieny L-2-, 3-methoxybenzo [b] thienyl-2-, 4-methoxybenzo [b] thienyl-2-, 5-methoxybenzo [b] thienyl-2-, 6-methoxybenzo [b] thienyl-2-, 7-methoxy-benzo [b] thienyl-2-, 2-methoxy-benzo [b] thienyl-3, benzo [b] thienyl-4-, benzo [b] thienyl-5, benzo [b] thienyl-6-, benzo [b] thienyl-7-, 4-methoxybenzo [b] thienyl-3, 5-methoxybenzo [b] thienyl-3, 6-methoxybenzo [b] thienyl -3-, 7-Methoxy-benzo [b] thienyl-3, 5,6-dimethoxy-benzo [b] thienyl-3, 5,6-methylenedioxy-benzo [b] thienyl-3,6-ethoxy benzo [b] thienyl-3, 6-propoxybenzo [b] thienyl-3, 6-isopropoxybenzo [b] thienyl-3, 6-mercapto-benzo [b] thienyl-3, e-methylcercapto -benzofbjthienyl-S, e -methylsulfinyl-benzotblethienyl -? -, 6-methylsulfonyl-benzo [b] thienyl-3, 6-methylsulfonyloxy-benzo [b] thienyl-3, 6-methoxycarbonylmethoxy-benzo [b] thienyl-3-, 6-ethoxycarbonylmethoxybenzo [b] thienyl-3, 6-carboxymethoxybenzo [b] thienyl-3, 6-aminobenzo [b] thienyl-3, 6-methylaminobenzo [b] thienyl-3, 6-dimethylamino-benzo [b] thienyl-3, 6-diethylamino-benzo [b] thienyl-3, 6-acetamino benzo [b] thienyl-3-, 6-methylsulfonylamino-benzo [b] thienyl-3, pyrazolyl-1, pyrazolyl-3, 3,5-dimethyl-pyrazolyl-i, 1,5-dimethyl- pyrazolyl-3, imidazolyl-1, imidazolyl-2, imidazolyl-4 (5) -, 1-methyl-imidazolyl-4-, 1-benzyl-imidazolyl-4-, S-nitro-methyl-imidazolyl- i, 2- (3,4-Dimethoxy-phenyl) -imidazolyl-4 (5) -, benzo [d] imidazolyl-1, 2-benzyl-benzo [d] imidazolyl-1, benzo [d] imidazolyl -2-, imidazo [1,2-a] pyridyl-3, oxazolyl-4, oxazolyl-5, isoxazolyl-3, 3-methylisoxazolyl-5, 5-methylisoxazolyl-3, 3,5-Dimethylisoxazolyl-4-, 4-methyl-thiazolyl-5, benzo [d] oxazolyl-2-, benzo [d] -isoxazolyl-3, benzo [d] thiazolyl-2-, 5-ethoxybenzo [ d] thiazolyl-2-, benzo [d] isothiazolyl-3-, benzo [d] pyrazolyl-1-, benzo [d] pyrazolyl-3, pyridyl-2-, pyridyl-3, pyridyl-4-, pyridyl 3-N-oxide, 4-nitro-pyridyl-2-, 4-amino-pyridyl-2-, 4-acetylamino-pyridyl-2-, 4-carbamoylamino-pyridyl-2-, 4-N-methylcarbamoylamino pyridyl-2-, 2-chloro-pyridyl-3, 2-chloro-pyridyl-4-, 6-chloro-pyridyl-2-, 6-hydroxymethyl-pyridyl-2, C hinolyl-2-isoquinolyl-1, 2-methyl-quinolyl-4-, 7-methyl-quinolyl-2-, 4-chloro-quinolyl-2-, 6,7-dimethoxy-quinolyl-4-, 6, 7-dimethoxyisoquinolyl-4- or 6,7-dimethoxy-isoquinolyl-4-N-oxide group.

For example, mention may be made of the following compounds which fall within the scope of the present invention: 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 - [N-methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyD-aminolpropan

l- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (4- (imidazolyl-1 ) -butyl) -amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dion-3-yl) -3- [N-methyl -N- (2- (pyridyl-4) ^: ethyl) amino] propane 1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-thion-3-yl ) -3- [N -methyl-N- (3- (furyl-2) -propyl) amino] propane 1- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-3-yl ) -3- [N -methyl-N- (2- (furyl-2) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine -2-on-3-yl) -3- [N -methyl-N- (3- (thienyl-2 -) - propyl) amino] propane 1- (7,8-dimethoxy-1,3,4, 5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2-furyl-2) -ethyl) -amino] -propane 1- (7,8- dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (3- (2-furyl) propyl) amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (thienyl-) 2 -) - ethyl) amino] propane

1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (3-thienyl) ethyl) -arnino] propane 1- (7,8-dimethoxy-1,3AB-tetrahydro-2H-3-ben2azepine-2-on-3-yl) -3- [N-methyl-N- (2- (imidazolyl-4 (5) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl -N- (2- (5,6-dimethoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one 3-yl) -3- [N -methyl-N- (2- (imidazo [1,2-a] pyridyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro -2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (benzo [b] thienyl-3) -ethy [) -amino] -propane 1- (7, 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (4- (2-thienyl) butyl) - amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- imidazolyl-1) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N-] (2- (1-methyl-imidazolyl-4) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzaz epin-2-on-3-yl) -3- [N -methyl-N- (2- (benzo [b] thienyl-3) -1-methyl-ethyl) -aminolpropane 1- (7,8-dimethoxy- 1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (furyl-2) -ethyl) -amino] -propane 1- (7, 8-Dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (1H-benzo [d] imidazolyl-1! -Ethyl ) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (2-benzyl-) 1H-benzo [d] imidazolyl-1) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 [N-methyl-N- (2- (4-methyl-thiazolyl-5) -ethyl] -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine) 2-on-3-yl) -3- [N -methyl-N- (2- (1-methyl-pyrrolyl-2) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3A5- tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2-picolyl) amino] propane

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (pyridyl-4 ) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N - (2- (pyridyl-2) -ethyl) amino] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (6,7-dimethoxy-isoquinolyl-4) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3- yl) -3- [N -methyl-N- (2- (pyridyl-3) -ethyl) amino] propane 1- (7,8-oimethoxy-1,2,4,5-tetrahydro-3H-3-) benzazepin-3-yl) -3- [N -methyl-N- (2- (pyridyl-4) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-) benzazepin-2-on-3-yl) -3- [N -methyl-N- (2- (pyridyl-4) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3,4, 5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2-benzo [blurfuryl-3 -) - ethyl) -amino] -propane 1- (7, 8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [blthienyl-3) ethyl) amino ] Propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (3- (benzo [b] thi enyl-3) -propyl) amino] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- ((benzo [b] thienyl-3) -methyl) amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (5-methyl-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-1-one) 2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1- (7, 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (4-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2 - (5-bromo-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 - [N-methyl-N- (2- (benzo [b] furyl-2) -ethylamino] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one 3-yl) -3- [N -methyl-N- {2- (2,5-dimethyl-thienyl-3) -ethyl} -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2r ^! 1-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (3- (pyridyl-3-N-oxide) -propyl) -amino] -propane 1- (7,8- dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-1,2-dione-3-yl) -3- [N-methyl-N- (2-pyridyl-4) ethyl) amino ] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2-pyridyl-3-N] oxide) ethyl) -amino] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepine-2,4-dione-3-yl) -3- [N-methyl-N- ( 2- (pyridyl-3-N-oxide) -ethyl) -aminolpropane 1- {7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2,4-dione-3-yl) -3- [N-methyl-N- (2- (6,7-dimethoxy-isoquinolyl-4-N-oxide) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3 -benzazepine-1,2-dione-3-yl) -3- [N-methyl-N- (2- (pyridyl-3-N-oxide) -ethyl] -aminolpropane 1- (7,8-dimethoxy-1 , 3A5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- {2- (6,7-dimethoxy-4-isoquinolyl-N-oxide) ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-1,2-dion-3-yl) -3- [N-methyl-N- (2-yl) (pyridyl-3) ethyl) amino] propane 1- (1-hydroxy-7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzaz epin-2-one-3-yl) -3- [N -methyl-N- (2- (pyridyl-3) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-) 2H-3-benzazepine-2,4-dion-3-yl) -3- [N -methyl-N- (2- (pyridyl-3) -ethyl) -amino] -propane 1- (7,8-dimethoxy- 1,3,4,5-tetrahydro-2H-3-benzazepin-2,4-dione-3-yl) -3- [N-methyl-N- (2- (6,7-dimethoxy-isoquinolyl-4) ethyl) -aminolpropane 1- (7 _/ 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-1,2-dion-3-yl) -3- [N-methyl-N-] (2- (6,7-dimethoxy-isoquinolyl-4) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 - [N-methyl-N- (3,5-dimethyl-isoxazolyl-4) -methyl] -aminolpropane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-thion-3-yl ) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro -2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (3-methyl-5-methoxy-benzo [b] furyl-3) -ethyl) -amino ] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N - ((thienyl-2) -methyl] amino] propane

T- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (4-methoxy benzo [b] furyl-3) -aminolpropan

aminolpropane! (T, -dimethoaminopropane

ethyl) -amino] propane T- (7,8-dimethoxy-1,3,4,5-t6-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- ( 2- (6-ethoxycarbonylmethoxy-benzo [b] thienyl-3) -ethyl) -amino] -propane 1: - <7,8-dirnethoxy-1,3,4,5-tetrahydro-2H-3-ben2azepine-2 on-3-yl) -3- [N -methyl-N- (2- (6-carboxymethoxy-benzo [b] thienyl-3) -ethyl) -amino] propane T- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-4) ethyl) amino] propane 1M7-bromo-8-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (4- (thienyl-2 ) -butyl-arnino] propane T- (7-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2 - (benzo [b] thienyl3) ethyl) amino] propane T- (1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl- N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -amino] propane T- (7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-benzazepine 2-on-3-yl) -3- [N -methyl-N- (2- (benzo [b] furyl-2) -ethyl) amino] propane T- (7,8-dimethyl-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-3) ethyl) amino] pr opant T- (7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (6- methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane T- (7 _/ 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 [N-methyl-N- (2-methyl-2- (benzo [b] thienyl-3) -ethyl) -aminolpropane T- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepine) 2-on-3-yl) -3- [N -methyl-N- (2- (2,5-dimethyl-thienyl-3) -ethyl) -amino] -propane T- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (3- (2,5-dimethyl-thienyl-3) -propyl) - aminolpropane 1 → 7.8-DImBtHyI-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (benzo [b ] furyl-3) -ethyl) -amino] propane T- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (6-acetamino-benzo [b] trienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-benzazepine -2-on-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane T- (7,8-methylenedioxy-1 , 3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] furyl-3) - eth yl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2-yl) (6-dimethylamino-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (benzo [b] furyl-3) -ethyl) -amino] propane

propyl) -amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-thion-3-yl) -3- [N-methyl-N- ( 2- (benzo [b] thienyl-3) -ethyl) -aminolpropane T- (7,8-dimethoxy-1 _/ 3,4,5-tetrahydro-2H-3-benzazepin-1,2-dione-3-yl ) -3- [N -methyl-N- (2- (benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-2,3-dihydro-1H-3-benzazepine-2 -on-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-2,3 -dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1 (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- {3- (6-methoxy-benzo [b] thienyl-3) -propyl) -aminolpropane 1- (7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (4- (2,5-dimethyl-thienyl-3) -butyl) -aminolpropane 1- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3 -yl) -3- [N -methyl-N- (2- (4,5,6,7-tetrahydro-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-1 , 3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (4- (2,5-di methyl-thienyl-3) -butyl) -aminolpropane 1- (7,8-ethylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N- Methyl N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4, B-tetrahydro-2H-3-benzazepine 2-on-3-yl) -3- [N -methyl-N- (2- (6-acetamino-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-2, 3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (benzo [b] furyl-2) -ethyl) -amino] -propane 1- ( 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- [5- {2-thienyl) pentyl ) -amino] propane 1- (7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-thion-3-yl) -3- [N-methyl-N- (2 (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-1,2-dione 3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethyl-1,3,4, 5-tetrahydro-2H-3-benzazepine-2-thion-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1 - (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N - {2- (benzo [b] furyl-2) -ethyl) amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3 -yl) -3- [N-methyl-N- (2- (3-phenyl-5-methoxy-benzo [b] furyl-2) -ethyl) -aminolpropan

