DE10260730A1 - Novel substituted nitrogen-containing heterobicyclene, their preparation and their use as pharmaceuticals - Google Patents

Abstract

The present invention relates to novel substituted nitrogen-containing heterobicyclics of the general formula DOLLAR F1 in which B, X · 1 · to X · 3 · and R · 1 · to R · 5 · are as defined in claim 1, their tautomers, their enantiomers, their diastereomers, their mixtures and their salts, in particular their physiologically acceptable salts with inorganic or organic acids or bases, which have valuable properties. DOLLAR A The compounds of the above general formula I and their tautomers, their enantiomers, their diastereomers, their mixtures and their salts, in particular their physiologically acceptable salts with inorganic or organic acids or bases, and their stereoisomers have valuable pharmacological properties, in particular an antithrombotic Effect and a factor Xa-inhibiting effect.

Description

deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze, insbesondere deren physiologisch verträgliche Salze mit anorganischen oder organischen Säuren oder Basen, welche wertvolle Eigeschaften aufweisen.The present invention relates to novel substituted nitrogen-containing heterobicyclics of the general formula

their tautomers, their enantiomers, their diastereomers, their mixtures and their salts, in particular their physiologically acceptable salts with inorganic or organic acids or bases, which have valuable properties.

The compounds of the above general Formula 1 and their tautomers, their enantiomers, their diastereomers, their mixtures and their salts, in particular their physiological compatible Salts with inorganic or organic acids or bases, and their Stereoisomers have valuable pharmacological properties, in particular an antithrombotic effect and a factor Xa-inhibiting action.

Subject of the present application are thus the new compounds of the above general formula I, their preparation containing the pharmacologically active compounds containing medicinal products, their manufacture and use.

in denen im heterocyclischen Teil jeweils ein Wasserstoffatom durch eine Methylsulfonylmethyl-, Amino-C_1-3-alkyl- oder Aminocarbonylgruppe ersetzt sein kann und
m die Zahl 1 oder 2 bedeutet,
R² ein Wasserstoff-, Fluor-, Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, eine C_{2- 3}-Alkenyl-, C_{2- 3}-Alkinyl-, C_1-3-Alkoxy- oder Trifluormethoxygruppe,
R³ ein Wasserstoffatom oder eine C_1-3-Alkylgruppe,
R⁴ ein Wasserstoffatom oder eine geradkettige oder verzweigte C_1-5-Alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C_1-3-Alkyloxy-, Mercapto-, C_1-3-Alkylsulfanyl-, C_1-3-Alkylsulfinyl-, C_1-3-Alkylsulfonyl-, Carboxy-, Aminocarbonyl-, C_1-3-Alkylaminocarbonyl-, Di-(C_1-3-alkyl)-aminocarbonyl-, C_3-6-Cycloalkyleniminocarbonyl-, Amino-, C_1-3-Alkylamino-, Di-(C_1-3-alkyl)-amino-, C_3-6-Cycloalkylenimino-, C_1-3-Alkylcarbonylamino-, C_3-6-Cycloalkylcarbonylamino-, Benzyloxycarbonylamino- oder Guanidinogruppe substituiert ist,
eine Phenyl- oder Heteroaryl, Phenyl-C_1-3-alkyl- oder Heteroaryl-C_1-3-alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C-Alkyloxy-, Benzyloxy-, Hydroxycarbonyl-C_1-3-alkoxy-, C_1-3-Alkyloxycarbonyl-C_1-3-alkyloxy-, Aminocarbonyl-C_1-3-alkyloxy-, C_1-3-Alkylaminocarbonyl-C_1-3-alkyloxy-, Di-(C_1-3-alkyl)-aminocarbonyl-C_1-3-alkyloxy-, C_3-6-Cycloalkyleniminocarbonyl-C_1-3-alkoxy-, Carboxy-, C_1-3-Alkyloxycarbonylgruppe substituiert ist,
eine 4- bis 7-gliedrige Cycolalkylenimino-C_1-3-alkylgruppe oder
eine 4- bis 7-gliedrige Cycloalkyl-C_1-3-alkylgruppe, in der eine oder zwei Methylengruppen durch eine -NH- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein können und in der eine oder zwei der -NH- oder -N(C_1-3-Alkyl)-Gruppe benachbarte Methylengruppen jeweils durch eine Carbonylgruppe ersetzt sein können, mit der Maßgabe, dass eine wie oben definierte Cycloalkylgruppe, in der zwei -NH- oder -N(C_1-3-Alkyl)-Gruppen durch genau eine -CH₂-Gruppe voneinander getrennt sind, ausgeschlossen sind,
R⁵ ein Wasserstoffatom oder eine C_1-3-Alkylgruppe oder
R⁴ und R⁵ zusammen mit dem Kohlenstoffatom, an dem sie gebunden sind, eine C_3-7-Cycloalkylgruppe, wobei
eine der Methylengruppen der C_3-7-Cycloalkylgruppe durch eine Imino-, C_1-3-Alkylimino-, Acylimino- oder Sulfonyliminogruppe ersetzt sein kann,
B eine Gruppe der Formeln

in der
n die Zahl 1 oder 2,
R⁶ ein Wasserstoffatom oder eine C_1-3-Alkyl-, Hydroxy-, Amino-, C_1-3-Alkylaminogruppe,
R⁷ ein Wasserstoff-, Fluor-, Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, eine C_{2- 3}-Alkenyl- oder C_{2- 3}-Alkinyl-, eine Hydroxy-, C_1-3-Alkoxy-, Trifluormethoxy- oder Cyanogruppe darstellen, und
X¹ bis X³ unabhängig voneinander jeweils ein Stichstoffatom oder eine CH-Gruppe,
wobei mindestens eine und höchstens zwei der Gruppen X¹ bis X³ ein Stickstoffatom darstellen,
wobei, soweit nichts anderes erwähnt wurde, unter dem Ausdruck „Heteroarylgruppe" eine im Kohlenstoffgerüst gegebenenfalls durch eine C_1-3-Alkyl-, Carboxy-, C_1-3-Alkoxycarbonyl- oder C_1-3-Alkoxy-carbonylaminogruppe substituierte monocyclische 5- oder o-gliedrige Heteroaryigruppe zu verstehen ist, wobei
die 6-gliedrige Heteroarylgruppe ein, zwei oder drei Stickstoffatome und
die 5-gliedrige Heteroarylgruppe eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe, ein Sauerstoff- oder Schwefelatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl-, Amino-C_1-3-alkyl-, C_1-3-Alkylamino-C_1-3-alkyl-, Di-(C_1-3-alkyl)-amino-C_1-3-alkyl-, C_3-6-Cycloalkylenimino-C_1-3-alkyl- oder Phenyl-C_{1- 3}-alkylgruppe substituierte Iminogruppe oder ein Sauerstoff- oder Schwefelatom und zusätzlich ein Stickstoffatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe und zwei oder drei Stickstoffatome enthält, und außerdem an die vorstehend erwähnten monocyclischen Heteroarylgruppen über zwei benachbarte Kohlenstoffatome ein Phenylring ankondensiert sein kann
und die Bindung über ein Stickstoffatom oder über ein Kohlenstoffatom des heterocyclischen Teils oder eines ankondensierten Phenylrings erfolgt, wobei die in den Definitionen enthaltenen Alkyl- und Alkoxygruppen, die mehr als zwei Kohlenstoffatome aufweisen, soweit nichts anderes erwähnt wurde, geradkettig oder verzweigt sein können,
und wobei die Wasserstoffatome der in den Definitionen enthaltenen Methyl- oder Ethylgruppen ganz oder teilweise durch Fluoratome ersetzt sein können.In the above general formula
R ^{1 is} an amino, C _1-5 -alkylamino, C _3-7 -cycloalkylamino or (phenyl-C _1-3 -alkyl) -amino group, each at the amine nitrogen atom by a phenylcarbonyl or phenylsulfonyl group or by an alkyl moiety optionally substituted by a carboxy group, a converted in vivo into a carboxy group, an amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _3-6 -Cycloalkyleniminogruppe substituted C _{1- 5-} alkyl or C _1-5 -alkylcarbonyl may be substituted, wherein two nitrogen atoms are separated from each other by at least two carbon atoms,
a di (C _1-5 alkyl) amino or N- (C _3-7 cycloalkyl) C _1-5 alkylamino group wherein the C _1-5 alkyl portion other than the 1 position is represented by a hydroxy , C _1-3 alkoxy, amino, C _1-3 -alkylamino, di (C _1-3 -alkyl) -amino or C _3-6 -cycloalkyleneimino may be substituted,
a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group, wherein
the cycloalkyleneimine moiety through one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 alkyl, di (C _1-3 alkyl) amino C _1-3 alkyl. C _1-5 alkyloxycarbonylamino C _1-3 alkyl, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -Alkylarninocarbonyl-, N- (C ₃ _ ₇ cycloalkyl ) -C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1 -5} alkylaminocarbonyl or di- _(C1-3 alkyl) aminocarbonyl group may be substituted or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted and / or
a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulfinyl or sulfonyl group, or
a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom or by an -NH-, -NC _1-3 -alkyl-, -N (C _{2 -3} -alkanoyl) -, sulfinyl- or sulfonyl group may be replaced and / or
a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) - CO group can be replaced,
an optionally substituted by one or two C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) - amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl, C _1-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl- , Di (C _1-3 alkyl) aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl-substituted 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulfonyl group,
wherein the double bond is not bonded to a nitrogen atom, an aminocarbonyl or aminosulfonyl group optionally substituted by one or two C _1-5 alkyl groups,
wherein the substituents may be the same or different and
each one of the C _1-5 alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxy C _1-3 alkyl, amino C _1-3 alkyl, C _1-3 -alkylamino-C _{1- 3} alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5-} alkyloxycarbonylamino-C _1-3 -alkyl, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl, N- (C _3-7 -cycloalkyl) -C _1-5 alkylaminocarbonyl, N- (phenylC _1-3 alkyl) -C _1-5 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl group can or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted,
a C _1-7 alkylcarbonyl or C _3-7 cycloalkylcarbonyl group, wherein
the methylene group in the 2-, 3- or 4-position in a C _3-7 cycloalkylcarbonyl group may be replaced by an oxygen or sulfur atom, a carbonyl, sulfinyl, sulfonyl or -NH group in which
the hydrogen atom of the -NH group may be replaced by a C _1-3 -alkyl or C _1-3 -alkylcarbonyl group,
a phenylcarbonyl or heteroarylcarbonyl group which in the phenyl or heteroaryl moiety is replaced by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, aminoC _1-3 -alkyl-, C _1-3 - Alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl or C _1-3 Alkoxy group may be substituted,
an optionally substituted by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, mono-, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _{1- 3-} alkyl group, wherein
the phenyl part by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, Di- (C _1-3 alkyl) amino C _1-3 alkyl, C _3-6 cycloalkylene imino C _1-3 alkyl or C _1-3 alkoxy may be substituted and / or
wherein a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO group or
a methylene group which is adjacent to the nitrogen atom may be replaced by a carbonyl group in a 5- to 7-membered cycloalkyleneimino group,
or a group of formulas

