MXPA01007986A - Modified amino-acid amides as cgrp antagonists - Google Patents

Abstract

The present invention relates to modified amino-acid amides of general formula (I), wherein A, R, R1, R2, X1, X2, X3 and Y are defined as in Claim 1. The invention also relates to the tautomeric derivatives, diastereomers, enantiomers, mixtures and salts thereof, especially the physiologically compatible salts thereof with inorganic or organic acids or bases, whereby said acids and bases are provided with CGRP-antagonistic activity. The invention further relates to medicaments containing said compounds, to the use thereof and to a method for producing the same. The invention also relates to the use of said medicaments for producing and purifying antibodies and to the use thereof as labelled compounds in RIA and ELISA assays and as diagnostic or analytic auxiliaries in neurotransmitter research.

Description

AMIDAS OF MODIFIED AMINO ACIDS, MEDICINES CONTAINING THESE COMPOUNDS AND PROCEDURE FOR YOUR PREPARATION DESCRIPTION OF THE INVENTION Modified amino acid amides of the general formula are subject of the present invention their tautomers, their diastereoisomers, their enantiomers, their mixtures and their salts, in particular their physiologically compatible salts with inorganic or organic acids or bases, medicaments containing these compounds, their use and processes for their preparation. In general formula I above, R means the 1-piper idini lo group, which in position 4 is substituted with an aza-, diaza- or triaza-heterocycle of 5-7 members, linked through a nitrogen atom, unsaturated once or twice, which contains one or two carbonyl groups bonded with a nitrogen atom, the aforementioned heterocycles may be substituted on a carbon atom with an optionally substituted phenyl group, an olefinic double bond of one of which may be condensed unsaturated heterocycles mentioned above with a ring of benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methyl-pyrrole, quinoline, imidazole or N-methyl-imidazole, or they may be condensed with benzo two olefinic double bonds in one of the aforementioned unsaturated heterocycles, and the phenyl group mentioned above may be mono-, di- or tri-substituted, as well as the condensed heterocycles with benzo, thieno, pyrido and diazino in the carbon skeleton, additionally with fluorine, chlorine or bromine atoms, with alkyl groups, cycloalkyl groups with 3 to 8 carbon atoms, nitro groups, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylsulfonylamino, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmethylamino, aminocarbonyl, alkylaminocarbonyl, di-alkyl aminocarbonyl, hydroxyalkylaminocarbonyl, (4-orpholinyl) carbonyl, (1-pyrrolidinyl) carbonyl, (1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) -carbonyl, (4-methyl-1-piperazinyl) carbonyl, methylenedioxy, aminocarbonyl-amino, aminocarbonyl-aminoalkyl, alkylamcarbonyl lamino, alkanoyl, cyano, trifluoromethoxy, trifluorornethyl io, tri fluoromet il sul finí lo or trifluoromet ilsulfonilo, substituents can be equal s or different, and means the divalent radicals wherein R represents an alkyl radical with 1 to 4 carbon atoms or a phenyl radical optionally substituted with a halogen atom, a methyl group or a methoxy group, X1, X2 and X3, which may be the same or different, mean the atom of hydrogen, the fluorine, chlorine or bromine atom, a branched or unbranched alkyl group, an alkoxy, trifluoromethyl, dialkylaminoalkyl, dialkylaminoalkoxy, nitro, hydroxy, amino, acetylamino, methylsulphonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, trifluoromethoxy, trifluorornethyl thio, trifluoromethylsulphinyl or trifluoromethylsulfonyl, A means a bond or the divalent radical, linked through the group -CO with the group NRXR2 of the formula I wherein R7 represents the hydrogen atom or the methyl group, R £ represents the hydrogen atom, the methyl group, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i sopropoxycarbonyl, tert-butoxycarbonyl or acetyl, R1 means the hydrogen atom , an alkyl group with 1 to 7 carbon atoms which, in the α position, can be substituted with a cyclohexyl, phenyl, pyridinyl, diazinyl, hydroxy, amino, alkylamino, dialkylamino, carboxy, aminocarbonyl, aminocarbonyl, amino, acetylamino, 1- group pyrrolidinyl, 1-piperidinyl or, 4 - (1-piperidini-1) -1-piperidinyl, 4-morpholinyl, hexahydro-1H-1-azepinyl, [bis- (2-hydroxyethyl)] amino, 4-alkyl-1-piperazinyl or - (β-hydroxyalkyl) -1-piperazinyl, a phenyl or pyridinyl group, the heterocyclic radicals and phenyl groups mentioned above may be mono-, di- or tri-substituted; additionally in the carbon skeleton, with fluorine, chlorine or bromine atoms, with methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, methyl sulphonyloxy, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulfonyl groups, and substituents can be the same or different, R2 means the hydrogen atom or an alkyl group with 1 to 3 carbon atoms, optionally substituted with a phenyl or pyridine group, or R1 and R2, together with the included nitrogen atom, mean a radical of the general formula III wherein Y1 means the carbon atom or, when R4 represents a pair of free electrons, also means the nitrogen atom, m means the numbers 0, 1 or 2, n means the numbers 0, 1 or 2, R3 means the hydrogen atom, an amino, alkylamino, dialkylamino, alkyl, cycloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminoimino ethyl, aminocarbonylamino, alkylaminocarbonylamino, cycloalkylaminocarbonylamino, phenyl aminocarbonylamino, aminocarbonylalkyl, aminocarbonyl-aminoalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxyalkyl group or carboxy, a phenyl, pyridinyl, diazinyl, 1-naphthyl, 2-naphthyl, pyridinylcarbonyl or phenylcarbonyl group which, in each case in the carbon skeleton, can be mono-, di-ot-substituted with fluorine atoms, chlorine or bromine, with alkyl, alkoxy, methylsulfonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonylamine groups ilo, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl,? - (dialkylamino) alkanoyl,? - (dialkylamino) alkyl,? - (dialkylamino) hydroxyalkyl,? - (carboxy) alkanoyl, trifluoromethoxy, t-trifluoromethyl thio, t-rifluoromet I 1 sulphi or tri luoromet ilsulfonyl, the substituents being the same or different, an azacycloalkyl group of 4 to 10 members, an oxaza-, thiaza- or diaza-cycloalkyl group of 5 to 10 members, or an azabicycloalkyl group of 6 to 10 members, the aforementioned monocyclic and bicyclic heterocycles being linked through a nitrogen atom or a carbon atom, a 1 -alkyl-4-piperidinylcarbonyl group or 4-alkyl-1-piperazinylcarbonyl, the above-mentioned monocyclic and bicyclic heterocycles, as well as the 1-alkyl-4-piperidinylcarbonyl and -alkyl-1-piperazinylcarbonyl groups in the ring with an alkyl group with 1 to 7 being able to be substituted. carbon atoms, with an alkanoyl, dialkylamino, phenylcarbonyl, pyridinylcarbonyl, carboxyalkanoyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylsulfonyl, cycloalkyl or cycloalkylalkyl group, with a cycloalkylcarbonyl, azacycloalkylcarbonyl, diazacycloalkylcarbonyl group or oxazacycloalkylcarbonyl optionally substituted with alkyl in the ring, the alicyclic parts contained in these substituents comprising 3 to 10 ring members and the heteroalicyclic portions comprising in each case 4 to 10 ring members, and the aforementioned phenyl and pyridinyl radicals They can be mono-, di-ot-ri-situted, by their p art, with fluorine, chlorine or bromine atoms, with alkyl, alkoxy, methylsulfonyl, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonyl-a, aminocarbonyl laminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl, ? - (dialkylamino) alkanoyl,? - (carboxy) alkane, trifluoromethoxy, trifluoromet il thio, trifluoromethylsulfinyl or trifluoromethylsulfonyl, the substituents being the same or different, or R3, together with R4 and Y1, means a cycloaliphatic ring of 4; to 7 members, wherein the methylene group can be replaced by an -NH- or - (alkyl) - group, a hydrogen atom attached to a nitrogen atom within the R group can be replaced by a protective radical, R4 means a hydrogen atom, an alkyl radical having 1 to 4 carbon atoms, it being possible to replace an unbranched alkyl radical, in the? -position, with a phenyl, pyridinyl, diazinyl, amino, alkylaryl group lamino, dialkylamino, 1-pyrrol idini lo, 1-piperidinyl, 4-methyl-1-piperazinyl, 4-morpholinyl or hexahydro-lH-1-azepinyl, an alkoxycarbonyl group, the cyano or aminocarbonyl group or a free electron pair, when Y1 represents a nitrogen atom, and R5 and R6 in each case mean a hydrogen atom or, if Y1 is a carbon atom, R4, together with R6, also represents another carbon-carbon bond, where R3 is defined as mentioned above and R5 represents a hydrogen atom, or if y1 is a carbon atom, R4, together with R6, it also represents another carbon-carbon bond and R3, together with R5 and the double bond included, represents a monocyclic or bicyclic carbocycle or heterocyclic, of five to seven members, partially hydrogenated or aromatic, being able to encompass all the alkyl and alkoxy mentioned above, as well as the alkyl groups present within the other mentioned radicals, if not otherwise indicated, 1 to 7 carbon atoms, and all the aforementioned cycloalkyl groups can be encompassed, as well as the cycloalkyl groups present within the other radicals mentioned, if not stated otherwise, from 5 to 10 carbon atoms. For example, for R 3, the 1-pyr rolidinyl, 1-piper idini lo, 4- (dimethylamino) -1-piperidinyl, 4-piperidinyl or 4-morpholinyl group may be substituted, the nitrogen atom of the group 4 -piperidini with an alkanoyl or alkyl group, in each case with 1 to 4 carbon atoms or with a me tyl sulphyl group, the hexahydro-lH-1-azepinyl group, 8-methyl-8-a-zabicyclo [3, 2, 1] oct-3-yl, 4-alkyl-1-piperazinyl, hexahydro-4-alkyl-lH-l, -diazepin-1-yl, 1-alkyl-4-piperidinylcarbonyl or 4-alkyl -l-piperazinyl carboni lo. For example, for R, the group 4 - (1,3-dihydro-4-phenyl-1-2 (2H) -oxoi-idazol-1-yl) -1-piperidinyl, 4- (1,3-dihydro-) 2 (2H) -oxobenzimidazol-1-yl) -1-piperidinyl, 4- [2, 4 (1 H, 3 H) -dioxoquinazolin-3-yl] -1-piperidinyl, 4- (1,3-dihydro-2 ( 2H) -oxoimidazo [4, 5-b] pyridin-3-yl, 4- (3,4-dihydro-2 (1H) -oxoquina zolin-3-yl) -1-piper idini lo, 4- (2, 3, 4, 5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) -1-piperidinyl, 4- (7-methoxy-2,3,3,5-tetrahydro-2 (1H) -oxo-1, 3-benzodiazepin-3-yl) -1-piperidinyl, 4 - [2 (1H) -oxoquinoli-3-yl] -1-piperidinyl, 4 - (2,4-dihydro-5-phenyl- 3 (3H) -oxo-1,2,4-triazol-2-yl) -1-piperidinyl, 4- (1,3-dihydro-2 (2H) -oxoimidazo [4, 5-c] quinol in 3 -yl) - 1-piperidini lo or 4 - (5, 7-dihydro-6-oxo-dibenzo [d, f] - [1, 3] diazepin-5-yl) -1-piperidinyl.For the mentioned protective radicals In the definitions that precede and that follow, the protective groups must be understood of the chemistry of the peptides, in particular a phenylalkoxycarbonyl group having 1 to 3 carbon atoms in the alkoxy part, substituted in the phenyl nucleus optionally with a halogen atom, with a nitro or phenyl group, with one or two methoxy groups, for example the benzyloxycarbonyl group, 2-nor t-benzyloxycarbonyl, 4-nitro-benzyloxycarbonyl, 4-methoxy-benzyloxycarbonyl, 2-chloro-benzyloxycarbonyl, 3-chloro-benzyloxycarbonyl, 4-chloro-benzyloxycarbonyl , 4-biphenylyl-α, α-dimethyl-benzyloxycarbonyl or 3,5-dimethoxy-, α-dimethyl-yl-benzyloxycarbonyl, an alkoxycarbonyl group with in total 1 to 5 carbon atoms in the alkyl part, for example the group methoxycarbonyl, oxycarbonyl, n-propoxycarbonyl, and sopropoxycarbonyl, n-butoxycarbonyl, 1-methylpropoxycarbonyl, 2-methylpropoxycarbonyl or tert-butyloxycarbonyl, the allyloxycarbonyl group, 2,2,2-trichloroethoxycarbonyl or 9-f luorenylmet oxycarbonyl or the formyl, acetyl or tri group fluoroacetyl, The present invention relates to racemates, if the compounds of the general formula I possess only one element of chirality. However, the application also covers the pairs of individual diastereomeric antipodes or their mixtures that occur when more than one chirality element is present in the compounds of the general formula (I) • Compounds that fall within the formula are particularly preferred. general I that, in relation to the partial structure of amino acids of the formula D or (R) are configured and, in relation to the partial amino acid structure of formula II, optionally present in radical A, L or (S) are configured. The compounds of the general formula I have valuable pharmacological properties that are based on their selective CGRP antagonist properties. Another object of the invention are drugs containing these compounds, their use and their preparation. Preferred compounds of the above general formula I are those, in which R represents the 1-piperidinyl group, which in the 4-position is substituted with an aza-, diaza- or triaza-heterocycle of 5-7 members, linked through a nitrogen atom, unsaturated once or twice, containing one or two carbonyl groups bonded with a nitrogen atom, the aforementioned heterocycles may be substituted on a carbon atom with a phenyl group, an olefinic double bond may be condensed of one of the above-mentioned unsaturated heterocycles with a benzene, pyridine or quinoline ring or with two olefinic double bonds being benzo-condensed in one of the aforementioned unsaturated heterocycles, and the heterocycles being mono-, di- or tri-substituted condensed in the above-mentioned carbon skeleton, and / or in the phenyl groups contained in these groups with fluorine atoms or, chloro or bromo, with C? _3 alkyl, t-fluoroumyl, C? _3 alkoxy, hydroxy, amino, nitro, phenyl, carboxy, methoxycarbonyl, oxycarbonyl, aminocarbonyl, methylaminocarbonyl, hydroxyethylaminocarbonyl, (4-morpholinyl) groups ) carbonyl, (1-piper idinyl) carbonyl or (4-methyl-1-piperazinyl) -carbonyl, the substituents being the same or different, and a multiple substitution being excluded with the three substituents mentioned above, and being particularly preferred , in particular, the monosurfation and, as substituents, the C1-3 alkyl group, C1-3 alkoxy and phenyl, Y means the divalent radicals wherein R9 represents an alkyl radical of C3_3 or a phenyl radical optionally substituted with a fluorine, chlorine or bromine atom, a methyl group or a methoxy group, X1, X2 and X3, which may be the same or different, mean the hydrogen atom, the fluorine, chlorine or bromine atom, an alkyl group of C1-3, C1-3 alkoxy, trifluoromethyl, hydroxy, amino or acetylamino, A means a bond or the divalent radical, linked through the -CO group with the group NR1nR2 of the formula I wherein R7 and R8, independently of one another, represent in each case the hydrogen atom or the methyl group, R1 