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-allyl-N- (2- (benzo [b ] furyl-2) -ethyl) -amino] propane 1- (73-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N -nethyl-N- ( 2- (6-methylsulfonyloxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3 -yl) -3- [N -methyl-N- (2- {benzo [b] thienyl-3) -ethyl) -aminolpropan-1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H 3-benzazepin-2-on-3-yl) -3- [N -methyl-N- (2- {6-methylsulfonyloxy-benzo [b] thienyl-3) -ethyl) -amino] -propane 1- (7 _/ 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (4- (2,5-dimethyl-thienyl -3) -butyl) -aminolpropane 1- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- {2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- {7,8-dimethoxy-1,3 _/ 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl ) -3- [N -methyl-N- (2- (3-methyl-5-methoxy-benzo [b] furyl-2) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3 , 4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- {6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-1,2-dione-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl (-amino] propane 1- (7,8-dimethyl-2,3-dihydro-1H-3-benzazepine -2-on-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -amino] -propane 1- {7,8-dimethyl -2,3-dihydro-1H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b] furyl-2) -ethyl) -amino] propane 1- (7,8-dimethyl-2,3-dihydro-1H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-3 ) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3A5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (benzo [b] thienyl-2) -ethyl) -amino] propane

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b ] thienyl-3) ethyl) -amino] butane 1- <7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N-] (2- (6-carboxymethoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethyl-1,3,4,5-tetrahydro-2H-3-benzazepine-1,2- dion-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) ethyl) - Aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (6 -carboxymethoxybenzo [b] thienyl-3) -ethyl) -amino] propane 1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl ) -3- [N -methyl-N- [2- (7-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-1,3,4,5-tetrahydro -2H-3-benzazepine-2-thion-3-yl) -3- [N -methyl-N- (2- (benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy -1,3,4,5-tetrahydro-2H-3-benzazepin-1,2-thion-3-yl) -3- [N-methyl-N- ( 2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1- (7,8-dimethyl-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) - 3- [N -methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-2,3-dihydro-1H-3-benzazepine -2-on-3-yl) -3- [N -methyl-N- (2-benzo [b] thienyl-3) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] thienyl-2) -ethyl) - aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (thienyl- 2) -ethyl) -amino] ethane 1- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2 - (6-ethoxycarbonylmethoxy-benzo [b] thienyl-3) -ethyl! -Amino] propane 1- (7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one 3-yl) -3- [N-methyl-N- (2-benzo [b] furyl-2) -ethyl) -amino] -propane 1- (7,8-methylenedioxy-1 _/ 3,4,5-tetrahydro -2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (benzo [b] furyl-3) -ethyl) -amino] -propane 1- (7,8 dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6-etho xycarbonylmethoxybenzo [b] thienyl-3) -ethyl) -amino] propane 1- (7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one-3-yl) -3- [ N-methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-) benzazepin-2-on-3-yl) -3- [N -methyl-N- [2- (6-methylsulfonyloxy-benzo [b] furyl-3) -ethyl) -amino] -propane 1- (7,8- methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-thion-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] thienyl 3) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-1,2-dion-3-yl) -3- [N-methyl- N- (2- (benzo [b] furyl-2) -ethyl) -aminolpropane 1- (7,8-methylenedioxy-2,3-dihydro-1H-3-benzazepin-2-thion-3-yl) -3 [N-methyl-N- (2- (benzo [b] furyl-2) -ethyl) amino] propane 1- (7,8-diniethyl-1,3,4,5-tetrahydro-2H-3-) benzazepine-2-thion-3-yl) -3- [N -methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -aminolpropane 1- (7,8-dimethyl- 1,3,4, B-tetrahydro-2H-3-benzazepin-2-thion-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-3) ethyl) - amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzaze pin-2-thion-3-yl) -3- [N -methyl-N- (2- (benzo [b] furyl-2) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-thion-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] furyl-3) ethyl ) -aminolpropane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- 4-nitro-pyridyl-2) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 - [N-methyl-N- (2- (4-amino-pyridyl-2) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3 -benzazepin-2-on-3-yl) -3- [N -methyl-N- (2- (4-acetylamino-pyridyl-2) -ethyl) -aminolpropane 1- (7,8-dimethoxy-1,3 , 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (4-carbamoylamino-pyridyl-2) -ethyl] -aminolpropane 1 (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (4-N-methyl -carbamoylamino-pyridyl-2) -

N- E - N - G - Het

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6,7 -dimethoxychinolyl-4) ethyl) -aminolpropan

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (N-methyl -pyrrolyl-3) -ethyl) -amino] -propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N methyl-N- (2- (3-pyrrolyl) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3 _r 4,5-tetrahydro-2H-3-benzazepin-2-one-3 -yl) -3- [N-methyl-N- (2- (3-methyl-isoxazolyl-5) ethyl) -atnino] propane

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (3-isoxazolyl ) -ethyl) -amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N - (2- (oxazolyl-4) -ethyl) amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) - 3- [N-methyl-N- (2- (oxazolyl-5) -ethyl) amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2 -on-3-yl) -3- [N -methyl-N- (2- (pyrazolyl-3) -ethyl) amino] propane 1- (7,8-dimethoxy-1,3,4,5-tetrahydro -2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (1,3-dimethyl-pyrazolyl-5) ethyl) -aminolpropan

However, preferred compounds are the compounds of the general formula

, (La)

in the

A is a -CH ₂ -CH ₂ -, -CH = CH-, -CH ₂ -CO-, -CO-CO-

or -CH-CO- group and B a methylene group or χ

A represents a -CH ₂ -CH ₂ - or -CH = CH- group and B represents a carbonyl or thiocarbonyl group, wherein the carbon atom indicated by χ is in each case linked to the phenyl nucleus, E is an n-propylene group,

G is an ethylene, n-propylene or n-butylene group,

Ri is a chlorine atom or bromine atom, a methyl, methoxy, nitro, amino, methylamino or dimethylamino group, R _{2 is} a chlorine or bromine atom, a methyl or methoxy group or R ₁ and R ₂ together form a methylenedioxy or ethylenedioxy group .

R3 is a hydrogen atom, a methyl, ethyl or allyl group and

Het a pyrrolyl-2, pyrrolyl-3, N-methyl-pyrrolyl-2-, N-methyl-pyrrolyl-3, furyl-2-, benzo [b] furyl-2, benzo [b] -furyl -3-, 7-methyl-benzo [b] furyl-3, 6-methoxy-benzo [b] furyl-3, 5-methoxy-3-phenyl-benzo [b] furyl-2, thienyl-2 -, thienyl-3, 5-methylthienyl ^ - ^ -dimethyl-thienyl-S-.B-bromo-thienyl-, benzo [b] thienyl-2-, benzo [b] thienyl-3-, 6- Hydroxybenzo [b] thienyl-3, 6-methoxybenzo [b] thienyl-3, 5,6-dimethoxybenzo [b] thienyl-3, 2,5-dimethylbenzo [b] thienyl -3-, 5-Methoxybenzo [b] thienyl-2-, 6-methoxybenzo [b] thienyl-2-, 6-methylmercapto-benzo [b] thienyl-3, 6-methylsulfinyl-benzo [b] thienyl-3-, 6-methylsulfonyl-benzo [b] thienyl-3, 6-methylsulfonyloxy-benzo [b] thienyl-3, B-ethoxycarbonylmethoxybenzobisienyl-S, 6-carboxymethoxy-benzo [b] thienyl-3, 6-dimethylamino-benzo [b] thienyl-3-, 6-methylsulfonylamino-benzo [b] thienyl-3, 6-aceto-benzo [b] thienyl-3, benzo [b] thienyl- 4-, pyrazolyl-1-, pyrazolyl-3-, 1,5-dimethyl-pyrazolyl-3-, i-methyl-imidazolyl-4-, 2- (3,4-dimethoxyphenyl) -imidazole olyl-4 (5), benzo [d] imidazolyl-1, 2-benzyl-benzo [d] imidazolyl-1, imidazo [1,2-a] pyridyl-3, oxazolyl-4, oxazolyl 5-, isoxazolyl-3-, 3-methylisoxazolyl-5-, 4-methyl-thiazolyl-5, pyridyl-2, pyridyl-3, pyridyl-4, pyridyl-3-N-oxide ,, 4 Nitro-pyridyl-2-, 4-aminopyridyl-2-, 4-acetylamino-pyridyl-2- "4-carbamoylamino-pyridyl-2-, 4-N-methylcarbamoylamino-pyridyl-2-, 6,7- Dimethoxy-quinolyl-4-, B ^ -Dimethoxy-isochinolyl ^ - or e ^ -Dimethoxy-isochinolyl ^ -N-oxide group, and their acid addition salts, in particular their physiologically acceptable acid addition salts with inorganic or organic acids.

Particularly preferred compounds of the above general formula I a but are those in which A is a-CH ₂ -CH ₂ - or-CH = CH- and B is a carbonyl or thiocarbonyl group, E is an n-propylene group,

G is an ethylene, n-propylene or n-butylene group,

R ₁ and R ₂ each represent a methoxy group or R ₁ and R ₂ together represent a methylenedioxy group, R _{3 is} a hydrogen atom or a methyl group and

Het a pyrrolyl-2, pyrrolyl-3, N-methyl-pyrrolyl-2-, N-methyl-pyrrolyl-3, thienyl-2-, thienyl-3, 5-methyl-thienyl-2-, 2 , 5-Dimethyl-thienyl-3, 5-bromo-thienyl-2, pyrazolyl-1, pyrazolyl-3, i-methyl-imidazolyl-4, isoxazolyl-3, benzo [b] furyl-2 -, benzo [b] furyl-3-, 7-methyl-benzo [b] furyl-3, 6-methoxy-benzo [b] furyl-3, 7-methoxy-benzo [b] furyl-3, Benzo [b] thienyl-2-, benzo [b] thienyl-3, 6-methoxybenzo [b] thienyl-3, 6-methylsulfonyloxy-benzo [b] thienyl-3, 6-ethoxycarbonylmethoxybenzo [b] thienyl- 3-, 6-Carboxymethoxy-benzo [b] thienyl-3, 6-acetamino-benzo [b] thienyl 3, benzo [d] imidazolyl-1, imidazo [1,2-a] pyridyl-3 or Pyridyl group, and their acid addition salts, in particular their physiologically acceptable acid addition salts with inorganic or organic acids.

According to the invention, the novel compounds are obtained by the following processes: a) reaction of a compound of the general formula

(II)

with a compound of the general formula V-G-Het

,(IN THE)

in which A, B, E, G and Het are defined as defined above,

R ₁ 'represents a protected by a protecting group hydroxy, amino or alkylamino group or for R, the beginning

possesses meanings mentioned,

R ₂ 'represents a protected by a protective hydroxy group or has the meanings mentioned for R ₂ , one of the radicals U or V, the R ₃ ' -NH group, wherein R ₃ 'represents a protective group for an amino group or for R ₃ has the meanings mentioned above, and the other of the radicals U or V has a nucleophilic leaving group such as a halogen atom or a sulphonyloxy group, for. Example, a chlorine, bromine or iodine atom, the Methansuifonyloxy-, p-Töluolsulfonyloxy- or Ethoxysulfonyloxygruppe represents, and optionally subsequent cleavage of a protective moiety used.