in each of which a hydrogen atom in the heterocyclic moiety may be replaced by a methylsulfonylmethyl, aminoC _1-3 alkyl or aminocarbonyl group, and
m is the number 1 or 2,
R ² is a hydrogen, fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C _{2- 3} -alkenyl, C ₃ -alkynyl _2- , C _1-3 alkoxy or trifluoromethoxy group,
R ^{3 is} a hydrogen atom or a C _1-3 -alkyl group,
R ^{4 is} a hydrogen atom or a straight-chain or branched C _1-5 -alkyl group which is optionally substituted by a hydroxy, C _1-3 -alkyloxy, mercapto, C _1-3 -alkylsulfanyl, C _1-3 -alkylsulfinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, C _3-6 cycloalkyleneiminocarbonyl, amino, C ₁ Substituted with _3- alkylamino, di (C _1-3 alkyl) amino, C _3-6 cycloalkyleneimino, C _1-3 alkylcarbonylamino, C _3-6 cycloalkylcarbonylamino, benzyloxycarbonylamino or guanidino group,
a phenyl- or heteroaryl, phenyl-C _1-3 -alkyl or heteroaryl-C _1-3 -alkyl group which is optionally substituted by a hydroxy, C 1-6 alkyloxy, benzyloxy, hydroxycarbonyl-C _1-3 -alkoxy-, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) -aminocarbonyl-C _1-3 -alkyloxy, C _3-6 -cycloalkyleneiminocarbonyl-C _1-3 -alkoxy, carboxy, C _1-3 -alkyloxycarbonyl group is substituted,
a 4- to 7-membered cyclobalkyleneimino-C _1-3 -alkyl group or
a 4- to 7-membered cycloalkyl-C _1-3 -alkyl group in which one or two methylene groups may be replaced by a -NH- or -N (C _1-3 -alkyl) group and in which one or two of the -NH- or -N (C _1-3 -alkyl) -group adjacent methylene groups may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as defined above, in which two -NH- or -N (C _1-3 -alkyl) groups are separated by exactly one -CH ₂ -group, are excluded,
R ^{5 is} a hydrogen atom or a C _1-3 alkyl group or
R ⁴ and R ⁵ together with the carbon atom to which they are attached form a C _3-7 cycloalkyl group, wherein
one of the methylene groups of the C _3-7 -cycloalkyl group may be replaced by an imino, C _1-3 -alkylimino, acylimino or sulfonylimino group,
B is a group of formulas

in the
n is the number 1 or 2,
R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxy, amino, C _1-3 -alkylamino group,
R ⁷ is a hydrogen, fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C _2- C ₃ alkenyl or alkynyl _{2- 3} - represent a hydroxy, C _1-3 alkoxy, trifluoromethoxy or cyano group, and
X ¹ to X ³ independently of one another each represent a nitrogen atom or a CH group,
wherein at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom,
Unless otherwise mentioned, the term "heteroaryl group" denotes a monocyclic 5 which is optionally substituted in the carbon skeleton by a C _1-3 -alkyl, carboxy, C _1-3 -alkoxycarbonyl or C _1-3 -alkoxycarbonylamino group - or o-membered heteroaryl group is to be understood, wherein
the 6-membered heteroaryl group contains one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group, an oxygen or sulfur atom or
an optionally represented by a C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di (C _1-3 -alkyl) -amino C _1-3 alkyl, C _3-6 -Cycloalkylenimino-C _1-3 -alkyl or phenyl-C _{1- 3} alkyl substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or
an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group and containing two or three nitrogen atoms, and further, a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl group via two adjacent carbon atoms
and the bond is via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused-on phenyl ring, wherein the alkyl and alkoxy groups contained in the definitions, which have more than two carbon atoms, unless mentioned otherwise, may be straight-chain or branched,
and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms.

Under a converted in vivo into a carboxy group is, for example, an esterified carboxy group with an alcohol in which the alcoholic moiety is preferably a C _1-6 -alkanol, a phenyl-C _1-3 -alkanol, a C _{3 -9} cycloalkanol, a C-cycloalkenol, a C _3-5 alkenol, a phenyl C _3-5 alkenol, a C _3-5 alkinol, or phenyl C _3-5 alkenol, with the proviso that no bond to the oxygen atom of starting from a carbon atom which carries a double or triple bond, a C _3-8 -cycloalkyl-C _{1 -3} -alkanol or an alcohol of the formula R ^{8 is} -CO-O- (R ⁹ CR ¹⁰ ) -OH, in the
R ^{8 is} a C _1-8 alkyl, C _5-7 cycloalkyl, phenyl or phenyl C _1-3 alkyl group,
R ^{9 is} a hydrogen atom, a C _1-3 alkyl, C 3-10 cycloalkyl or phenyl group and
R ^{10 represents} a hydrogen atom or a C _1-3 -alkyl group,
to understand.

Preferred residues which can be split off from a carboxy group in vivo are a C _1-6 -alkoxy group such as the methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, n-pentyloxy, n-hexyloxy or cyclohexyloxy group or a phenyl-C _1-3 alkoxy group such as the benzyloxy group into consideration.

Those compounds of the general formula I in which R ¹ contains a group which can be converted into a carboxy group in vivo represent prodrugs for those compounds of the general formula I in which R ¹ contains a carboxy group.

in denen im heterocyclischen Teil jeweils ein Wasserstoffatom durch eine Methylsulfonylmethyl-, Amino-C_1-3-alkyl- oder Aminocarbonylgruppe ersetzt sein kann und m die Zahl 1 oder 2 bedeutet,
R² ein Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, oder eine C_{2 -3}-Alkenylgruppe,
R³ ein Wasserstoffatom oder eine C_1-3-Alkylgruppe,
R⁴ ein Wasserstoffatom oder eine geradkettige oder verzweigte C_1-5-Alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C_1-3-Alkyloxy-, Mercapto-, C_1-3-Alkylsulfanyl-, C_1-3-Alkylsulfinyl-, C_1-3-Alkylsulfonyl-, Carboxy-, Aminocarbonyl-, C_1-3-Alkylaminocarbonyl-, Di-(C_1-3-alkyl)-aminocarbonyl-, C_{3 -6}-Cycloalkyleniminocarbonyl-, Amino-, C_1-3-Alkylamino-, Di-(C_1-3-alkyl)-amino-, C_{3 -6}-Cycloalkylenimino-, C_1-3-Alkylcarbonylamino-, C_{3 -6}-Cycloalkylcarbonylamino-, Benzyloxycarbonylamino- oder Guanidinogruppe substituiert ist,
eine Phenyl- oder Heteroaryl, Phenyl-C_1-3-alkyl- oder Heteroaryl-C_1-3-alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C-Alkyloxy-, Benzyloxy-, Hydroxycarbonyl-C_1-3-alkoxy-, C_1-3-Alkyloxycarbonyl-C_1-3-alkyloxy-, Aminocarbonyl-C_1-3-alkyloxy-, C_1-3-Alkylaminocarbonyl-C_1-3-alkyloxy-, Di-(C_1-3-alkyl)-aminocarbonyl-C_1-3-alkyloxy-, C_{3 -6}-Cycloalkyleniminocarbonyl-C_1-3-alkoxy-, Carboxy-, C_1-3-Alkyloxycarbonylgruppe substituiert ist,
eine 4- bis 7-gliedrige Cycolalkylenimino-C_1-3-alkylgruppe oder
eine 4- bis 7-gliedrige Cycloalkyl-C_1-3-alkylgruppe, in der eine oder zwei Methylengruppen durch eine -NH- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein können und in der eine oder zwei der -NH- oder -N(C_1-3-Alkyl)-Gruppe benachbarte Methylengruppen jeweils durch eine Carbonylgruppe ersetzt sein können, mit der Maßgabe, dass eine wie oben definierte Cycloalkylgruppe, in der zwei -NH- oder -N(C_1-3-Alkyl)-Gruppen durch genau eine -CH₂-Gruppe voneinander getrennt sind, ausgeschlossen sind,
R⁵ ein Wasserstoffatom oder eine C_1-3-Alkylgruppe oder
R⁴ und R⁵ zusammen mit dem Kohlenstoffatom, an dem sie gebunden sind, eine C_3-7-Cycloalkylgruppe, wobei
eine der Methylengruppen der C_3-7-Cycloalkylgruppe durch eine Imino-, C_1-3-Alkylimino-, Acylimino- oder Sulfonyliminogruppe ersetzt sein kann,
B eine Gruppe der Formeln

in der
n die Zahl 1,
R⁶ ein Wasserstoffatom oder eine C_1-3-Alkyl-, Hydroxy-, Amino-, C_1-3-Alkylaminogruppe,
R⁷ ein Wasserstoff-, Fluor-, Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, eine C_{2- 3}-Alkenyl- oder C_{2- 3}-Alkinyl-, eine Hydroxy-, C_1-3-Alkoxy-, Trifluormethoxy- oder Cyanogruppe darstellen, und
X¹ bis X³ unabhängig voneinander jeweils ein Stichstoffatom oder eine CH-Gruppe,
wobei mindestens eine und höchstens zwei der Gruppen X¹ bis X³ ein Stickstoffatom darstellen,
wobei, soweit nichts anderes erwähnt wurde, unter dem Ausdruck „Heteroarylgruppe" eine im Kohlenstoffgerüst gegebenenfalls durch eine C_1-3-Alkyl-, Carboxy-, C_1-3-Alkoxycarbonyl- oder C_1-3-Alkoxy-carbonylaminogruppe substituierte monocyclische 5- oder 6-gliedrige Heteroarylgruppe zu verstehen ist, wobei
die 6-gliedrige Heteroarylgruppe ein, zwei oder drei Stickstoffatome und
die 5-gliedrige Heteroarylgruppe eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe, ein Sauerstoff- oder Schwefelatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl-, Amino-C_{1- 3}-alkyl-, C_1-3-Alkylamino-C_1-3-alkyl-, Di-(C_1-3-alkyl)-amino-C_1-3-alkyl-, C_{3- 6}-Cycloalkylenimino-C_1-3-alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe oder ein Sauerstoff- oder Schwefelatom und zusätzlich ein Stickstoffatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe und zwei oder drei Stickstoffatome enthält,
und außerdem an die vorstehend erwähnten monocyclischen Heteroarylgruppen über zwei benachbarte Kohlenstoffatome ein Phenylring ankondensiert sein kann
und die Bindung über ein Stickstoffatom oder über ein Kohlenstoffatom des heterocyclischen Teils oder eines ankondensierten Phenylrings erfolgt,
wobei die in den Definitionen enthaltenen Alkyl- und Alkoxygruppen, die mehr als zwei Kohlenstoffatome aufweisen, soweit nichts anderes erwähnt wurde, geradkettig oder verzweigt sein können,
und wobei die Wasserstoffatome der in den Definitionen enthaltenen Methyl- oder Ethylgruppen ganz oder teilweise durch Fluoratome ersetzt sein können,
deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze.Preferred compounds of general formula I are those in which
R ¹ is an amino, C _1-5 alkylamino, C _{3 -7} cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each having a on the amine nitrogen atom by a phenylcarbonyl or phenylsulfonyl group or in the alkyl moiety optionally substituted by a carboxy group, a converted in vivo into a carboxy group, an amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _3-6 -Cycloalkyleniminogruppe substituted C _{1- 5-} alkyl or C _1-5 -alkylcarbonyl may be substituted, wherein two Btickstoffatome are separated by at least two carbon atoms,
a di (C _1-5 alkyl) amino or N- (C _3-7 cycloalkyl) C _1-5 alkylamino group wherein the C _1-5 alkyl portion other than the 1 position is represented by a hydroxy , C _1-3 alkoxy, amino, C _1-3 -alkylamino, di (C _1-3 -alkyl) -amino or C _3-6 -cycloalkyleneimino may be substituted,
a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group, wherein
the cycloalkyleneimine moiety through one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _{1 -3} alkyl, C _3-6 -Cycloalkylenimino-C _1-3 alkyl, C _1-5 alkyloxycarbonylamino-C _{1- 3} -alkyl-, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl, N- (C _3-7 -cycloalkyl) -C _1-5 -alkylaminocarbonyl-, N- (phenyl-C _1-3 -alkyl) C _1-5 -alkylaminocarbonyl, di (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -cycloalkyleneiminocarbonyl may be substituted or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted and / or
a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulfinyl or sulfonyl group, or
a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom or by an -NH-, -NC _1-3 -alkyl-, -N (C _{2 -3} -alkanoyl) -, sulfinyl- or sulfonyl group may be replaced and / or
a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) - CO group can be replaced,
an optionally substituted by one or two C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) - amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl, C _1-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl- , di (C _1-3 alkyl) aminocarbonyl or C _{3 -6} -Cycloalkyleniminocarbonylgruppen substituted 5- to 7-membered Cycloalkenyleniminocarbonyl- or Cycloalkenyleniminosulfonylgruppe, wherein the double bond is not attached to a nitrogen atom,
an aminocarbonyl or aminosulfonyl group optionally substituted by one or two C _1-5 alkyl groups,
wherein the substituents may be the same or different and
each one of the C _1-5 alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _{3 -6} -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5-alkyloxycarbonylamino} C _1-3 alkyl, C _{3 -6} -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _1-5 alkylaminocarbonyl, N- (phenylC _1-3 alkyl) -C _1-5 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl group can or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted,
a C _1-7 alkylcarbonyl or C _3-7 cycloalkylcarbonyl group, wherein
the methylene group in the 2-, 3- or 4-position in a C _3-7 cycloalkylcarbonyl group may be replaced by an oxygen or sulfur atom, a carbonyl, sulfinyl, sulfonyl or -NH group in which
the hydrogen atom of the -NH group may be replaced by a C _1-3 -alkyl or C _1-3 -alkylcarborsyl group,
a phenylcarbonyl or heteroarylcarbonyl group which in the phenyl or heteroaryl moiety is replaced by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, aminoC _1-3 -alkyl-, C _1-3 - Alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl or C _1-3 Alkoxy group may be substituted,
an optionally substituted by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, mono-, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _{1- 3-} alkyl group, wherein
the phenyl part is replaced by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -Cycloalkylenimino-C _{1 -3} alkyl or C _1-3 alkoxy group may be substituted and / or
wherein a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO group or
a methylene group which is adjacent to the nitrogen atom may be replaced by a carbonyl group in a 5- to 7-membered cycloalkyleneimino group,
or a group of formulas

