TH64995A - New substrate tedpiperidines, pharmaceutical mixtures containing these compounds, their uses and processes for the preparation of them. - Google Patents

Abstract

DC60 (08/07/46) This invention concerns substituted piperidines of general formula (chemical formula) (I), in which R, R2 through R5, A, X, Z and n are defined as in claim 1, totomers, diasteromers, enanchiomers, mixtures and salts of such compounds, in particular salts of such compounds which are physiologically acceptable in combination with inorganic or organic acids or bases and possess valuable pharmacological properties, in particular CGRP-antagonist properties, pharmaceutical mixtures of such compounds, their uses and methods for their preparation. This invention concerns substituted piperidines of general formula (chemical formula) (I), in which R, R2 through R5, A, X, Z and n have the same meanings as defined in Reputation 1, totomers, diasteriomers, enanziomers, mixtures and salts of such compounds, in particular salts of such compounds which are physiologically acceptable in combination with inorganic or organic acids or bases and possess valuable pharmacological properties, in particular CGRP-antagonist properties, pharmaceutical mixtures of such compounds, their uses and methods for their preparation.

Claims (17)

1. Compounds of general formula (chemical formula) (I), R means the asa, diaza, triasa, oxaza, thiasa, thiadiasa or S,S-dioxydo-thiadiasa-heterocyclic 5 to 7 member saturated, unsaturated at one point or unsaturated at two points, in the case of 6 and 7 member heterocyclic groups, in which the aforementioned heterocyclic groups are connected through carbon. Or a nitrogen atom and one or two carbonyl groups, attached to at least one nitrogen atom, may be replaced by an alkyl group at any of the nitrogen atoms, or at one or two carbon atoms, in each case by an alkyl group, phenyl, phenyl methyl, naphthyl, biphenyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methyl-pyrazolyl, imidazolyl, or 1-methylimidazolyl, which may be the same substituent. Or differently, and which double bonds of one group of the unsaturated heterocyclic groups mentioned above may fuse with the benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methyl-pyrrole or quinoline ring, with the 2(1H)-oxoquinoline ring which is selectively replaced by an alkyl group at the nitrogen atom, or with the imidazole or N-methyl-imidazole ring, or including two olephenic double bonds of one group of the unsaturated heterocyclic groups mentioned above. Fuses with the benzene ring in each case, which includes the phenyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazoyl, or 1-methylimidazoyl present in R, and the benzo-, thieno-, pirido-, and diazino-fuse groups. Heterocyclic carbon atoms in a carbon structure may be replaced by one, two, or three additional groups with fluorine, chlorine, bromine, or iodine atoms, or by alkyl groups, alkoxy, nitro, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylsulfonylamino, phenyl, trifluoromethyl, difluoromethyl, difluoromethoxy, alkoxycarbonyl, carboxyl, dialkylamino, hydroxyl, amino, acetylamino, propionylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (4-morpholino)carbonyl, (1-pyrrolidinyl)carbonyl, (1- (piperidinyl)carbonyl, (hexahydro-1-acepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino, alkanoyl, cyanoyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl, or trifluoromethylsulfonyl, where the substituents may be the same or different, X denotes an oxygen atom, or if Z denotes the -NR1- group, it may also refer to any one of the =N-CN- or =N-SO2-R6 groups, where R6 means an alkyl group with 1 to 4 carbon atoms or a selectively substituted phenyl group. With a halogen atom, methyl group, or methoxy group, Z refers to any one of the -CH2 groups, from which a hydrogen atom can be freely replaced by another group. By a fluorine atom, or the C1-3-alkyl group, or -NR1, where R1 refers to a hydrogen atom, an alkyl group which may be replaced in the alkyl portion except at position 1 by an amino group, C1-3-alkyl-amino or di-(C1-3-alkyl)-amino, or a phenylalkyl group which may be replaced one or two groups in the phenyl portion by fluorine, chlorine, bromine or iodine atoms, by the C1-3-alkyl group, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino. Carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, where the substituents may be the same or different, A means a carbon atom replaced by a hydrogen atom or by a C1-3-alkyl group, n means the number 1 or 2, R2 means the group (chemical formula) where Ra, Rb, and Rc group one means hydrogen, fluorine, chlorine, bromine, or iodine atoms, branched or unbranched alkyl group, hydroxyl group, alkoxy, trifluoromethyl. Difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethyl thio, amino, acetylamino, dialkylaminoalkyl, dialkylaminoalkoxy, nitro, methylsulfonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkyl aminocarbonyl, alkanoyl, cyano, trifluoromethylsulfinyl or trifluoro Methylsulfonyl, Ra, Rb, and Rc. Second group refers to hydrogen, fluorine, chlorine, bromine, or iodine atoms; branched or unbranched alkyl groups; hydroxyl groups; alkoxy groups; trifluoromethyl; difluoromethyl; trifluoromethoxy; difluoromethoxy; trifluoromethyl thio; amino; acetylamino; alkanoyl; aminocarbonyl; alkylaminocarbonyl. Or dialkylaminocarbonyl and Ra, Rb and Rc. The third group refers to hydrogen, fluorine, chlorine, bromine or iodine atoms, branched or non-branched alkyl groups, hydroxyl groups, alkoxy groups, trifluoromethyl groups, difluoromethyl groups, difluoromethoxy groups, or trifluoromethoxy groups, which may have the same or different substituents, R3 and R4, which may be the same or different. In each case, it refers to a hydrogen atom, a C1-4-alkyl group, an amino-C1-3-alkyl