As a protective radical for a hydroxy group is, for example, the trimethylsilyl, acetyl, benzoyl, benzyl or

Tetrahydropyranyegroup and

As a protective group for an amino or alkylamino group, the acetyl, benzoyl, ethoxycarbonyl or benzyl group into consideration.

The reaction is conveniently carried out in a solvent or solvent mixture such as acetone, diethyl ether, methylformamide, dimethylformamide, dimethylsulfoxide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene / tetrahydrofuran T, dioxane or in an excess of the compounds of the general formulas II and / or III and optionally in the presence of an acid-binding agent, e.g. Example, an alcoholates such as potassium tert.butylat, an alkali metal hydroxide such as sodium or potassium hydroxide, an alkali metal carbonate such as potassium carbonate, an alkali metal such as sodium amide, an alkali metal hydride such as sodium hydride, a tertiary organic base such as triethylamine or pyridine, the latter at the same time as a solvent can serve, or a reaction accelerator such as potassium iodide, depending on the reactivity of the nucleophilically exchangeable radical expediently at temperatures between 0 and 15O ⁰ C, preferably at temperatures between 50 and 120 ⁰ C, for example at the boiling temperature of the solvent used. However, the reaction can also be carried out without a solvent. However, the reaction is particularly advantageous in the presence of a tertiary organic base or an excess of the amine of general formula III

carried out.

The optional subsequent cleavage of a protective moiety used is preferably carried out hydrolytically in an aqueous solvent, for. Example, in water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid ₍ such as hydrochloric acid or sulfuric acid or in the presence of a Alkalibase _t such as sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ° C, preferably at the boiling point of however, takes place the reaction mixture. The cleavage of a benzyl group preferably by hydrogenolysis, for. example with hydrogen in the presence of a catalyst such as palladium / charcoal in a solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid optionally with the addition of an acid such as hydrochloric acid at temperatures between 0 and 50 ⁰ C. but preferably at room temperature, and one

Hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar.

b) For the preparation of compounds of the general formula I in which AdJe-CH ₂ -CH ₂ -GrUpPe, B is the methylene or carbonyl group and R _{3 is} not an alkenyl group having 3 to 5 carbon atoms:

Hydrogenation of a compound of the general formula

R-

-E-N-G- Het

(IV)

in the

R ₁ to R ₃ , E, G and Het are as defined above and B 'represents the methylene or carbonyl group.

The hydrogenation is carried out in a solvent or solvent mixture such as methanol, ethanol, ethyl acetate or glacial acetic acid with catalytically excited hydrogen, for. Example, with hydrogen in the presence of platinum or palladium / carbon, at a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar, and at temperatures between 0 and 75 "C, preferably

However, at temperatures between 20 and 5O ⁰ C performed.

If an alkenyl group is used in a compound of the general formula IR ₃ , then it becomes a benzyloxy group in the reduction at the same time into the corresponding alkyl group or R ₁ and / or R ₂ , this becomes the corresponding in the reduction

Converted hydroxy group.

c) For the preparation of compounds of general formula I in which B represents a thiocarbonyl group:

Reaction of a compound of the general formula

N-E-N-G-Jiet / CO

in the

R ₁ to R ₃ , A, E, G and Het are as defined above, with a sulfur-introducing agent.

The reaction is carried out with a sulfur introducing agent such as phosphorus pentasulfide, 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2,4-disulfide or 2,4-bis (methylthio) -1,3 -dithia-2,4-diphosphetane-2,4-disulfide advantageously in a solvent such as toluene or xylene at temperatures between 50 and 150 ⁰ C, for example at the boiling point of

Reaction mixture, carried out.

d) For the preparation of compounds of general formula I,

₉ H in which A represents a -CH-CO group:

Reduction of a compound of the general formula

-E-N-G- Het

in the

Ri to R ₃ , E, G and Het are as defined above.

The reaction is carried out in the presence of a suitable reducing agent, such as a metal hydride, e.g. For example, sodium borohydride, in a suitable solvent such as water / methanol or methanol / ether, at temperatures between 0 and 80 ⁰ C, preferably

However, at temperatures between 15 and 40 ⁰ C, carried out.

e) For preparing compounds of general formula I, in which A is a-CH ₂ -CH ₂ -or-CH = CH-and legs

Represent methylene group:

Reduction of a compound of the general formula

- N -G - Het

(VII)

in the

R ₁ to R _3, E, G and Het are as hereinbefore defined and A 'represents a-CH ₂ -CH ₂ - or -CH = CH-.

The reduction is preferably carried out with a metal hydride such as lithium aluminum hydride or diborane or with a complex of borane and a thioether, e.g. B. with borane-dimethyl sulfide complex, in a purified solvent such as diethyl ether or tetrahydrofuran at temperatures between 0 and 50 ⁰ C, but preferably at temperatures between 10 and 25 ⁰ C,

carried out.

f) For the preparation of compounds of general formula I in which A represents the COCO group:

Oxidation of a compound of the general formula

N - E R. r - G - Het CH "C0 - N

, (VIII)

in the

Ri to R ₃ , E, G and Het are as defined above.

The oxidation is preferably carried out with an oxidizing agent such as potassium permanganate, selenium dioxide or sodium dichromate in a suitable solvent or solvent mixture such as water, water / dioxane, glacial acetic acid, water / acetic acid or acetic anhydride at temperatures between 0 and 100 ° C, preferably at temperatures between 20 and 8O ⁰ C, performed.

g) reaction of a compound of the general formula

-E-H

, (IX)

in the

A, B, E, R ₁ and R _{2 are} as defined above, but in the radical E two hydrogen atoms in a-CH ₂ - or CH ₃ group of the radical E are replaced by an oxygen atom, with a compound of the general formula

B ₃ HNG-Het

in the

R ₃ , G and Het are as defined above, in the presence of a reducing agent.

The reaction is conveniently performed in a suitable solvent or solvent mixture such as methanol, ethanol, ethanol / Essigsäureethylesteroder dioxane at temperatures between 0 and 100 ⁰ C, but preferably at temperatures between 20 and 8O ⁰ C.

The reductive amination is particularly advantageously carried out in the presence of a complex metal hydride, such as sodium borohydride, lithium cyanoborane or sodium cyanoborohydride, preferably at a pH of 6-7 and at room temperature or in the presence of palladium / carbon at a hydrogen pressure of 5 bar. In this case, any benzyl groups which may be present can be simultaneously eliminated by hydrogenolysis and / or double bonds can be hydrogenated.

h) reaction of a compound of the formula

(XI)

in the ~ -

R ₁ 'represents a protected by a protective hydroxy, amino or alkylamino group or have the meanings mentioned for R ₁ , and

R ₂ 'represents a protected by a protective hydroxy group or has the meanings mentioned for R ₂ , with a compound of the general formula

R ₃ 'WENG-Het

(XII)

in the

E, G and Het are as defined above,

R ₃ 'represents a protective group for an amino group or has the meanings mentioned for R ₃ , and

W is a nucleophilic leaving group such as a halogen atom or a sulphonyloxy group, e.g. represents a chlorine, bromine or iodine atom, the methanesulfonyloxy, p-toluenesulfonyloxy or ethoxysulfonyloxy group, and optionally subsequent cleavage of a protective moiety used.

As a protective group for a hydroxy group is, for example, the trimethylsilyl, acetyl, benzoyl, benzyl or tetrahydropyranyl group and as a protective group for an amino or alkylamino group, the acetyl, benzoyl, ethoxycarbonyl or benzyl group into consideration.

The reaction is conveniently carried out in a solvent or solvent mixture such as methylformamide, dimethylformamide, dimethylsulfoxide, benzene, chlorobenzene, tetrahydrofuran, benzene / tetrahydrofuran or dioxane in the presence of an acid-binding agent, e.g. As an alcoholate such as Kaliumtert.butylat, an alkali metal hydroxide such as sodium or potassium hydroxide, an alkali metal carbonates such as potassium carbonate, an alkali metal such as sodium or an alkali metal such as sodium hydride expediently at temperatures between 0 and 15O ⁰ C, preferably at temperatures between 0 and 5O ⁰ C. , carried out.

The optional subsequent cleavage of a protective moiety used is preferably carried out hydrolytically in an aqueous solvent, for. Example in water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid ie hydrochloric acid or sulfuric acid or in the presence of an alkali metal base such as sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ⁰ C, preferably at the boiling temperature of the reaction mixture , However, the cleavage of a benzyl radical is preferably carried out by hydrogenolysis, for example with hydrogen in the presence of a catalyst such as palladium / carbon in a solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid, if appropriate with the addition of an acid such as hydrochloric acid at temperatures between 0 and 50 ° C, but preferably at room temperature, and a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar.

The resulting compounds of general formula I can be further converted into their acid addition salts, especially in their physiologically acceptable acid addition salts with inorganic or organic acids. Examples of suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, citric acid, tartaric acid, succinic acid, maleic acid or fumaric acid.

The compounds of the general formulas II to XII used as starting materials are known from the literature in some cases or are obtained by processes known per se.

Thus, for example, a starting compound of the general formula II is obtained by reacting a corresponding benzazepine with a corresponding halogen compound and optionally by subsequent reaction with a corresponding amine. The required for this purpose unsubstituted in the 3-position corresponding benzazepine is obtained by cyclization of a corresponding compound, for. B. by cyclization of a compound of the general formula

HGHJ

(XlIl)

CH ₂ CO

N - CH ₂ - CH "- ν; ^Χ OCH ^

or the general formula

, (XIV) CH ₂ CH ₂ - NH - COCH ₂ Cl

optionally subsequent catalytic hydrogenation and / or reduction of the carbonyl group, for example with sodium borohydride / glacial acetic acid (see EP-AI 0.007.070) and / or oxidation, for. With selenium dioxide.

A compound of the general formulas IV to VIII used as starting material is preferably obtained by reacting a corresponding halogen compound with a corresponding amine and, if appropriate, subsequent removal of protective radicals which are used to protect hydroxyl and / or amino groups.

A compound of the general formula IX is obtained, for example, by reaction of a benzazepine unsubstituted in the 3-position with a corresponding haloacetal or haloketal and subsequent hydrolysis.

As already mentioned, the novel compounds of the general formula I and their physiologically tolerated acid addition salts with inorganic or organic acids have valuable pharmacological properties, in particular a long-lasting heart rate-lowering effect and a reduction in the O ₂ requirement of the heart.

For example, the compounds were

A = 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-3) ethyl) -

amino] propane hydrochloride, B) = 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl- N- (2- (6-methoxy-benzo [b] thienyl-3) ethyl) -

amino-propane hydrochloride and C = 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- ( 2- (benzo [b] furyl-2) -ethyl) -amino] propane

dihydrochloride for its biological properties as follows:

Effect on heart rate in rats:

The effect of the substances to be tested on the heart rate was investigated per dose in 2 to 4 rats with an average weight of 250-30Og. The rats were anesthetized with pentobarbital (50 mg / kg i.p. and 20 mg / kg s.c.). The substances to be investigated were injected in aqueous solution into the jugular vein (0.1 ml / 100 g). Blood pressure was measured via a cannula attached to the A. carotid and the heart rate was recorded from an ECG (II or III lead) derived from needle electrodes. The heart rate of the animals in the control period was between 330 and 420 beats / minute (bpm).

The following table contains the found values:

substance dose Heart rate reduction [%], [Mg / kg] measured minutes after substance application t = 5 t = 20 A 5 66 52 B 5 67 60 C 2.5 47 36

In the pharmacological investigations, no toxic side effects were observed, the new compounds are therefore well tolerated.