in each case one hydrogen atom in the heterocyclic part can be replaced by a methylsulfonylmethyl, aminoC _1-3 -alkyl or aminocarbonyl group and m is the number 1 or 2,
R ^{2 is} a chlorine or bromine atom, a C _1-3 -alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C _{2 -3} alkenyl group,
R ^{3 is} a hydrogen atom or a C _1-3 -alkyl group,
R ^{4 is} a hydrogen atom or a straight-chain or branched C _1-5 -alkyl group which is optionally substituted by a hydroxy, C _1-3 -alkyloxy, mercapto, C _1-3 -alkylsulfanyl, C _1-3 -alkylsulfinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, C _{3 -6} cycloalkyleneiminocarbonyl, amino, C _{1 3} alkylamino, di- (C _1-3 -alkyl) -amino, C _{3 -6} -Cycloalkylenimino-, C _1-3 alkylcarbonylamino, C _{3 -6} -Cycloalkylcarbonylamino-, benzyloxycarbonylamino or guanidino group is substituted,
a phenyl- or heteroaryl, phenyl-C _1-3 -alkyl or heteroaryl-C _1-3 -alkyl group which is optionally substituted by a hydroxy, C 1-6 alkyloxy, benzyloxy, hydroxycarbonyl-C _1-3 -alkoxy-, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) aminocarbonyl-C _1-3 -alkyloxy, C _{3 -6} -Cycloalkyleniminocarbonyl-C _1-3 alkoxy, carboxy, C _1-3 alkyloxycarbonyl group is substituted,
a 4- to 7-membered cyclobalkyleneimino-C _1-3 -alkyl group or
a 4- to 7-membered cycloalkyl-C _1-3 -alkyl group in which one or two methylene groups may be replaced by a -NH- or -N (C _1-3 -alkyl) group and in which one or two of the Each of the adjacent methylene groups may be replaced by a carbonyl group with the proviso that a cycloalkyl group as defined above in which two -NH- or -N (C ₁ -NH- or -N (C _1-3 -alkyl) -group _3- alkyl) groups are separated by exactly one -CH ₂ group, are excluded,
R ^{5 is} a hydrogen atom or a C _1-3 alkyl group or
R ⁴ and R ⁵ together with the carbon atom to which they are attached form a C _3-7 cycloalkyl group, wherein
one of the methylene groups of the C _3-7 -cycloalkyl group may be replaced by an imino, C _1-3 -alkylimino, acylimino or sulfonylimino group,
B is a group of formulas

in the
n is the number 1,
R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxy, amino, C _1-3 -alkylamino group,
R ⁷ is a hydrogen, fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C _2- C ₃ alkenyl or alkynyl _{2- 3} - represent a hydroxy, C _1-3 alkoxy, trifluoromethoxy or cyano group, and
X ¹ to X ³ independently of one another each represent a nitrogen atom or a CH group,
wherein at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom,
Unless otherwise mentioned, the term "heteroaryl group" denotes a monocyclic 5 which is optionally substituted in the carbon skeleton by a C _1-3 -alkyl, carboxy, C _1-3 -alkoxycarbonyl or C _1-3 -alkoxycarbonylamino group or 6-membered heteroaryl group is understood, wherein
the 6-membered heteroaryl group contains one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group, an oxygen or sulfur atom or
an optionally by a C _1-3 -alkyl, amino-C _{1- 3} alkyl, C _1-3 alkylamino-C _1-3 -alkyl, di- (C _1-3 alkyl) amino C _1-3 alkyl, C _{3- 6} alkyl or C _1-3 -Cycloalkylenimino-phenyl-C _1-3 -alkyl substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group which is optionally substituted by a C _1-3 -alkyl or phenyl-C _1-3 -alkyl group and contains two or three nitrogen atoms,
and further, a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups through two adjacent carbon atoms
and the bond is via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused-on phenyl ring,
the alkyl and alkoxy groups having more than two carbon atoms contained in the definitions, unless otherwise mentioned, may be straight-chain or branched,
and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms,
their tautomers, their enantiomers, their diastereomers, their mixtures and their salts.

in denen im heterocyclischen Teil jeweils ein Wasserstoffatom durch eine Methylsulfonylmethyl-, Amino-C_1-3-alkyl- oder Aminocarbonylgruppe ersetzt sein kann und m die Zahl 1 oder 2 bedeutet,
R² ein Chlor- oder Bromatom, eine C_{1- 3}-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, oder eine C_{2- 3}-Alkenylgruppe,
R³ ein Wasserstoffatom,
R⁴ ein Wasserstoffatom oder eine geradkettige oder verzweigte C_{1- 5}-Alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C_1-3-Alkyloxy-, Mercapto-, C_1-3-Alkylsulfanyl-, C_1-3-Alkylsulfinyl-, C_1-3-Alkylsulfonyl-, Carboxy-, Aminocarbonyl-, C_1-3-Alkylaminocarbonyl-, Di-(C_1-3-alkyl)-aminocarbonyl-, C_{3- 6}-Cycloalkyleniminocarbonyl-, Amino-, C_1-3-Alkylamino-, Di-(C_1-3-alkyl)-amino-, C_{3- 6}-Cycloalkylenimino-, C_1-3-Alkylcarbonylamino-, C_{3- 6}-Cycloalkylcarbonylamino-, Benzyloxycarbonylamino- oder Guanidinogruppe substituiert ist,
eine Phenyl- oder Heteroaryl, Phenyl-C_1-3-alkyl- oder Heteroaryl-C_1-3-alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C_1-4-Alkyloxy-, Benzyloxy-, Hydroxycarbonyl-C_1-3-alkoxy-, C_1-3-Alkyloxycarbonyl-C_1-3-alkyloxy-, Aminocarbonyl-C_1-3-alkyloxy-, C_1-3-Alkylaminocarbonyl-C_1-3-alkyloxy-, Di-(C_1-3-alkyl)-aminocarbonyl-C_1-3-alkyloxy-, C_3-6-Cycloalkyleniminocarbonyl-C_1-3-alkyloxy, Carboxy-, C_1-3-Alkyloxycarbonylgruppe substituiert ist,
eine 4- bis 7-gliedrige Cycolalkylenimino-C_1-3-alkylgruppe oder
eine 4- bis 7-gliedrige Cycloalkyl-C_1-3-alkylgruppe, in der eine oder zwei Methylengruppen durch eine -NH- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein können und in der eine oder zwei der -NH- oder -N(C_1-3-Alkyl)-Gruppe benachbarte Methylengruppen jeweils durch eine Carbonylgruppe ersetzt sein können, mit der Maßgabe, dass eine wie oben definierte Cycloalkylgruppe, in der zwei -NH- oder -N(C_1-3-Alkyl)-Gruppen durch genau eine -CH₂-Gruppe voneinander getrennt sind, ausgeschlossen sind,
R⁵ ein Wasserstoffatom oder
R⁴ und R⁵ zusammen mit dem Kohlenstoffatom, an dem sie gebunden sind, eine C_3-7-Cycloalkylgruppe, wobei
eine der Methylengruppen der C_3-7-Cycloalkylgruppe durch eine Imino-, C_1-3-Alkylimino-, Acylimino- oder Sulfonyliminogruppe ersetzt sein kann,
B eine Gruppe der Formeln