group, a C1-3-alkyl-amino-C1-3-alkyl group, or a di-(C1-3-alkyl)-amino-C1-3-alkyl group, a phenyl or naphthyl group, which in each case may be replaced by 1 or 2 groups with Rd, which may have substituents that... Are they the same or different? And Rd means fluorine, chlorine, bromine, or iodine atoms, C1-3-alkyl group, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or Di-(C1-3-alkyl)-amino-C1-3-alkyl or cycloalkyleneimino-carbonyl groups of the 4- to 7-member type, in which one or two hydrogen atoms are replaced by C1-3-alkyl groups and/or, in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneimino portion may be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl)-, or heteroaryl groups. A 5- or 6-member monocyclic group is selectively replaced in its carbon structure with a C1-3-alkyl, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl group, which is a 6-member heteroaryl group containing 1, 2, or 3 nitrogen atoms, and may also be further replaced with fluorine, chlorine, or bromine. Or an iodine atom, a C1-3-alkyl group, C1-3-alkoxy, amino, C1-3-alkylamino, or di-(C1-3-alkyl)amino, and a 5-member heteroaryl group with a selectively substituted imino group, C1-3-alkyl, acetyl, trifluoroacetyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, oxygen or sulfur atom, or a selectively substituted imino group. C1-3-alkyl, acetyl, trifluoroacetyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl or di-(C1-3-alkyl)-amino-C1-3-alkyl or oxygen or sulfur atom And an additional nitrogen atom is added, or the eminoselic group is replaced by a C1-3-alkyl, acetyl, trifluoroacetyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl group. and two nitrogen atoms, or R3 and R4 combined (meaning) group 1,3-butadiene-1,4-eline, in which each of the methine groups 1, 2 or 3 may be selectively replaced by a nitrogen atom, a hydrogen atom may be replaced by a fluorine, chlorine, bromine or iodine atom, by the groups C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, amino carbonyl, C1-3-alkyl-aminocarbonyl, Di-(C1-3-alkyl)-aminocarbonyl, di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or by a 4- to 7-member cycloalkyleneimino-carbonyl group in which one or two hydrogen atoms are selectively replaced by a C1-3-alkyl group and/or, in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneimino portion may be replaced by an oxygen atom. Or a sulfur atom, with a sulfhenyl, sulfonyl, -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl-) group, and a second hydrogen atom may be further replaced by a fluorine, chlorine, bromine or iodine atom, by a C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy or trifluoromethoxy group, and R5 denotes the -(CH2)m-Re group, where m denotes the number 0 and Re denotes the hydrogen atom, phenyl or naphthyl group, which in each case may be replaced by 1 or 2 groups with Rf, which is the substituent group. They may be the same or different, and Rf means fluorine, chlorine, bromine, or iodine atom, C1-3-alkyl group, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, amino carbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or Di-(C1-3-alkyl)-amino-C1-3-alkyl, or pyridinyl, pyracinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, pyrazoyl, imidazoyl, oxazolyl, isoxazolyl, thiazolyl, or isothiazoyl are selectively replaced in the carbon structure by a C1-3-alkyl group, in which the hydrogen atom attached to the nitrogen atom may be replaced by a C1-3-alkyl or acetyl group, or a C3-7-cycloalkyl group, in which the hydrogen atom of the C3-7-cycloalkyl group It may be replaced by an amino group, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, and/or a methylene group at position 3 of the cyclopentyl group. The methylene group at position 4 of the cyclohexyl and cycloheptyl groups may be replaced by oxygen or sulfur atoms, by sulfinyl, sulfonyl, -NH, -N(C1-3-alkyl, or -N(C1-3-alkyl-carbonyl)- groups, or m denotes one of the numbers 1 to 5 and Re denotes a hydrogen atom, aminomethylene group, C1-3-alkylaminomethylene, di-(C1-3-alkyl)-aminomethylene, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, or C3-7-cycloalkyl, where the hydrogen atom of the C3-7-cycloalkyl group. It may be replaced by an amino group, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, and/or a methylene group at position 3 of the cyclopentyl group. The methylene group at position 4 of the cyclohexyl and cycloheptyl groups may each be replaced by an oxygen or sulfur atom, by sulfinyl, sulfonyl, -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl)- groups, 4- to 7-member cycloalkyleneamino groups in which one or two cyclogen atoms may each be replaced by a C1-3-alkyl group and/or in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneamino group may be replaced by an oxygen. Or a sulfur atom, with a sulfhenyl, sulfonyl, -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl)- group, a phenyl or naphthyl group, which may be replaced by one or two groups with Rg, in each case independently. Another group, where the substituents may be the same or different, and Rg means fluorine, chlorine, bromine, or iodine atom, C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or Di-(C1-3-alkyl)-amino-C1-3-alkyl, or a 5- or 6-member heteroaryl monocyclic group, is selectively substituted in the structure. Carbon with the group C1-3-alkyl, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, in which the 6-member heteroaryl group has 1, 2, or 3 nitrogen atoms and may be selectively replaced by fluorine, chlorine, bromine, or iodine atoms, C1-3-alkyl, C1-3-alkoxy, Amino, C1-3-alkylamino or di-(C1-3-alkyl)amino and 5-member heteroaryl groups have an emino group selectively substituted by a C1-3-alkyl group, acetyl, trifluoroacetyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl or di-(C1-3-alkyl)-amino-C1-3-alkyl, oxygen or sulfur atom, or an emino group selectively substituted by a C1-3-alkyl group, acetyl, trifluoroacetyl, C1-3- Alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or oxygen, or sulfur atom. and an additional nitrogen atom, or a selective emino group replaced by a C1-3-alkyl, acetyl, trifluoroacetyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl group and 2 nitrogen atoms, where the alkyl group mentioned above, or an alkyl group present in the groups mentioned above, unless otherwise specified, has 1 to 5 carbon atoms and may be branched or non-branched chain. Totomers, diasteriomers, enanchiomers, mixtures, and salts of these compounds. 