Because of their pharmacological properties, the compounds according to the invention are suitable for the treatment of sinus tachycardia of various origins and for the prophylaxis and therapy of ischemic heart diseases. The dosage required to achieve a corresponding effect is expediently once or twice daily 0.03 to 1 mg / kg body weight, preferably 0.07 to 0.5 mg / kg body weight. For this purpose, the compounds of general formula I according to the invention and their physiologically tolerated acid addition salts with inorganic or organic acids, optionally in combination with other active substances, together with one or more inert customary carriers and / or diluents, eg with corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerol, water / sorbitol, water / polyethylene glycol, propylene glycol, carboxymethylcellulose or fatty substances _t such as hard fat or suitable mixtures thereof, galenical in usual Prepare preparations ₍ such as tablets, dragees, capsules, powders, suspensions, drops, ampoules, juices or suppositories.

embodiment

The following examples are intended to explain the invention in more detail:

Production of the starting compounds: Example A

7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

a) 3,4-dimethoxyphenylacetic acid chloride

600 ml of thionyl chloride are added dropwise with stirring to a suspension of 549.4 g of 3,4-dimethoxyphenylacetic acid in 600 ml of methylene chloride over 2 hours. After completion of gas evolution (16 hours) is cooked for one hour at reflux. After removal of the volatile components, the residue is distilled in vacuo.

Yield: 486 g (80.8% of theory),

Bp: 134-136 ° C / 1.95mbar. .. - · _s

b) (N-2,2-dimethoxyethyl) -3,4-dimethoxy-phenylacetamide

Under ice cooling, a solution of 485,2g 3,4-Dimethoxyphenylessigsäurechlorid in 1.11 Methyienchlorid ^c at 15-20 C is added dropwise to a solution of 246.2 ml of aminoacetaldehyde dimethyl acetal and 315 ml of trimethylamine in 2.21 Methyienchlorid and one hour at 16- 18 ° C stirred. It is then extracted several times with water, dried over magnesium sulfate and evaporated. The resulting oil crystallizes slowly

 Yield: 608 g (95% of theory), m.p .: 66-69 ° C.

c) 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

A solution of 600.6 g of N- (2,2-dimethoxyethyl) -3,4-dimethoxy-phenylacetamide in 31% concentrated hydrochloric acid is added to 31% vinegar. After standing at room temperature for 17 hours, the batch is poured onto ice. The precipitated crystals are filtered off with suction, washed neutral with water and dried

 Yield: 350g (75.4% of theory), m.p .: 234-237X.

Example B

7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

A suspension of 21.9 g (0.1 mole) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one and 1.5 g of palladium / carbon (10%) in 200 ml of glacial acetic acid is added 5O ⁰ C and a hydrogen pressure of 5bar hydrogenated. After filtering off the catalyst, the solvent is evaporated in vacuo and the residue taken up in methylene chloride. After extraction with sodium bicarbonate solution and washing with water, dried over magnesium sulfate, concentrated and purified on silica gel with methylene chloride and then with increasing amounts of methanol (up to 10%). Yield: 12.6 g (57% of theory), m.p .: 188-191 ° C.

- I / - £. · + 1

Example C

7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepine

A solution is added to a suspension of 1.3 g (6 mmol) of 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 1.1 g (3 mmol) of sodium borohydride in 20 mmol of dioxane added dropwise of 1.8 g of glacial acetic acid in 1OmI dioxane, boiled under reflux for 3 hours, concentrated and decomposed with water. The mixture is extracted by shaking twice with methylene chloride, the extract is concentrated and the residue is taken up in ether. After filtration, the ether is removed in vacuo. Yield: 1.1 g (92.7% of theory), m.p .: 86-89 ° C.

Example D

6,9-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one

2.0 g (0.007 mol) of N- (2,2-dimethoxyethyl) -2,5-dimethoxyphenyl-acetamide are poured over with 3 ml of polyphosphoric acid and stirred at 9O ⁰ C for 60 minutes. Then filtered off with suction and dried

Yield: 0.98 g (64% of theory), Melting point: 188-191 ⁰ C.

Example E 7,8-Dimethyl-1,3-dihydro-2H-3-benzazepin-2-one

Prepared analogously to Example D from N- (2,2-dimethoxyethyl) -3,4-dimethylphenylacetamide and polyphosphoric acid. Yield: 40.1% of theory, Melting point: 220-224 ⁰ C.

Example F

7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione

a) 7,8-Dimethoxy-2-amino-4-bromo-1 H-3-benzazepine hydrobromide

3.7 g (0.017 mol) of 3,4-dimethoxy-o-phenylene-diacetonitrile are suspended in 10 ml of glacial acetic acid and treated at 20 ⁰ C with 12 ml of 30% hydrobromic acid in glacial acetic acid. Stirring is continued for 3 hours at room temperature, the precipitate is filtered off with suction, washed with glacial acetic acid and then with acetone / ether and dried. Yield: 5.3 g (82.8% of theory), Melting point: 210-211 ⁰ C (dec.).

b) 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione

5.3 g (0.014 mol) of 7,8-dimethoxy-2-amino-4-bromo-1 H-3-benzazepine hydrobromide are dissolved in 100 ml of 85 ⁰ C hot water, treated with 1.3 g of anhydrous sodium acetate and for one hour 90 ⁰ C heated. The reaction mixture is cooled, filtered off, washed with cold water and dried

 Yield: 2.9 g (88%) of theory, melting point: 235 ° C (dec.).

Example G N- [3- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -propyl] methylamine hydrochloride 5.9g (0.020 mol ) 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloro-propane and 14g (0.45 mol) of methylamine heated in the containment tube for one hour to 13O ⁰ C. The cooled reaction product is taken up in half-concentrated sodium hydroxide solution and extracted with methylene chloride. After drying and concentration of the extract, the hydrochloride is precipitated from acetone / ether with ethereal hydrochloric acid

Yield: 5.2 g (80% of theory), Melting point: 110 ⁰ C (dec.).

Example H

7,8-dimethoxy-2,3-dihydro-1H-3-benzazepine

A boiling suspension of 0.8 g of lithium aluminum hydride in 100 ml of absolute dioxane is mixed with 2.2 g (0.01 mol) of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one and then for 3 hours under Reflux heated. With ice-water cooling, 10% ammonium chloride solution is added and the precipitate formed is filtered off with suction. The filtrate is concentrated in vacuo to a volume of about 20 ml, the precipitated white precipitate is filtered off with suction and washed with a little dioxane

 Yield: 0.9 g (43.8% of theory), m.p .: 162-163 ° C.

Example I

1 - (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane

a) 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane 131.5 g (0.6 mol) 7,8- Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one are suspended in 900 ml of dimethyl sulfoxide and admixed with 80.8 g (0.72 mol) of potassium tert-butylate with stirring. After 10 minutes, the resulting solution is added dropwise with cooling with ice water to 77 ml (0.72 mol) of 1-bromo-3-chloropropane in 300 ml of dimethyl sulfoxide. After an hour you pour on ice water. After a short time, the greasy precipitate begins to crystallize. After precipitation is filtered off with suction, dissolved in acetone, precipitated again with water, filtered off with suction and dried

Yield: 155,5g (87.3% of theory), Melting point: 101-103 ⁰ C.

b) 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane 59.2g (0.2 mol) 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane are dissolved in 500 ml of glacial acetic acid in the presence of 5 g of 10% palladium-carbon Hydrogenated for 6 hours at 50 ⁰ C and 5bar. The catalyst is filtered off, the glacial acetic acid distilled off in vacuo and the residue after addition of water with potassium carbonate neutralized. The precipitate is filtered off with suction, washed salt-free with water and dried.

Yield: 53 g (89%) of theory),

Melting point: 85-86 ° C

Example J

1.5 g (0.005 mol) of 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane are dissolved in 20 ml of tetrahydrofuran dissolved and heated after addition of 0.55 ml (0.0044 mol) of boron trifluoride etherate and 3 ml (0.006 mol) of a 2 molar solution of borane-dimethyl sulfide in toluene for two hours to reflux. Subsequently, a further 3 ml of the borane-dimethyl sulfide solution are added and heated again for two hours to reflux. After decomposition with methanol, the solvents are distilled off and the residue is heated to 100 ^° C. with 6 ml of half-concentrated hydrochloric acid for 10 minutes. The reaction product is extracted with ethyl acetate, the acidic aqueous phase made alkaline and extracted again with ethyl acetate. The extract is dried, concentrated and purified over an alumina column (activity level H-III) with methylene chloride. Yield: 0.55 g (39% of theory), Melting point: 62-64 ⁰ C

Example K 3- (N-methyl-2-aminoethyl) benzo [b] thiophene

a) Benzo [b] thienyl-3-acetic acid N-methyl-amide

A solution of 2.3 g (0.012 mol) of benzo [b] thienyl-3-acetic acid in 40 mL of ethyl acetate is added portionwise with 2.0 g (0.012 mol) of carbonyldiimidazole and stirred for five hours at room temperature. After addition of 7 ml of an 18% solution of methylamine in ethyl acetate, the mixture is stirred for a further 3 hours, the mixture is extracted with 1 M sodium hydroxide solution, the organic phase is washed with water, dried over sodium sulfate and purified by chromatography on a silica gel column

 Yield: 0.98 g (40% of theory), m.p .: 123-124 ° C

b) 3- {N-Methyl-2-aminoethyl) benzo [b] thiophene

In a heated to reflux solution of 1.9 g (0.0093 mol) of benzo [b] thienyl-3-acetic acid-N-methyl-amide and 1.3 g (0.0093 mol) of boron trifluoride etherate in 40 ml of tetrahydrofuran is added dropwise slowly 0.85 g (0.011 mol) of borane-dimethyl sulphide (1.1 ml of a 10M solution in tetrahydrofuran) and heated to reflux for a further 4.5 hours. After concentration of the mixture is heated to 100 ⁰ C, treated with 1.6 ml of 6 M hydrochloric acid and kept at this temperature for 30 minutes. It is allowed to cool, added 2.3 ml of 6 M sodium hydroxide solution, saturated with potassium carbonate and extracted with ether. The extract is washed, dried, concentrated and purified on an aluminum oxide column of activity level II

 Yield: 0.85 g (48% of theory), oil, R f: 0.40 (alumina, methylene chloride / methanol = 50: 1).

Calc .: C 69.06 H 6,85 N 7,32 S 16.76 Found .: 69.15 6.63 7.20 16,66

Example L 2- (N -methyl-2-amino-ethyl) -furan

a) 2- (N-formyl-2-amino-ethyl) -furan

10.0 g (0.090 mol) of 2- (2-amino-ethyl) -furan are refluxed with 80 ml (1.0 mol) of ethyl formate for 12 hours. The reaction product is concentrated and distilled in vacuo

 Yield: 11.6 g (93% of theory), boiling point: 140 ° C / 0.06 Torr

Calc .: C 60.42 H 6.52 N 10.07

Gef .: 60.71 6.35 10.24

b) 2- (N-methyl-2-amino-ethyl) -furan

1.4 g (0.010 mol) of 2- (N-formyl-2-amino-ethyl) -furan are added dropwise at 0-5 ⁰ C under nitrogen in a suspension of 0.50 g (0.013 mol) of lithium aluminum hydride in 20 ml of ether, 30th Stirred for minutes at room temperature and then heated to reflux for 7 hours. After cooling, it is decomposed with dilute sodium hydroxide solution and filtered with suction. The organic phase is dried, concentrated and distilled in vacuo.

Yield: 1.0 g (80% of theory),

Boiling point: 110 ° C / 12 torr

Rr value: 0.78 (alumina, methylene chloride / methanol = 9: 1).

Example M

1- (7-bromo-8-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloro-propane

a) 8-Wiethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

56,8g (0.3 mol) 8-methoxy-1,3-dihydro-2H-benzazepin-2-one (melting point: 190-191 ⁰ C) dissolved in 600ml of glacial acetic acid are dissolved in the presence of 5 g of 10% palladium carbon hydrogenated at 8O ⁰ C and 5bar for 12 hours. The catalyst is sucked off and the

Distilled off acetic acid in vacuo. The residue is mixed with water, neutralized with potassium carbonate, the precipitate was filtered off with suction, washed with water and dried.