in der
n die Zahl 1,
R⁶ ein Wasserstoffatom oder eine C_1-3-Alkyl-, Hydroxy-, Amino-, C_1-3-Alkylaminogruppe,
R⁷ ein Fluor-, Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, eine C_{2- 3}-Alkenyl-, C_{2- 3}-Alkinyl- oder eine Hydroxygruppe darstellen, und
X¹ bis X³ unabhängig voneinander jeweils ein Stichstoffatom oder eine CH-Gruppe,
wobei mindestens eine und höchstens zwei der Gruppen X¹ bis X³ ein Stickstoffatom darstellen,
wobei, soweit nichts anderes erwähnt wurde, unter dem Ausdruck „Heteroarylgruppe" eine im Kohlenstoffgerüst gegebenenfalls durch eine C_1-3-Alkyl-, Carboxy-, C_1-3-Alkoxycarbonyl- oder C_1-3-Alkoxy-carbonylaminogruppe substituierte monocyclische 5- oder 6-gliedrige Heteroarylgruppe zu verstehen ist, wobei
die 6-gliedrige Heteroarylgruppe ein, zwei oder drei Stickstoffatome und
die 5-gliedrige Heteroarylgruppe eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe, ein Sauerstoff- oder Schwefelatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl-, Amino-C_1-3-alkyl-, C_1-3-Alkylamino-C_1-3-alkyl-, Di-(C_1-3-alkyl)-amino-C_1-3-alkyl-, C_{3- 6}-Cycloalkylenimino-C_1-3-alkyl-, oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe oder ein Sauerstoff- oder Schwefelatom und zusätzlich ein Stickstoffatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe und zwei oder drei Stickstoffatome enthält,
und außerdem an die vorstehend erwähnten monocyclischen Heteroarylgruppen über zwei benachbarte Kohlenstoffatome ein Phenylring ankondensiert sein kann
und die Bindung über ein Stickstoffatom oder über ein Kohlenstoffatom des heterocyclischen Teils oder eines ankondensierten Phenylrings erfolgt,
wobei die in den Definitionen enthaltenen Alkyl- und Alkoxygruppen, die mehr als zwei Kohlenstoffatome aufweisen, soweit nichts anderes erwähnt wurde, geradkettig oder verzweigt sein können,
und wobei die Wasserstoffatome der in den Definitionen enthaltenen Methyl- oder Ethylgruppen ganz oder teilweise durch Fluoratome ersetzt sein können,
deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze.Particularly preferred compounds of general formula I are those in which
R ¹ is an amino, C _{1- 5} alkylamino, C _3-7 cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each on the amine nitrogen atom by a phenylcarbonyl or phenylsulphonyl group or by a in the alkyl moiety optionally substituted by a carboxy group, a converted in vivo into a carboxy group, an amino, C _{1- 3} alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe substituted C _{1- 5} alkyl or C _{1- 5} alkylcarbonyl group may be substituted, wherein two nitrogen atoms are separated by at least two carbon atoms,
a di- (C _{1- 5} alkyl) amino or N- (C _3-7 cycloalkyl) C _{1- 5} alkylamino group, wherein the C _{1- 5} alkyl moiety with the exception of the 1-position in each case by a hydroxy -, C _1-3 alkoxy, amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted,
a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group, wherein
the cycloalkyleneimine moiety through one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-CC _1-3 alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5} alkyloxycarbonylamino-C _{1- 3} alkyl, C _{3- 6} -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _{3- 6} -cycloalkyleneiminocarbonyl may be substituted or
a non-adjacent imino group of the methyl group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _{1- 3} alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted and / or
a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulfinyl or sulfonyl group, or
a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom or by an -NH-, -NC _1-3 alkyl, -N (C _{2- 3} alkanoyl) -, sulphinyl or sulfonyl group may be replaced and / or
a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) - CO group can be replaced,
an optionally by one or two C _1-3 alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _{1- 3} alkyl, di (C _1-3 alkyl) - amino-C _1-3 alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 -alkyl, C _1-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl- , di _{(C_-C3} alkyl) aminocarbonyl or C _{3- 6} -Cycloalkyleniminocarbonylgruppen substituted 5- to 7-membered Cycloalkenyleniminocarbonyl- or Cycloalkenyleniminosulfonylgruppe, wherein the double bond is not attached to a nitrogen atom,
a substituted optionally substituted by one or two C _{1- 5} alkyl aminocarbonyl or aminosulfonyl,
wherein the substituents may be the same or different and
each one of the C _1-5 alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5-alkyloxycarbonylamino} C _1-3 alkyl, C _{3- 6} -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, be di (C _1-3 alkyl) aminocarbonyl or substituted C _{3- 6} -cycloalkyleneiminocarbonyl can or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino no-, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted,
an optionally substituted by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, mono-, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _{1- 3-} alkyl group, wherein
the phenyl moiety by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, aminoC _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 alkyl, C _{3- 6} alkyl or -Cycloalkylenimino-C _1-3 C _1-3 alkoxy group may be substituted and / or
wherein a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO group or
a methylene group which is adjacent to the nitrogen atom may be replaced by a carbonyl group in a 5- to 7-membered cycloalkyleneimino group,
or a group of formulas

in each case one hydrogen atom in the heterocyclic part can be replaced by a methylsulfonylmethyl, aminoC _1-3 -alkyl or aminocarbonyl group and m is the number 1 or 2,
R ² is a chlorine or bromine atom, a C _{1- 3} alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C _{2- 3} alkenyl group,
R ^{3 is} a hydrogen atom,
R ⁴ is a hydrogen atom or a linear or branched C _{1- 5} alkyl group optionally substituted by a hydroxy, C _1-3 -alkyloxy, mercapto, C _1-3 alkylsulphanyl, C _1-3 alkylsulphinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 alkyl) aminocarbonyl, C _{3- 6} -Cycloalkyleniminocarbonyl-, amino, C _{1- 3} alkylamino, di- (C _1-3 -alkyl) -amino, C _{3- 6} -Cycloalkylenimino-, C _1-3 alkylcarbonylamino, C is substituted _{3- 6} -Cycloalkylcarbonylamino-, benzyloxycarbonylamino or guanidino,
a phenyl- or heteroaryl, phenyl-C _1-3 -alkyl or heteroaryl-C _1-3 -alkyl group which is optionally substituted by a hydroxy, C _1-4 -alkyloxy, benzyloxy, hydroxycarbonyl-C _1-3 alkoxy, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) aminocarbonylC _1-3 alkyloxy, C _3-6 cycloalkyleneiminocarbonylC _1-3 alkyloxy, carboxy, C _1-3 alkyloxycarbonyl group,
a 4- to 7-membered cyclobalkyleneimino-C _1-3 -alkyl group or
a 4- to 7-membered cycloalkyl-C _1-3 -alkyl group in which one or two methylene groups may be replaced by a -NH- or -N (C _1-3 -alkyl) group and in which one or two of the Each of the adjacent methylene groups may be replaced by a carbonyl group with the proviso that a cycloalkyl group as defined above in which two -NH- or -N (C ₁ -NH- or -N (C _1-3 -alkyl) -group _3- alkyl) groups are separated by exactly one -CH ₂ group, are excluded,
R ^{5 is} a hydrogen atom or
R ⁴ and R ⁵ together with the carbon atom to which they are attached form a C _3-7 cycloalkyl group, wherein
one of the methylene groups of the C _3-7 -cycloalkyl group may be replaced by an imino, C _1-3 -alkylimino, acylimino or sulfonylimino group,
B is a group of formulas

in the
n is the number 1,
R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxy, amino, C _1-3 -alkylamino group,
R ⁷ is a fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C _{2- 3} -alkenyl, C ₃ -alkynyl or _2- Represent hydroxy group, and
X ¹ to X ³ independently of one another each represent a nitrogen atom or a CH group,
wherein at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom,
Unless otherwise mentioned, the term "heteroaryl group" denotes a monocyclic 5 which is optionally substituted in the carbon skeleton by a C _1-3 -alkyl, carboxy, C _1-3 -alkoxycarbonyl or C _1-3 -alkoxycarbonylamino group or 6-membered heteroaryl group is understood, wherein
the 6-membered heteroaryl group contains one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group, an oxygen or sulfur atom or
an optionally represented by a C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di (C _1-3 -alkyl) -amino C _1-3 alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl, or phenyl-C _1-3 -alkyl substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group which is optionally substituted by a C _1-3 -alkyl or phenyl-C _1-3 -alkyl group and contains two or three nitrogen atoms,
and further, a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups through two adjacent carbon atoms
and the bond is via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused-on phenyl ring,
the alkyl and alkoxy groups having more than two carbon atoms contained in the definitions, unless otherwise mentioned, may be straight-chain or branched,
and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms,
their tautomers, their enantiomers, their diastereomers, their mixtures and their salts.

in denen im heterocyclischen Teil jeweils ein Wasserstoffatom durch eine Methylsulfonylmethyl-, Amino-C_1-3-alkyl- oder Aminocarbonylgruppe ersetzt sein kann und
m die Zahl 1 oder 2 bedeutet,
R² ein Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der tie Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, oder eine C_2–3-Alkenylgruppe,
R³ ein Wasserstoffatom,
R⁴ ein Wasserstoffatom oder eine geradkettige oder verzweigte C_{1- 5}-Alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C_1-3-Alkyloxy-, Mercapto-, C_1-3-Alkylsulfanyl-, C_1-3-Alkylsulfinyl-, C_1-3-Alkylsulfonyl-, Carboxy-, Aminocarbonyl-, C_1-3-Alkylaminocarbonyl-, Di-(C_1-3-alkyl)-aminocarbonyl-, C_3-6-Cycloalkyleniminocarbonyl-, Amino-, C_1-3-Alkylamino-, Di-(C_1-3-alkyl)-amino-, C_3-6-Cycloalkylenimino-, C_1-3-Alkylcarbonylamino-, C_3-6-Cycloalkylcarbonylamino-, Benzyloxycarbonylamino- oder Guanidinogruppe substituiert ist,
eine Phenyl- oder Heteroaryl, Phenyl-C_1-3-alkyl- oder Heteroaryl-C_1-3-alkylgruppe, die gegebenenfalls durch eine Hydroxy-, C-Alkyloxy-, Benzyloxy-, Hydroxycarbonyl-C_1-3-alkoxy-, C_1-3-Alkyloxycarbonyl-C_1-3-alkyloxy-, Aminocarbonyl-C_1-3-alkyloxy-, C_1-3-Alkylaminocarbonyl-C_1-3-alkyloxy-, Di-(C_1-3-alkyl)-aminocarbonyl-C_1-3-alkyloxy-, C_3-6-Cycloalkyleniminocarbonyl-C_1-3-alkyloxy-, Carboxy-, C_1-3-Alkyloxycarbonylgruppe substituiert ist,
eine 4- bis 7-gliedrige Cycolalkylenimino-C_1-3-alkylgruppe oder
eine 4- bis 7-gliedrige Cycloalkyl-C_1-3-alkylgruppe, in der eine oder zwei Methylengruppen durch eine -NH- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein können und in der eine oder zwei der -NH- oder -N(C_1-3-Alkyl)-Gruppe benachbarte Methylengruppen jeweils durch eine Carbonylgruppe ersetzt sein können, mit der Maßgabe, dass eine wie oben definierte Cycloalkylgruppe, in der zwei -NH- oder -N(C_1-3-Alkyl)-Gruppen durch genau eine -CH₂-Gruppe voneinander getrennt sind, ausgeschlossen sind,
R⁵ ein Wasserstoffatom,
B eine Gruppe der Formeln