2. Compounds of general formula I according to claim 1, where R means a 5- to 7-member heterocyclic group, saturated or unsaturated at one point, in which the aforementioned heterocyclic group is connected through a nitrogen atom and a carbonyl group is connected to one or two nitrogen atoms of the heterocyclic group, may be replaced at one of the carbon atoms by an alkyl, phenyl, pyridinyl, furyl, thienyl or pyrrallyl group, and in which the double bond of any of the unsaturated heterocyclic groups in question may Fuses with benzene, piridine, or thiophene rings, including phenyl, piridinyl, furyl, thienyl, pyrrolyl groups present in R, and benzo-, thieno-, and pirido-condensate groups. Heterocyclic carbon atoms in a carbon structure may be replaced by one or two substituents with fluorine, chlorine, bromine, or iodine atoms; with alkyl, alkoxy, nitro, alkylthio, trifluoromethyl, difluoromethyl, alkoxycarbonyl, carboxylic, dialkylamino, hydroxyl, amino, acetylamino, aminocarbonyl, alkylaminocarbonyl, alkanoyl, cyanoyl, or trifluoromethoxylicates, which may be the same or different substituents. X represents an oxygen atom, or if Z is the -NR1- group, it means, or it may also mean the =N-CN group, Z represents any one of the -CH2 or -NR1 groups, where R1 represents a hydrogen atom. Or alkyl groups, A means a carbon atom replaced by a hydrogen atom or by a C1-3-alkyl group, n means the number 1 or 2, R2 means the group (chemical formula) which Ra, Rb and Rc. The first group means hydrogen, fluorine, chlorine, bromine or iodine atoms, branched or unbranched alkyl groups, hydroxyl groups, alkoxy groups, trifluoromethyl groups, difluoromethyl groups, trifluoromethoxy groups, amino groups, acetylamino groups, dialkylaminoalkyl groups, dialkylaminoalkoxy groups, aminocarbonyl groups, alkylaminocarbonyl groups, dialkylaminocarbonyl groups, alkanoyl groups, cyanoyl groups or trifluoromethylsulfonyl groups, Ra, Rb and Rc. The second group means hydrogen, fluorine, chlorine, Bromine or iodine atom, branched or unbranched alkyl group, alkoxy group, trifluoromethyl, amino, acetylamino. or alkanoyls, and Ra, Rb, and Rc. The third group refers to hydrogen, fluorine, chlorine, bromine, or iodine atoms, or branched or non-branched alkyl groups, the substituents of which may be the same or different; R3 refers to a hydrogen atom or C1-3-alkyl group; R4 refers to a hydrogen atom, C1-4-alkyl group, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, phenyl groups which may be replaced by one or two groups with Rd, the substituents of which may be the same or different; and Rd refers to fluorine, chlorine, bromine, or iodine atoms, C1-3-alkyl groups, trifluoromethyl, difluoromethyl, cyclopropyl. Hydroxy, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl or di-(C1-3-alkyl)-amino-C1-3-alkyl, or pyridinyl group, pyrazinyl, pyrimidinyl, pyridacinyl, pyrrolyl, furyl, thienyl. Pirazolyl, imidazolyl, oxazolyl, isoxazyl, thiazolyl, or isothiazolyl are selectively substituted in the structure. Carbon with a C1-3-alkyl group, in which the hydrogen atom attached to the nitrogen atom may be replaced by a C1-3-alkyl or acetyl group, or R3 and R4 combined to mean the 1,3-butadiene-1,4-ilene group, in which the hydrogen atom may be replaced by fluorine, chlorine, bromine, or iodine atom, by the C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl. Di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, di-(C1-3-alkyl)-amino-C1-3-alkyl, or by a 5- to 7-member cycloalkyleneimino-carbonyl group in which one or two hydrogen atoms may each be replaced by a C1-3-alkyl group and/or in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneimino portion may be replaced by an oxygen atom. Or a sulfur atom, by the group -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl)-, and a second hydrogen atom may be optionally replaced by a fluorine, chlorine, bromine or iodine atom, by a C1-3-alkyl or trifluoromethyl group, and R5 denotes the group -(CH2)m-Re, where m denotes the number 0 and Re denotes the hydrogen atom or the C5-6-cycloalkyl group, where the methylene group at position 3 of the cyclopentyl group and the methylene group at position 4 of the cyclohexyl group. Each group may be replaced by -NH, -N(C1-3-alkyl), or -N(C1-3-alkyl-carbonyl), or m represents one of the numbers 1 through 5, and Re represents the hydrogen atom, aminomethylene group, C1-3-alkylaminomethylene, di-(C1-3-alkyl)-aminomethylene, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, or C5-6-cycloalkyl, where the methylene group is at position 3 of the cyclopentyl group and the methylene group is at position 4 of the cyclohexyl group. Each substituent may be replaced by -NH, -N(C1-3-alkyl), or -N(C1-3-alkyl-carbonyl) groups; 5- to 6-member cycloalkyleneamino groups, in which the methylene group at position 4 of the 6-member cycloalkyleneamino group may be replaced by -NH, -N(C1-3-alkyl), or -N(C1-3-alkyl-carbonyl)-; phenyl groups, which may be replaced by one or two substituents with R9, where the substituents may be the same or different; and R8 denotes fluorine, chlorine, bromine, or iodine