signifies the hydrogen atom or an alkyl group having 1 to 4 carbon atoms, optionally substituted in position? with an amino group, methylamino, dimethylamino or 4- (l-piperidinyl) -1-piper idini lo, R2 means the hydrogen atom, the methyl or ethyl group, or R1 and R2, together with the nitrogen atom included, mean a radical of the general formula wherein Y1 means the carbon atom or, when R4 represents a pair of free electrons, also means the nitrogen atom, m means the numbers O or 1, n means the numbers 1 or 2, R3 means the hydrogen atom, a phenyl, pyridinyl or diazinyl group which, in each case in the carbon skeleton, can be substituted with a fluorine, chlorine or bromine atom, with a methyl or methoxy group, an azacycloalkyl group of 5-7 members, an oxaza group - or diaz a-cycloalkyl of 5 to 7 members, or an azabi cycloalkyl group of 7 to 9 members, the aforementioned monocyclic and bicyclic heterocycles being linked through a nitrogen atom or a carbon atom, and may be substituted with an alkyl group having 1 to 3 carbon atoms, with an alkanoyl group of C? _4, dialkylamino of C1-3 or alkylsulfonyl of C? _3, R4 means a hydrogen atom, an alkyl radical with 1 to 3 carbon atoms • carbon, being able an unbranched alkyl radical, in the α-position, with a phenyl or pyridinyl group, or a free electron pair, is substituted when Y1 represents a nitrogen atom, and R5 and R6 in each case mean a hydrogen atom, its tautomers, its diastereoisomers, its enantiomers, its mixtures and its salts. Especially preferred compounds of the general formula I above are those, in which R means the 1-piper idinyl group, which in position 4 is substituted with a 1,3-dihydro-4-phenyl-2 (2H) -oxoimidazol-1-yl group, 1,3-dihydro-2 (2H) -oxobenzimide zol-1-yl, 2,4 (1H, 3H) -dioxoquinazolin-3-yl, 1,3-dihydro-2 (2H) -oxoimidazo [4, 5-b] pyridin-3-yl, 3, -dihydro-2 (1H) -oxoquinazolin-3 -yl, 2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl, 2 (1H) -oxoquinolin-3-yl, 2,4-dihydro-5-phenyl -3 (3H) -oxo- 1, 2, -triazol-2-yl, 1,3-dihydro-2 (2H) -oxoimidazo- [4,5-c] quinolin-3-yl or 5,7-dihydro 6-oxo-dibenzo [d, f] [1, 3] diazepin-5-yl, wherein the aforementioned bicyclic heterocycles may be mono-, di- or tr i -substituted in the carbon skeleton and / or in the groups phenyl contained in these groups with fluorine, chlorine or bromine atoms, with methyl, trifluoromethyl, methoxy, hydroxy, amino, nitro, phenyl, phenylmethyl, carboxy, methoxycarbonyl, and oxycarbonyl, aminocarbonyl, methylaminocarbonyl, hydroxyethylaminocarbonyl groups, 4 -mor fol ini 1) carboni lo, (1-p) iper idinyl) carbonyl or (4-methyl-l-piperazinyl) carbonyl, the substituents being the same or different, and a multiple substitution being excluded with the three substituents mentioned last, and being particularly preferred, the monostock i and as substituents the methyl, methoxy and phenyl group, Y means the divalent radicals wherein R9 represents the methyl group or the phenyl radical, X1 means the fluorine, chlorine or bromine atom, or the methyl group, X2 means the fluorine, chlorine or bromine atom, the methyl, methoxy, hydroxy or amino group, X - means the fluorine atom, chlorine bromine, or the methyl group, A means a bond or the divalent radical, linked through the group -CO with the group NRXR2 of the formula I wherein R7 and R8 represent hydrogen atoms, R1 and R2, together with the included nitrogen atom, mean a radical of the general formula where it means the carbon atom or, when R represents a pair of free electrons, also means the nitrogen atom, m means the number 1, n means the number 1, R3 means a phenyl or pyridinyl group which, in each case in the carbon skeleton, can be substituted with a fluorine, chlorine or bromine atom, with a methyl or methoxy group, a 1-pyr rolidinyl group, 1-piperidinyl, 4 - (dimethylamino) -1-piperidinyl, 4-piperidinyl or 4-morpholinyl, may be substituted the nitrogen atom of the 4-piperidinyl group with an alkyl group each having 1 to 2 carbon atoms, a hexahydro-1H-1-azepinyl, 4-methyl-1-piperazinyl or 4-yl-1-piperazinyl group , R < means a hydrogen atom, an alkyl radical with 1 or 2 carbon atoms or a pair of free electrons, when Y 1 represents a nitrogen atom, and R 5 and R 6 represent in each case a hydrogen atom, its tautomers, its diastereomers, its enantiomers, its mixtures and its salts. As particularly preferred compounds there may be mentioned, for example, the following: (1) l- [4-amino-3,5-dibromo-N - [[4- (3,4-dihydro-2 (1H) -oxoquinazolin- 3-yl) -1-piperidinyl] -methylsulfonyl inomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piper idine, (2) l- [4-amino-3, 5-dibromo-N- [[4- (3,4-dihydro-2 (1 H) -oxoquinazolin-3-yl) -1-piperidinyl] -cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine, (3) 1 - [4-amino-3,5-dibromo-N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] -phenylsulfonyl imi-ethyl] -D-phenylalanyl ] -4- (1-piperi-dinyl) -piperidine, (4) 1- [3, 5-dibromo-N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyanimino-ethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine, (5) 1- [N2- [3, 5-dibromo-N- [[4- (3,4 -dihydro-2 (1 H) -oxoquinazolin-3-yl) -1-piperidinyl] methyl sul-phenyl-n -yl-ethyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine, (6 ) 1- [N2- [3, 5-dibromo-N- [[4- (3, 4-dihydro-2 (1H) -oxoquinazolin) -3-yl) -1-piperidinyl] phenylsulfo-nili inomethyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine, (7) 1- [4-amino-3,5-dibromo-N- [[4- (3,4-dihydro-2 (1H) -oxoquina-zol-3-yl) -1-piperidinyl] -cyanimino ethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperidine, (8) 1- [4-bromo-N- [[4- (3,4-dihydro-2 (lH ) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -3,5-dimethyl-D, L-phenylalanyl] -4- (1-piperidinyl) -piperidine, (9) 1- [3, 5-dibromo -N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyanimino-methyl] -D-tyrosyl] -4- (4-pyridinyl) -piperazine, (10) l- [4-amino-3,5-dibromo-N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] -cyaniminomethyl] -D phenylalanyl] -4- (4-pyridinyl) -piperazine, (11) 1- [3, 5-dibromo-N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-) il) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperidine, (12) 1- [3, 5-dibromo-N- [[4- [3, 4-dihydro-2 (1H) -oxoquinaZolin-3-yl] -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (4-methyl-1-piperazinyl) -piperidine, (13) 1- [4- bromo-N- [[4- (3, 4-dihydro -2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -3,5-dimethyl-D, L-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperidine, (14) l- [4-amino-3,5-dibromo-N- [[4- [1,3-dihydro-4-phenyl-2 (2H) -oxoimidazol-1-yl] -1-piperidi-nil Icy iminomethyl] -D-phenylalanyl] -4- (4-methyl-1-piperazinyl) -piper idine, (15) l- [4-amino-3,5-dibromo-N- [[4- (2, 3,4,5 <; tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (4-methyl-1-piperazyl) -piperldine, (16) 1- [4-amino-3, 5-dibromo-N- [[4- (2,4-dihydro-5-phenyl-3 (3H) -oxo- 1,2,4-triaZol-2-yl) - 1-piperidinyl] cyaniminoraet il] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine, (17) 1- [4-amino-3, 5-dibromo-N- [[4- (2, 3, 4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine, (18) 1 - [3, 5-dibromo-N- [[4- (2,4-dihydro-5-phenyl-3 (3H) -oxo-1,2,4-triazol-2-yl) -1-piperidinyl] - cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine, (19) 1- [3, 5-dibromo-N- [[4- (2,3,4,5-tetra-hydro-2 (1 H) -oxo-1, 3-benzodiazepin-3-yl) -1-piperi-dinyl] cyanimethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine, (20) 1- [3, 5-dibromo-N- [f4- (2,4-dihydro-5-phenyl-3 (3H) -oxo-1,2,4-triazol-2-yl) -1-piperidinyl] -cyaniminomethyl] -D- tyrosyl] -4- (1-met il-4 -piperi dinyl) -piperazine, (21) 1- [3, 5-dibromo-N- [[4- (2, 3, 4, 5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) ) - 1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperazine, (22) l- [4-amino-3,5-dibromo-N- [[4- (2,4-Dihydro-5-phenyl-3 (3H) -oxo-1,2,4-triazol-2-yl) -1-pip-ridinyl] -cyaniminomethyl] -D-phenylalanyl] -4- (1-methyl) -4-piperidinyl) -piperazine, (23) 1- [4-amino-3, 5-dibromo-N- [[4- (2, 3,4,5-tetrahydro-2 (1H) -oxo-1, 3-benzodiazepin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-met i 1-4 -piperidyl) -piperazine, (24) 1- [3, 5-dibromo- N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -4-methyl-D, L-phenylalanyl] -4- (l-methyl- 4-piperi-dinyl) -piper idine, (25) 1- [3, 5-dibromo-N- [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl ] cyaniminomethyl] -4-met il-D, L-phenylalanyl] -4- (1-piperidinyl) -piperidine, (26) 1- [3, 5-dibromo-N- [[4- (3, -dihydro- 2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -4-methyl-D, L-phenylalanyl] - A - (4-pyridinyl) -piperazine, (27) 1- [4-amino-3, 5-dibromo-N- [[4 - [1,3-dihydro-2 (2H) -oxoimidazo [4, 5-c] quinolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine, (28) 1- [4-amino-3, 5-dibromo-N- [[4- (7-methoxy-2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiaze-pin -3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine, (29) l- [4-amino-3,5-dibromo-N- [[4- (5,7-dihydro-6-oxodibenzo [d, f] [1,3] diazepin-5-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine, (30) l- [4-amino-3,5-dibromo-N- [[4- (7-methoxy-2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiaze -pin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperazine, (31) 1- [4-amino-3,5-dibromo- N- [[4- [1, 3-dihydro-2 (2H) -oxoimidazo [4, 5-c] quinolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalani l] -4- (1-methy1-piperidinyl) -piperazine, (32) l- [4-amino-3,5-dibromo-N- [[4- (2, 3,4,5-tetrahydro- 2 (1 H) -oxo-1, 3-benzodiazepin-3-yl) -1-piperidinyl] sulfonyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperazine, (33) 1- [ 3, 5-dibromo-N- [[4- (7-methoxy-2, 3,, 5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine, (34) l- [3,5-dibromo-N - [[4- (7-methoxy-2, 3,, 5-tetrahydro-2 ( 1H) -oxo-1, 3-benzodiazepin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (1-methyl-4-piperidinyl) -piperazine, (35) 1- [3, 5-dibromo-N- [[4- [1, 3-dihydro-2 (2H) -oxoimidazo [4, 5-c] quinolin-3-yl] -1-piperidi-nyl] cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine, (36) 1- [3, 5-dibromo-N- [[4- [1,3-dihydro-2 (2H) -oxoimidazo [4, 5-c] quinolin -3-yl) -1-piperidi-nyl] cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperazine, (37) l- [4-amino-3,5-dibromo- N- [[4- (7-methoxy-2, 3, 4, 5-tet rahydro-2 (1H) -oxo-1, 3-benzodiaze-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (4-methyl-1-piperazinyl) -piperidine and (38) l- [4-amino-3, 5- dibromo-N- [[4- [1, 3-dihydro-2 (2H) -oxoimidazo [4, 5-c] quinolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4 - (4-methyl-1-piperazinyl) -piperidine, and its salts. The compounds of the general formula I are prepared according to methods known in principle, using also methods derived from the chemistry of the peptides (see, for example, Houben-yyl, Methoden der Organischen Chemie, volume 15/2). Suitable amino protecting groups are those described in Houben-yyl, Methoden der Organischen Chemie, volume 15/1, with urethane protecting groups being preferred, such as, for example, the fluorenylmethoxycarbonyl, phenylmethoxycarbonyl or tert-butyloxycarbonyl group. Functional groups optionally present in the radical A of the compounds of the general formula I or in their precursors are additionally protected, in order to avoid side reactions, by suitable protecting groups (see, for example: GB Fields et al., Int. J. Peptide Protein Res. 35, 161 (1990); T.W. Greene, Protective Groups in Organic Synthesis). As protected amino acids in the side chain of this type, mention must be made, in particular, of Lys (Boc), Lys (Cl-Z) and Lys (Teoc) which, as a rule, are commercially available and are available in the form of derivatives. Instead of protecting amino groups in position of the side chain, it is also possible to use amino acids or their derivatives carrying precursor functions and substituted in the side chain, in particular with nitro or cyano, for example 5-cyanonorval ina. Any protective groups present in the side chains of partial structures of a-amino acids are separated, after the constitution of the substituted N- and C-terminal amino acid derivative, subsequently with suitable reagents, known in principle also by the literature, for example arylmethoxycarbonyl protectants by hydrogenolysis, for example with hydrogen in the presence of palladium black and with the use of glacial acetic acid as a solvent. Functions of precursors optionally present in the α-amino acid side chain can then also be transformed, by hydrogenolysis, into the desired amino functions; in this case, nitroalkyl groups provide, under the usual conditions for the chemical, aminoalkyl groups and the cyano group is transformed into the aminomethyl group. The following processes are particularly suitable for the preparation of the compounds of the general formula I according to the invention: a) For the preparation of compounds of the general formula I, in which Y means one of the divalent iminomethyl radicals wherein R is defined as indicated at the beginning: reaction of compounds of the general formula wherein A, R1, R2, X1, X2 and X3 are defined as at the beginning, Y 'represents one of the two iminomethyl radicals indicated above and Nu is a leaving group, for example an alkoxy, aryloxy, alkylthio, alkylsulfinyl group or alkylsulphonyl, in each case with up to 10 carbon atoms, for example the methoxy, ethoxy, phenyloxy, methylthio, ethylthio, methylsulfinyl, ilsul finyl, propylsulfinyl, isopropyl, finyl, methylsulphonyl or ethylsulphonyl group, the chlorine or bromine atom, the group S02H, S03H or OPOCl2, but preferably the phenoxy group, with secondary amines of the general formula RH (VI), in which R is defined as at the beginning. The reactions are carried out in analogy to procedures known from the literature (See G.B.L Smith, J. Amer. Chem. Soc. 51, 4-76

[1929]; B. Rathke, Chem. Ber. 17, 297 [1884]; R. Phillips and H. T. Clarke, J. Amer. Chem. Soc. 45, 1755 [1923]; S. J. Angyal and W. K. Warburton, J. Amer. Chem. Soc. 73, 2492 [1951]; H. Lecher and F. Graf, Chem. Ber. 56_, 1326 [1923]; J. Wityak, S. J. Gould, S. J. Hein and D. A. Keszler, J. Org. Chem. 52, 2179 [1987]; T. Teraji, Y. Nakai, G. J. Durant, WO-A-81/00109, Chem. Abstr. 94, 192336z [1981]; C. Maryanoff A., R. C. Stanzione, J. N. Plampin and J. E. Mills, J. Org. Chem. 5_1_, 1882-1884 [1986]; A. E. Miller and J. J. Bischoff, Synthesis 1986, 777; R. A. B. Bannard, A. Casselman, W. F. Cockburn and G. M. Brown, Can. J. Chem. 36, 1541 [1958]; Akt iesels kabet Grea, kopenhagen, document DE2826452-C2; K. Kim, Y. T. Lin and H. S. Mosher, Tetrah. Letters 2_9, 3183-3186 [1988]; H. B. Arzeno et al., Synth. Commun. 20, 3433-3437 [1990]; H.