in der
n die Zahl 1,
R⁶ ein Wasserstoffatom oder eine C_1-3-Alkyl-, Hydroxy-, Amino-, C_1-3-Alkylaminogruppe,
R⁷ ein Fluor-, Chlor- oder Bromatom, eine C_1-3-Alkylgruppe, in der die Wasserstoffatome ganz oder teilweise durch Fluoratome ersetzt sein können, eine C_{2- 3}-Alkenyl-, C_{2- 3}-Alkinyl- oder eine Hydroxygruppe darstellen, und
X¹ bis X³ unabhängig voneinander jeweils ein Stichstoffatom oder eine CH-Gruppe,
wobei mindestens eine und höchstens zwei der Gruppen X¹ bis X³ ein Stickstoff atom darstellen,
wobei, soweit nichts anderes erwähnt wurde, unter dem Ausdruck „Heteroarylgruppe" eine im Kohlenstoffgerüst gegebenenfalls durch eine C_1-3-Alkyl-, Carboxy-, C_1-3-Alkoxycarbonyl- oder C_1-3-Alkoxy-carbonylaminogruppe substituierte monocyclische 5- oder 6-gliedrige Heteroarylgruppe zu verstehen ist, wobei
die 6-gliedrige Heteroarylgruppe ein, zwei oder drei Stickstoffatome und
die 5-gliedrige Heteroarylgruppe eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_{1- 3}-alkylgruppe substituierte Iminogruppe, ein Sauerstoff- oder Schwefelatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl-, Amino-C_1-3-alkyl-, C_1-3-Alkylamino-C_1-3-alkyl-, Di-(C_1-3-alkyl)-amino-C_1-3-alkyl-, C_{3- 6}-Cycloalkylenimino-C_1-3-alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe oder ein Sauerstoff- oder Schwefelatom und zusätzlich ein Stickstoffatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe und zwei oder drei Stickstoffatome enthält,
und außerdem an die vorstehend erwähnten monocyclischen Heteroarylgruppen über zwei benachbarte Kohlenstoffatome ein Phenylring ankondensiert sein kann
und die Bindung über ein Stickstoffatom oder über ein Kohlenstoffatom des heterocyclischen Teils oder eines ankondensierten Phenylrings erfolgt,
wobei die in den Definitionen enthaltenen Alkyl- und Alkoxygruppen, die mehr als zwei Kohlenstoffatome aufweisen, soweit nichts anderes erwähnt wurde, geradkettig oder verzweigt sein können,
und wobei die Wasserstoffatome der in den Definitionen enthaltenen Methyl- oder Ethylgruppen ganz oder teilweise durch Fluoratome ersetzt sein können,
deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze.Very particularly preferred compounds of the above general formula I are those in which
R ¹ is an amino, C _{1- 5} alkylamino, C _3-7 cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each on the amine nitrogen atom by a phenylcarbonyl or phenylsulphonyl group or by a in the alkyl moiety optionally substituted by a carboxy group, a converted in vivo into a carboxy group, an amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe substituted C _{1- 5} alkyl or C _{1- 5} alkylcarbonyl group may be substituted, wherein two nitrogen atoms are separated by at least two carbon atoms,
a di- (C _{1- 5} alkyl) amino or N- (C _3-7 cycloalkyl) C _{1- 5} alkylamino group, wherein the C _{1- 5} alkyl moiety with the exception of the 1-position in each case by a hydroxy -, C _1-3 alkoxy, amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted,
a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group, wherein
the cycloalkyleneimine moiety through one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5} alkyloxycarbonylamino-C _{1- 3} alkyl-, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylamino-carbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} -alklaminocarbonyl -, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -cycloalkyleneiminocarbonyl may be substituted or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted and / or
a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulfinyl or sulfonyl group, or
a methylene group in the 4-position of a 6- or 7-membered Cyuloalkyleniminogruppe by an oxygen or sulfur atom or by an -NH-, -NC _1-3 alkyl, -N (C _{2- 3} alkanoyl) -, sulphinyl or sulfonyl group may be replaced and / or
a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) - CO group can be replaced,
an optionally substituted by one or two C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) - amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl, C _1-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl- , Di (C _1-3 alkyl) -aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl-substituted 5- to 7-membered cycloalkenylene-ininocarbonyl or cycloalkenyleneiminosulfonyl groups, wherein the double bond is not bonded to a nitrogen atom,
a substituted optionally substituted by one or two Cß_ ₅ alkyl aminocarbonyl or aminosulfonyl,
wherein the substituents may be the same or different and
each one of the alkyl C _{1- 5} alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxy-C _1-3 amino-C _{1 -3} alkyl, C _{1 -3} -Alkylamino-C _1-3 -alkyl-, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl-, C _3-6 -cycloalkylenimino-C _1-3 -alkyl-, C _{1- 5-} alkyloxycarbonylamino-C _1-3 -alkyl, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 -alkylaminocarbonyl, N- (C _3-7 -cyc cloalkyl) -C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -Cycloalkyleniminocarbonylgruppe may be substituted or
a methylene group not adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted,
an optionally substituted by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, mono-, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _{1- 3-} alkyl group, wherein
the phenyl moiety by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, aminoC _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, Di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkylenimino-C _1-3 -alkyl or C _1-3 -alkoxy may be substituted and / or
wherein a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO group or
a methylene group which is adjacent to the nitrogen atom may be replaced by a carbonyl group in a 5- to 7-membered cycloalkyleneimino group,
or a group of formulas

in each of which a hydrogen atom in the heterocyclic moiety may be replaced by a methylsulfonylmethyl, aminoC _1-3 alkyl or aminocarbonyl group, and
m is the number 1 or 2,
R ^{2 is} a chlorine or bromine atom, a C _1-3 -alkyl group in which tie hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C _2-3 alkenyl group,
R ^{3 is} a hydrogen atom,
R ⁴ is a hydrogen atom or a linear or branched C _{1- 5} alkyl group optionally substituted by a hydroxy, C _1-3 -alkyloxy, mercapto, C _1-3 alkylsulphanyl, C _1-3 alkylsulphinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, C _3-6 cycloalkyleneiminocarbonyl, amino, C ₁ Substituted with _3- alkylamino, di (C _1-3 alkyl) amino, C _3-6 cycloalkyleneimino, C _1-3 alkylcarbonylamino, C _3-6 cycloalkylcarbonylamino, benzyloxycarbonylamino or guanidino group,
a phenyl- or heteroaryl, phenyl-C _1-3 -alkyl or heteroaryl-C _1-3 -alkyl group which is optionally substituted by a hydroxy, C 1-6 alkyloxy, benzyloxy, hydroxycarbonyl-C _1-3 -alkoxy-, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) aminocarbonylC _1-3 alkyloxy, C _3-6 cycloalkyleneiminocarbonylC _1-3 alkyloxy, carboxy, C _1-3 alkyloxycarbonyl group,
a 4- to 7-membered cyclobalkyleneimino-C _1-3 -alkyl group or
a 4- to 7-membered cycloalkyl-C _1-3 -alkyl group in which one or two methylene groups may be replaced by a -NH- or -N (C _1-3 -alkyl) group and in which one or two of the Each of the adjacent methylene groups may be replaced by a carbonyl group with the proviso that a cycloalkyl group as defined above in which two -NH- or -N (C ₁ -NH- or -N (C _1-3 -alkyl) -group _3- alkyl) groups are separated by exactly one -CH ₂ group, are excluded,
R ^{5 is} a hydrogen atom,
B is a group of formulas

in the
n is the number 1,
R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxy, amino, C _1-3 -alkylamino group,
R ⁷ is a fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C _{2- 3} -alkenyl, C ₃ -alkynyl or _2- Represent hydroxy group, and
X ¹ to X ³ independently of one another each represent a nitrogen atom or a CH group,
wherein at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom,
Unless otherwise mentioned, the term "heteroaryl group" denotes a monocyclic 5 which is optionally substituted in the carbon skeleton by a C _1-3 -alkyl, carboxy, C _1-3 -alkoxycarbonyl or C _1-3 -alkoxycarbonylamino group or 6-membered heteroaryl group is understood, wherein
the 6-membered heteroaryl group contains one, two or three nitrogen atoms and
the 5-membered heteroaryl group contains an alkyl group optionally by a C _1-3 alkyl or phenyl-C _{1- 3-substituted} imino group, an oxygen or sulfur atom or
an optionally represented by a C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di (C _1-3 -alkyl) -amino C _1-3 alkyl, C _{3- 6} alkyl or C _1-3 -Cycloalkylenimino-phenyl-C _1-3 -alkyl substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group which is optionally substituted by a C _1-3 -alkyl or phenyl-C _1-3 -alkyl group and contains two or three nitrogen atoms,
and further, a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups through two adjacent carbon atoms
and the bond is via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused-on phenyl ring,
the alkyl and alkoxy groups having more than two carbon atoms contained in the definitions, unless otherwise mentioned, may be straight-chain or branched,
and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms,
their tautomers, their enantiomers, their diastereomers, their mixtures and their salts.

in der
R⁶ ein Wasserstoffatom,
R⁷ ein Chloratom darstellen, und
X¹ bis X³ unabhängig voneinander jeweils ein Stichstoffatom oder eine CH-Gruppe,
wobei mindestens eine und höchstens zwei der Gruppen X¹ bis X³ ein Stickstoffatom darstellen, bedeuten,
deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze.Outstandingly preferred compounds of the above general formula I are those in which
R ^{1 is} a 2,5-dihydro-1H-pyrrol-1-yl-carbonyl, pyrrolidin-1-yl-carbonyl, 2- (aminomethyl) -pyrrolidin-1-yl-carbonyl, 2- (N-tert -Butoxycarbonylaminomethyl) -pyrrolidin-1-ylcarbonyl, 3-oxopiperazin-1-ylcarbonyl or morpholin-4-ylcarbonyl group,
R ^{2 is} a hydrogen, chlorine or bromine atom or a C _1-3 -alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms,
R ^{3 is} a hydrogen atom,
R ^{4 is} a hydrogen atom or the methyl group,
R ^{5 is} a hydrogen atom,
B is a group of formulas

in the
R ^{6 is} a hydrogen atom,
R ^{7 represents} a chlorine atom, and
X ¹ to X ³ independently of one another each represent a nitrogen atom or a CH group,
where at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom,
their tautomers, their enantiomers, their diastereomers, their mixtures and their salts.

• (1) 4-[(5-Chlor-1H-benzimidazol-2-yl)-methylamino]-7-(pyrrolidin-1-yl-carbonyl)-chinolin,
• (2) 6-Chlor-4-[C-(5-chlor-1 H-benzimidazol-2-yl)-methylamino]-7-(pyrrolidin-1-yl-carbonyl)-chinazolin,
• (3) 4-[C-(5-Chlor-1H-benzimidazol-2-yl)methylamino]-7-(pyrrolidin-1-yl-carbonyl)-chinazolin,
• (4) 6-Chlor-4-[1-(5-chlor-1H-benzimidazol-2-yl)-ethylamino]-7-(2,5-dihydropyrrol-1-yl-carbonyl)-chinazolin,
• (5) 6-Chlor-4-[1-(5-chlor-1H-benzimidazol-2-yl)-ethylamino]-7-(2-tert.-butoxycarbonyl-aminomethyl-pyrrolidin-1-yl-carbonyl)-chinazolin,
• (6) 6-Chlor-4-[1-(5-chlor-1 H-benzimidazol-2-yl)-ethylamino]-7-(2-aminomethylpyrrolidin-1-yl-carbonyl)-chinazolin,
• (7) 6-Chlor-4-[1-(5-chlor-1H-benzimidazol-2-yl)-ethylamino]-7-(morpholin-4-yl-carbonyl)-chinazolin,
• (8) 6-Chlor-4-[1-(S)-(5-chlor-1H-benzimidazol-2-yl)-ethylamino]-7-(piperazin-3-on- 1-yl-carbonyl)-chinazolin,
• (9) 6-Chlor-4-[1-(S)-(5-chlor-1H-benzimidazol-2-yl)-ethylamino]-7-(2,5-dihydropyrrol-1-yl-carbonyl)-chinazolin,
• (10) 6-Chlor-4-[1-(S)-(5-chlor-1H-benzimidazol-2-yl)-ethylamino]-7-(pyrrolidin-1-yl-carbonyl)-chinazolin

und deren Salze.For example, the following preferred compounds of general formula I may be mentioned:

• (1) 4 - [(5-chloro-1H-benzimidazol-2-yl) -methylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinoline
• (2) 6-chloro-4- [C- (5-chloro-1H-benzimidazol-2-yl) -methylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinazoline,
• (3) 4- [C- (5-chloro-1H-benzimidazol-2-yl) methylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinazoline,
• (4) 6-chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2,5-dihydropyrrol-1-yl-carbonyl) -quinazoline,
• (5) 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2-tert-butoxycarbonyl-aminomethyl-pyrrolidin-1-yl-carbonyl) - quinazoline,
• (6) 6-chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (2-aminomethylpyrrolidin-1-ylcarbonyl) quinazoline,
• (7) 6-chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (morpholin-4-ylcarbonyl) quinazoline,
• (8) 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (piperazin-3-one-1-ylcarbonyl) -quinazo lin,
• (9) 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2,5-dihydropyrrol-1-yl-carbonyl) quinazoline .
• (10) 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinazoline

and their salts.