atoms; C1-3-alkyl, trifluoromethyl, difluoromethyl, hydroxyl, C1-3-alkoxy, amino, C1-3-alkyl-amino. Di-(C1-3-alkyl)-amino, aminocarbonyl-C1-3-alkyl-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, pyrazoyl, imidazoyl, oxazolyl, isoxazolyl, thiazolyl, or isothiazoyl which is selectively replaced in the carbon structure by a C1-3-alkyl group, where the hydrogen atom is attached to the nitrogen. The atom is replaced by a C1-3-alkyl or acetyl group, which the alkyl groups mentioned above, or alkyl groups present in the groups mentioned above, unless otherwise specified, contain 1 to 4 carbon atoms and may be branched or non-branched chain, totomers, diasteromers, enanzaomers, and salts of them. 3. Compounds of general formula I according to claim 2, where R means one unsaturated heterocyclic diazae group of the 5- to 7-member type connected through a nitrogen atom, in which the aforementioned heterocyclic group has a carbonyl group connected through both nitrogen atoms of the heterocyclic group, each group may be freely substituted with another group at one nitrogen atom and one saturated carbon atom by a C1-3-alkyl group, and in which the double bond of the unsaturated heterocyclic group in question fuses with a benzene ring which is selectively substituted by a fluorine, chlorine, bromine or iodine atom, or by a C1-3-alkyl, C1-3-alkoxy, trifluoromethyl, carboxy, C1-3-alkoxy-carbonyl, amino, acetyl amino, hydroxyl, aminocarbonyl group. Or alkanoyl, X means oxygen atom, Z means either -CH2 or -NR1 group, where R1 means hydrogen atom or C1-3-alkyl group, A means carbon atom replaced by a hydrogen atom or by a C1-3-alkyl group, n means the number 1, R2 means the group (chemical formula) where Ra, Rb and Rc first group means hydrogen, fluorine, chlorine, bromine or iodine atoms, C1-3-alkyl, trifluoromethyl, hydroxyl, alkoxy or amino group, Ra, Rb and Rc second group means hydrogen, fluorine, chlorine, bromine or iodine atoms, C1-3-alkyl or trifluoromethyl group and Ra, Rb and Rc second group means hydrogen, fluorine, chlorine, bromine or iodine atoms. The substituent groups may be the same or different; R3 refers to a hydrogen atom or a C1-3-alkyl group; R4 refers to a phenyl group which can be selectively replaced by a fluorine, chlorine, bromine, or iodine atom, with a C1-3-alkyl, trifluoromethyl, hydroxyl, C1-3-alkoxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, carboxy, or C1-3-alkoxy-carbonyl group; or R3 and R4 combined refer to the 1,3-butadiene-1,4-elene group, where the hydrogen atom may be replaced by a fluorine, chlorine, bromine, or iodine atom, with a C1-3-alkyl, trifluoromethyl, hydroxyl, C1-3-alkoxy, carboxy, or C1-3-alkoxy-carbonyl group. Carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, or di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl, or with a 5- to 7-member cycloalkyleneimino-carbonyl group, in which the methylene group at position 4 of the 6-member cycloalkyleneimino fraction may be replaced by -NH, -N(C1-3-alkyl), or -N(C1-3-alkyl-carbonyl)-, and a second hydrogen atom may be optionally replaced by a fluorine, chlorine, bromine, or iodine atom, or by a C1-3-alkyl group, and R5 denotes the -(CH2)m-Re group, where m denotes 0 and Re denotes 0. Hydrogen atom, or m denotes one of the numbers 1 through 3, and Re denotes hydrogen atom, aminomethylene group, C1-3-alkylaminomethylene or di-(C1-3-alkyl)-aminomethylene, which the alkyl group mentioned above, or alkyl groups present in the above-mentioned groups, unless otherwise specified, may be branched or non-branched chain, totomer, diasteriomer, enanchiomer, and salts of such substances. 4. Compounds of general formula I according to claim 1, where R, X, Z, A, n, R2 and R5 have meanings as defined in claim 1, and R3 means hydrogen atom or C1-4-alkyl group, and R4 means hydrogen atom, C1-4-alkyl group, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl or di-(C1-3-alkyl)-amino-C1-3-alkyl, phenyl or naphthyl group which may be replaced by one or two groups by Rd in each case independently of the other group, which may be the same or different substituents, and Rd means fluorine, chlorine, bromine or iodine atom, C1-3-alkyl group, trifluoromethyl, difluoromethyl, cyclopropyl, Hydroxy, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl or di-(C1-3-alkyl)-amino-C1-3-alkyl, or heteroaryl group A 5- or 6-member monocyclic group is selectively replaced in the carbon structure by a C1-3-alkyl, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxy, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl group, where the 6-member heteroaryl group has 1, 2, or 3 nitrogen atoms, and the 5-member heteroaryl group... There is an amino group that is selectively replaced by a C1-3-alkyl group, acetyl, trifluoroacetyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, oxygen or sulfur atom, or an amino group that is selectively replaced by a C1-3-alkyl group, acetyl, trifluoroacetyl-C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)- Aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or an oxygen or sulfur atom and a nitrogen atom added, or an amino group selectively replaced by a C1-3-alkyl group, acetyl, trifluoroacetyl-C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl And two nitrogen atoms, totomers, diasteriomers, enanchiomers, mixtures, and salts of those substances. 5. Compounds of general formula I according to claim 2, where R, X, Z, A, n, R2, and R5 have the same meanings as defined in claim 2, and R3 means a hydrogen atom or a C1-3-alkyl group, and R4 means a phenyl group which may be replaced by one or two Rds, which may be the same or different substituents, and Rd means a fluorine, chlorine, bromine, or iodine atom, where C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or pyridinyl, pyracinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, pyrazoyl, imidazoyl, oxazolyl, isoxazolyl, thiazolyl, or isothiazoyl groups that are selectively substituted in the structure. Carbon with a C1-3-alkyl group, in which the hydrogen atom attached to the nitrogen atom may be replaced by a C1-3-alkyl or acetyl group, totomers, diasteromers, enanchiomers, mixtures and salts of such substances. 