Bredereck and K. Bredereck, Chem. Ber. 94_, 2278 [1961]; H. Eilingsfeld, G. Neubauer, M. Seefelder and H. Weidinger, Chem. Ber. 91_, 1232 [1964]; P. Pruszynski, Can. J. Chem. 6_5_, 626 [1987]; D. F. Gavin, W. J. Schnabel, E. Kober and M. A. Robinson, J. Org. Chem. 32, 2511 [1967]; N. K. Hart, S. R. Johns, J. A. Lamberton and R. I. Willing, Aust. J. Chem. 23, 1679 [1970]; CIBA Ltd., Belgian patent 655403; Chem. Abstr. 64_, 17481 [1966]; J. P. Greenstein, J. Org. Chem. 2_, 480 [1937]; F. L. Scott and J. Reilly, J. Amer. Chem. Soc. 7_4_, 4562 [1952]; W. Roush and A. E. Walts, J. Amer. Chem. Soc. 106, 721 [1984]; M. S. Bernatowicz, Y. Wu and G. R. Matsueda, J. Org. Chem. 57, 2497-2502 [1992]; H. Tsune atsu, T. Imamura and S. Makisu i, J. Biochem. 9 _, 123-128 [1983]; R. Mohr, A. Buschauer and W. Schunack, Arch. Pharm. 321, 221-227 [1988]; K. Atwal, F. N. Ferrara and S. Z. Ahmed, Tetrah. Lett. 35. ' 8085-8088 [1994]; P. J. Garratt, C. J. Hobbs and R. Wrigglesworth, J. Org. Chem. 5, 1062-1069 [1989]; PJ Garratt and SN Thorn, Tetrahedron 4_9, 6885-6898 [1993]), at temperatures between 0 ° C and + 100 ° C, preferably + 40 ° C and + 80 ° C, and with use of inert solvents, for example from dichloromethane, tetrahydrofuran, 1,4-dioxane, acetonityl, dimethylformamide, 2-pentanol, dimethylacetamide, N-methylpyrrolidone or mixtures thereof and, as a rule, in the presence of auxiliary bases, in particular alkali metal carbonates such as carbonate of sodium or potassium, or of tertiary amines, preferably N-ethyl-diisopropylamina or triethylamine. b) For the preparation of compounds of the general formula I, in which Y means the divalent radical -SO2-: reaction of compounds of the general formula are defined as mentioned at the beginning, Y "means the group SO2 and Nu 'is a leaving group, for example a halogen atom such as the chlorine, bromine or iodine atom, an alkyl or arylsulfo-nyloxy group or a group alkoxy in each case with up to 10 carbon atoms, for example the methoxy or ethoxy group, or a phenoxy or naphthoxy group mono-, di- or tri-substituted optionally with chlorine or bromine atoms, with methyl, nitro or hydroxy groups, the substituents being the same or different, with secondary amines of the general formula RH (VI) in which R is defined as at the beginning and, if necessary, subsequent separation of protective groups or transformation of precursor functions according to the processes described above. If in the general formula VII Nu 'means a halogen atom, an alkyl or aryl sulphonyloxy group, then the reaction is carried out under the conditions of Schott en-Baumann or Einhorn, ie the components are made react in the presence of at least one equivalent of an auxiliary base at temperatures between -50 ° C and + 120 ° C, preferably between -10 ° C and + 100 ° C and, possibly, in the presence of solvents. Suitable auxiliary bases are, preferably, alkali and alkaline earth metal hydroxides, for example sodium hydroxide, potassium hydroxide, alkali metal carbonates, for example sodium carbonate, potassium carbonate or cesium carbonate, alkali metal acetates, for example sodium or potassium acetate, as well as tertiary amines, for example pyridine, 2,4,6-trimethylpyridine, quinoline, triethylamine, N-ethyldiisopropylamine, N-ethyldicyclohexylamine, 1,4-diazabicyclo- [2, 2, 2] octane or 1,8-diazicyclo [5, 4, 0] undec-7-ene, as solvents, for example dichloromethane, tetrahydrofuran, 1,4-dioxane, acetonitrile, dimethylformamide, dimethylacetamide, N-me Tilpirrolidone or mixtures thereof; if alkali metal or alkaline earth metal hydroxides, alkali metal carbonates or acetates are used as auxiliary bases, water such as codisol ent e may also be added to the reaction mixture. As a nucleating group Nu 'in compounds of the general formula VII, the 2-hydroxy phenoxy group is preferred and, as solvents for the reaction with amines of the general formula VI, boiling dioxane is preferred. The non-isolating azasulfenos of the general formula are to be accepted as intermediates of the reaction (VIII) The modified amino acids of the general formula I according to the invention contain at least one center of chirality. If radical A is also chiral, then the compounds can be in the form of two pairs of diastereomeric antipodes. The invention encompasses the individual isomers, as well as their mixtures. The separation of the respective diastereoisomers is achieved by virtue of their different physicochemical properties, for example by fractional crystallization in suitable solvents, by high pressure liquid chromatography or column chromatography using chiral stationary phases or, preferably, achiral phases. The separation of racemates falling under the general formula I is achieved, for example, by HPLC in suitable chiral stationary phases (for example Chiral AGP, Chiralpak AD), Racemates that contain a basic or acidic function, can also be separated. through the diastereomeric, optically active salts, which result in the reaction with an optically active acid, for example (+) - or (-) - tartaric acid, (+) - or (-) - diacetyltartaric acid, tartarate (+) or (-) - monomethyl or (+) - canesphosphonic acid, or with an optically active base, for example with (R) - (+) - 1-phenylethylamine, (S) - (-) - 1 - fenilet i lamina or (S) -brucina. According to a usual process for the separation of isomers, the racemate of a compound of the general formula I is reacted with one of the above-described optically active acids or bases in an equimolar amount in a solvent, and the crystalline salts, shallow ereoi days and optically active obtained are separated taking advantage of their different solubility. This reaction can be carried out in any type of solvent, as long as they have a sufficient difference in relation to the solubility of the salts. Preferably, methanol, ethanol or mixtures thereof are used, for example in the 50:50 volume ratio. Thereafter, each of the optically active salts is dissolved in water, neutralized with a base such as sodium carbonate or potassium carbonate, sodium hydroxide solution or potassium hydroxide solution and, thereby, the corresponding free compound is obtained in the way (+) or (-). In each case only the enantiomer (R) or a mixture of two optically active diastereomeric compounds and falling under the general formula I is also obtained by carrying out the syntheses described above in each case with a suitable configured reaction component (R) . The starting materials of the general formulas V, VI and VII, necessary for the synthesis of the compounds of the general formula I, are prepared analogously to processes known in the literature. The starting compounds of the general formula V are obtained, for example, by reaction of the phenylalanine derivatives, already described in WO 98/11128, of the general formula wherein A, R1, R2, X1, X2 and X3 are defined as above, with inocarbons of the general formula Nu-Y'-Nu "(X) in which Nu and Y 'are defined as above under the heading a), and Nu ", which can be different from Nu or also equal to Nu, can adopt the same meaning as Nu. The reactions are carried out in analogy to the indications of R. Mohr, A. Buschauer and W. Schunack, Arch Pharm. 321, 221-227 [1988] or either A. Buschauer, Arch. Pharm 320, 377-380 [1987] or P. J. Garratt and S. N. Thorn Tetrahedron 4_9, 6885-6898 [1993]. Compounds of the general formula VI have already been described, as a general rule, in WO 98/11128. The compound that falls under the general formula VI, not yet described previously it can be easily prepared from 2-amino-2'-nitrobiphenyl by reductive amination with 1- (phenylmethyl) -4-piperidone, subsequent reduction of the nitro group, cyclization using N, N'-carbonyldiimidazole and hydrogenolytic separation of the benzyl group based on methods known in the literature. The compounds of the general formula VII, required as starting compounds, can be prepared from phenylalanine derivatives of the above-defined general formula IX, by reaction with sulfates of the general formula Nu'-V-Nu "'(XII) in which Nu' e Y "are defined as above in section b) and Nu" ', which may be different from Nu' or also equal to Nu ', may adopt the same meanings as Nu' As sulfates the cyclic compound is preferred (see also: G. E. DuBois and R. A. Stephanson, J. Org. Chem. 45, 5371-5373 [1980]). The compounds of the general formula I obtained can be converted, in particular for pharmaceutical applications, into their physiologically compatible salts with inorganic or organic acids. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, mandelic acid, malic acid, citric acid, tartaric acid or maleic acid. In addition, the novel compounds of formula I, thus obtained, if they contain an acid function, for example a carboxy group, can be converted into their salts by addition with inorganic or organic bases, in particular in physiologically compatible addition salts, suitable for the pharmaceutical application. Suitable bases are, for example, sodium hydroxide, potassium hydroxide, ammonia, cyclohexylamina, dicyclohexylamine, ethanolamine, diethanolamine and triethanolamine. The new compounds of the general formula I and their physiologically compatible salts possess CGRP antagonist properties and show good affinities in CGRP receptor binding studies. The compounds exhibit antagonistic properties of CGRP in the pharmacological test systems described below. For the detection of the affinity of compounds of the general formula I by human CGRP receptors and their antagonistic properties, the following tests were carried out: A. Fixation studies with SK-N-MC cells (expressing the human CGRP receptor) SK-N-MC cells are cultured in "Dulbecco's modified Eagle's medium". The medium is removed from confluent cultures. The cells are washed twice with PBS buffer (Gibco 041- 04190 M), detached by the addition of PBS buffer, mixed with 0.02% EDTA, and isolated by centrifugation. After resuspension in 20 ml of "balanced salt solution" [BSS (in mM): NaCl 120, KCl 5.4, NaHC03 16.2, MgSO4 0.8, NaHP04 1.0, CaCl2 1.8, D-glucose 5.5, HEPES 30, pH 7.40] , the cells are centrifuged twice at 100 xg and resuspended in BSS. After determining the number of cells, the cells are homogenized with the aid of an Ultra-Turrax and centrifuged for 10 minutes at 3000 x g. The supernatant is discarded and the sediment is recentrifuged in Tris buffer (10 mM Tris, 50 M NaCl, 5 M MgCl 2, 1 mM EDTA, pH 7.40), enriched with 1% bovine serum albumin and 0.1% bacitracin, and resuspended (1 ml / 1, 000,000 cells). The homogenate is frozen at -80 ° C. The membrane preparations are stable under these conditions for more than 6 weeks. After thawing, the homogenate is diluted in the ratio of 1:10 with assay buffer (50 mM Tris, 150 M NaCl, 5 M MgCl 2, 1 m EDTA, pH 7.40) and homogenized for 30 seconds with a tl a -Turrax 230 μl of the homogenate are incubated for 180 minutes at room temperature with 50 pM of peptide related to the gene of 125 [beta] -iodotyrosyl-calcitonin (Amersham) and increasing concentrations of the test substances in a total volume of 250 [mu] l. Incubation is completed by rapid filtration through a GF / B glass fiber filter treated with polyethylenimine (0.1%) by a cell harvester. The radioactivity bound to the protein is determined with the help of a gamma counter. As a non-specific binding, the fixed radioactivity is defined after the presence of 1 μM of human CGRP-alpha during incubation. The analysis of the concentration-fixation curves is carried out with the help of a non-linear curve adaptation supported by a computer. The compounds of the general formula I show in the test described IC 50 values < _ 10,000 nM.

B. Antagonism of CGRP in SK-N-MC cells SK-N-MC cells (1 million cells) are washed twice with 250 μl of incubation buffer (Hanks HEPES), 3-M isobutyl-1-met ilxant ina 1 M, 1% BSA, pH 7.4) and preincubate for 15 minutes at 37 ° C. After the addition of CGRP (10 μl) as an agonist in increasing concentrations (10-11 to 10 ~ 6 M) or additionally to the substance in 3 to 4 different concentrations, it is incubated again for 15 minutes. Next, the intracellular cAMP is extracted by the addition of 20 μl of 1 M HCl and centrifugation (2000 x g, 4 ° C for 15 minutes). The supernatants are frozen in liquid nitrogen and stored at -20 ° C. The cAMP contents of the samples are determined by radioimmunoassay (Amersham signature), and the pA2 values of antagonist action substances are calculated graphically. The compounds of the general formula I show in the in vitro test model described antagonist properties of CGRP in a dose range between 10"11 and 10" 5 M. By virtue of their pharmacological properties, the compounds of the general formula I and its salts with physiologically compatible acids or bases are therefore suitable for the acute and prophylactic treatment of headaches, in particular migraine or Cluster headache. In addition, the compounds of the general formula I also positively influence the following diseases: non-insulin-dependent diabetes mellitus ("NIDDM"), cardiovascular diseases, skin diseases, in particular thermal and radiation-induced skin lesions, including sunburn, inflammatory diseases, for example inflammatory diseases of the joints (arthritis), inflammatory diseases of the lungs, allergic rhinitis, asthma, diseases that are accompanied by excessive dilation of the vessels and a reduced risk of tissues caused by the above, for example shock and sepsis, as well as tolerance to morphine. In addition, the compounds of the general formula I show a calming action on pain states in general and, moreover, they are suitable for combating menopausal hot flashes. The dosage necessary to achieve a corresponding effect is, in the case of intravenous or subcutaneous administration, conveniently at 0.0001 to 3 mg / kg of body weight, preferably at 0.01 to 1 mg / kg of body weight and, in the case of oral administration , nasal or by inhalation, at 0.01 to 10 mg / kg of body weight, preferably at 0.1 to 10 mg / kg of body weight, in each case 1 to 3 times a day. For this purpose, the compounds of the general formula I, prepared according to the invention, can be incorporated into customary galenic preparations such as tablets, dragees, capsules, powders, suspensions, solutions, dosing aerosols or suppositories, optionally in combination with other active substances such as, for example, antiemetics, prokinetics, neuroleptics, antidepressants, neurokinin antagonists, anticonvulsants, histamine Hl receptor antagonists, antimuscarinics, β-blockers, agonists and antagonists, ergotalcaloids, weak analgesics, antiphlogistics steroids, corticosteroids, calcium antagonists, 5-HT? D agonists, 5-HT? F agonists or other antimigraine agents, together with one or more usual inert carrier substances and / or diluents, for example with corn starch, lactose, sucrose, microcrystalline cellulose, magnesium stearate, poly inilpir olidone, citric acid, tartaric acid or, water, water / ethanol, water / glycerol, water / sorbitol, water / polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethylcellulose, substances with a fat content such as hard fat or their suitable mixtures. For the above-mentioned combinations, therefore, as other active substances, for example meloxicam, ergotamine, dihydroergotamine, methoclopra ida, domperidone, di-phenhydramine, cyclin, promethazine, chlorpromazine, dexamethasone, flunarizine, dextropropoxyphene, meperidine, propanoiol, nadolol, atenolol, clonidine, indoramin, carbamazepine, phenytoin, valproat, amitriptyline, lidocaine, diltiazem or sumatriptan and other 5-HTiD agonists such as, for example, naratriptan, zol and triptan, avitriptan, rizatriptan and eletriptan. In this case, the dose for these active substances amounts, conveniently, to 1/5 of the lowest dosage usually recommended up to 1/1 of the dosage normally recommended, that is, for example, from 20 to 100 mg of sumatriptan. Another object of the invention is the use of the compounds of the general formula I as valuable adjuvants for the creation and purification (affinity chromatography) of antibodies, as well as, after suitable radioactive labeling, for example by direct labeling with 125? 0131I or by titration of suitable precursors, for example by replacement of halogen atoms by tritium, RIA and ELISA assays and as diagnostic or analytical adjuvants in neurotransmitter research. The following Examples should explain the invention in more detail: Previous observations: Elemental analyzes, IR, UV, 1H-NMR and, as a rule, also satisfactory mass spectra are present for all compounds.