Yield: 51.1 g (89.1% of theory),

Melting point: 160-161 ⁰ C.

b): 7-Bromo and S-bromo-S-methoxy-1SAS-tetrahydro-1H-benzazepine ^ -on ZuIAq (0.04 mol) 8-methoxy-1,3,4,5-tetrahydro-2H -3- benzazepin-2-one in 100 ml of 80% acetic acid are added dropwise at 3-5 ° C with stirring 6.4 g = 2.03ml (0.04 mol) of bromine in 10 ml of glacial acetic acid. After 15 minutes, it is poured into ice-water, neutralized with potassium carbonate, the precipitate is filtered off with suction, washed with a little water and dried. The isomer mixture obtained is separated by chromatography on a silica gel column (eluent: ethyl acetate).

Yield: 5.7 (52.8% of theory) 9-bromo isomer

IR spectrum (methylene chloride): 3400 cm ^-1 (NH)

1660cm " ¹ (C = O)

4i1g (39% of theory) 7-bromine isomeric IR spectrum (potassium bromide): 3220 cm ^-1 (NH)

1665cm " ¹ (CO)

e) 1- {7-Bromo-8-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane To 1.35 g (5 mmol ) 7-Bromo-8-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one in 15 ml dimethyl sulphoxide 0.24 g (5.5 mmol) sodium hydride dispersion in oil (55%) added and stirred for V2 hours at room temperature and 10 minutes at 35-4O ⁰ C. The solution is added dropwise to 0.79 g (5.5 mmol) of 1-bromo-3-chloropropane in 5 ml of dimethyl sulfoxide with stirring. The mixture is then stirred for 2 hours at room temperature, poured into ice-water and extracted 4 times with methylene chloride. The methylene chloride extracts are washed several times with water, dried and concentrated in vacuo. The residue is purified over a silica gel column with ethyl acetate as eluent. Yield: 210 mg (12% derThe'orie), Melting point: 119-120 ⁰ C.

Example N 1- (7-Methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane

a) 7-Methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one

3.1 g (0.0136 mol) of N-chloroacetyl-N- (2- (3-methoxyphenyl) ethyl) -amine are dissolved in 270 ml of ethanol and 1 530 ml of water and TO. Hours under nitrogen atmosphere at 20-25 ⁰ C exposed with a high-pressure mercury lamp. The solution is concentrated to a volume of about 400 ml, mixed with sodium bicarbonate and shaken out several times with ethyl acetate. The extracts are dried over magnesium sulfate, concentrated and the residue is purified on a silica gel column with ethyl acetate as eluent.

Yield: 820mg (31.5% of theory),

Melting point: 152-154 ° C.

b) 1- (7-Methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane

1.15 g (6 mmol) of 7-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one are dissolved in 30 ml of absolute tetramethylurea, mixed with 300 mg of 55% sodium hydride dispersion (in oil) and under a nitrogen atmosphere for 2 hours at 20-25 ⁰ C stirred. The resulting reaction mixture is added dropwise with stirring at 15-20 ° C under nitrogen to 1.6 g (7.8 mmol) of i-chloro-3-iodopropane, dissolved in 20 ml of tetramethylurea, and stirred for 3 hours at room temperature. Then it is mixed with about 300mi ethyl acetate and extracted 6 times with water. The organic solution is dried over magnesium sulfate, concentrated and the residue is purified on a silica gel column with methylene chloride and increasing proportions of ethanol (to 2%). Yield: 410 mg (25.5% of theory), IR spectrum (methylene chloride): 1 650 cm ^-1 ( CO).

Example O '1- {7-nitro-8-methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane 28.5g (0.106 mol ) 1- (8-Methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-propane are dissolved in 350 ml of concentrated nitric acid for ² hours at 20-25 ° C C stirred. The solution is poured onto ice-water, neutralized with potassium carbonate and extracted twice with methylene chloride. The extract is dried over magnesium sulfate, concentrated in vacuo and the residue is purified on a silica gel column with ethyl acetate as eluent. Yield: 11g (33.2% of theory), Melting point: 127-128 ⁰ C.

Example P 1- (1,3,4,5-Tetrahydro-2H-3-benzazepine-2,4-dione-3-yl) -3-chloropropane

a) 2-Amino-4-bromo-1 H-3-benzazepine hydrobromide

Made from 5.0 g (0.032 mol) of o-phenylenediacetonitrile analogously to Example Fa

 Yield: 8.0g (78.6% of theory)

b) 1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione

Prepared from 8.0 g (0.025 mole) of 2-amino-4-bromo-1 H-3-benzazepine hydrobromide analogously to Example Fb. Yield: 3.7 g (66.1% derTheorie), Melting point: 189-191 ⁰ C.

c) 1- (1,3,4,5-Tetrahydro-2H-3-benzazepine-2,4-dione-3-yl) -3-chloro-propane

3.5 g (0.020 mol) of 1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione are suspended in 30 ml of dimethylformamide and treated while stirring with 2.5 g of potassium tert-butoxide. After 10 minutes, the resulting solution is added dropwise with ice cooling to 3.5 ml of 1-bromo-3-chloropropane in 20 ml of dimethylformamide. After an hour you pour on ice water. After a short time, the greasy precipitate crystallizes. The precipitate is filtered off with suction, dissolved in acetone, again filled with water, filtered off with suction and dried.

Yield: 4.7 g (90.4% of theory).

Example Q 3- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -propionaldehyde

a) 3- (7,8-Dimethoxy-1,3-dihydro-2H-S-benzazepin ^ -on-S-y-O-propionaldehyde diethyl acetal

Prepared analogously to Example 1 by reaction of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one with 3-chloropropionaldehyde diethyl acetal.

Yield: 93.3% of theory.

b) 3- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -propionaldehyde

3.5 g (0.01 mol) of 3- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -propionaldehyde diethyl acetal are dissolved in 50 ml of 2N sulfuric acid and 50 ml Ethanol heated to 40 ⁰ C for 2 hours. In vacuo, the alcohol is distilled off, the residue is made alkaline with cooling with saturated potassium carbonate solution and extracted several times with ethyl acetate. The ethyl acetate extract is shaken twice with 5% sodium hydrogen sulfite solution. The bisulphite extract is acidified with concentrated hydrochloric acid and heated to 40 ^° C. in vacuo for ² hours to remove the sulfur dioxide. Then it is mixed with saturated potassium carbonate solution, extracted several times with methylene chloride, dried over magnesium sulfate and evaporated. Melting point: 95-96 ° C Yield: 1.7g (61.8% of theory), Preparation of the final products:

example 1

1- {7,8-Dirnethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-l \ l- (2- (6 -methoxy-benzo [b] thienyl-3) -tehyi) -amino] -propane-dihydrochloride 0.80 g (0.0027 mol) of 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H- 3-benzazepin-2-on-3-yl) -3-chloropropane and 0.60 g (0.0027 mol) of 3- (N-methyl-2-amino-ethyl) -6-methoxy-benzo [b] -thiophene are heated in 5 ml of triethylamine at 60 ° C for 30 minutes. The temperature is then increased to reflux and maintained for 3 hours. After distilling off the triethylamine is heated for a further 5 hours at 100 ° C. The product obtained is purified on a silica gel column with methylene chloride / methanol = 25: 1 as the eluent, taken up in methanol and precipitated with ethereal hydrochloric acid as the hydrochloride. Yield: 0.69 g (46% of theory),

Calc .: C 58,36 H 6,53 N 5.04 Cl 12,76 S 5,77 Found .: 58.43 6.83 4.71 12.86 5.65

Rf value of the free base: 0.48 (silica gel, methylene chloride / methanol = 9: 1).

Example 2 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N -methyl-N- (4- (imidazolyl -l) -butyl) -amino] propane 1.65 g (0.0050 mol) of 1S-dimethoxy-1-α-tetrahydro-1H-benzazepine -on-S-yD-S-fN-methyl-amino- propane hydrochloride are refluxed with 0.80 g (0.0050 mole) of 4- (imidazolyl-1) -l-chlorobutane and 2.6 g (0.020 mole) of anhydrous potassium carbonate in dimethylformamide for two hours. The solvent is distilled off, the residue taken up in half-concentrated sodium hydroxide solution and extracted with chloroform. The extract is washed with brine, dried with sodium sulfate, concentrated and purified over an alumina column (activity grade II, eluent: methylene chloride).

Yield: 0 ^ 91 g (44% of theory), Rf value: 0.53 (silica gel, methylene chloride / methanol = 9: 1).

Example 3

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2,4-dione-3-yl) -3- [N-methyl-N- (2- (pyridyl -4) -ethyl) -amino] propane dihydrochloride monohydrate 1.55 g (0.0066 mol) of 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione are obtained gentle heating in 40 ml of dimethylformamide. After cooling to 0 ⁰ C is added 0.9 g (0.008 mol) of potassium tert.butylatzu, stirred for 5 minutes and then treated with 1.7 g (0.0066 mole) of 3- [N-methyl-N (2- ( pyridyl-4) ethyl) amino] -l-bromo-propane. It is allowed to stir overnight at room temperature, the solvent is rotated off and the residue is purified on a silica gel column (elution with methylene chloride / ethanol). The purified base is taken up in methanol and the hydrochloride is precipitated with ethereal hydrochloric acid.

Yield: 0.75 g (23% of theory),

Calc .: C 54.97 H 6,62 N 8.36 Cl 14,11 Found .: 55,20 6.82 8.17 13.82

Rf value of the free base: 0.25 (silica gel, methylene chloride / ethanol = 9: 1).

Example 4 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-thion-3-yl) -3- [N-methyl-N- (3-furyl -2) -propyl) -amino] propane 0.80g (0.0020 mol) of 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3- yl) -3- [N -methyl-N- (3- (furyl-2) -propyl) -amino] -propane and 0.40 g (0.0010 mol) 2,4-bis- (4-methoxy-phenyl) -1,3-dithia-2,4-diphosphetane-2,4-disulfide are suspended in 10 ml of toluene and refluxed for 3 hours. The mixture is then concentrated by rotary evaporation and purified on a silica gel column with methylene chloride and increasing proportions of methanol. Yield: 0.26 g (29% of theory),

Calc .: C 66.31 H 7.74 N 6.73 S 7.70

Gef .: 66.13 7.72 6.14 7.71

Rf value: 0.58 (silica gel, methylene chloride / methanol = 9: 1).

Example 5

1- (7,8-Dimethoxy-2,3-dihydro-1H-3-benzazepin-3-yl) -3- [N -methyl-N- (2- (furyl-2) -ethyl) -amino] A solution of 0.77 g (0.0020 mol) of 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl- N- (2- (furyl-2) -ethyl) -aminolpropane in 5 ml of absolute dioxane is added dropwise to a boiling suspension of 0.2 g (0.005 mol) of lithium aluminum hydride in 20 ml of absolute dioxane and kept at reflux temperature for 2 hours. It is then decomposed with sodium hydroxide solution, filtered off with suction and purified on a silica gel column. Yield: 0.50 g (67% of theory),

Calc .: C71.32 H8.16 N7.56

G .: 70.90 7.88 7.35

Rr value: 0.70 (silica gel, methylene chloride / methanol = 9: 1). Example 6

hydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 2- (3 Methylamino-propyl) -thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 21% of theory, Rr value of the free base: 0.40 (silica gel, methylene chloride / methanol = 9: 1).

Example 7 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [IM-methyl-N- (2- (furyl -2) -ethyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) 3-chloropropane with 2- (2-methylamino-ethyl) -furan. Yield: 50% of theory,

Calc .: C 68.37 H 7.82 N 7.25

Gef .: 67.45 7.73 6.33

Rf value: 0.44 (silica gel, methylene chloride / methanol = 9: 1).