6. Compounds of general formula I according to claim 3, where R, X, Z, A, n, R2, and R5 have the same meanings as defined in claim 3, and R3 means a hydrogen atom or a C1-3-alkyl group, and R4 means a phenyl group selectively replaced by a fluorine, chlorine, bromine, or iodine atom, with a C1-3-alkyl, trifluoromethyl, hydroxyl, C1-3-alkoxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, carboxy or C1-3-alkoxy-carbonyl, totomer, diasteriomer, enanchiomer, mixtures and salts of such compounds. 7. Compounds of general formula I according to claim 1, where R, X, Z, A, n, R2, and R5 are synonymous with those defined in claim 1, and R3 and R4 together represent the group. 1,3-butadiene-1,4-eline, in which one, two, or three methine groups may each be replaced by a nitrogen atom; a hydrogen atom may be replaced by a fluorine, chlorine, bromine, or iodine atom; by the groups C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, amino carbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl. Di(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or by a 4- to 7-member cycloalkyleneaminocarbonyl group in which one or two hydrogen atoms may each be replaced by a C1-3-alkyl group and/or, in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneaminocarbonyl group may be replaced by an oxygen atom. Or a sulfur atom, by sulfhinyl, sulfonyl, -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl)- groups, and a second hydrogen atom may be further selectively replaced by a fluorine, chlorine, bromine or iodine atom, by C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy or trifluoromethoxy, totomers, diasteriomers, enanzaomers, mixtures and salts of those substances. 8. Compounds of general formula I according to claim 2, where R, X, Z, A, n, R2, and R5 are synonymous with those defined in claim 2, and R3 and R4 together represent the group. 1,3-butadiene-1,4-ileen, in which the hydrogen atom may be replaced by fluorine, chlorine, bromine, or iodine atoms; by C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, or di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl, or by 5- to 5- cycloalkylemine-amino-carbonyl groups. 7-members in which one or two hydrogen atoms may each be replaced by a C1-3-alkyl group and/or, in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneamino portion may be replaced by an oxygen or sulfur atom, by -NH, -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl)-, and a second hydrogen atom may be selectively further replaced by a fluorine, chlorine, bromine, or iodine atom, by a C1-3-alkyl or trifluoromethyl group, totomers, diasteriomers, enanzaomers, mixtures, and salts of those substances. 9. Compounds of general formula I according to claim 3, where R, X, Z, A, n, R2, and R5 have the same meaning as defined in claim 3, and R3 and R4 together mean the same group. 1,3-butadiene-1,4-eline, where the hydrogen atom may be replaced by fluorine, chlorine, bromine, or iodine atoms; by C1-3-alkyl, trifluoromethyl, hydroxyl, C1-3-alkoxy, carboxyl, C1-3-alkoxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, or di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl; or by 5- to 7-member cycloalkyleneimino-carbonyl groups, where the methylene group at position 4 of the 6-member cycloalkyleneimino fraction may be replaced by -NH₃. With a -N(C1-3-alkyl) or -N(C1-3-alkyl-carbonyl) group, the second hydrogen atom may be selectively replaced by a fluorine, chlorine, bromine, or iodine atom, or by a C1-3-alkyl group, totomer, diasteriomer, enanchiomer, mixtures, and salts of those substances. 10. The following compounds of general formula I according to claim 1: (1) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(3-dimethylamino-propyl)-1H-benzosimidazole-2-il]-ethyl}-amide, (2) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(2-dimethylamino-ethyl)-1H-benzimidazole-2-il]-ethyl}-adeed, (3) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepine-3-il)-piperidin-1-carboxylic acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1-methyl-1H-benzimidazole-2-il)-ethyl]-adeed, (4) 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepine-3-il)-piperidin-1-carboxylic Acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1H-benzimidazole-2-il)-ethyl]-amide, (5) Methyl 2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,4-dihydro-3H-quinazolin-3-il)-piperidin-1-carbonyl]-amino}-ethyl)-1H-benzimidazole-5-carboxylate, (6) Methyl 2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetradihydro-1,3- (7) 2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetradihydro-1,3-benzodiazepin-3-il)-piperidin-1-carbonyl]-amino}-ethyl)-1H-benzimidazole-5-carboxylic acid, (8) 4-(2-oxo-1,2,4,5-tetradihydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[6-(4-methyl-piperazine-1-carbonyl)-1H-benzimidazole-2-yl]-ethyl}-amide, (9) 2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetradihydro-1,3-benzodiazepine-3-yl)-piperidin-1-carbonyl]-amino}-ethyl)-1H-benzimidazole-5-carboxylic acid-(3-dimethylamino-propyl)-amide, (10)2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetradihydro-1,3-benzodiazepin-3-yl)-piperidin-1-carbonyl]-amino}-ethyl)-1H-benzimidazole-5-carboxylic