Unless indicated otherwise, the Rf values were determined using plates prepared from CCD of silica gel 60 F 5 (E. Merck, Darmstadt, item no. 5729) without saturation in the chamber. In the case that more precise data are missing for the configuration, it remains open whether it is pure enantiomers or if a partial or even complete racemization has been manifested. For chromatography, the following eluting agents or mixtures of eluting agents were used: FM1 = dichloromethane / cyclohexane / methanol / ammonia 7 / 1.5 / 1.5 / 0.2 (v / v / v / v) FM2 = di chloromethane / me tanol / ammonia 7.5 / 2.5 / 0.5 (v / v / v) FM3 = dichloromethane / methanol 8/2 (v / v) FM4 = dichloromethane / ethyl acetate / methanol / cyclohexane / aqueous ammonia concentrate = 59/25 / 7.5 / 7.5 / 1 (v / v / v / v / v) FM5 =: ethyl acetate / dichloromethane = 7/3 (v / v) FM6 = ethyl acetate / petroleum ether = 1/1 (v / v) FM7 = dichloromethane / methanol / aqueous ammonia concentrate = 80/20/1 (v / v / v). In the description of the tests the following abbreviations are used: Pf: melting point (D): (decomposition) DIEA: N, N-diisopropyl-N-eti lamin Boc: (1, 1-dimet iletoxi) carboni lo TBTÜ: 2 - (lH-benzot ria zol-l-yl) - 1, 1, 3, 3-tetramethyluronium HOBt: 1-hydroxybenzotriazole hydrate CDT 1, 1 '-carbonyldi- (1, 2, 4-triazole) THF tetrahydrofuran DMF dimethylformamide Fmoc: (9-fluorenylmethoxy) carbonyl EE ethyl ester of acetic acid PE petroleum ether LM solvent Example 1 1- [4-amino-3,5-dibromo-N- £ [4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -l-piperidinyl] methylsul-fonyliminomethyl] -D phenylalanyl] -4- (1-piperidinyl) -piperidine a) 1- [4-amino-3, 5-dibromo-N- j (phenoxy) ethylsulfonyliminomethyl] -D-phenylalanyl] -4- (l-piperidinyl) - piperidine The mixture based on 0.5 g (1,716 millimoles) of N-met anulul foni limino-diphenyl carbonate, 0.72 g (1,005 millimoles) of bis- (trifluoroacetate) of l- (4-amino-3,5-dibromo- D-phenylalanyl) -4- (1-piperidinyl) -piper idine, 0.5 ml (3.0 millimoles) of DIEA and 50 ml of dichloromethane were stirred for 1 hour at room temperature, then concentrated in vacuo, collected again in 50 ml of dichloromethane were successively washed in each case with 20 ml of 0.5N sodium hydroxide solution and water, dried over magnesium sulfate and concentrated by evaporation in vacuo. The crude product obtained in a yield of 0.67 g (97% of theory) was used in the next step without further purification. b) 1- [4-amino-3,5-dibromo-N- [[4- (3,4-dihydro-2 (1 H) -oxog inazolin-3-yl) -1-piperidinyl] -methylsulfonyliminomethyl] -D -phenylalanyl] -4- (1-piperi-dini) -piperidine The mixture based on 0.4 g (0.584 mmol) of 1- [4-amino-3,5-dibromo-N- [(phenoxy) methylsulfonyliminomethyl] -D phenylalanyl] -4- (1-piperidinyl) -piperidine, 0.46 g (1.989 mmol) of 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 10 ml of 2-pentanol was boiled at reflux for 14 hours. The mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (silica gel MN 60, Macherey-Nagel, 30-60 μm) using initially dichloromethane and then methanol / concentrated ammonia (9 / 1 v / v) for elution. After the usual work-up, 130 mg (27% of theory) of a colorless, amorphous solid product were obtained. IR (KBr): 1664 cm-1 (C = 0) Rf: 0.53 (FM1) ESI-MS: (M + H) + = 821/823/825 (Br2) Example 2 1- [4-amino-3 , 5-dibromo-N- [[4- (3, 4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (-piperidinyl) -piperidine a) 1- £ 4-amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example la), from carbonate of N-cyanoiminodi phenyl and bis- (trifluoroacetate) of 1- (4-amino-3,5-dibromo-D-phenylalanyl) -4- (1-piperidinyl) -piperidine in quantitative yield. The unpurified product obtained was used in the next step without further purification. *) 1- [4-amino-3,5-dibromo-N- [[4- (3, 4-dihi.-dro-2 (1H) -oxoquinazolin-3-yl) -1-piperjdinyl] cyaniminomethyl] - D-phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1- [4 -amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidini 1) -piperidine in a yield of 43% of theory. Colorless and amorphous substance IR (KBr): 1664 cm "1 (C = 0), 2173 (CN) cm" 1 Rf • 0.48 (FM1) ESI-MS: (M + H) + = 768/770/772 (Br2 Example 3 1- £ 4 -amin-3, 5-dibomo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -l-piperidinyl] phenylsul-fonyliminomethyl ] -D-phenylalanyl] -4- (-piperidinyl) -piperidine a) 1- £ 4-amino-3,5-dibromo-N- (phenoxy) phenyl-sulfonyliminomethyl] -D-phenylalanyl] -4- (1 -pjperidi-nil) -piperidine Prepared analogously to Example la), from N-benzenesul foni 1-iminyl-ifnyl carbonate and 1- (4-amino-3,5-dibromo-D-phenylalanyl) bis- (trifluoroacetate) ) -4- (1-piperidinyl) -piperidine in a yield of 60% of theory. Colorless and amorphous substance of Rf 0.41 (eluting agent: di chloroform / methanol / concentrated ammonia 9/1 / 0.1). b) 1- £ 4-amino-3 f 5 -dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] phenylsulfonyliminomethyl] -D phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 3,4-dihydro-3- (4-piper idinyl) -2 (1H) -quinazolinone and 1 - [4 - amino-3, 5-dibromo-N- [(phenoxy) phenylsulfonyliminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine in a yield of 33% of theory. Colorless and amorphous substance. IR (KBr): 1664 cm "1 (C = 0) Rf: 0.50 (FM1) ESI-MS: (M + H) + = 883/885/887 (Br2) Example 4 1- £ 3, 5 -dibromo -N- £ 4 - (3,4-dihydro-2 (1H) -oxop; uinazolin-3-yl) -1-piperidinyl) cyaniminomethyl] -D-tyrosyl] - 4- (-piperidinyl) -piperidine a) 1- £ 3, 5-dibromp-N- (phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example la) , from N-cyanimino-diphenyl carbonate and bis- (trifluoroacetate) of 1- (3,5-dibromo-Dt-irosyl) -4- (1-piperidinyl) -piperidine in a yield of 23% of theory. After mixing by grinding with t-but ilmet ileter / isopropanol (1/1 v / v); colorless and amorphous substance. b > 1- £ 3, 5-dib omo-N- £ £ 4- (3, 4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- ( 1-piperidinyl) -piperidine Prepared analogously to Example lb), from 3,4-dihydro-3- (4-piper idinyl) -2 (1 H) -quinazolinone and 1- [3, 5-dibromo-N- [ (phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidi-nyl) -piperidine in a yield of 20% of theory. Colorless and amorphous substance. IR (KBr): 1658 (C = 0), 2173 (CN) cm "1 Rf: 0.28 (FM1) ESI-MS: (M + H) +" 769/771/773 (Br2) Example 5 1- £ N2- £ 3,5-dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) - -piperidinyl] methylsulfonyl-iminomethyl] -D-tyrosyl ] -L-lysyl] -4- (4-pyridinyl) -piperazine a) 1- N2- £ 3,5-dibromo-N- £ 4- (3,4-dihydro-2 (1H) -oxoquinazolin- 3-yl) -1-piperidinyl] methylsulfo-niliminomethyl] -D-tyrosyl] -N6- (1,1-di-β-letoxica -bonyl) -L-lysyl] -4- (4-pyridinyl) -piperazine To the solution of 1.0 g (1,402 millimoles) of 1- [N2 ~ [3,5-dibromo-D-tyrosyl] -N6- (1,1-dimethylethoxy-carbonyl) -L-lysyl] -4- (4-pyridinyl) -piperazine in 50 ml of dioxane were added 0.4 g (1,373 millimoles) of N- (meth ansulfonyl) -iminodi feni lo carbonate and stirred for 2 hours at room temperature. After the complete reaction (CCD), 0.33 g (1427 millimoles) of 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone was added and boiled for 6 hours at reflux. The reaction mixture was concentrated by evaporation in vacuo, and the remaining residue was purified by column chromatography on silica gel (silica gel 60 MN, Macherey-Nagel, 30-60 μm) with the use of dichloromethane at first and then t anol / ammonia concentrated (9/1 v / v) for elution After usual work-up, 590 mg (41% of theory) of a colorless, amorphous solid product was obtained IR (KBr): 1655 cm " 1 (C = 0) ESI-MS: (M + H) 1045/1047/1049 (Br2) b) 1- £ N2- £ 3, 5-dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoquinazoalin-3-yl) -1-piperidinyl] methylsuloniminomethyl] -D- tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine To a mixture based on 0.58 g (0.554 mmol) of 1- [N2- [3, 5-dibromo-N- [[4- (3, 4-dihydro-2 (1H) -oxoquinazolin-3-yl) -l-piperidinyl] methylsulfo-niliminomethyl] -D-tyrosyl] -N6- (1, 1-dimethylethoxycarbonyl) -L-lysyl] - - (4-pyridinyl) -piperazine in 20 ml of methylene chloride were added 10 ml of trichloroacetic acid. The reaction mixture was stirred for 3 hours at room temperature and then concentrated in vacuo. The remaining residue was taken up in 50 ml of water and carefully alkalized with solid sodium acid carbonate. The resulting precipitate was filtered with suction, washed well with water and then with t-butylmethyl ether and, finally, air-dried. 0.36 g (69% of theory) of a colorless and amorphous solid were obtained. IR (KBr): 1649 cm "1 (C = 0) Rf: 0.07 (FM1) ESI-MS: (M + H) + = 945/947/949 (Br2) Example 6 1- £ N2- £ 3,5-dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoq; uinazolin-3-yl) - -piperidinyl] phenylsulfonyl-iminomethyl] -D -tyrosyl] -L-lysyl] -4- (4 ~ pyridinyl) -piperazine a) 1- EN2- £ 3, 5 -dibromo-N- £ £ 4- (3,4-dihydro-2 (IB) -oxoquinazolin -3-yl) -1-piperidinyl] phenylsulf-nimiminomethyl] -D-tyrosyl] -N6- (1,1-dimethylethoxycarbo-nyl) -L-lysyl] -4- (4-pyridinyl) -piperazine Prepared analogously to Example 5a), from N- (benzenesul fonyl) -iminodi phenyl carbonate, 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1- [N2- (3, 5-dibromo -Dt irosyl] -N6- (1, 1-dimethylethoxycarbonyl) -L-lysyl] -4- (4-pyridinyl) -piperazine in a yield of 43% of theory.Colorless and amorphous substance IR (KBr): 1657 cm "1 (C = 0) ESI-MS: (M + H) + = 1107/1109/1111 (Br2) (M + H + Na) 565/566/567 (Br2) b) 1- £ N2- E3,5-dibromo-N- ££ 4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] enylsulfo-nili inomethyl] -D- tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine Prepared analogously to Example 5b), from 1- [N2- [3,5-dibromo-N- [[4 - (3, 4 - dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] phenylsulfo-nyl iminome-tl] -D-tyrosyl] -N6- (1,1-dimethyl-t-oxycarbonyl) -Ll isi] - 4 - (4 -pyr idini 1) -piperazine and trifluoroacetic acid in a yield of 91% of theory. Colorless and amorphous substance. IR (KBr): 1649 (C = 0) cm "1 Rf: 0.13 (FM1) ESI-MS: (M + H) + = 1007/1009/1111 (Br2) Example 7 1- £ 4-amino -3,5-dibromo-N- [£ 4- (3,4-dihydro- (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperidine The mixture based on 0.35 g (1,469 mmol) of N-cyano-iminodiflyl carbonate, 0.75 g (1,493 mmol) of 1- [-amino-3, 5-Dibromo-D-phenylalanyl] -4- (1-met il-4-piperidinyl) -piperidine and 30 ml of anhydrous dichloromethane was stirred for 14 hours at room temperature. The reaction mixture was freed from solvent, ultimately under vacuum, and the residue was mixed with 0.35 g (1513 millimoles) of 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and ml of 2-pentanol and boiled under reflux for 24 hours. The mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (silica gel MN 60, Macherey-Nagel, 30-60 μm) using initially dichloromethane and then methanol / concentrated ammonia. (9/1 v / v) for the elution. After the usual work-up, 700 mg (61% of theory) of a colorless, amorphous solid product were obtained. IR (KBr): 1668 (C = 0), 2173 (CN) c "1 Rf: 0.87 (eluent: di chloromethane / methanol / concentrated ammonia 80/20/2 v / v /) ESI-MS: (M + H) + = 782/784/786 (Br2) Example 8 1- £ 4-bromo-N- £ 4 - (3,4-dihydro-2 (1H) -oxagui-nazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -3,5-dimethyl-D , -phenylalanyl] -4- (1-piperidinyl) -piperidine a) 1- £ 4-bromo-N- (phenoxy) sianiminomethyl] • 3, 5-dimethyl-D, L-phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example la), but using dioxane as solvent, from N-cyano-iminodi phenyl carbonate and bis - (trifluoroacetate) of 1- (4-bromo-3,5-dimethyl-D, L-phenylalanyl) -4- (1-piperidinyl) -piperidine in a yield of 51% of theory. Colorless and amorphous substance. b) 1- £ 4-bromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxo-uinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -3,5-dimethyl-D, L-phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1- [4 - bromo-Nt (phenoxy) cyaniminomethyl] -3,5-dimethyl-D, L-phenylalanyl] -4- (1-piperidinyl) -piperidine in a yield of 45% of theory. Colorless and amorphous substance. IR (KBr): 1664 (C = 0), 2173 (CN) cm "1 Rf: 0.37 (eluent: dichloromethane / acetat or ethyl / cyclohexane / methanol / concentrated ammonia 60/16/5/5 / 0.6 v / v / v / v / v) MS: M + = 702/704 (Br2) Example 9 l- £ 3,5-dibromo-N- £ 4 - (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) ~ 1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (4-pyridinyl) -piperazine Prepared analogously to Example lb), from 3, -dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1 - [3,5-dibromo-N- [(phenoxy) cyanimins-methyl] -Dt iros il] - 4 - (4-pyridinyl) -piperazine in a yield of 10% of theory. Colorless and amorphous substance. IR (KBr): 1657 (C = 0), 2171 (CN) cm "1 Rf: 0.68 (eluent: methanol) ESI-MS: (M + H) + = 764/766/768 (Br2) Example 10 1 - £ 4 -amino -3,5-dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) - -piperidinyl] cyanimino-methyl] -D-phenylalanyl] - 4- (4-pyridinyl-piperazine Prepared analogously to Example 7, from N-cyano-iminodiflyl carbonate, 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1- [4-amino-3,5-dibromo-D-phenylalanyl] -4- (4-pyridinyl) -piperazine in a yield of 43% of theory The substance is colorless and amorphous IR (KBr): 1660 (C = 0) , 2171 (CN) cm "1 Rf: 0.27 (eluent: dichloromethane / methanol / concentrated ammonia 9/1 / 0.1 v / v / v) ESI-MS: (M + H) + = 763/765/767 (Br2 ) Example 11 1- £ 3,5-dibromo-N- £ 4 - (3,4-dihydro-2 (1H) -oxoguinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperidine Prepared analogously to Example 7, from N-cyano-iminodi-phenyl carbonate, 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1- [3,5-dibromo-D-tyrosyl] -4- (4-pyridinyl) -piperazine in a yield of 12% of theory. Colorless and amorphous substance. IR (KBr): 2175 (CN) cm "1 Rf: 0.22 (eluent: dichloromethane / me tanol / concentrated ammonia 8/2 / 0.2 v / v / v) ESI-MS: (M + H) + = 733 / 785/787 (Br2) Use 12 1- £ 3, 5-dibromo-Nl-4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- ( 4-methyl-1-piperazinyl) -piperidine Prepared analogously to Example 7, starting with N-cyano-iminodiphenyl carbonate, 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quina zol inona and 1- [3,5-dibromo-D-tyrosyl] -4- (4-methyl-1-piperazinyl) -piperidine in a yield of 13% of theory.