According to the invention gives the compounds of general formula I according to known methods, for example according to the following procedures:

in der R³ bis R⁵ wie eingangs erwähnt definiert sind und Z¹ das Wasserstoffatom oder eine Schutzgruppe bedeuten und B' eine Gruppe der Formel

darstellt, in der R⁶ und R⁷ wie eingangs erwähnt definiert sind und X das Stickstoffatom oder die CH-Gruppe bedeutet:
Cyclisierung einer gegebenenfalls im Reaktionsgemisch gebildeten Verbindung der allgemeinen Formel

in der
R³ bis R⁷ wie eingangs erwähnt definiert sind, X das Stickstoffatom oder die CH-Gruppe und Z¹ das Wasserstoffatom oder eine Schutzgruppe bedeutet, wobei anschließend eine eventuell vorhandene Schutzgruppe abgespalten wird.(a) For the preparation of compounds of the general formula

in which R ³ to R ⁵ are defined as mentioned above and Z ^{1 is} the hydrogen atom or a protective group and B 'is a group of the formula

in which R ⁶ and R ⁷ are defined as mentioned above and X is the nitrogen atom or the CH group:
Cyclization of a compound of the general formula optionally formed in the reaction mixture

in the
R ³ to R ⁷ are defined as mentioned above, X is the nitrogen atom or the CH group and Z ^{1 is} the hydrogen atom or a protective group, with subsequent removal of any protecting group present.

The cyclization is conveniently in a solvent or solvent mixture such as ethanol, isopropanol, glacial acetic acid, benzene, chlorobenzene, toluene, Xylene, glycol, glycol monomethyl ether, diethylene glycol dimethyl ether, Sulfolane, dimethylformamide or tetralin, dimethyl sulfoxide, methylene chloride, Chloroform, carbon tetrachloride, for example at temperatures between 0 and 250 ° C, but preferably between 20 and 100 ° C, optionally in the presence a condensing agent such as phosphorus oxychloride, thionyl chloride, sulfuryl chloride, Sulfuric acid, p-toluenesulfonic acid, methane, Hydrochloric acid, Phosphoric acid, polyphosphoric Acetic acid, acetic anhydride, N, N-dicyclohexylcarbodiimide or optionally also in the presence a base such as potassium ethylate or potassium tert-butylate. The However, cyclization may also be carried out without a solvent and / or condensing agent carried out become.

in der(b) For the preparation of a compound of the general formula

in the

in er
R¹, R² und X¹ bis X³ wie eingangs erwähnt definiert sind und Z eine Austrittsgruppe wie ein Halogenatom, eine Sulfonyloxy- oder Aryloxygruppe darstellt, z.B. ein Chlor-, Brom- oder Iodatom, eine Trifluormethylsulfonyloxy-, Phenoxy- oder p-Nitrophenoxygruppe,
mit einer Verbindung der allgemeinen Formel

in der B und R³ bis R⁵ wie eingangs erwähnt definiert sind.B, X ¹ to X ³ and R ¹ to R ⁵ are defined as mentioned above:
Coupling of a compound of the general formula

in he
R ¹ , R ² and X ¹ to X ^{3 are} as defined above and Z is a leaving group such as a halogen atom, a sulphonyloxy or aryloxy group, for example a chlorine, bromine or iodine atom, a Trifluormethylsulfonyloxy-, phenoxy or p- nitrophenoxy group,
with a compound of the general formula

in which B and R ³ to R ⁵ are defined as mentioned above.

The coupling reaction is conveniently in a solvent such as toluene, dioxane, dimethoxyethane, dimethylformamide or tetrahydrofuran preferably in the presence of a base such as sodium tert-butoxide, Bis (trimethylsilyl) lithium amide, potassium carbonate, cesium carbonate or triethylamine at a temperature between 0 ° C and 150 ° C, preferably between 0 ° C and 100 ° C, optionally using a suitable catalyst, for example Bis (tri-o-tolylphosphine) palladium (II) chloride, tris (dibenzylideneacetone) dipalladium (0) / tris-o-tolylphosphine, Tris (dibenzylideneacetone) dipalladium (0) / tris (2-furyl) phosphine, tris (dibenzylideneacetone) dipalladium (0) / 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl, tetrakis - (triphenylphosphine) palladium (0), 1,1'-bis (diphenylphosphino) ferrocene palladium dichloride or palladium (II) acetate / 1,3-bis (diphenylphosphino) -propane, carried out.

But the coupling reaction can also without the addition of solvents in substance by melting the compounds of the general formulas V and VI at temperatures between room temperature and 150 ° C, optionally in the presence of one of the abovementioned bases and / or optionally using one of the aforementioned catalysts, carried out become.

in der
R¹ und R² wie eingangs erwähnt definiert sind, X¹ und X³ jeweils ein Stickstoffatom und Z eine Austrittsgruppe wie ein Halogenatom, beispielsweise ein Chlor- oder Bromatom, darstellen: (c) For the preparation of a compound of the general formula

in the
R ¹ and R ^{2 are} as defined above, X ¹ and X ^{3 are} each a nitrogen atom and Z is a leaving group such as a halogen atom, for example a chlorine or bromine atom, represent:

in der
R¹ und R² wie eingangs erwähnt definiert sind und X eine Hydroxy- oder C_1-4-Alkoxygruppe oder ein Halogenatom darstellt, mit Formamid und anschließende Umsetzung der daraus resultierenden Verbindung der allgemeinen Formel

in der
R¹ und R² wie eingangs erwähnt definiert sind, mit einem Halogenierungsmittel, beispielsweise mit Thionylchlorid, Thionylbromid oder Oxalylchlorid.Cyclization of a compound of the general formula

in the
R ¹ and R ² are defined as mentioned above and X represents a hydroxy or C _1-4 alkoxy group or a halogen atom, with formamide and subsequent reaction of the resulting compound of the general formula

in the
R ¹ and R ^{2 are} as defined above, with a halogenating agent, for example with thionyl chloride, thionyl bromide or oxalyl chloride.

The cyclization becomes, for example in a high boiling solvent such as chlorobenzene, xylene, dimethylformamide, dimethyl sulfoxide, sulfolane or even without further solvent in the presence of excess formamide at temperatures between 100 and 200 ° C, preferably between 130 and 170 ° C, performed.

Subsequent reaction with a halogenating agent, for example with thionyl chloride, thionyl bromide or oxalyl chloride, is expediently either without solvent in substance in the presence of dimethylformamide as a catalyst or by adding a solvent such as dimethylformamide, pyridine, benzene, carbon tetrachloride, 1,2-dichloroethane or chloroform at temperatures between 20 and 120 ° C performed.

The used as starting materials Compounds of the general formulas II to IX, some of which are known from the literature are, get one after literature procedures. Furthermore, their production described in the examples.

The production of compounds of the general formulas II and IV, for example, analogous to K. Maekawa, J. Ohtani, Agr. Biol. Chem. 1976, 40, 791-799.

Methods for amide coupling are, for example in P.D. Bailey, I.D. Collier, K.M. Morgan in "Comprehensive Functional Group Interconversion", Vol. 5. page 257ff., Pergamon 1995 described.

In the case described above Implementations can optionally present reactive groups such as hydroxyl, carboxy, Amino, alkylamino or imino groups during the reaction by conventional protecting groups protected will be split off after the implementation.

For example, the protective group for a hydroxy group is the methoxy, benzyloxy, trimethylsilyl, acetyl, benzoyl, tert-butyl, trityl, benzyl or tetrahydropyranyl group,
as protecting groups for a carboxyl group, the trimethylsilyl, methyl, ethyl, terf.-butyl, benzyl or tetrahydropyranyl group and
as a protective group for an amino, alkylamino or imino group, the acetyl, trifluoroacetyl, benzoyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group and for the amino group additionally the Phthalyl group into consideration.

Further protective groups and their separation are in T.W. Greene, P.G.M. Wuts, "Protecting Groups in Synthesis," Wiley, 1991.

The optionally subsequent cleavage of a protective moiety used is carried out, for example hydrolytically in an aqueous solvent, for example in water, isopropanol / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid or in the presence of an alkali metal base such as lithium hydroxide, sodium hydroxide or potassium hydroxide or by ether cleavage, for example in the presence of iodotrimethylsilane, at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C.

The cleavage of a benzyl, methoxybenzyl or benzyloxycarbonyl radical, however, takes place, for example, by hydrogenolysis, e.g. with hydrogen in the presence of a catalyst such as palladium / carbon in a solvent such as methanol, ethanol, ethyl acetate, Dimethylformamide, dimethylformamide / acetone or glacial acetic acid, if necessary with the addition of an acid like hydrochloric acid at temperatures between 0 and 50 ° C, but preferably at room temperature, and at a hydrogen pressure of 1 to 7 bar, but preferably from 1 to 5 bar.

The cleavage of a methoxybenzyl group can also in the presence of an oxidizing agent such as cerium (IV) ammonium nitrate in a solvent such as methylene chloride, acetonitrile or acetonitrile / water at temperatures between 0 and 50 ° C, but preferably at room temperature.

The cleavage of a methoxy group conveniently takes place in the presence of boron tribromide in a solvent such as methylene chloride at temperatures between -35 and -25 ° C.

The cleavage of a 2,4-dimethoxybenzyl radical however, it is preferably carried out in trifluoroacetic acid in the presence of anisole.

The elimination of a tert-butyl or terf.-Butyloxycarbonylrestes is preferably carried out by treatment with an acid such as trifluoroacetic acid or hydrochloric acid optionally using a solvent such as methylene chloride, dioxane or ether.

The cleavage of a phthalyl radical preferably in the presence of hydrazine or a primary amine such as methylamine, ethylamine or n-butylamine in a solvent such as methanol, ethanol, isopropanol, toluene / water or dioxane Temperatures between 20 and 50 ° C.

The cleavage of an allyloxycarbonyl radical is carried out by treatment with a catalytic amount of tetrakis (triphenylphosphine) palladium (0) preferably in a solvent such as tetrahydrofuran and preferably in the presence of an excess from a base such as morpholine or 1,3-dimedone at temperatures between 0 and 100 ° C, preferably at room temperature and under inert gas, or by treatment with a catalytic amount of tris (triphenylphosphine) rhodium (i) chloride in a solvent like watery Ethanol and optionally in the presence of a base such as 1,4-diazabicyclo [2.2.2] octane at temperatures between 20 and 70 ° C.