acid-(2-dimethylamino-ethyl)-amide, (11)4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(3-dimethylamino-propyl)-5-phenyl-1H-imidazole-2-yl]-ethyl}-amed, (12)4-(2-oxo-1,2,4,5tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1-butyl-1H-benzimidazole-2-il)-ethyl]-ameed, (13)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(3-pyrrolidin-1-il-propyl)-1H-benzimidazole-2-il]-ethyl}-amide, (14)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1-pyridin-3-ilmethyl-1H-benzimidazole-2-il)-ethyl]-ameed, (15)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1-benzyl-1H-benzimidazole-2-il)-ethyl]-ameed, (16)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(1-methyl-pyridin-4-ylmethyl)-1H-benzimidazole-2-yl]-ethyl}-amide, (17)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromophenyl)-1-[1-(4-dimethylamino-butyl)-1H-benzimidazole-2-il]-ethyl}-amide, (18)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(1-methyl-piperidin-4-il)-1H-benzimidazole-2-il]-ethyl}-amide, (19)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1-cyclohexyl-1H-benzimidazole-2-il)-ethyl]-ameed, (20)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-[(R)-2-(4-amino-3,5-dibromo-phenyl)-1-(1-cyclopentyl-1H-benzimidazole-2-il)-ethyl]-ameed, (21)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(5-dimethylamino-pentyl)-1H-benzimidazole-2-il]-ethyl}-amide, (22)methyl 4-[2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carbonyl]-amino}-ethyl)-benzimidazole-1-il]-butyrate, (23)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[6-chloro-1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]-ethyl}-amide, (24)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromophenyl)-1-[1-(3-dimethylamino-propyl)-6-fluoro-1H-benzimidazole-2-yl]-ethyl}-amed, (25)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[1-(3-dimethylamino-propyl)-5-fluoro-1H-benzimidazole-2-yl]-ethyl}-amide, (26)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{(R)-2-(4-amino-3,5-dibromo-phenyl)-1-[5,6-dichloro-1-(3-dimethylamino-propyl)-1H-benzimidazole-2-yl]-ethyl}-amide, (27)methyl 2-((R)-2-(4-amino-3,5-dibromo-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carbonyl]-amino}-ethyl)-1-(3-pyrrolidin-1-yl-propyl)-1H-benzimidazole-5-carboxylate, (28)2-(2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carbonyl]-amino}-ethyl)-1-(3-pyrrolidin-1-yl-propyl)-1H-benzimidazole-5-carboxylic acid, (29)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{(R)-2-(3,5-dibromo-4-hydroxyphenyl)-1-[1-(1-methyl-piperidin-4-ylmethyl)-1H-benzimidazole-2-yl]-ethyl}-amide, (30)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{(R)-2-(3,5-dibromo-4-hydroxyphenyl)-1-[1-(1-methyl-piperidin-4-il)-1H-benzimidazole-2-il]-ethyl}-ameed, (31)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(3,5-dibromo-4-hydroxyphenyl)-1-[1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]-ethyl}-amide, (32)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{(R)-2-(3,5-dibromo-4-hydroxyphenyl)-1-[1-(3-pyrrolidin-1-il-propyl)-1H-benzimidazole-2-il]-ethyl}-amide, (33)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-[1-[6-chloro-1-(3-dimethylamino-phenyl)-1H-benzimidazole-2-il]-2-(3,4-dibromo-phenyl)-ethyl]-amide, (34)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,4-dibromo-phenyl)-1-[5,6-dichloro-1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]-ethyl}-amide, (35)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-[1-[7-chloro-1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]-2-(3,4-dibromo-phenyl)-ethyl]-amide, (36)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,4-dibromo-phenyl)-1-[1-(3-dimethylamino-propyl)-6-fluoro-1H-benzimidazole-2-il]-ethyl}-amed, (37)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-{2-(3,4-dibromo-phenyl)-1-[1-(1-methyl-piperidin-4-il)-1H-benzimidazole-2-il]-ethyl}-amed, (38)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,4-dibromo-phenyl)-1-[1-(3-pyrrolidin-1-il-propyl)-1H-benzimidazole-2-il]- ethyl}-ameed, (39)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-{2-(3,4-dibromo-phenyl)-1-[1-(1-methyl-piperidin-4-ilmethyl)-1H-benzimidazole-2-il]- ethyl}-ameed, (40)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-[2-(3,4-dibromo-phenyl)-1-(1-pyridin-3-ylmethyl-1H-benzimidazole-2-yl)-ethyl]-ameed, (41)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic acid-{2-(3,4-dibromo-phenyl)-1-[1-(3-dimethylamino-propyl)-1H-benzimidazole-2-yl]-ethyl}-ameed, (42)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{2-(3,4-dibromo-phenyl)-1-[1-(4-dimethylamino-butyl)-1H-benzimidazole-2-il]- ethyl}-ameed, (43)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-{2-(3,4-diethyl-phenyl)-1-[1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]- ethyl}-ameed, (44)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,4-diethyl-phenyl)-1-[1-(4-dimethylamino-butyl)-1H-benzimidazole-2-il]-ethyl}-ameed, (45)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,4-diethyl-phenyl)-1-[1-(1-methyl-piperidin-4-il)-1H-benzimidazole-2-il]-ethyl}-ameed, (46)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,4-diethyl-phenyl)-1-[1-(3-pyrrolidin-1-il-propyl)-1H-benzimidazole-2-il]- ethyl}-ameed, (47)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic acid-{2-(3,4-diethyl-phenyl)-1-[1-(1-methyl-piperidin-4-ilmethyl)-1H-benzimidazole-2-il]- ethyl}-ameed, (48)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-[2-(3,4-diethyl-phenyl)-1-(1-pyridin-3-ylmethyl-1H-benzimidazole-2-yl)-ethyl]-adeed, (49)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepine-3-yl)-piperidin-1-carboxylic acid-{2-(3,5-bis-trifluoromethyl-phenyl)-1-[1-(1-methyl-piperidin-4-yl)-1H-benzimidazole-2-yl]-ethyl}-adeed, (50)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepine-3-yl)-piperidin-1-carboxylic Acid-{2-(3,5-bis-trifluoromethyl-phenyl)-1-[1-(3-pyrrolidin-1-il-propyl)-1H-benzimidazole-2-il]-ethyl}-amide, (51)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(3,5-bis-trifluoromethyl-phenyl)-1-[1-(1-methyl-piperidin-4-ylmethyl)-1H-benzimidazole-2-yl]-ethyl}-amide, (52)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{2-(3,5-bis-trifluoromethyl-phenyl)-1-[1-(3-dimethylamino-propyl)-1H-benzimidazole-2-yl]-ethyl}-amide, (53)methyl 