Example 8 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N -methyl-N- (3- (furyl -2) -propyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) 3-chloropropane with 2- (3-methylamino-propyl) -furan. Yield: 48% of theory,

Calc .: C 68.97 H 8.05 N 6.99

Gef .: 68.76 7.99 6.78

Rr value: 0.44 (silica gel, methylene chloride / methanol · = 9: 1).

Example 9

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (2-thienyl ) ethyl) amino] propane dihydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 2- (N- Methyl 2-aminoethyl) thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 42% of theory,

Melting point: 215 ° C (dec.).

Example 10

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (3-thienyl ) ethyl) amino] propane dihydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 3- (N- Methyl 2-aminoethyl) thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 40% of theory,

Melting point: 185 ⁰ C (dec.).

Example 11 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (imidazolyl -4 (5) -ethyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H, 3-benzazepin-2-one-3- yi) -3-chloropropane with 4- (N-methyl-2-amino-ethyl) -imidazole.

Yield: 45% of theory, Rr value: 0.60 (alumina, methylene chloride / methanol = 10: 1).

Example 12

1- (7,8-dimethoxy-1 _r 3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (5,6 dimethoxy-benzotb] thienyl-3) ethyl) -aminolpropan

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 3- (2-methylamino -ethyl) -5,6-dimethoxy-benzo [b] thiophene. Yield: 43% of theory,

Calc .: C 65.60 H 7.08 N 5.46

F .: 65.31 6.89 5.72

Rr value: 0.27 (silica gel, methylene chloride / methanol = 9: 1).

Example 13

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (imidazo [1,2 -a] pyridyl-3) -ethyl) -amino] -propane hydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2 -on-3-yl) -3- (N -methyl-amino) -propane with 2- (imidazo [1,2-a] pyridyl-3) -ethyl chloride and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 17% derTheorie, Melting point: 130 ⁰ C (dec.).

Example 14

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b ] thienyl-3) ethyl) -aminolpropane hydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) 3-chloropropane with 3- (N-methyl-2-aminoethyl) benzo [b] thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 65% of theory, m.p .: 195 ° C (dec.).

Example 15

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (4- (2-thienyl ) butyl) amino] propane dihydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 2- (N- Methyl 4-amino-butyl) -thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 30% of theory,

Calc .: C 57.25 H 7.21 N, 5.56 Cl 14.08 S 6.37

Found: 57,60 7,55 5,41 13,82 6,43

Rr value of the free base: 0.55 (silica gel, methylene chloride / methanol = 9: 1).

Example 16 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3j; N-methyl-N- (2- {imidazolyl 1) -ethyl-amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 Chloropropane with 1- (N-methyl-2-amino-ethyl) -imidazole.

Yield: 52% of theory, Rr value: 0.55 (alumina, methylene chloride / methanol = 20: 1).

Example 17

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-rnethyl-N- (2- {l-rnethyl -irnidazolyl-4) ethyl) -arnino] propane

Prepared analogously to Example 1 by reacting 1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 1-methyl-4 - (N-methyl-2-amino-ethyl) imidazole.

Yield: 45% of theory, Rf value: 0.70 (alumina, methylene chloride / methanol = 20: 1).

-23 Example 18

amino] propane hydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 3- (N-methyl-2-amino-propyl) -benzo [b] thiophene and subsequent precipitation of the hydrochlorides with ethereal hydrochloric acid.

Yield: 29% of theory, Rf value of free base: 0.65 (silica gel, methylene chloride / methanol = 5: 1).

Example 19 1- _{(7/8-Dirnethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl)} -3- [N-methyl-N- (2- (furyl-2) - ethyl) -arnino] propane hydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 2- (2-methylamino-ethyl) -furan and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 67% of theory,

Calc .: C 62,77 H 6,94 N 6.66 Cl 8,42 Found .: 62,80 7.19 6.49 8.32

Rr value of the free base: 0.57 (silica gel, methylene chloride / methanol = 9: 1).

Example 20

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (1H-) benzo [d] imidazolyl-1) -ethyl) -amino] -propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2 on-3-yl) -3-chloropropane with 1- (2-methylamino-ethyl) -1H-benzo (d) imidazole Yield: 62% of theory,

Calc .: C, 68.78, H, 7.39, N, 12.83

Gef .: 68.50 7.39 12.57

Rf value: 0.57 (silica gel, methylene chloride / methanol = 9: 1).

Example 21

1- (7 _/ 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- {2-benzyl 1H-ben2o [d] imidazolyl-1) -ethyl) -aminolpropane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2 on-3-yl) -3-chloropropane with 1- (2-methylamino-ethyl) -2-benzyl-1H-benzo [d] imidazole.

Yield: 20% of theory, Rr value: 0.49 (silica gel, methylene chloride / methanol = 9: 1).

Example 22

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzazepin-2-on-3-yl) -3- [N-methyl-N- {2- {4-methyl-thiazolyl -5) -ethyl) -amino] -propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl ) -3- 'chloropropane with 4-methyl-5- (N-methyl-2-amino-ethyl) thiazole and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 18% of theory, Melting point: 196 to 197.5 ⁰ C (dec.).

Example 23

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (1-methyl -pyrrolyl-2) -ethyl) -amino] -propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3 -yl) -3-chloropropane with 1-methyl-2- (N-methyl-2-amino-ethyl) -pyrrole. Yield: 11% of theory,

Calc .: C 69.14 H 8.33 N 10.52

Gef .: 70.01 8,24 10,76

Rr value: 0.76 (alumina N, methylene chloride / ethanol = 19: 1).

Example 24 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (picolyl-2) -amino] propanedihydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with N- (picolyl-2) -methylamine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 54% of theory, Rr value of the free base: 0.50 (silica gel, methylene chloride / ethanol = 4: 1).

Example 25

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzazepin-2-one-3-yl) -3-chloropropane with N- (picolyl-3) - methylamine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 20% of theory, melting point: 176-178 ° C.

Example 26

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- {2- (4-pyridyl ) -ethyl) -amino] propanedihydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 Chloropropane with 4- (2-methylamino-ethyl) pyridine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 19% of theory, melting point: 116-118 ° C.

Example 27

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- {2-pyridyl ) -ethyl) -amino] propanedihydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 Chloropropane with 2- (2-methylamino-ethyl) pyridine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 6.4% of theory, melting point: 165-167 ° C.

Example 28

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- {6,7 -dimethoxy-isoquinolyl-4) -ethyl) -amino] propane-dihydrochloride monohydrate Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine 2-on-3-yl) -3-chloropropane with 6,7-dimethoxy-4- {2-methylamino-ethyl) -isoquinoline and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 22% of theory,

Calc .: C 58.18 6.56 N 7.02 Cl 11,84 Found .: 57.75 7.19 7.28 12.03

Rf value of the free base: 0.60 (silica gel, ethyl acetate / ethanol / ammonia = 50: 45: 5).

Example 29

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (3-pyridyl ) -ethyl) -amino] propanedihydrochloride-semihydrate Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 3- (2-methylamino-ethyl) -pyridine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 27% of theory, Melting point: 110-112 ⁰ C.

Calc .: C 57.62 H7,14 N 8,76 Cl 14,79 Found .: 57.23 7.34 8.67 14.52.

Example 30

1- (7,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl) -3- [N-methyl-N- {2- (4-pyridyl) ethyl) -amino] propanetrihydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl) -3-chloropropane with 4- (2 -Methylamino-ethyl) -pyridine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 25% of theory, m.p .: 257-259X

Calc .: C 56.04 H 7,36 N 8,52 Cl 21,58 Found .: 55.82 7.31 8.52 21.53

Example 31

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- {2-pyridyl-4) -ethyl) -amino] propanedihydrochloride 1.1 g (0.0040 mol) of 3- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -propionaldehyde are dissolved in 30 ml of ethanol in the presence of 0.60 g (0.0044 mol) of 4- (2-methylamino-ethyl) -pyridine and 0.2 g of 10% palladium carbon at 50X20 hours at 5 bar hydrogenated. The catalyst is filtered off with suction, concentrated by evaporation, purified via an aluminum oxide column of activity level II-III with methylene chloride / ethanol as eluent and the hydrochloride is precipitated with ethereal hydrochloric acid. Yield: 0.98 g (62% of theory), m.p .: 116-118 ° C.

Example 32 1- {7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (benzo [b] furyl-3 -) - ethyl] -amino] propane 1.5g (0.005 mol) of 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one 3-yl) -3-chloropropane are refluxed with O, 88 g (0.005 mol) of 3- (N-methyl-2-aminoethyl) benzo [b] furan and 7 g of anhydrous potassium carbonate in 50 ml of dimethylformamide for 4 hours , The solvent is distilled off, the residue taken up in half-concentrated sodium hydroxide solution and extracted with chloroform. The extract is washed with brine, dried with sodium sulfate, concentrated and purified by silica (eluent: methylene chloride / methanol = 20: 1 to 5: 1). Yield: 0.2 g (9% of theory),

Calc .: 71.53 H, 7.39 N, 6.42

Gef .: 71.43 7.21 6.22

Rf value: 0.35 (silica gel, methylene chloride / methanol = 9: 1) Example 33

hydrochloride Prepared analogously to Example 32 by reacting 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 3- (N-methyl 2-aminoethyl) benzo [b] thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 35% of the theory,

Calc .: C 64,12 H 6,42 N 5.75 S 6,58 Cl 7:28 Found .: 63.93 6.71 5.70 6.32 7.39

Rr value of the free base: 0.55 (silica gel, methylene chloride / methanol = 9: 1). Example 34

hydrochloride Prepared analogously to Example 32 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzaz'epin-2-one-3-yl) -3-chloropropane with 3- (3-Methylamino-propyl) benzo [b] thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 8% of theory,

Calc .: C 64.46 H 7.01 N 5.57 S 6,37 Cl 7.05 Found .: 64.32 7.00 5.47 6.61 7.12

Rf value of the free base: 0.30 (silica gel, methylene chloride, methanol = 9: 1).

Example 35

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N - {(benzo [b] thienyl -3) -methyl) -amino] propanedihydrochloride Prepared analogously to Example 2 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- (N-methyl-amino) -propane with 3-chloromethyl-benzo [b] thiophene and subsequent precipitation of the dihydrochloride with ethereal hydrochloric acid.

Yield: 16% derTheorie, melting point 218-220 ⁰ C.

Calc .: C 58,70 H 6,31 N 5.48 S 6,27 , Cl 13,86 Fd: 58.68 6.25 5.25 6.71 13.62

Example 36

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- {2- (5-methyl benzo [b] thienyl-3) -ethyl) -amino] propane dihydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine 2-on-3-yl) -3-chloropropane with 3- (N-methyl-2-aminoethyl) -5-methyl-benzo [b] thiophene and subsequent precipitation of the dihydrochloride with ethereal hydrochloric acid. Yield: 32% of the theory,

Calc .: 60.10 H 6,73 N 5.19 S 5.94 Cl 13,14 Found .: 60.08 6.57 5.15 6.36 13.46

Rf value of the free base: 0.40 (silica gel, methylene chloride / methanol = 9: 1).

Example 37

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] furyl-3) -ethyl) -amino] propane hydrochloride Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2 on-3-yl) -3-chloropropane with 3- (2-methylamino-ethyl) -6-methoxy-benzo [b] furan and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

-26- 247 Yield: 14% of theory,

Ber. C 64.47 H 7.01 Cl 7.05 N 5.57 Found .: 64.52 6.99 7.20 5.37

Rf value of the free base: 0.35 (silica gel, methylene chloride / methanol = 10: 1).