Colorless and amorphous substance. IR (KBr): 1674 (C = 0), 2173 (CN) cm "1 Rf: 0.30 (eluent: dichloromethane / methanol / concentrated ammonia 8/2 / 0.2 v / v / v) ESI-MS: (M + H) + = 784/786/788 (Br2) Example 13 1- £ 4-bromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoqui-nazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -3,5-dimethyl-D phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperidine Prepared analogously to Example 7, from N-cyano-iminodi phenyl carbonate, 3,4-dihydro-3- (4-piperidinyl) -2 - (1 H) -quinazolinone and 1 - [4-bromo-3,5-dimethyl-l-D-phenylalani 1] -4- (l-methyl-4-piperidinyl) -piper idine in a yield of 44% of theory. Colorless and amorphous substance. IR (KBr): 1666 (C = 0), 2173 (CN) cm "1 Rf: 0.63 (eluent: dichloroethane / cyclohexane / methanol / concentrated ammonia 70/15/15/2 v / v / v / v) MS: M + = 716/718 (Br2) Example 14 1- £ 4-amino-3, 5 -dibromo-N- £ 4 - £ 1, 3-dihydro-4-phenyl- (1H) -oxo-imidazol-1-yl] -1-piperidinyl] cyaniminomethyl ] -D-phenylalanyl] -4- (4-methy1-piperazyl-nyl) -piperidine a) 1- [4-amino-3,5-dibromo-N- (phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (4-methyl-l-piperazyl-nyl) -piperidine Prepared analogously to Example la), from N-cyano-iminodi-phenyl carbonate and bis- (trifluoroacetate) of 1- (4-amino-3) , 5-dibromo-D-phenylalanyl) -4- (4-met il-1-piperazinyl) -piperidine in a yield of 82% of theory. Colorless and crystalline substance of Rf 0.56 (MLl). IR (KBr): 1610 (C = 0), 2195 (CN) cm "1 ESI-MS: (M + H) + = 646/648/650 (Br2) b) 1- £ 4-amino-3, 5-dibromo-N- ££ 4- £ l, 3-dihydro-4-phenyl-2 (1H) -oxoimidazol-1-yl] -1-piperidi-nil] cyaniminomethyl] -DF nilalanyl] -4- (4-methyl--pperazinyl) -piperidine Prepared analogously to Example lb), from 1,3-dihydro-1- (4-piperidinyl) -4-phenyl-2 (2H ) -imidazolone and 1 - [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenyl-alanyl] -4- (4-methyl-1-piperazinyl) -piperidine in a yield of 19% of the theoretical Colorless and amorphous substance. IR (KBr): 1699 (C = 0), 2173 (CN) cm "1 Rf: 0.15 (eluent: dichloromethane / methanol / concentrated ammonia 9/1 / 0.1 v / v /) ESI-MS: (M + H ) + = 796/798/800 (Br2) Example 15 1- £ 4 -amino-3,5-dibromo-N- ££ 4- (2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) - 1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (4-methyl-1-piperazinyl) -piperidine Prepared analogously to Example lb), from 3- (1-piperidinyl) -2, 3, 4, 5 -t et rahidro-l, 3-benzodiazepin-2 (1H) -one and 1- [4-amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (4- methyl-1-piperazinyl) -piperidine in a yield of 5% of theory. Colorless and amorphous substance. IR (KBr): 1653 (C-0), 2173 (CN) cm "1 Rf: 0.27 (eluent: dichloromethane / methanol / concentrated ammonia 9/1 / 0.1 v / v /) ESI-MS: (M + H ) + = 797/799/801 (Br2) Example 16 1- £ 4-amino-3, 5-dibromo-Nl [4- (2, 4-dihydro-5-pheny1-3 (3H) -oxo-1,2,4-tria-ol-2-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidi-nyl) -piperidine a) 1- £ 4-amino-3 5-dibromo-N- (phenoxy) cyan-iminomethyl] -D phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example la), from N-cyano-1-inodiphenyl carbonate and l- (4-amino-3,5-dibromo-D-phenylalanyl) -4- (1-piperidinyl) -piperidine in a yield of 93% of theory. Colorless and crystalline substance of R 0.25 (eluent: dichloromethane / methanol 9/1 v / v). IR (KBr): 1616 (C = 0), 2197 (CN) cm "1 ESI-MS: (M + H) + = 631/633/635 (Br2) b) 1- £ 4 -amino-3, 5 -dibromo-N- ££ 4- (2,4-dihydro-5-enyl-3 (3H) -oxo-1,2,4-triazole -2-il ) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 2,4-dihydro-2- (4-piperidinyl) -5-phenyl - 1, 2, 4-1-riazole-3 (3H) -one and 1 - [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-piperi) -dinil) -piperidine in a yield of 31% of theory. Colorless and amorphous substance. IR (KBr): 1695 (C = 0), 2173 (CN) cm "1 Rf: 0.26 (eluent: dichloromethane / methanol / concentrated ammonia 9/1 / 0.1 v / v / v) ESI-MS: (M + H) + = 781/783/785 (Br2) Example 17 1- £ 4-amino-3, 5-dibromo-N- £ 4 - (2, 3, 4, 5 tetrahydro-2 (1H) -oxo-, 3-benzodiazepin-3-yl) -1- piperidinyl] cyaniminomethyl] -DF nilalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 3- (4-piperidinyl) -2,3,4,5-tetrahydro-1,3- benzodiazepin-2 (1H) -one and 1- [4-amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine in a yield of 22 % of the theoretical Colorless and amorphous substance. IR (KBr): 1658 (C = 0), 2171 (CN) c "1 Rf: 0.33 (eluent: dichloromethane / methanol / concentrated ammonia 9/1 / 0.1 v / v / v) ESI-MS: (M + H) + = 782/784/786 (Br2) Example 18 1- £ 3, 5-dibromo-N- £ 4 -4 (2,4-dihydro-5-phenyl-3 (3H) -oxo-1,2,4-triazol-2-yl) -1 - piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (-piperidinyl) -piperidine a) l-3, 5-dibromo-N- (phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example la), from N-cyano-iminodiphenyl carbonate and 1- (3,5-dibromo-D-tyrosyl) -4- (1-piperidinyl) -piperidine in a yield of 51% of the theoretical. Colorless and crystalline substance of Rf 0.86 (eluent: dichloromethane / methanol / concentrated ammonia 75/25/5 v / v / v) ESI-MS: (M + H) + = 632/634/636 (Br2) (MH) ~ = 630/632/634 (Br2) b) l- £ 3,5-dibromo-NE £ 4- (2,4-dihydro-5-enyl-3 (3H) -oxo-1,2,4-triazol-2-yl) -1-piperidinyl] -cyaniminomethyl] -D-tyrosyl] -4- (-piperidinyl) -piperi-dine Prepared analogously to Example Ib), from 2,4-dihydro-2- (4-piperidinyl) -5-phenyl-1, 2 , 4-1 ria zol -3 (3H) -one and 1- [3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine in a yield of 32% of the theoretical. Colorless and amorphous substance. IR (KBr): 1695 (C = 0), 2173 (CN) cm "1 Rf: 0.33 (FM1) ESI-MS: (M + H) + = 782/784/786 (Br2) Example 19 1- £ 3, 5-dibromo-N- ££ 4- (2,3,4, 5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) -1-piperidinyl] -cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 3- (4-piper idinyl) -2, 3, 4, 5-tetrahydro-l, 3 -benzodiazepin-2 (1H) -one and 1- [4-amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidi-nyl) -piperidine in a yield of 40% of the theoretical. Colorless and amorphous substance. IR (KBr): 1653 (C = 0), 2171 (CN) cm "1 Rf: 0.44 (FM1) ESI-MS: (M + H) + = 783/785/787 (Br2) Ex e plo 20 1- £ 3, 5 -dibromo-N- £ £ 4- (2,4-dihydro-5-phenyl-3 (3H) -oxo-1,2,4-triazole-2-yl) - 1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (1-methyl-1-piperidinyl) -piperazine a) l-3, 5-dibromo-N- (phenoxy) cyaniminomethyl] -D-tyrosyl] - 4- (l-methyl-4-piperidinyl) -piperazine Prepared analogously to Example la), from N-cyano-iminodiflyl carbonate and 1- (3,5-dibromo-Dt i ros i 1) -4- (l-methyl-4-piperidinyl) -piperazine in a yield of 44% of theory. Colorless and crystalline substance of Rf 0.50 (eluent: dichloromethane / methanol / concentrated ammonia 75/25/5 v / v / v). IR (KBr): 1622 (C = 0) c "1 ESI-MS: (M + H) + = 647/649/651 (Br2) (M-H)" = 645/647/649 (Br2) b) 1- £ 3, 5-dibromo-N- £ £ 4- (2,4-dihydro-5-enyl-3 (3H) -oxo-1,2,4-triazol-2-yl) -1 - piperidinyl] -cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidi-nyl) -piperazine Prepared analogously to Example lb), from 2,4-dihydro-2- (4-piper idinyl) -5-phenyl-1,2,4-triazole-3 (3H) -one and 1- [3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-met) il-4-piperidini 1) -piperazine in a yield of 20% of theory. Colorless and amorphous substance. IR (KBr): 1701 (C = 0), 2173 (CN) cm "1 Rf: 0.18 (eluent: dichloroethane / methanol / concentrated ammonia 8/2 / 0.2 v / v / v) ESI-MS: (M + H) + = 797/799/801 (Br2) Example 21 1- £ 3, 5-dibromo-N- £ £ 4- (2, 3 f 4, 5-tetrahydro-2 (1H) -oxo-, 3-benzodiazepin-3-yl) -1-piperidinyl] - cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidi-nyl) -piperazine Prepared analogously to Example Ib), from 3- (4-piper idinyl) -2, 3, 4, 5 - 1 et rahidro- 1, 3-benzodia zepin-2 (1H) -one and 1- [3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) ) -piperazine in a yield of 32% of theory. Colorless and amorphous substance. IR (KBr): 1653 (C = 0), 2171 (CN) cm "1 Rf: 0.19 (eluent: dichloromethane / methanol / concentrated ammonia 8/2 / 0.2 v / v / v) ESI-MS: (M + H) + = 793/800/802 (Br2) (MH) "= 796/798/800 (Br2) Example 22 1- £ 4-amino-3,5-dibromo-N- £ 4 - (2,4-dihydro-5-phenyl-3 (3H) -oxo-1,2,4-triazol-2-yl ) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperazine a) l-4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidi-nyl) -piperazine Prepared analogously to Example la), from N-cyano-iminodiphenyl carbonate and l- (4-amino-3. -dibromo- D-phenylalanyl) -4- (l-methyl-4-piperidini 1) -piperazine in a yield of 38% of theory. Colorless and crystalline substance of Rf 0.57 (FM1). IR (KBr): 1689 (C = 0) cm "1 ESI-MS: (M + H) + = 646/648/650 (Br2) b) 1- £ 4-amino-3, 5-dibromo-N- £ 4- (2,4-dihydro-5-f nyl-3 (3H) -oxo-l, 2,4-triazole- 2-yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperazine Prepared analogously to Example lb), from 2, 4-dihydro-2- (4 -piperidinyl) -5-phenyl-1,2,4-t-riazole-3 (3H) -one and 1 - [4-amino-3,5-dibromo-N- [(phenoxy) -cyaniminomethyl] -D-phenylalanyl] -4- (1-methyl-4-piperidinyl) -piperazine in a yield of 9% of theory. Colorless and amorphous substance. IR (KBr): 1701 (C = 0), 2171 (CN) cm "1 Rf: 0.33 (FM1) EST-MS: (M + H) + = 796/798/800 (Br2) Example 23 1- £ 4 -amino-3,5-dibromo-N- ££ 4- (2, 3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) - 1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-methyl-1-piperidinyl) -piperazine Prepared analogously to Example lb), from 3- (4-piper idinyl) -, 3, 4, 5 - tetrahydro-1,3-benzodiazepin-2 (1H) -one and 1- [4-amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-methyl- 4-piperidinyl) -piperazine in a yield of 15% of theory. Colorless and amorphous substance. IR (KBr): 2173 (CN) cm "1 Rf: 0.19 (FM1) ESI-MS: (M + H) + = 797/799/801 (Br2) Example 24 1- £ 3, 5 -dibromo -N- £ £ 4- (3,4-dihydro-2 (1H) -oxoq-inazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -4-methyl-D , - enylalanyl] -4- (1-methyl-l-piperidinyl) -piperidine Prepared analogously to Example 7, from N-cyano-iminodifeni carbonate, 3,4-dihydro-3- (4-piperidini 1) -2 (1H) -quinazolinone and 1- [3,5-dibromo-4-methyl-D, L-phenylalanyl] -4- (1-methyl-1-piperidinyl) -piperidine in a yield of 49% of theory . Colorless and crystalline substance. IR (KBr): 1668 (C = 0), 2175 (CN) cm "1 Rf: 0.5 (FM1) ESI-MS: (M + H) + = 781/783/785 (Br2) (MH)" = 779 / 781/783 (Br2) Example 25 1- £ 3, 5-dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -4-methyl-D, Lf nilalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example 7, from N-cyano-iminodiphenyl carbonate, 3,4-dihydro-3- (4-piperidinyl) -2 (1H) -quinazolinone and 1- [3,5-dibromo-4-methyl-D, L-phenylalanyl] -4- (1-piperidi-nyl) -piperidine in a yield of 34% of theory. Colorless and crystalline substance. IR (KBr): 1664 (C = 0), 2175 (CN) cm "1 Rf: 0.55 (FM1) ESI-MS: (M + H) + = 767/769/771 (Br2) (MH)" = 765 / 767/769 (Br2) E g 26 1- £ 3, 5-dibromo-N- £ £ 4- (3,4-dihydro-2 (1H) -oxoq ^ uinazolin-3-yl) -1-piperidinyl] cyaniminomethyl] -4-methyl- D, L-phenylalanyl] -4- (4-pyridinyl) -piperidine Prepared analogously to Example 7, from N-cyano-iminodifeni carbonate, 3,4-dihydro-3- (4-piperidini 1) -2 (1H) -quinolinone and 1- [3, 5 -dibromo-4-methyl-D, L-phenylalanyl] -4- (4-pyridinyl) -piperazine in a yield of 6% of theory. Colorless and crystalline substance. IR (KBr): 2171 (CN) cm "1 Rf: 0.60 (FM1) ESI-MS: (M + H) + - 762/764/766 (Br2) Example 27 1- £ 4-amino-3, 5-dibromo-N- £ 4 - (1,3-dihydro-2 (2H) -oxoimidazo £ 4, 5-c] guiolinin-3-yl) -1 - piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidi-nil) -piperidine Prepared analogously to Example lb), from 1,3-dihydro-3- (4-piper idini 1) -imidazo [4 , 5-C] quinolin-2 (2H) -one and 1 - [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl-D-phenylalanyl] -4- (1-piperidinyl) - piper idina in a yield of 9% of the theoretical. Colorless and amorphous substance. IR (KBr): 1712 (C = 0), 2173 (CN) cm "1 Rf: 0.45 (FM1) ESI-MS: (M + H) + = 805/307/309 (Br2) Example 28 1- £ 4 -amino-3, 5-dibromo-N- £ 4- (7-methoxy-2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3 -yl) -1-piperidinyl] cyaniminomethyl] -D-enylalanyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 7-methoxy-3- (4-piperidine 1) -2 , 3, 4, 5 -tetrahydro-1,3-benzodiazepin-2 (1H) -one and l- [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4 - (1-piperidinyl) -piper idine in a yield of 51% of theory. Colorless crystals (in acetone). IR (KBr): 1658 (C = 0), 2173 (CN) cm "1 Rf: 0.65 (FM1) ESI-MS: (M + H) + = 812/814/816 (Br2) EXAMPLE 29 1- £ 4-amino-3,5-dibromo-N- £ 4 - (5,7-dihydro-6-oxodiben or £ d, f] - £ l, 3] diazepin-5-yl) - 1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (-piperidin-nyl) -piperidine a) 2-nitro-2'-β-1- (f-nylmethyl) -4-piperidinyl] amino] -biphenyl To solution of 30.0 g (0.140 mol) of 2-amino-2'-nitrobiphenyl and 111.5 g (0.630 mol) of 1- (phenylmethyl) -4-piperidone in 1200 ml of dichloromethane were added in portions, maintaining a reaction temperature of 0 ° C, in total 140.5 g (0.630 moles) of sodium triacetoxyborohydride and then stirred for 14 hours at room temperature. The mixture was basified with sodium hydroxide, the dichloromethane phase was separated, dried over sodium sulfate and concentrated by evaporation. The residue was digested with methanol, after which it was filtered. The filtrate was concentrated by evaporation and the remaining residue was purified by chromatography on aluminum oxide (activity step 3) using PE / EE 9/1 (v / v) as eluent. The corresponding fractions were combined, freed of solvent and used in the next step without further purification. Yield: 40.0 g (74% of theory). b) 2-amino-2 '- £ 1- (nylmethyl) -4-piperidinyl] amino] -biphenyl The solution of 40.0 g (0.103 mol) of 2-nitro-2' - [[1- (phenylmethyl) - 4-piperidinyl] mino] -biphenyl in 500 ml of methanol was hydrogen for 2 hours in the presence of rhodium moistened with 5 percent water. The catalyst was removed by filtration, the obtained solution was concentrated by evaporation and the unpurified product, thus obtained, was used in the next step without further purification. Yield: 36.0 g (98% of theory). c) 5, 7-dihydro-5- £ 1- (phenylmethyl) -4-piperidinyl] -dibenzo- £ d, f] £ 1,3] diazepin-6-one To the solution of 36.0 g (0.101 moles) ) of 2-amino-2 '- [[1- (phenylmethyl) -4-piperidinyl] amino] -biphenyl in 200 ml of dimethylformamide was added 40.5 g (0.250 moles) of N, N'-carbonyldiimidazole, then The mixture was stirred for 2 hours at 100 ° C, after which the solvent was removed in vacuo. The residue was mixed with water and then extracted to exhaustion with dichloromethane. The combined organic extracts were dried over sodium sulfate, clarified with activated charcoal and concentrated by evaporation. The residue (60 g) was purified by chromatography on aluminum oxide with an activity step 3 using PE / EE 2/1 (v / v). The desired compound was obtained from the corresponding fractions in a yield of 6.2 g (16% of theory). IR (KBr): 1676 (C = 0) cm "1 Rf: 0.35 (eluent: dichloromethane / methanol 9.5 / 0.5 v / v) MS: M 383 d) 5, 7-dihydro-5- (4-piperidinyl) -diben-zo [d, f] £ 1, 3] diazepin-6-one The solution of 6.0 g (0.016 mole) of 5,7-dihydro- 5- [1- (phenylmethyl) -4-piperidinyl] dibenzo- [d, f] [1,3] diazepin-6-one in 200 ml of methanol was hydrogenated at 50 ° C in the presence of 1.5 g of palladium / carbon at 10 percent until the completion of hydrogen absorption. After separating the catalyst and the solvent, 3.5 g (76% of theory) of the desired compound was obtained which was used in the next step without further purification. Rf: 0.15 (FM1) MS: M + = 293 e) 1- £ 4 -amino-3, 5 -dibromo-N- £ £ 4- (5,7-dihydro-6-oxodibenzo-d, f] -3,3] diazepin-5-yl) - -piperidinyl ] cyaniminomethyl] -DF nilalanyl] -4- (1-piperi-dini) -piperidine Prepared analogously to Example lb), from 5,7-dihydro-5- (4-piperidinyl) -dibenzo [d, f] [ 1,3] diazepin-6-one and 1- [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-piperidinyl) -piperidine in a yield of 25% of the theoretical Colorless crystals IR (KBr): 1684 (C = 0), 2173 (CN) c "1 Rf: 0.65 (FM1) ESI-MS: (M + H) + * 830/832/834 (Br2) EXAMPLE 30 1- £ 4 -amino-3, 5-dibromo-N- £ £ 4- (7-methoxy-2,3,4,5-tetrahydro-2 (1H) -oxo-, 3-bonzodiazepin-3- il) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperazine Prepared analogously to Example lb), from 7-methoxy -3- (4-piperidinyl) - 2, 3, 4, 5 -tet rahydro-1, 3-benzodiazepin-2 (1H) -one and l- [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (1-methyl-4-piperidinyl) -piperazine in a yield of 53% of theory. Colorless crystals (di- i sopropi lé t er). IR (KBr): 1647 (C = 0) c "1 Rf: 0.75 (eluent: dichloromethane / methanol / concentrated ammonia 70/25/5 v / v / v) ESI-MS: (M + H) + = 827 / 829/831 (Br2) (MH) "= 825/827/829 (Br2) EXAMPLE 31 1- £ 4 -amino-3, 5 -dibromo-N- £ £ 4- £ 1, 3 -dihydro-2 (2H) -oxoimidazo- £ 4, 5-c] quinolin-3-yl] -1 -piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) piperane Prepared analogously to Example lb), from 1,3-dihydro-3- (4-piperidinyl) - imidazo [4, 5-c] quinolin-2 (2H) -one and 1- [4-amino-3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenyl-alanyl] -4- (1 -methyl-4-piperidinyl) piperazine in a yield of 13% of theory. Colorless and crystalline substance. IR (KBr): 1711 (C = 0) c "1 Rf: 0.70 (eluent: dichloromethane / methanol / concentrated ammonia 70/25/5 v / v / v) ESI-MS: (M + H) + = 820 / 822/824 (Br2) (MH) "= 818/820/822 (Br2) Example 32 1- £ 4-amino-3,5-dibromo-N-f-4- (2, 3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) - 1-pipe-ridinyl] sulfonyl] -D-phenyl-alanyl] -4- (l-methyl-4-pipe-ridinyl) -piperazine a) 1- £ 4-imino-3, 5-dibromo-N- (2 -hydroxyphene-oxysilon) -D-enylalanyl] -4- (l-methyl-4-piperidi-nyl) -piperazine Under external cooling with ice were added, to the solution of 2,000 g (3,974 millimoles) of 1 - ( 4-amino-3, 5-dibromo-D-phenylalanyl) -4 - (1-met il-4-piperidinyl) -piperazine and 0.61 ml (0.004 millimoles) of triethylamine in 50 ml of dimethylformamide, 1.377 g (7.998 millimoles) of equine pyrocat sulfate and then stirred for 1 hour under cooling with additional ice and for 2 hours at room temperature. The reaction mixture was concentrated in vacuo at a maximum bath temperature of + 40 ° C, the residue was triturated with diethyl ether, air dried and used in the next step without further purification. Yield: 2.68 g (100% of theory).