2-(2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carbonyl]-amino}-ethyl)-1-(3-pyrrolidin-1-yl-propyl)-1H-benzimidazole-5-carboxylate methyl, (54)2-(2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carbonyl]-amino}-ethyl)-1-(3-pyrrolidin-1-yl-propyl)-1H-benzimidazole-5-carboxylic acid, (55)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-[1-(1-methyl-piperidin-4-il)-1H-benzimidazole-2-il]-ethyl}-amide, (56)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-[1-(3-pyrrolidin-1-il-propyl)-1H-benzimidazole-2-il]-ethyl}-amed, (57)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-il)-piperidin-1-carboxylic Acid-{2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-[1-(1-methyl-piperidin-4-yl-methyl)-1H-benzimidazole-2-yl]-ethyl}-ameed, (58)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-[2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-(1-pyridin-3-ylmethyl-1H-benzimidazole-2-yl)-ethyl]-amed, (59)4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-carboxylic Acid-{2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-[1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]-ethyl}-amed, (60)3-(1-{4-(3,4-diethyl-phenyl)-3-[1-(3-dimethylamino-propyl)-1H-benzimidazole-2-il]-butyryl}-piperidin-4-il)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, (61)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(3-pyrrolidin-1-propyl)-1H-benzimidazole-2-il]-butyryl}-piperidin-4-il)1,3,4,5-tetrahydro-1,3-benzo Diacepin-2-one, (62)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(3-imidazole-1-il-propyl)-1H-benzimidazole-2-il]-butyryl}-piperidin-4-il)-1,3,4,5-tetrahydro-1,3-benzodiacepin-2-one, (63)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[5-(3-dimethylamino-propyl)-1- Ethyl-1H-benzimidasol-2-il]-butyryl}-piperidin-4-il)1,3,4,5-tetrahydro-1,3-benzo Diazepin-2-one, (64)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(3-diethylamino-propyl)-1H-benzimidazole-2-il]-butyryl}-piperidin-4-il)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, (65)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(4-hydroxy-butyl)-1H-benzimidazole-2-il]-butyryl}-piperidin-4-il)1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one 2-one, (66)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(1-methyl-piperidin-3-ylmethyl)- 1H-benzimidazole-2-yl]-butyryl}-piperidin-4-yl)-1,3,4,5-tetrahydro-1,3-benzo Diacepin-2-one, (67)3-[1-(4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-{1-[2-(4-methyl-piperazine-1-il)-ethyl]-1H-benzimidazole-2-il}-butyryl)-piperidin-4-il]-1,3,4,5-tetrahydro-1,3-benzo Diazepin-2-one, (68)3-{1-[4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-(1-piperidin-4-ilmethyl-1H-benzimidazole-2-il)-butyryl]-piperidin-4-il}-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, (69)3-{1-[4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-(1-piperidin-4-ilmethyl-1H-benzimidazole-2-il)-butyryl]-piperidin-4-il}-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one 2-one, (70)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[1-(3-dimethylamino-2,2-dimethyl-propyl)-1H-benzimidazole-2-il]-butyryl}-piperidin-4-il)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, (71)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[7-(3-dimethylamino-propoxy)- 1H-benzimidazole-2-il]-butyril}-piperidin-4-il)-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one, (72)3-{1-[4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-(1piperidin-4-ilmethyl-1H-imidazole[4,5-c]piridin-2-il)-butyril]-piperidin-4-il}-1,3,4,5-tetrahydro-1,3-benzodiazepin-2-one Diacepin-2-one, (73)3-(1-{4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-[3-(3-pyrrolidin-1-il-propyl)- 3H-imidazole[4,5-c]pyridin-2-il]-butyryl}-piperidin-4-il)1,3,4,5-tetrahydro-1,3-benzo Diacepin-2-one, (74)3-{1-[4-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-3-(1-methyl-6-pyrrolidin-1-ylmethyl-1H-benzimidazole-2-yl)-butyryl]-piperidin-4-yl}-1,3,4,5-tetrahydro-1,3-benzodiacepin-2-one, stereoisomers and salts of these compounds. 11. A physiologically acceptable salt of at least one of the compounds under Reputation 1 through 10 containing an inorganic or organic acid or base. 12. A pharmaceutical mixture containing at least one of the compounds specified in claims 1 through 10 or a physiologically acceptable salt according to claim 11, may be selected and combined with one or more carriers and/or inert diluents. 13. The use of at least one of the compounds listed in claims 1 through 11 for the preparation of pharmaceutical mixtures for the immediate and preventive treatment, particularly of migraine or unilateral frontal pain (unilateral eye pain). 14. A procedure for preparing pharmaceutical mixtures under claim 12, which is characterized by at least one of the compounds under claims 1 through 11 being mixed with one or more carriers and/or inert diluents by a non-chemical method. 15. The procedure for preparing the compounds according to Reservations 1 to 11 is characterized as follows: a) In preparing compounds of general formula I, where X means oxygen atom and Z means -NR1, and where A, n, R, R1, R2, R3 and R4 and A have the same meanings as defined in Reservations 1 to 10, an amine of general formula II, (chemical formula) (II), where R has the same meanings as defined in Reservations 1 to 10, is reacted with a carbonic acid derivative of general formula III, (chemical formula) (III), where X1 means nucleophilic group, and with a compound of general formula IV, (chemical formula) (IV), where R1, R2, R3, R4, R5, A and n have the same meanings as defined in Reservations 1 to 10, and then, if necessary, any protective group is broken. or change the precursor functional group, or b) in the preparation of compounds of general formula I in which A, n, R, R1, R2, R3 and R4 and A have the same meaning as defined in claims 1 through 10 and R3 and R4 combine to form a group. 