Example 38

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- {4-methoxy benzo [b] thienyl-3) -ethyl) -amino] propane hydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 3- (2-methylamino -ethyl) -4-methoxy-benzo [b] thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid

 Yield: 7% of theory,

Calc .: C 62.47 H 6.80 Cl 6,83 N 5.40 Found .: 62.36 6.94 6.44 5.51

Rr value of the free base: 0.41 (silica gel, methylene chloride / methanol = 9: 1).

Example 39

1- (7,8-Dimethoxy-1,3,4 _r 5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N -methyl-N- (2- (5-bromo benzo [b] thienyl-3) ethyl) amino] propane

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzazepin-2-on-3-yl) -3-chloropropane with 3- (2-methylaminoethyl) ) -5-bromo-benzo (b] thiophene Yield: 53% of theory,

Calc .: 58.75 H 5.88 N 5.27 S 6.03 Found .: 58.63 5.63 5.03 6.20

Rr value: 0.50 (silica gel, methyl chloride / methanol = 9: 1).

Example 40

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b ] furyl-2) -ethyl) -amino] propane dihydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with 2- (2- Methylaminoethyl) benzo [b] furan and subsequent precipitation of the dihydrochloride with ethereal hydrochloric acid. Yield: 19% of theory,

Calc .: C 61.30 H 6.53 Cl 13.92 N 5.50

F .: 61.33 6.63 13.53 5.66

Rf value of the free base: 0.42 (silica gel, methylene chloride / methanol = 10: 1).

Example 41

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-IM {2- (2,5 -dimethyl-thienyl-3) ethyl) -aminolpropan dihydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 2,5-dimethyl -3- (2-methylamino-ethyl) thiophene and subsequent precipitation of the dihydrochloride with ethereal hydrochloric acid

 Yield: 19% of theory,

Calc .: C 57,25 H 7,21 N 5.56 S 6,37 Cl 14.08 Found .: 57.42 7.44 5.51 6.76 13.88

Rr value of the free base: 0.40 (silica gel, methylene chloride / methanol = 10: 1).

Example 42

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (3- (3-pyridyl N-oxide) propyl) amino] propane dihydrochloride semihydrate

2.9 g (0.010 mol) of 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methylamino-propane and 0.86 g (0.005 mol) of 3- (3-chloro-propyl) -pyridine-N-oxide are melt-reacted at 130 ^° C. for 8 hours. The reaction product is dissolved in ethanol, purified on an alumina column with methylene chloride / ethanol as eluant and the hydrochloride is precipitated with ethereal hydrochloric acid

Yield: 0.40 g (15% derTheorie), Melting point: 105-115 ⁰ C.

Example 43

dihydrochloride monohydrate Prepared analogously to Example 1 by reacting i ^ propane with 4- (2-methylaminoethyl) pyridine and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid.

Yield: 18% of theory, melting point: 128-132 ° C.

Example 44

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (3-pyridyl N-oxide) -ethyl) -amino] propanedihydrochloride semihydrate T, 7g (0.011 mol) of 3- (2-methylamino-ethyl) -pyridine-N-oxide and 3.1 g (0.011 mol) of 3- (7, 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -propionaldehyde are dissolved in 100 ml abs. Dissolved ethanol and mixed with 20g molecular sieve 3A. After addition of 0.6 g (0.016 mol) of sodium borohydride is stirred for 45 minutes at room temperature. It is suctioned off, decomposed with 150 ml of 2N HCl and evaporated. The residue is washed with methylene chloride / conc. Ammonia was added and the aqueous phase extracted three more times with methylene chloride. The combined organic phases are dried, concentrated, and purified on a silica gel column, and the dihydrochloride is precipitated with ethereal hydrochloric acid. Yield: 2.0 g (37% of theory), m.p .: 216-218 ° C.

Example 45

1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-3 ) ethyl) amino] propane hydrochloride

Prepared analogously to Example 31 by reaction of 3- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -propionaldehyde with 3- (2-methylamino-ethyl) benzo [b] thiophene and subsequent precipitation of the hydrochloride with ethereal hydrochloric acid. Yield: 85% of theory, Rf value of the free base: 0.55 (silica gel, methylene chloride / methanol = 9: 1).

Example 46

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b ] furyl-2) -ethyl) -amino] propane dihydrochloride

Prepared analogously to Example 31 by reacting 3- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-y-O-propionaldehyde with 2- (2-methylamino-ethyl ) benzo [b] furan and subsequent precipitation of the dihydrochloride with ethereal hydrochloric acid.

Yield: 25% of theory, R _r value of free base: 0.42 (silica gel, methylene chloride / methanol = 10: 1).

Example 47 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dion-3-yl) -3- [N-methyl-N- (2-one) (pyridyl-3) -ethyl) -amino] propane Prepared analogously to Example 31 by reaction of 3- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione) 3-yl) -propion-aldehyde with 3- (2-methylamino-ethyl) -pyridine, but the hydrogenation was carried out at room temperature. Yield: 56% derTheorie, mp 78-8O ⁰ C.

Example 48

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2,4-dione-3-yl) -3- [N-methyl-N- {2- (6 , 7-dimethoxy-isoquinolyl-4) -ethyl) -amino] propane

Prepared analogously to Example 31 by reaction of 3- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2,4-dione-3-yl) -propion-aldehyde with 4- ( 2-methylamino-ethyl) -6,7-dimethoxy-isoquinoline, but the hydrogenation was carried out at room temperature.

Yield: 51% of theory, Rr value: 0.45 (silica gel, ethyl acetate / ethanol / ammonia = 90: 10: 1).

Example 49

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N - ((3,5-dimethyl -isoxazolyl-4) methyl) -aminolpropan

Prepared analogously to Example 2 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methylamino-propane with 4 chloromethyl-3,5-dimethyl-isoxazole. Yield: 55% of theory, melting point: 93-95 ° C.

Example 50

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-thion-3-yl) -3- [N-methyl-N- {2- (6-methoxy benzo [b] thienyl-3) -ethyl) amino] propane Prepared analogously to Example 4 from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one 3-yl) -3- [N -methyl-N- (2- (6-methoxybenzo [b] thienyl-3) -ethyl) amino] propane and 2,4-bis (methylthio) -1,3- dithia-2,4-diphosphetane-2,4-disulfide.

Yield: 77% of theory, Rr value: 0.37 (silica gel, methylene chloride / methanol = 9: 1).

Example 51

ethyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane mit2- (2-benzylamino-ethyl) -3-methyl-5-methoxy-benzo [b] furan.

Yield: 26% of theory, Rr value: 0.65 (silica gel, methylene chloride / methanol = 9: 1).

Example 52 1- {7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N - ((thienyl-2) -methyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 2 aminomethyl-thiophene. Yield: 69% of theory,

Calc .: C 64,14 H 7,00 N 7.48 S 8,56 Found .: , 63.90 7.06 7.41 8.81

Rr value: 0.32 (silica gel, methylene chloride / methanol = 9: 1).

Example 53

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-IM {2- (4-methoxy benzo [b] furyl-3) -ethyl) -amino] propane

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 3- (2-methylamino ethyl) -4-methoxy-benzo [b] furan.

Yield: 24% of theory, Rr value of the free base: 0.21 (silica gel, methylene chloride / methanol = 9: 1).

Example 54

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (4,5 , 6,7-tetrahydro-benzotb] thienyl-3) -ethyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3- benzazepin-2-on-3-yl) -3-chloropropane with 3- (2-methylaminoethyl) -4,5,6,7-tetrahydrobenzo [b] thiophene.

Yield: 26% of theory, Rr value of the free base: 0.40 (silica gel, methylene chloride / methanol = 10: 1).

Example 55

1- {7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (6-hydroxy benzo [b] thienyl-3) -ethyl) -amino] propane

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- (N-methyl-amino) -propane with 3- (2-chloro-ethyl) -6-hydroxy-benzo [b] thiophene.

Yield: 24% of theory, Rf value: 0.45 (alumina, methylene chloride / methanol = 10: 1).

Example 56

1- {7,8-dimethoxy-1,3,4 _/ 5-tetrahydro-2H-3-benzazepin-2-one-3-yl} -3- [N -methyl-N- (2- (6-methylsulfohyloxy benzo [b] thienyl-3) -ethyl) -amino] propane Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2 on-3-yl) -3- (N -methyl-amino) -propane with 3- (2-chloro-ethyl) -6-methylsulfonyloxy-benzo [b] thiophene.

Yield: 43% of theory, Rr value: 0.49 (silica gel, methylene chloride / methanol = 9: 1).

Example 57

1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- [N-methyl-N- (2- (benzo [b ] thienyl-4) -ethyl) -amino] propane dihydrochloride

Prepared analogously to Example 1 by reacting 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane with 4- (2- Methylaminoethyl) benzo [b] thiophene and subsequent precipitation of the dihydrochloride with ethereal hydrochloric acid.

Yield: 36% of theory, melting point: 198 ° C. (dec.)

Calc .: C 59.42 H 6,52 N 5.33 Cl 13,49 S6,10 Found .: 59.26 6.58 5.39 13.28 6.51

Claims (27)