Rf: 0.30 (FM1). b) 1- £ 4-amino-3, 5-dibromo-N-££ 4- (2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) - 1-piperidinyl] sulfonyl] -D-phenylalanyl] -4- (-methyl-4-piperidinyl) -piperazine The mixture based on 2,680 g (3,968 millimoles) of 1- [4-amino-3, 5-dibromo-N - (2-hydroxyphenoxysulfonyl) -D-phenylalanyl] -4- (l-methyl-4-piperidinyl) -piperazine, 1.472 g (6.00 millimoles) of 3- (4-piperidinyl) -2, 3, 4, 5-tetrahydro ~ l, 3-benzo-diazepin-2 (1H) -one and 100 ml of dioxane were refluxed for 1 hour, then concentrated by evaporation in vacuo and the residue was added with stirring in 200 ml of aqueous ammoniacal solution at room temperature. 10 percent. The mixture thus obtained was extracted to exhaustion with ethyl acetate. The combined organic extracts were dried over sodium sulfate and freed from solvent. The residue was purified by chromatography on silica gel (silica gel MN 60, Macherey-Nagel, 30-60 μm) using FM1 as eluent. The suitable fractions were combined, concentrated by evaporation, the residue was mixed by triturating with diethyl ether, suction filtered and dried under vacuum. 0.1 g (3.1% of theory) of the target compound were obtained in the form of colorless crystals of Rf 0.65 (FM1). IR (KBr): 1657 (C = 0) cm "1 ESI-MS: (M + H) + = 809/811/813 (Br2) Example 33 1- £ 3, 5 -dibromo-N- £ 4 - (7-methoxy-2, 3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl) - 1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (1-piperi-dinyl) -piperidine Prepared analogously to Example lb), from 7-methoxy-3 - (4-piper idini 1) -2, 3 , 4,5-tetrahydro-1,3-benzodiazepin-2 (1H) -one and l- [3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piper idina in a yield of 24% of the theoretical. Colorless crystals (diethyl ether). IR (KBr): 1653 (C = 0) cm "1 Rf: 0.31 (FM1) ESI-MS: (M + H) + = 813/815/817 (Br2) Ex em 1o 34 1- £ 3, 5 -dibromo-N- £ £ 4- (7-methoxy -2, 3,4,5-t trahydro-2 (1H) -oxo-1,3-benzodiazepin- 3- il) -1-piperidinyl] cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperazine Prepared analogously to Example lb), from 7-methoxy-3- (4-piperidini 1) -2, 3, 4, 5 -tetrahydro-1, 3-benzodiazepin-2 (1H) -one and l- [3,5-dibromo-N- [(phenoxy) cia iminomethyl] -D-tyrosyl] -4- (1-ethyl-4-piperidinyl) -piperazine in a yield of 23% of the theoretical. Colorless crystals (diethyl ether).