1,3-butadiene-1,4-eline, in which one, two, or three methylene groups may each be replaced by a nitrogen atom; hydrogen atoms may be replaced by fluorine, chlorine, bromine, or iodine atoms; by the groups C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, amino carbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl. Di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl, amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or by a 4- to 7-member cycloalkyleneimino-carbonyl group in which one or two hydrogen atoms may each be replaced by a C1-3-alkyl group and/or, in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneimino portion may be replaced by an oxygen atom. or a sulfur atom, by the groups sulfhinyl, sulfonyl, -NH, -N(C1-3-alkyl) or -N(C1-3-alkylcarbonyl)-, a second hydrogen atom may be optionally replaced by a fluorine, chlorine, bromine or iodine atom, by the groups C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy or trifluoromethoxy, perform an annealed adedo of the general formula (chemical formula) (V), in which R, X, Z, A, n, R2 and R5 have the same meanings as defined in Reputations 1 to 10, R3 and R4 combine to form a group. 1,3-butadiene-1,4-eline, in which one, two, or three methylene groups may each be replaced by a nitrogen atom. The hydrogen atom may be replaced by a fluorine, chlorine, bromine, or iodine atom, by the groups C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy, trifluoromethoxy, cyano, nitro, amino, C1-3-alkyl-amino, di-(C1-3-alkyl)-amino, carboxyl, C1-3-alkoxy-carbonyl, amino carbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, di-(C1-3-alkyl)-amino-C2-3-alkyl-aminocarbonyl. Amino-C1-3-alkyl, C1-3-alkyl-amino-C1-3-alkyl, or di-(C1-3-alkyl)-amino-C1-3-alkyl, or by a 4- to 7-member cycloalkyleneimino carbonyl group in which one or two hydrogen atoms may each be replaced by a C1-3-alkyl group and/or, in each case, the methylene group at position 4 of the 6- or 7-member cycloalkyleneimino portion may be replaced by an oxygen atom. or sulfur atom, by sulfinyl, sulfonyl, -NH, -N(C-1-3-alkyl) or -N(C1-3-alkyl-carbonyl) groups, the second hydrogen atom may be further replaced by fluorine, chlorine or bromine atom, by C1-3-alkyl, trifluoromethyl, difluoromethyl, cyclopropyl, hydroxyl, C1-3-alkoxy, difluoromethoxy or trifluoromethoxy, or c) in the preparation of compounds of general formula I where R, A, n and R2 through R5 are synonymous. Defined in Reliefs 1 to 10, and X means oxygen atom and Z means -CH2 group: d) combine a carboxylic acid of general formula (chemical formula) (VI), in which R2 to R5, A and n are defined as in Reliefs 1 to 10, with a compound of general formula (chemical formula) (II), in which R is defined as in Reliefs 1 to 10, or d) to prepare a compound of general formula I, in which R, A, n and R2 to R5 are defined as in Reliefs 1 to 10. Defined in Reliefs 1 to 10, and X means oxygen atom and Z means -CH2 group: compounds of general formula (chemical formula) (VII), in which A, n, and R2 to R5 are synonymous with the definitions in Reliefs 1 to 10, and Nu means the detachable group, coupled with compounds of general formula (chemical formula) (II), in which R is synonymous with the definitions in Reliefs 1 to 10, or e) in the preparation of compounds of general formula I in which R, A, n, and R2 to R5 are synonymous with the definitions in Reliefs 1 to 10. As defined in Retentions 1 to 10, and X means oxygen atom and Z means -NH- group: react an isoyanate of general formula VIII, (chemical formula) (VIII), in which R2 to R5 are synonymous with those defined in Retentions 1 to 10, and then, if necessary, break the protective group or change the precursor functional group, or f) prepare a compound of general formula I in which R, A, n and R2 to R5 are synonymous with those defined in Retentions 1 to 10. As defined in Retentions 1 to 10, and X' represents one of the groups =N-CN or =N-SO2-R6, and Z' represents the -NR1- group, where R1 and R6 are defined as in Retentions 1 to 10: Take a compound of general formula (chemical formula) (IX), where A, n, and R2 to R5 are defined as in Retentions 1 to 10, X' represents one of the groups =N-CN or =N-SO2-R6, Z' represents the -NR1- group, where R1 and R6 are defined as in Retentions 1 to 10, and Nu is the detachable group, react with a secondary amine of general formula (chemical formula) (II), where R is defined as in Retentions 1 to 10, and break any protective group. For reactive groups such as hydroxyl groups, carboxylate groups, amino groups, or imino groups, and/or the separation of compounds of general formula I into stereoisomers of those substances, and/or the conversion of compounds of general formula I into salts of those substances, especially for pharmaceutical use, into pharmaceutically acceptable salts containing inorganic or organic acids or bases. 16. The use of at least one of the compounds listed in claims 1 through 11 for the preparation of pharmaceutical mixtures for the treatment of insulin-independent diabetes mellitus (NIDDM). 17. The use of at least one of the compounds referred to in claims 1 through 11 for the preparation of pharmaceutical mixtures for the treatment of cardiovascular disease, morphine intolerance, skin diseases, especially radiation and heat-induced skin damage, namely sunburn, inflammatory diseases, e.g., especially inflammatory diseases of the joints, e.g., rheumatoid arthritis, pneumonia, allergic rhinitis, asthma, diseases associated with excessive vasodilation and reduced blood flow through tissues for any reason, e.g., especially shock or sepsis, for the relief of generalized pain, or for immediate or preventive therapeutic effects on menopausal flushing syndromes caused by vasodilation and increased blood flow in women with estrogen deficiency and hormone-treated patients with prostate cancer.