Furthermore, the compounds obtained of general formula I into their enantiomers and / or diastereomers be separated.

Thus, for example, the obtained compounds of general formula I, which in racemates occur according to methods known per se (see Allinger N.L. and Eliel E. L. in "Topics in Stereochemistry ", Vol. 6, Wiley Interscience, 1971) into their optical antipodes and Compounds of general formula I with at least two asymmetric Carbon atoms due to their physicochemical differences according to methods known per se, e.g. by chromatography and / or fractionated crystallization, break into their diastereomers, which, if they occur in racemic form, then like mentioned above can be separated into the enantiomers.

The enantiomer separation takes place preferably by column separation on chiral phases or by recrystallization from an optical active solvents or by reacting with one, with the racemic compound salts or derivatives such as e.g. Ester or amide-forming optically active Substance, especially acids and their activated derivatives or alcohols, and separating the this diastereomeric salt mixture or derivative obtained, e.g. due to different solubilities, where from the pure diastereomeric salts or derivatives of the free antipodes can be released by the action of appropriate means. Especially common, optically active acids are e.g. the D and L forms of tartaric or dibenzoyltartaric, di-o-toluenoic, malic, camphorsulfonic, glutamic, aspartic or China acid. As an optically active alcohol, for example, (+) - or (-) - menthol and as an optically active acyl radical in amides, for example, the (+) - or (-) - menthyloxycarbonyl radical in Consideration.

Furthermore, the compounds obtained of the formula I in their salts, in particular for the pharmaceutical application in their physiologically tolerable Salts with inorganic or organic acids are converted. When acids come therefor for example, hydrochloric acid, Hydrobromic acid, sulfuric acid, methanesulfonic acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic into consideration.

In addition, the thus obtained new compounds of formula I, if this is a carboxy group included, if desired subsequently into their salts with inorganic or organic bases, in particular for the pharmaceutical application in their physiologically acceptable Salts, convert. As bases For example, sodium hydroxide, potassium hydroxide, cyclohexylamine, Ethanolamine, diethanolamine and triethanolamine into consideration.

As already mentioned, show the compounds of general formula I and their tautomers, their enantiomers, their diastereomers and their physiologically acceptable Salts have valuable pharmacological properties, in particular an antithrombotic effect, preferably on a thrombin or Factor Xa influencing effect is based, for example on a thrombin-inhibiting or factor Xa-inhibiting effect, on a extend the aPTT time Effect and on an inhibitory effect on related serine proteases such. As urokinase, Factor VIIa, Factor IX, Factor XI and Factor XII.

The compounds listed in the Experimental Section were tested for their effect on the inhibition of factor Xa as follows examined:

Methodology:

Enzyme kinetic measurement with chromogenic substrate. The amount of p-nitroaniline (pNA) released by human factor Xa from the colorless chromogenic substrate is determined photometrically at 405 nm. It is proportional to the activity of the enzyme used. The inhibition of the enzyme activity by the test substance (based on the solvent control) is determined at various test substance concentrations and from this the IC _{50 is} calculated as the concentration which inhibits the factor Xa used by 50%.

Material:

Tris (hydroxymethyl) aminomethane buffer (100 mmol) and sodium chloride (150 mmol), pH 8.0 plus 1 mg / ml Human Albumin Fraction V, protease-free
Factor Xa (Calbiochem), Specific Activity: 217 IU / mg, final concentration: 7 IU / ml per reaction
Substrate S 2765 (Chromogenix), final concentration: 0.3 mM / L (1 KM) per reaction
Test substance: final concentration 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001 μmol / l

Procedure: 10 μl of a 23.5-fold more concentrated starting solution the test substance or solvent (Control), 175 μl TRIS / HSA buffer and 25 μl Factor Xa-use solution of 65.8 U / L are incubated for 10 minutes at 37 ° C. After adding 25 μl S 2765 working solution (2.82 mmol / L), the sample in the photometer (SpectraMax 250) at 405 nm for 600 seconds at 37 ° C measured.

Evaluation:

• 1. Determination of the maximum increase (deltaOD / minutes) over 21 measuring points.
• 2. Determination of the% inhibition based on the solvent control.
• 3. Create a dose response curve (% inhibition vs substance concentration).
• 4. Determination of the IC ₅₀ by interpolation of the X value (substance concentration) of the dose-response curve at Y = 50% inhibition.

All compounds tested showed IC ₅₀ values less than 100 μmol / L.

The compounds prepared according to the invention are generally well tolerated.

Because of their pharmacological properties, the novel compounds and their physiologically acceptable salts are suitable for the prevention and treatment of venous and arterial thrombotic disorders, such as the prevention and treatment of deep vein thrombosis, the prevention of reocclusion after bypass surgery or angioplasty (PT C) A), as well as occlusion in peripheral arterial diseases, as well as prevention and treatment of pulmonary embolism, disseminated intravascular coagulation, prevention and treatment of coronary thrombosis, prophylaxis of stroke and prevention of occlusion of shunts. In addition, the compounds of the invention are useful for antithrombotic support in thrombolytic treatment, such as alteplase, reteplase, tenecteplase, staphylokinase or streptokinase, for the prevention of long-term restenosis according to PT (C) A, for the prophylaxis and treatment of ischemic events in patients of all forms coronary heart disease, for preventing the metastasis and growth of tumors and inflammatory processes, for example in the treatment of pulmonary fibrosis, for the prophylaxis and treatment of rheumatoid arthritis, for the prevention or prevention of fibrin-dependent tissue adhesions and / or scar tissue formation and for the promotion of Wound healing processes suitable. The novel compounds and their physiologically acceptable salts can be used therapeutically in combination with acetylsalicylic acid, with inhibitors of platelet aggregation such as fibrinogen receptor antagonists (eg abciximab, eptifibatide, tirofiban, roxifiban), with physiological activators and inhibitors of the coagulation system and their recombinant analogues (eg protein C, TFPI, antithrombin) with inhibitors of ADP-induced aggregation (eg clopidogrel, ticlopidine), with P ₂ T receptor antagonists (eg cangrelor) or with combined thromboxane receptor antagonists / synthetase inhibitors (eg Terbogrel).

To achieve a corresponding Effect required dosage is expediently with intravenous administration 0.01 to 3 mg / kg, preferably 0.03 to 1.0 mg / kg, and in oral Administration 0.03 to 30 mg / kg, preferably 0.1 to 10 mg / kg, each 1 up to 4 times a day.

For this purpose, the invention can be prepared Compounds of formula I, optionally in combination with others Active substances, together with one or more inert usual Carriers and / or Diluents, e.g. with corn, starch, Lactose, cane sugar, microcrystalline cellulose, magnesium stearate, Polyvinylpyrrolidone, citric acid, Tartaric acid, Water, water / ethanol, water / glycerine, water / sorbitol, Water / polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethylcellulose or fatty substances such as hard fat or its suitable Mixtures, in usual galenic preparations such as tablets, dragees, capsules, powders, Suspensions or suppositories incorporated.

The following examples are meant to be the invention closer explain, without, however, limiting their scope:

experimental part

Melting points, IR, UV, ¹ H-NMR and / or mass spectra are generally present for the compounds prepared. Unless otherwise stated, R _f values were determined using GC-finished DC plates Kieselgel 60 F ₂₅₄ (E. Merck, Darmstadt, Article No. 1.05714) without chamber saturation. The R _f values determined under the name Alox were determined using TLC plates alumina 60 F ₂₅₄ (E. Merck, Darmstadt, Article No. 1.05713) without chamber saturation. The R _f values determined under the designation Reversed-Phase-8 were determined using GC-finished precast plates RP-8 F _254s (E. Merck, Darmstadt, Article No. 1.15684) without chamber saturation. The ratios indicated for the flow agents relate to volume units of the respective solvents. For chromatographic purifications, silica gel from Millipore (MATREX ^™ , 35-70 my) was used. If further information on the configuration is missing, it is unclear whether they are pure stereoisomers or mixtures of enantiomers / diastereomers.

The test descriptions use the following abbreviations: Boc terf.-butoxycarbonyl DMSO dimethyl sulfoxide DMF dimethylformamide O ortho rac. racemic TBTU: O- (benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate tert. tertiary

The HPLC / MS data were generated on the following system:
Waters ZMD, Alliance 2690 HPLC, Waters 2700 autosampler, Waters 996 diode array detector

As mobile phase was used:
A: water with 0.1% trifluoroacetic acid
B: acetonitrile with 0.1% trifluoroacetic acid

The stationary phase used was a column of Waters X-Terra ^™ MS C ₁₈ 3.5 μm, 4.6 mm × 50 mm (column temperature: constant at 25 ° C.).

The diode array detection took place in the wavelength range 210-500 nm

Range of mass spectrometry Detection: m / z 120 to m / z 950

Example 1 4 - [(5-Chloro-1H-benzimidazol-2-yl) -methylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinoline

(a) N'-tert-butoxycarbonyl-N- (2-amino-4-chloro) phenyl-glycinamide and N'-tert-butoxycarbonyl-N- (2-amino-5-chloro) phenyl-glycinamide

14.3 g (0.100 mol) of 4-chloro-o-phenylenediamine are combined with 17.5 g (0.100 mol) of N-tert-butoxycarbonyl-glycine in 250 ml of tetrahydrofuran with ice cooling and nitrogen atmosphere within 20 minutes of 20.6 g (0.100 mol) of N, N'-dicyclohexylcarbodiimide and subsequently Stirred for 16 hours at room temperature. The mix will be in 750 poured ice-water, the precipitate is filtered off, with little Washed with water and taken up in 500 ml of ethyl acetate. Insoluble ingredients are filtered off and washed with ethyl acetate and tetrahydrofuran. The filtrate is over Dried magnesium sulfate and over Silica gel filtered.