IR (KBr): 1647 (C = 0) cm "1 Rf: 0.42 (eluent: dichloromethane / methanol / concentrated ammonia 75/25/5 v / v / v) ESI-MS: (MH)" = 826/828 / 830 (Br2) Example 35 1- £ 3,5-dibromo-N- £ 4 - £ 1, 3-dihydro-2 (2H) -oxomidazo-4,4-c] -quinolin-3-yl] -1-piperidinyl] - cyaniminomethyl] -D-tyrosyl] -4- (1-piperidinyl) -piperidine Prepared analogously to Example lb), from 1,3-dihydro-3- (4-piperidini-1) -imide zo [4, 5-c ] quinolin-2 (2H) -one and 1 - [3,5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (1-piperidi-nyl) -piperidine in a yield of 10% of the theoretician. Colorless and crystalline substance. IR (KBr): 1709 (C = 0) cm "1 Rf: 0.21 (FM1) ESI-MS: (M + H) + = 806/808/810 (Br2) (MH) ~ = 804/806/808 ( Br2) Example 36 1- £ 3, 5 -dibromo-N- £ £ 4- £ 1, 3 -dihydro -2 (2H) -oxomidazo £ 4, 5-c] -quinolin-3-yl] -1-piperidinyl] cyaniminomethyl ] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperazine Prepared analogously to Example lb), from 1,3-dihydro-3- (4-piperidini-1) -imidazo [4, 5] -c] quinolin-2 (2H) -one and 1 - [3, 5 -dibromo-N- [(phenoxy) cyaniminomethyl] -D-tyrosyl] -4- (l-methyl-4-piperidinyl) -piperazine in a yield of 31% of the theoretical. Colorless and crystalline substance. IR (KBr): 1635, 1705 (C = 0) cm "1 Rf: 0.07 (eluant: dichloro et anus / ethanol / ammonium concentrate 80/20/2 v / v / v) ESI-MS: (M + H) + = 821/823/825 (Br2) (MH) "= 819/821/823 (Br2) Example 37 1- £ 4-amino-3,5-dibromo-N-£ 4 - (7-methoxy-2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3 -yl) -1-piperidinyl] cyaniminomethyl] -D-phenylalanyl] -4- (4-methyl-1-piperazinyl) -piperidine Prepared analogously to Example lb), from 7 -metox-3- (4-piperidinyl) ) -2, 3, 4, 5-tet rahydro-1, 3-benzodiazepin-2 (1H) -one and l- [4-amino-3,5-di-romo-N- [(phenoxy) cyaniminomethyl] -D phenylalanyl] -4- (4-methyl-1-pipera zini 1) -piperidine in a yield of 21% of theory. Colorless crystals (diethyl ether). Rf: 0.53 (eluent: dichloromethane / methanol / concentrated ammonia 80/20/2 v / v / v) ESI-MS: (M + H) + = 827/829/831 (Br2) (MH) "= 825 / 827/829 (Br2) (M + Na) + = 849/851/853 (Br2) Example 38 1- £ 4-amino-3, 5 -dibromo-N- £ £ 4- £, 3 -dihyd or-2 (2H) -oxoimidazo- £ 4, 5-c] uinolin-3-yl] -1 -piperidinyl] cyaniminomethyl] -D-enylalanyl] -4- (4-methyl-1-piperazinyl) -piperidine Prepared analogously to Example lb), from 1,3-dihydro-3- (4-piperidinyl) -imide zo . { 4,5-C] quinolin-2 (2H) -one and 1 - [4-amino-3, 5-dibromo-N- [(phenoxy) cyaniminomethyl] -D-phenylalanyl] -4- (4-methyl-1 -pipe zini 1) -piperidine in a yield of 8% of theory. Colorless and crystalline substance (dii sopropi ether), IR (KBr): 1714 (C = 0) cm "1 Rf: 0.43 (eluent: dichloromethane / methanol / concentrated ammonia 80/20/2 v / v / v) ESI- MS: (M + H) + = 820/822/824 (Br2) (MH) "= 818/820/822 (Br2) The following Examples describe the preparation of pharmaceutical application forms which, as an active ingredient, contain a compound arbitrary of general formula I: Ex e l I Capsules for the inhalation of dust with 1 mg of active principle Composition; 1 capsule for inhalation of powder contains: Active ingredient 1.0 mg Lactose 20. b mg Hard gelatin capsules 50.0 mg 71.0 mg Preparation procedure: The active principle is milled to the grain size necessary for inhalatives. The milled active ingredient is mixed homogeneously with the lactose. The mixture is filled into hard gelatin capsules.

Example II Solution for inhalation for Respi at® with 1 mg of active ingredient Composition: 1 run contains: Active principle 1.0 mg Benzalkonium chloride 0.002 g Disodium edetate 0.0075 mg Purified water up to 15.0 μl Preparation procedure: The active ingredient and benzalkonium chloride are dissolved in water and packed in Respimat® cartridges.

Example III Solution for inhalation for nebulizers with 1 mg of active principle. Composition: 1 vial contains: Active principle 0.1. g Sodium chloride 0.18 .g Benzalkonium chloride 0.002 g Purified water up to 20.0 ml Preparation procedure: The active substance, sodium chloride and benzalkonium chloride are dissolved in water.

Example IV Dosing aerosol with propellant gas with 1 mg of active ingredient Composition: 1 run contains: Active principle 1.0 mg Lecithin 0.1% Propellant gas up to 50.0 μl Preparation procedure: The micronized active ingredient is suspended homogeneously in the mixture based on lecithin and propellant gas. The suspension is packaged in a pressure vessel with a metering valve.

EXAMPLE V Nasal spray with 1 mg of active ingredient Composition: Active principle 1.0 mg Sodium chloride 0.9 mg Benzalkonium chloride 0.025 mg Disodium edetate 0.05 mg Purified water up to 0.1 ml Preparation procedure: The active principle and the adjuvants are dissolved in water and packed in a corresponding container.

Example VI Solution for injection with 5 mg of active substance per 5 ml Composition: Active substance 5 mg Glucose 250 mg Human serum albumin 10 mg Glycofurol 250 mg Water for injection purposes up to 5 ml Preparation: Dissolve glycofurol and glucose in water for injection purposes (AFI); add human serum albumin; dissolve the active ingredient under heating; complete with AFI up to the volume of the batch; Pack in ampoules under gasification with nitrogen.

Example VII Solution for injection with 100 mg of active substance per 20 ml Composition: Active substance 100 mg Monopotassium dihydrogen phosphate = KH2P04 12 mg Disodium hydrogen phosphate = Na2HP04.2H20 2 mg Sodium chloride 180 mg Human serum albumin 50 mg Polysorbat 80 20 mg Water for injection purposes up to 20 ml Preparation: Dissolve Polysorbate 80, sodium chloride, dihydrogen phosphate or monopotassium and disodium hydrogen phosphate in water for injection purposes (AF I); add human serum albumin; dissolve the active ingredient under heating; complete with AFI up to the volume of the batch; pack in ampoules.

Example VIII Lyophilized with 10 mg of active substance Composition: Active substance 10 mg Mannitol 300 mg Human serum albumin 20 mg Preparation: Dissolve the mannitol in water for injection purposes (AFI); add human serum albumin; dissolve the active ingredient under heating; complete with AFI up to the volume of the batch; pack in vials; lyophilize.

Solvent for lyophilisation: Polysorbat 80 = Tween 80 20 mg Manite 200 mg Water for injection purposes up to 10 ml Preparation: Dissolve Polysorbat 80 and manita in water for injection purposes (AFI); pack in ampoules.

Example IX Tablets with 20 mg of active substance Composition: Active substance 20 mg Lactose 120 mg Corn starch 40 mg Magnesium stearate 2 mg Povidone K 25 18 mg Preparation: Mix homogenously the active substance, the lactose and the corn starch; granulate with an aqueous solution of Povidone; mix with magnesium stearate; pressing in a tablet press; tablet weight 200 mg.

Example X Capsules with 20 mg of active substance Composition: Active substance 20 mg Corn starch 80 mg Silicic acid, very dispersed 5 mg Magnesium stearate 2.5 mg Preparation: Mix homogenously the active substance, corn starch and silicic acid; mix with magnesium stearate; pack the mixture in a capsule packing machine in hard gelatin capsules of size 3.

Example XI Suppositories with 50 mg of active substance Composition: Active substance 50 mg Hard fat (solid fat) q.s. Up to 1700 mg Preparation : Melt the fat hard to approximately 38 ° C; homogeneously disperse the milled active substance in the hard melted fat; After cooling, pour into previously cooled molds up to approximately 35 ° C.

Example XII Aqueous solution for nasal application with 10 mg of active substance Composition: Active substance 10.0 mg Hydrochloric acid in the amount necessary for the formation of a neutral salt Parahydroxybenzoic acid methyl ester (PHB) O.Ol mg Parahydroxybenzoic acid propyl ester (PHB) 0. 005 mg Purified water up to 1.0 ml Preparation: The active principle is dissolved in purified water; Hydrochloric acid is added until the solution becomes clear; PHB methyl and propyl ester are added; the solution is completed with purified water up to the volume of the batch. The solution is filtered under sterile conditions and packaged in a corresponding container.

Example XIII Aqueous solution for nasal application with 5 mg of active substance Composition: Active substance 5 mg 1,2-propandiol 300 mg Hydroxyethylcellulose 5 mg Sorbic acid 1 mg Purified water up to 1 ml Preparation: The active substance is dissolved in 1,2-propanediol; A solution of hydroxyethylcellulose in sorbic acid with purified water content is prepared and added to the active ingredient solution; The solution is filtered under sterile conditions and packaged in a corresponding container.

Example XIV Aqueous solution for intravenous application with 5 mg of active substance Composition: Active substance 5 mg 1,2-propanediol 300 mg Mannitol 50 mg Water for injection purposes (AFI) up to 1 ml Preparation: The active substance is dissolved in 1,2-propanediol; the solution is completed with AFI up to approximately the volume of the batch; the hand is added and it is completed with AFI up to the volume of the batch; The solution is filtered under sterile conditions, packaged in individual containers and autoclaved.

Example XV liposomal formulation for intravenous injection with 7.5 mg of active substance Composition: Active substance 7.5 mg Egg lecithin, for example Lipoid E 80 100.0 mg Cholesterol 50.0 mg Glycerol 50.0 mg Water for injection purposes up to 1.0 ml Preparation; The active principle is dissolved in a mixture based on lecithin and cholesterol; the solution is added to a mixture based on glycerol and AFI and homogenized by high pressure homogenization or microfluidizer technique; The liposomal formulation, thus obtained, is packaged in a corresponding container under aseptic conditions.

EXAMPLE XVI Suspension for nasal application with 20 mg of active substance Composition: Active substance 20.0 mg Carboxymethylcellulose (CMC) 20.0 mg Monohydrogen phosphate buffer or sodium / dihydrogen phosphate or sodium pH 6. c.s.

Sodium chloride 8.0 mg Parahydroxybenzoic acid methyl ester 0.01 mg Parahydroxybenzoic acid propyl ester 0.003 mg Purified water up to 1.0 ml Preparation: The active ingredient is suspended in an aqueous solution of CMC; the other components are added successively to the suspension and the suspension is completed to the volume of the batch with purified water.

Example XVII Aqueous solution for subcutaneous application with mg of active substance Composition: Active substance 10.0 mg Sodium monohydrogen phosphate buffer / sodium dihydrogen phosphate c.s. up to pH 7.0 Sodium chloride 4.0 mg Water for injection purposes up to 0.5 ml Preparation: The active ingredient is dissolved in the phosphate buffer solution and, after the addition of the common salt, the volume of the batch is completed with water. The solution is filtered under sterile conditions and autoclaved after incorporation into a corresponding container.

Example XVIII Aqueous suspension for subcutaneous application with 5 mg of active substance Composition: Active substance 5.0 mg Polysorbate 80 0.5 mg Water for injection purposes 0.5 ml Preparation: The active ingredient is suspended in the solution of _ Polysorbat 80 and crumbles to a particle size of approximately 1 μm by a suitable dispersion technique (eg wet grinding, high pressure homogenization, microfluidization, etc.) . The suspension is packaged in a corresponding container under aseptic conditions.

Claims (11)