wherein the carbon atom indicated by χ is in each case linked to the phenyl nucleus, E is a straight-chain alkylene group optionally substituted by an alkyl group having 1 to 3 carbon atoms and 2 up to 4 carbon atoms, G is a straight-chain alkylene group optionally substituted by an alkyl group having 1 to 3 carbon atoms and 1 up to 5 carbon atoms, Ri is a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl, nitro, amino, alkylamino, dialkylamino, alkyl, alkylmercapto, hydroxy, alkoxy or phenylalkoxy group, each alkyl part in each case being 1 to 3 carbon atoms can contain R _{2 is} a hydrogen atom, chlorine or bromine atom, a hydroxy, alkoxy, phenylalkoxy or alkyi group, each Alkyl part may contain 1 to 3 carbon atoms, or R ₁ and R ₂ together represent an alkylenedioxy group having 1 or 2 carbon atoms, R _{3 is} a hydrogen atom, an alkenyl group having 3 to 5 carbon atoms, an alkyl or phenylalkyl group, wherein the Alkyl part may contain 1 to 3 carbon atoms, and Het a 5- or 6-membered heteroaromatic ring bonded via a carbon or nitrogen atom, which contains an oxygen, sulfur or nitrogen atom, two nitrogen atoms or a nitrogen atom and an oxygen or sulfur atom, and to which additionally a phenyl ring may be fused, wherein in this case also the bond via the phenyl nucleus can take place, or an imidazo [1,2-a] pyridyl group, in which the carbon skeleton of the abovementioned radicals is represented by a halogen atom, an alkyl, hydroxyl, alkoxy, phenylalkoxy, phenyl , Dimethoxyphenyl, nitro, amino, acetylamino, carbamoylamino, N-alkylcarbamoylamino, hydroxymethyl, mercapto, alkylmercapto, alkylsulfinyl, alkylsulfonyl, alkylsulfonyloxy, alkylsulfonylamino, alkoxycarbonylmethoxy, carboxymethoxy or Alkoxymethyl group mono- or disubstituted or may be substituted by a methylene or ethylenedioxy group and at the same time an optionally present Iminogrup In the above-mentioned heteroaromatic radicals, may be substituted by an alkyl, phenylalkyl or phenyl group, wherein the above-mentioned alkyl moieties may each contain 1 to 3 carbon atoms, their N-oxides and their acid addition salts, characterized as a result of that a) a compound of the general formula (II) with a compound of the general formula V-G-Het , (Hl) in which A, B, E, G and Hetwie are defined in claims 1 to 8, Ri 'represents a hydroxy, amino or alkylamino group protected by a protecting group or has the meanings mentioned for R- in claims 1 to 8 'R ₂ ' represents a hydroxy-protected by a protecting group or has the meanings mentioned for R ₂ in claims 1 to 8; one of U or V represents the R ₃ '-NH group, where R ₃ ' is a protective group for an amino group represents or has the meanings mentioned for R ₃ in claims 1 to 8, and the other of the radicals U or V represents a nucleophilic leaving group, reacted and, if appropriate, then a used protective moiety is cleaved or b) for the preparation of compounds of general formula I in which AdIe CH ₂ -CH ₂ -GrUpPe, B is the methylene or carbonyl group and R _{3 is} not alkenyl group having 3 to 5 carbon atoms, a compound of general formula R- -E-N-G- Het (IV) in which R ₁ to R ₃ , E, G and Het are as defined in claims 1 to 8 and B 'represents the methylene or carbonyl group, is hydrogenated or c) for the preparation of compounds of the general formula I, in which B represents a thiocarbony! group, a compound of the general formula -E-N-G- Het wherein R ₁ to R ₃ , A, E, G and Hetwie are defined in claims 1 to 8, is reacted with a sulfur-introducing agent d) for the preparation of compounds of general formula I, ? ^H in the A represents a -CH-CO- group, a compound of the general formula CO-CO ^ Het (Vl) in which R ₁ to R ₃ , E, G and Het are as defined in claims 1 to 8, is reduced or e) for preparing compounds of the general formula I, in which A is a-CH ₂ -CH ₂ - represent a methyl group or-CH = CH- and B, a compound of general formula (VLI) -N- G> Het in the ^; Ri are as defined to R _3, E, G and Het is as defined in claims 1 to 8 and A 'is a-CH ₂ -CH ₂ - or -CH = CH-group, is reduced or f) For the preparation of compounds of general formula I in which A represents the COCO group, a compound of general formula CH ₂ CO \ ' ³ N-E-N-G- Het , (VIII) in the R ₁ to R ₃ , E, G and Het are as defined in claims 1 to 8, is oxidized or g) a compound of the general formula -E-H , (IX) in the A, B, E, R ₁ and R _{2 are} as defined in claims 1 to 8, but in the radical E two hydrogen atoms in a -CH ₂ orCH ₃ group of the radical E are replaced by an oxygen atom, with a compound of the general formula B ₃ HNG-Het in the R ₃ , G and Het are as defined in claims 1 to 8, in the presence of a reducing agent is reacted or h) in a compound of formula (XI) in the """ - R ₁ 'represents a hydroxy, amino or alkylamino group protected by a protecting group or has the meanings mentioned for R ₁ in claims 1 to 8, and R ₂ "represents a hydroxy-protected hydroxy group or R ₂ in the claims Has 1 to 8 mentioned meanings, with a compound of the general formula R ₃ W-E-N-G-Het, (XII) in the E, G and Het are as defined in claims 1 to 8, R ₃ 'represents a protective group for an amino group or has the meanings mentioned for R ₃ in claims 1 to 8, and W is a nucleophilic leaving group, reacted and, if appropriate, a protective residue used is subsequently eliminated and, if desired, subsequently a compound of the general formula I thus obtained is converted into its acid addition salt, in particular into its physiologically tolerated acid addition salt, with an inorganic or organic acid. 2. The method according to item 1, characterized in that the reaction is carried out in a solvent. 3. The method according to points 1 a and 2, characterized in that the reaction is carried out in the presence of an acid-binding agent. 4. The method according to points 1 a and 2, characterized in that the elimination of protective radicals is carried out hydrolytically or hydrogenolytically. 5. Method according to the points 1 a and 2, characterized in that the reaction at temperatures between 0 and 150 ° C, z. B. at the boiling temperature of the solvent used is carried out. 6. The method according to points 1 b and 2, characterized in that the catalytic hydrogenation at a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5bar, and at temperatures between 0 and 75 ⁰ C, but preferably at temperatures between 20 and 50 ° C, is performed. 7. The method according to item 1 c, characterized in that the reaction with phosphorus pentasulfide, 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetan-2,4-disulfide or 2,4- Bis (methylthio) -1,3-dithia-2,4-diphosphetane-2,4-disulfide is performed. 8. The method according to points 1 c, 2 and 7, characterized in that the reaction at temperatures between 50 ⁰ C and 15O ⁰ C, or at the boiling temperature of the reaction mixture, is performed. 9. The method according to item 1 d, characterized in that the reaction is carried out with a metal hydride such as sodium borohydride. 10. The method according to points 1 d, 2 and 9, characterized in that the reaction at temperatures between 0 and 80 ⁰ C, preferably at temperatures between 15 and 40 ⁰ C, is performed. 11. The method of item 1 e, characterized in that the reaction with a metal hydride such as lithium aluminum hydride or diborane or with a complex of borane and a thioether, z. B. with the complex of diborane and dimethyl sulfide is performed. 12. The method according to points 1 e, 2 and 9, characterized in that the reaction at temperatures between 0 and 25 ⁰ C, preferably at temperatures between 10 and 25 ° C, is performed. 13. The method according to points 1 f and, 2, characterized in that the oxidation is carried out with potassium permanganate, selenium dioxide or sodium dichromate. 14. The method according to the items 1f, 2 and 13, characterized in that the oxidation is carried out at temperatures between 0 ⁰ C and 100 ⁰ C. 15. The method according to the items 1 g and 2, characterized in that the reaction is carried out in the presence of a complex metal hydride. 16. The method according to the items 1 g and 2, characterized in that the reaction is carried out in the presence of hydrogen and palladium / carbon. 17. The method according to the items 1 g, 2,15 and 16, characterized in that the reaction at temperatures between 0 ⁰ C and 100 ° C, but preferably at temperatures between 20 ⁰ C and 80 ° C, is performed. 18. The method according to the items 1 h and 2, characterized in that the reaction is carried out in the presence of an acid-binding agent. , 19. The method according to the items 1 h and 2, characterized in that the elimination of protective radicals is carried out hydrolytically or hydrogenolytically. 20. The method according to the items 1 h and 2, characterized in that the reaction at temperatures between 0 ° C and 150 ⁰ C, z. B. at the boiling temperature of the solvent used is carried out. 21. The method according to items 1 to 20, characterized in that new heteroaromatic amine derivatives of the general formula G - Het , (La) getting produced,
in the A is a -CH ₂ -CH ₂ -, -CH = CH-, -CH ₂ -CO-, -CO-CO ? ^H or -CH-CO- group and B is a methylene group or
χ A represents a -CH ₂ -CH ₂ - or -CH = CH group and B represents a carbonyl or thiocarbonyl group, wherein the carbon atom denoted by χ is in each case linked to the phenyl nucleus, E is an n-propylene group, G is an ethylene, n-propylene or n-butylene group, R _{1 is} a chlorine atom or bromine atom, a methyl, methoxy, nitro, amino, methylamino or dimethylamino group, R _{2 is} a chlorine or bromine atom, a methyl or methoxy group or R ₁ and R ₂ together form a methylenedioxy or ethylenedioxy group . R _{3 is} a hydrogen atom, a methyl, ethyl or allyl group and A pyrrolyl-2, pyrrolyl-3, N-methylpyrrolyl-2, N-methylpyrrolyl-3, furyl-2, benzo [b] furyl-2, benzo [b] -furyl 3-, 7-methyl-benzo [b] furyl-3, 6-methoxy-benzo [b] furyl-3, 5-methoxy-3-phenyl-benzo [b] furyl-2, thienyl-2 , Thienyl-3, 5-methylthienyl-2-, 2,5-dimethyl-thienyl-3, 5-bromo-thienyl-2-, benzo [b] thienyl-2-, benzo [b] thienyl-3 , 6-Hydroxybenzo [b] thienyl-3, 6-methoxybenzo [b] thienyl-3, 5,6-dimethoxybenzo [b] thienyl-3, 2,5-dimethylbenzo [b ] thienyl-3, 5-methoxy-benzo {b} thienyl-2-, 6-methoxybenzo [b] thienyl-2-, 6-methoxymercapto-benzo [b] thienyl-3, 6-methylsulfinylbenzo [b ] thienyl-3, 6-methylsulfinyl-benzo [b] thienyl-3, 6-methylsulfonyloxy-benzo [b] thienyl-3, 6-ethoxycarbonylmethoxy-benzotbuthienyl-S-, 6-carboxymethyloxybenzo [b] thienyl -3, 6-dimethylamino-benzo [b] thienyl-3, 6-methylsulfonylamino-benzo [b] ^thienyl-3, 6-acetamido-benz [b] thienyl-3, benzo [b] thienyl-4 -, pyrazolyl-1, pyrazolyl-3, 1,5-dimethyl-pyrazolyl-3, i-methyl-imidazolyl-4-, 2- (3,4-dimethoxy-phenyl) -imidazolyl-4 (5) -, benzo [d] imidazolyi-1, 2-benzyl-benzo [d] imidazolyl-1, imidazo [1,2-a] pyridyl-3, oxazolyl-4, oxazolyl -5-, isoxazolyl-3-, 3-methylisoxazolyl-5-, 4-methyl-thiazolyl-5, pyridyl-2, pyridyl-3, pyridyl-4, pyridyl-3-N-oxide, 4-Nitro-pyridyl-2-, 4-amino-pyridyl-2-, 4-acetylamino-pyridyl-2-, 4-carbamoyl-amino-pyridyl-2-, 4-N-methyl-carbamoyl-amino-pyridyl-2, ej -Dimethoxy-quinolym, 6,7-dimethoxy-isoquinolyl-4- or 6,7-dimethoxy-isoquinolyl-4-N-oxide group, and their acid addition salts. 22. The method according to the items 1 to 20, characterized in that new compounds of general formula I a are prepared according to point 2, in the A is a -CH ₂ -CH ₂ or -CH =CH- and B is a carbonyl or thiocarbonyl group, E is an n-propylene group,. G is an ethylene, n-propylene or n-butylene group, R ₁ and R ₂ each represent a methoxy group or R ₁ and R ₂ together form a methylenedioxy group R _{3 is} a hydrogen atom or a methyl group and Het a pyrrolyl-2, pyrrolyl-3, N-methyl-pyrrolyl-2-, N-methyl-pyrrolyl-3, thienyl-2-, thienyl-3, 5-methyl-thienyl-2-, 2 , 5-Dimethyl-thienyl-3, 5-bromo-thienyl-2, pyrazolyl-1, pyrazolyl-3, i-methyl-imidazolyl-4, isoxazolyl-3, benzo [b] furyl-2 -, benzo [b] furyl-3-, 7-methyl-benzo [b] furyl-3-, e-methoxy-benzotblfuryl-S-, 7-methoxy-benzo [b] furyl-3, benzo [b ] thienyl-2-, benzo [b] thienyl-3, 6-methoxy-benzo [b] thienyl-3, 6-methylsulfonyloxy-benzo [b] thienyl-3, 6-ethoxycarbonylmethoxybenzo [b] thienyl-3 -, 6-Carboxymethoxy-benzo [b] thienyl-3, 6-acetamidobenzo [b] thienyl-3, benzo [d] imidazolyl-1, imidazo [1,2-a] pyridyl-3 or pyridyl group, and their acid addition salts. 23. Method according to items 1 to 20, characterized in that 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] thienyl-3) -ethyl) -amino] propane and its acid addition salts with inorganic or organic acids. 24. Method according to items 1 to 20, characterized in that 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (6-methoxy-benzo [b] furyl-3 -) -ethyl) -amino] propane and its acid addition salts with inorganic or organic acids. 25. Method according to items 1 to 20, characterized in that 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2-benzo [b] furyl-2 -) - ethyl) -amino] propane and its acid addition salts with inorganic and organic acids. 26. Method according to items 1 to 20, characterized in that 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (2- (benzo [b] thienyl-3 -) - arnino] propane and its acid addition salts with inorganic or organic acids. 27. Method according to items 1 to 20, characterized in that 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- [N-methyl-N- (4-thienyl-2 -) - butyl] amino] propane and its acid addition salts with inorganic and organic acids.