1. CLAIMS 1. Amides of modified amino acids of the general formula wherein R means the group 1 -piperidinyl, which in the 4-position is substituted with a aza-, diaza- or triaza-heterocycle of 5-7 members, attached through a nitrogen atom, unsaturated once or twice, containing one or two carbonyl groups bonded with a nitrogen atom, the above-mentioned heterocycles may be substituted on a carbon atom with an optionally substituted phenyl group, an olefinic double bond of one of the aforementioned unsaturated heterocycles may be condensed with a ring of benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methyl-pyrrole, quinoline, imidazole or N-met il-imidazole, or two benzene olefinic bonds may be fused with benzo in one of the above-mentioned unsaturated heterocycles, and the phenyl group mentioned above may be mono-, di- or trisubstituted, as well as the heterocycles condensed with benzo, thieno, pyri and diazino in the carbon skeleton, additionally with fluorine, chlorine or bromine atoms, with alkyl groups, cycloalkyl groups with 3 to 8 carbon atoms, nitro, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylsulphonyl groups amino, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, benzoyl, benzoylamino, benzoylmetylamino, aminocarbonyl, alkynylcarbonyl, dialkylatedcarbonyl, hydroxy-alkylaminocarbonyl, (4 - mor folinyl) -carbonyl, (1-pyrrolidini 1) carbonyl or, (1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) carbonyl, (4-methyl-1-piperazinyl) carbonyl, methylenedioxy, to incarcarinyl, aminocarbonyl aminoalkyl, alkylaminocarbonylamino, alkanoyl, cyano, trifluoromethoxy, trifluoromet ilthio, t-rifluoromethyl-sulfinyl or. trif luoromet ilsul foni lo, the substituents being the same or different, and Y stands for the divalent radicals wherein R represents an alkyl radical with 1 to 4 carbon atoms or a phenyl radical optionally substituted with a halogen atom, a methyl group or a methoxy group, X1, X2 and X3, which may be the same or different, mean the atom of hydrogen, the fluorine, chlorine or bromine atom, a branched or unbranched alkyl group, an alkoxy, trifluoromethyl, dialkylaminoalkyl, dialkylaminoalkoxy, nitro, hydroxy, amino, acetylamino, methylsulphonyloxy, aminocarbonyl, alkyl aminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, trifluoromethoxy, trifluor or ethyl thio, trifluoromethoxy sulphonyl or tri-fluoromethylsulfoyl, A means a bond or the divalent radical, linked through the -CO group with the group NR ^ 'R2 of the formula I (II), wherein R7 represents the hydrogen atom or the methyl group, R8 represents the hydrogen atom, the methyl group, methoxycarbonyl, and oxycarbonyl or, n-propoxycarbonyl, i sopropoxycarbonyl, tert-butyl carbonyl or acetyl, R1 means the hydrogen atom, an alkyl group with 1 to 7 carbon atoms which, in the? position, can be substituted with a cyclohexyl, phenyl, pyridinyl, diazinyl, hydroxy, amino, alkylamino, dialkylamino, carboxy, aminocarbonyl, aminocarbonyl group 1 amino, acetylamino, 1 -pyr rol idini lo, 1 -piper idinyl, 4- (l-piperidinyl) -1-piper idini lo, 4 -morfolini lo, hexahydro-lH-1-azepinyl, [bis- (2 - hydroxyethyl)] -amino, 4-alkyl-1-piperazinyl or 4 - (γ-hydroxyalkyl) -1-piperazinyl, a phenyl or pyridinyl group, the heterocyclic radicals being mono-, di- or trisubstituted and the aforementioned phenyl groups, additionally in the carbon skeleton, with fluorine, chlorine or bromine atoms, with g methyl, alkoxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, cyano, methylsulfonyl, trifluoromethoxy, trifluoro, and thio, trifluoromethyl sulphonyl or tri-fluoromethylsulfonyl, and the substituents may be the same or different, R2 denotes the hydrogen atom or an alkyl group with 1 to 3 carbon atoms, optionally substituted with a phenyl or pyridinyl group, or R1 and R2, together with the included nitrogen atom, mean a radical of the general formula wherein Y1 means the carbon atom or, when R4 represents a pair of free electrons, also means the nitrogen atom, m means the numbers 0, 1 or 2, n means the numbers 0, 1 or 2, R3 means the hydrogen atom, an amino, alkylamino, dialkylamino, alkyl, cycloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminoiminomethyl, aminocarbonylamino, alkylaminocarbonylamino, cycloalkylaminocarbonylamino, phenylaminocarbonylamino, aminocarbonylalkyl, aminocarbonylaminoalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, carboxyalkyl or carboxy , a phenyl, pyridinyl, diazinyl, 1-naphthyl, 2-naphthyl, pyridinylcarbonyl or phenylcarbonyl group which, in each case in the carbon skeleton, can be mono-, di- or tri-substituted with fluorine, chlorine or bromine atoms , with alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonyl, amino, aminocarbonylaminomethyl groups , cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl,? - (dialkylamino) alkanoyl,? - (dialkylamino) alkyl, - (dialkylamino) -hydroxyalkyl,? - (carboxy) -alkanoyl, trifluoromethoxy, trifluoromethylthio, trifluoro ethyl sul finyl or trifluoromet ilsulfonyl, the substituents being the same or different, an azacycloalkyl group of 4 to 10 members, an oxaza-, thiaza- or dia za-cycloalkyl group of 5 to 10 members, or an azabicycloalkyl group of 6 to 10 members, the aforementioned monocyclic and bicyclic heterocycles being linked through a nitrogen atom or a carbon atom, a 1-alkyl-4-piperidinylcarbonyl group or 4-alkyl-1-piperazinylcarbonyl, the heterocycles may be substituted. monocyclic and bicyclic mentioned above, as well as the 1-alkyl-piperidinylcarbonyl and 4-alkyl-1-piperazinylcarbonyl groups in the ring with an alkyl group having 1 to 7 carbon atoms, with a alkanoyl, dialkylamino, phenylcarbonyl, pyridinylcarbonyl, carboxyalkanoyl, carboxyalkyl, alkoxycarbonyl-alkyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, alkylsulfonyl, cycloalkyl or cycloalkylalkyl, with a cycloalkylcarbonyl, azacycloalkylcarbonyl, diazacycloalkylcarbonyl or oxazacycloalkylcarbonyl group optionally substituted with alkyl in the ring, the alicyclic parts contained in these substituents comprising 3 to 10 ring members and the heteroalicyclic portions comprising in each case 4 to 10 ring members, and the phenyl and pyridinyl radicals mentioned above may be mono-, di- or their compounds, for their part, with fluorine, chlorine or bromine atoms, with alkyl, alkoxy, methylsulphonyloxy, trifluoromethyl, hydroxy, amino, acetylamino, aminocarbonyl, aminocarbonylamino, aminocarbonyl, laminomethyl, cyano, carboxy, carbalkoxy, carboxyalkyl, carbalkoxyalkyl, alkanoyl,? - (dialk) i lamino) -alkanoyl,? - (carboxy) alkanoyl, t-fluoromethoxy, trifluormet-ilthio, trifluoro-ylsulfonyl or trifluoromethylsulfonyl, the substituents being the same or different, or R3, together with R4 and Y1, means a cycloaliphatic ring of 4 to 7 members, in which the methylene group can be replaced by a group -NH- or - (alkyl) -, a hydrogen atom attached to a nitrogen atom within the group R3 can be replaced by a protective radical, R 4 means a hydrogen atom, an alkyl radical having 1 to 4 carbon atoms, an unbranched alkyl radical, in position or with a phenyl, pyridinyl, diazinyl, amino, alkylamino, dialkylamino group, may be substituted. -pi r rolidini lo, 1-piperidinyl, 4- eyl-1-piperazyl, 4 -morpholinyl or hexahydro-1H-1-azepinyl, an alkoxycarbonyl group, the cyano or aminocarbonyl group or a free electron pair, when Y1 represents a nitrogen atom, and R5 and R6 mean in each case a hydrogen atom or, if Y1 is a carbon atom, R4, together with R6, also represents another carbon-carbon bond, where R3 is defined as mentioned above and R5 represents a hydrogen atom, or if Y1 is a carbon atom, R4, together with R6, it also represents another carbon-carbon bond and R3, together with R5 and the double bond included, represents a monocyclic or bicyclic carbocycle or heterocyclic, of five to seven members, partially hydrogenated or aromatic, being able to encompass all the alkyl groups and alkoxy mentioned above, as well as the alkyl groups present within the other mentioned radicals, if not otherwise indicated, 1 to 7 carbon atoms, and all the aforementioned cycloalkyl groups, as well as the cycloalkyl groups present within the other radicals mentioned, if not stated otherwise, from 5 to 10 carbon atoms, their tautomers, their diastereoisomers, their enantiomers, their mixtures and their salts .
2. 2. Amides of modified amino acids of the general formula I according to claim 1, wherein the amino acid partial structure of the formula is configured D or (R) and, in relation to the partial structure of amino acid, eventually present in radical A, of the formula L or (S) is set.
3. 3. Amides of modified amino acids of the general formula I according to at least one of claims 1 or 2, in which R is the group 1-piper idini lo, which in the 4-position is substituted with an aza-, diaza-ot riaza 5- to 7-membered heterocycle, attached through a nitrogen atom, unsaturated once or twice, containing one or two carbonyl groups bonded with a nitrogen atom, the aforementioned heterocycles possibly being substituted in a carbon atom with a phenyl group, an olefinic double bond of one of the above-mentioned unsaturated heterocycles can be condensed with a benzene, pyridine or quinoline ring or two olefinic double bonds can be condensed with benzo in one of the aforementioned unsaturated heterocycles, and can be The heterocycles condensed in the above-mentioned carbon skeleton, and / or in the phenyl groups, are mono-, di-ot, and their titrids. contained in these groups with fluorine, chlorine or bromine atoms, with C? -3 alkyl groups, trifluoromethyl, C 1-3 alkoxy, hydroxy, amino, nitro, phenyl, carboxy, methoxycarbonyl, and oxycarbonyl, aminocarbonyl, met i laminocarbonyl, hydroxyethylaminocarbonyl, (4 -mor folini 1) carbonyl, (1 -piper idini 1) carboni lo or (4-met il-1-pipera z inil) -carbonyl, the substituents being the same or different, and a multiple substitution with the three substituents mentioned last being excluded, Y means the divalent radicals wherein R represents a C 1-3 alkyl radical or a phenyl radical optionally substituted with a fluorine, chlorine or bromine atom, a methyl group or a methoxy group, X 1, X 2 and X 3, which may be the same or different, mean the hydrogen atom, fluorine, chlorine or bromine atom, a C1-3 alkyl group, C3-3 alkoxy, trifluoromethyl, hydroxy, amino or acetylamino, A means a bond or the divalent radical, linked through the group -CO with the group NR1R2 of the formula I wherein R7 and R8, independently of one another, represent in each case the hydrogen atom or the methyl group, R1 means the hydrogen atom or an alkyl group having 1 to 4 carbon atoms, optionally substituted at the? with an amino group, methylamino, dimethylamino or 4- (1-piperidinyl) -1-piperidinyl, R 2 signifies the hydrogen atom, the methyl or ethyl group, or R 1 and R 2, together with the included nitrogen atom, mean a radical of the general formula where Y1 means the carbon atom or, when R4 represents a pair of free electrons, also means the nitrogen atom, m means the numbers 0 or 1, n means the numbers 1 6 2, R3 means the hydrogen atom, a phenyl, pyridinyl or diazinyl group which, in each case in the carbon skeleton, they may be substituted with a fluorine, chlorine or bromine atom, with a methyl or methoxy group, an azacycloalkyl group of 5-7 members, an oxaza- or diaza-cycloalkyl group of 5-7 members, or a cycloalkyl group of 7 to 9 members with cycloalkyl, the aforementioned monocyclic and bicyclic heterocycles being linked through a nitrogen atom or a carbon atom, and may be substituted with an alkyl group having 1 to 3 carbon atoms with an alkanoyl group of C? -4, dialkylamino of C1-3 or alkylsulfonyl of C3, R4 means a hydrogen atom, an alkyl radical with 1 to 3 carbon atoms, an unbranched alkyl radical may be substituted, position?, c on a phenyl or pyridinyl group, or a pair of free electrons, when Y1 represents a nitrogen atom, and R5 and R6 signify in each case a hydrogen atom, its tautomers, its diastereoisomers, its enantiomers, its mixtures and its salts.
4. 4. Modified amino acid amides of the general formula I according to at least one of claims 1 or 2, wherein R means the 1-piperidinyl group, which in position 4 is substituted with a 1,3-dihydro-4-phenyl-2 (2H) -oxoimidazol-1-yl, 1,3-dihydro-2-group (2 H) -oxobenzimidazol-1-yl, 2,4 (1 H, 3 H) -dioxoquina zol in-3-yl, 1,3-dihydro-2 (2 H) -oxoimidazo [4, 5-b] pyridin-3 11o, 3, 4 -dihydro-2 (1H) -oxoquinazol-3-yl, 2,3,4,5-tetrahydro-2 (1H) -oxo-1,3-benzodiazepin-3-yl, 2 (1H ) -oxoquinolin-3-yl, 2,4-dihydro-5-phenyl-3 (3H) -oxo-1,2,4-t-riazol-2-yl, 1,3-dihydro-2 (2H) -oxoimide zo- [4, 5-c] -quinolin-3-yl or 5,7-dihydro-6-oxo-dibenzo [d, f] [1, 3] dia zepin-5-i, and may be mono-, The above-mentioned bicyclic heterocycles are mentioned in the carbon skeleton and / or in the phenyl groups contained in these groups with fluorine, chlorine or bromine atoms, with methyl, trifluoromethyl, methoxy, hydroxy, amino groups, nitro, phenyl, phenylmethyl, carboxy, methoxycarbonyl, oxycarbonyl, aminocarbonyl, met i laminoca rboni lo, hydroxyethylaminocarbsnyl, (4-morpholinyl) carbonyl, (1-piperidinyl) carbonyl or (4-methyl-1-piperazinyl) carbonyl, it being possible for the substituents to be the same or different, and a multiple substitution being excluded with the three substituents mentioned last, means the divalent radicals wherein R9 represents the methyl group or the phenyl radical, X1 means the fluorine, chlorine or bromine atom, or the methyl group, X2 means the fluorine, chlorine or bromine atom, the methyl, methoxy, hydroxy or amino group, X3 means the fluorine, chlorine or bromine atom, or the methyl group, A means a bond or the divalent radical, linked through the -CO group with the group NR1R2 of the formula I wherein R7 and R8 represent hydrogen atoms, R1 and R2, together with the included nitrogen atom, mean a radical of the general formula wherein Y1 means the carbon atom or, when R4 represents a pair of free electrons, also means the nitrogen atom, m means the number 1, n means the number 1, R3 means a phenyl or pyridinyl group which, in each case in the carbon skeleton, it may be substituted with a fluorine, chlorine or bromine atom, with a methyl or methoxy group, a 1-pyrrolidinyl, 1-piper idini lo, 4- (dimethylamino) -1-piper idini lo, 4-piperidinyl or 4-morpholinyl, it being possible to replace the nitrogen atom of group 4 -piperidinium with an alkyl group in each case with 1 to 2 carbon atoms, a hexahydro-1H-1-azepinyl group, -methyl-l-piperazinyl or 4 -et i 1- 1 -piperazinyl, R 4 means a hydrogen atom, an alkyl radical with 1 or 2 carbon atoms or a free electron pair, when Y 1 represents a nitrogen atom, and R5 and R6 represent in each case a hydrogen atom, its tautomers, its diastereoisomers, its enantiomers, their mixtures and their salts.
5. 5. Physiologically compatible salts of the compounds according to at least one of claims 1 or 2 with inorganic or organic acids or bases.
6. Medicament containing a compound according to at least one of claims 1 to 4 or a physiologically compatible salt according to claim 5, together with optionally one or more support substances and / or inert diluents.
7. Use of a compound according to at least one of claims 1 to 5 for the preparation of a medicament which is suitable for the acute and prophylactic treatment of headaches, for the treatment of non-insulin-dependent diabetes mellitus, of diseases cardiovascular diseases, skin diseases, inflammatory diseases, allergic rhinitis, asthma, diseases that are accompanied by excessive dilation of the vessels and a reduced risk of tissue caused by the above, tolerance to morphine or to combat menopausal hot flashes.
8. 8. Process for the preparation of a medicament according to claim 6, characterized in that, by non-chemical route, a compound according to at least one of claims 1 to 5 is incorporated in one or more support substances and / or inert diluents.
9. 9. Process for the preparation of the compounds of the general formula I according to at least one of claims 1 or 2, characterized in that a) for the preparation of compounds of the general formula I, wherein Y means one of the iminomethyl radicals divalent where R is defined as in claims 1 to 5, a compound of the formula 1 is reacted wherein A, R1, R2, X1, X2 and X3 are defined as in claims 1 to 5, Y 'represents one of the two iminomethyl radicals indicated above and Nu is a leaving group, with a secondary amine of the general formula RH (VI), in which R is defined as in claims 1 to 5, or b) for the preparation of compounds of the general formula I, in which Y means the divalent radical -S02-, a compound of the general formula wherein A, R1, R2, X1, X2 and X3 are defined as in claims 1 to 5, Y "means the group S02 and Nu 'is a leaving group, with a secondary amine of the general formula RH (VI), in which R is defined as in claims 1 to 5 and, if necessary, is separated from new a protective radical used in the reactions described above and / or optionally used precursor functions are transformed into a compound thus obtained, and / or if desired, a compound of the general formula I, thus obtained, is separated into its stereoisomers, and / or a compound of the general formula I, thus obtained, is transformed into its salts, in particular for the pharmaceutical application, into its physiologically compatible salts
10. 10. Use of the compounds of the general formula I according to at least one of the claims 1 6 2, for the production and purification of antibodies
11. 11. Use of the labeled compounds of the general formula I according to at least one of claims 1 or 2 in RIA and ELISA tests and as diagnostic adjuvants. and analytical studies in neurotransmitter research.