Subsequently, the solvent is removed in vacuo.
Yield: 16.6 g (55%)
R _f value: 0.41 (silica gel, dichloromethane / ethyl acetate = 1: 1 + 0.5% ammonia solution)

(b) N-tert-butoxycarbonyl-C- (5-chloro-1H-benzimidazol-2-yl) methylamine

16.6 g (55.4 mmol) of a mixture of N'-tert-butoxycarbonyl-N- (2-amino-4-chloro) -phenyl-glycinamide and N = tert-butoxycarbonyl-N- (2-amino-5-chloro ) Phenyl-glycinamide are initially charged in 160 ml of glacial acetic acid and the mixture is heated to reflux for 1.5 hours. Then the majority of glacial acetic acid is distilled off and the residue is poured into a mixture of crushed ice and concentrated ammonia solution. Insoluble matters are filtered off, extracted with 500 ml of ethyl acetate, the organic phase washed with saturated sodium chloride solution and dried over magnesium sulfate. After removal of the solvent in vacuo, the residue is purified by chromatography on silica gel (gradient: methylene chloride / methanol = 98: 2 → 95: 5 + 0.2% ammonia solution).
Yield: 6.70 g (43%)
R _f value: 0.45 (silica gel, petroleum ether / ethyl acetate = 8: 2)
C ₁₃ H ₁₆ ClN ₃ O ₂ (281.74)
Mass spectrum: (M + H) ⁺ = 282/284 (chloroisotopes)

(c) C- (5-Chloro-1H-benzimidazol-2-yl) -methylamine

4.62 g (16.4 mmol) of N'-tert-butoxycarbunyl-C- (5-chloro-1N-benzimidazol-2-yl) metiylamine are dissolved in 100 ml of saturated ethanolic hydrogen chloride solution and stirred at room temperature for 2 hours. Subsequently, all volatile constituents are removed under reduced pressure and the crude product is reacted further.
Yield: quantitative
R _f value: 0.35 (silica gel, petroleum ether / ethyl acetate = 8: 2)

(d) 4-chloro-quinoline-7-carboxylic acid

10.0 g (43.2 mmol) of 4-chloro-7-trifluoromethyl-quinoline are concentrated in 200 ml of conc. Sulfuric acid irradiated for 2 hours at 550 watts in the microwave. The reaction solution is poured into ice-water and adjusted to pH 3-4 with sodium hydroxide solution. The precipitated product is filtered off with suction, washed with water and dried.
Yield: 8.9 g (99%)
R _f value: 0.45 (silica gel, toluene / ethanol = 4: 1)
C ₁₀ H ₆ ClNO ₂ (207.62)
Mass spectrum: (M + H) ⁺ = 208/10 (chloroisotopes)

(e) 4-chloro-7- (pyrrolidin-1-ylcarbonyl) quinoline

5.2 g (25 mmol) of 4-chloro-quinoline-7-carboxylic acid and 2.1 ml (25 mmol) of pyrrolidine are suspended in 125 ml of ethyl acetate, 14.0 ml (128 mmol) of N-methylmorpholine is added and then 29.2 ml (50.8 mmol ) Propanephosphonsäureanhydrid added dropwise. After 40 hours, washed with 20 ml of sodium bicarbonate solution and extracted with ethyl acetate. The combined organic extracts are dried over sodium sulfate and evaporated. The residue is chromatographed on silica gel (eluent: toluene / ethanol = 95: 5).
Yield: 4.7 g (72%)
R _f value: 0.18 (silica gel, toluene / ethanol = 9: 1)
C ₁₄ H ₁₃ ClN ₂ O (260.72)
Mass spectrum: (M + H) ⁺ = 261/63 (chloroisotopes)

(f) 4- [C- (5-Chloro-1H-benzimidazol-2-yl) methylaminol-7- (pyrrolidin-1-yl-carbonyl) -quinoline

260 mg (1.00 mmol) of 4-chloro-7- (pyrrolidin-1-yl-carbonyl) quinoline, together with 330 mg (1.51 mmol) of (5-chloro-1H-benzimidazol-2-yl) -methylamine with stirring for Heated to 100 ° C for 20 hours. The resulting mixture is taken up in dichloromethane / methanol. After addition of silica gel, the solvent is removed in vacuo. The mixture is then purified by chromatography on silica gel (eluent: dichloromethane / ethanol = 20: 1).
Yield: 66 mg (15%)
R _f value: 0.85 (silica gel, dichloromethane / ethanol = 95: 5)
C ₂₂ H ₂₀ ClN ₅ O (405.89)
Mass spectrum: (M + H) ⁺ = 406/408 (chloroisotopes)

Example 2 6-Chloro-4- [C- (5-chloro-1H-benzimidazol-2-yl) -methylamino] -7- (pyrrolidin-1-yl-carbonyl) quinazoline

(a) 6-Chloro-4-oxo-3,4-dihydroquinazoline-7-carboxylic acid hydrochloride

20.0 g (92.8 mmol) of 2-amino-5-chloro-terephthalic acid are added in portions to 35 ml (0.80 mol) of formamide at 160 ° C. under nitrogen and the mixture is kept at 160 ° C. for 4 hours with stirring. The mixture is then poured into 500 ml of ice water and brought to pH 3-4 with 2 molar hydrochloric acid solution. It is diluted with a further 500 ml of water and stirred for 15 minutes at room temperature. Thereafter, the precipitate is filtered off, washed neutral with water and dried at 40 ° C. The solid obtained is stirred for a further 30 minutes at room temperature in ether, filtered off and dried.
Yield: 15.1.5 g (73%)
R _f value: 0.30 (silica gel, dichloromethane / ethanol = 4: 1 + 1% acetic acid)
C ₉ H ₅ ClN ₂ O ₃ × HCl (224.60 / 261.07)
Mass spectrum: (M + H) ⁺ = 225/227 (chloroisotopes)

(b) 4,6-dichloroquinazoline-7-carboxylic acid chloride

2.50 g (11.1 mmol) of 6-chloro-4-oxo-3,4-dihydro-quinazoline-7-carboxylic acid are refluxed in 50 ml of thionyl chloride and 0.3 ml of dimethylformamide for 15 hours. Subsequently, volatile constituents are removed in vacuo and the product immediately reacted further without further purification.
Yield: 2.91 g (98%)
C ₉ H ₃ Cl ₃ N ₂ O (261.50)
Mass spectrum: (MH) ^- = 260/262/264 (chloroisotopes)

(c) 4,6-Dichloro-7- (pyrrolidin-1-ylcarbonyl) quinazoline

0.56 ml (6.3 mmol) of pyrrolidine are dissolved in 10 ml of dichloromethane, at -65 ° C is added dropwise within 20 minutes, a solution of 1.65 g (6.3 mmol) of 4,6-dichloro-quinazoline-7-carbonyl chloride in 70 ml of dichloromethane and Stirred for 5 minutes. Subsequently, at -65 ° C., 0.31 ml (3.1 mmol) of 10 molar sodium hydroxide solution are added dropwise and then stirred for 2 hours without cooling. The solvent is distilled off and the residue is purified by chromatography on silica gel (eluent: dichloromethane → dichloromethane / isopropanol = 9: 1).
Yield: 0.59 g (32%)
R _f value: 0.45 (silica gel; dichloromethane)
C ₁₃ H ₁₁ Cl ₂ N ₃ O (296.16)
Mass spectrum: (M + H) ⁺ = 296/298/300 (chloroisotopes)

(d) 6-Chloro-4 - [(5-chloro-1H-benzimidazol-2-yl) -methylaminol-7- (pyrrolidin-1-yl-carbonyl) -quinazoline

114 mg (0.53 mmol) of (5-chloro-1H-benzimidazol-2-yl) -methylamine hydrochloride are combined with 150 mg (0.51 mmol) of 4,6-dichloro-7- (pyrrolidin-1-yl-carbonyl) quinazoline under nitrogen atmosphere dissolved in 5 ml of N, N-dimethylformamide and with 77 μl (0.55 mmol) of triethylamine. The mixture is added for 3 hours Room temperature stirred. Subsequently is poured into ice-water and extracted three times with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, over sodium sulfate dried and the solvent removed in a vacuum.

The residue is purified by chromatography on silica gel (eluent: dichloromethane / ethanol = 1: 0 → 25: 1 → 19: 1 → 9: 1).
Yield: 42 mg (29%)
R _f value: 0.45 (silica gel, dichloromethane / ethanol = 1: 1)
C ₂₁ H ₁₈ Cl ₂ N ₆ O (441.32)
Mass spectrum: (MH) ^- = 439/441/443 (chloroisotopes)

Example 3 4- [C- (5-Chloro-1H-benzimidazol-2-yl) methylamino] -7- (pyrrolidin-1-yl-carbonyl) quinazoline

Prepared analogously to Example 2d from 4-chloro-7- (pyrrolidin-1-yl-carbonyl) quinazoline, C- (5-chloro-1H-benzimidazol-2-yl) -methylamine hydrochloride and triethylamine in N, N-dimethylformamide followed by purification by addition of ethyl acetate and water, filtration of the resulting precipitate and drying at 50 ° C.
Yield: 60
R _f value: 0.37 (silica gel, dichloromethane / ethanol = 9: 1)
C ₂₁ H ₁₉ ClN ₆ O (406.88)
Mass spectrum: (M + H) ⁺ = 407/409 (chloroisotopes) Example 4 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (2.5- dihydropyrrol-1-yl-carbonyl) -quinazoline

(a) N'-Benzyloxycarbonyl-N- (2-amino-4-chloro) phenyl-alaninamide and N'-benzyloxycarbonyl-N- (2-amino-5-chloro) phenyl-alaninamide

4.50 g (20.2 mmol) of N-benzyloxycarbonylalanine and 3.60 g (22.2 mmol) of N, N'-carbonyldiimidazole are stirred in 25 ml of dimethylformamide for 10 minutes and then slowly with a solution of 4-chloro-o-phenylenediamine (6.00 g, 42.1 mmol ) and 4.88 ml (44.4 mmol) of N-methylmorpholine in 25 ml of dimethylformamide and stirred for 16 hours at room temperature. It is then mixed with water and extracted three times with methylene chloride. The combined organic phases are dried with sodium sulfate and concentrated. The residue is purified by chromatography on silica gel (gradient: methylene chloride / ethanol = 100: 0 → 95: 5). The title compounds are contaminated with portions of diacylated phenylenediamine.
Yield: 6.0 g (mixture)
R _f value: 0.35 (silica gel, dichloromethane / ethanol = 19: 1)

(b) N-Benzyloxycarbonyl-1- (5-chloro-1H-benzimidazol-2-yl) ethylamine

The mixture (6.0 g) prepared in Example 4a is dissolved in 30 ml of glacial acetic acid and heated to boiling for 8 hours and stirred at room temperature for a further 16 hours. The acetic acid is distilled off and the crude product is purified by chromatography on silica gel (gradient: methylene chloride / ethanol = 100: 0 → 98: 2).
Yield: 5.00 g (contaminated, ca. 80% title compound)
R _f value: 0.40 (silica gel, dichloromethane / ethanol = 19: 1)

(c) 1- (5-chloro-1H-benzimidazol-2-yl) ethylamine

5.00 g (contaminated) of N-benzyloxycarbonyl-1- (5-chloro-1H-benzimidazol-2-yl) ethylamine are dissolved in a mixture of 100 ml of methanol and 40 ml of methylene chloride, treated with 1.0 g of palladium on carbon and for 1 hour with Hydrogen treated at 3.4 bar pressure. The solvents are distilled off and the crude product is purified by chromatography on silica gel (eluant: methylene chloride / ethanol = 95: 5 + 0.2% ammonia).
Yield: 1.08 g (25% over 3 steps)
R _f value: 0.37 (silica gel, dichloromethane / ethanol = 4: 1 + 2% ammonia)
C ₉ H ₁₀ ClN ₃ (195.65)
Mass spectrum: (M + H) ⁺ = 196/198 (chloroisotopes)

(d) 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2,5-dihydropyrrol-1-yl-carbonyl) quinazoline

Prepared analogously to Example 2d from 4,6-dichloro-7- (dihydropyrrol-1-yl-carbonyl) quinazoline, 1- (5-chloro-1H-benzimidazol-2-yl) ethylamine and triethylamine in N, N-dimethylformamide.
Yield: 46%
R _f value: 0.55 (silica gel, dichloromethane / ethanol = 9: 1)
C ₂₂ H ₁₈ Cl ₂ N ₆ O (453.33)
Mass spectrum: (M + H) ⁺ = 453/455/457 (chloroisotopes) Example 5 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (2 tert-butoxycarbonylaminomethyl-pyrrolidin-1-yl-carbonyl) -quinazoline

Prepared analogously to Example 2c from 4,6-dichloro-quinazoline-7-carboxylic acid chloride, 2-tert-butoxycarbonylaminomethyl-pyrrolidine and sodium hydroxide solution in dichloromethane and subsequent reaction analogously to Example 2d with 1- (5-chloro-1H-benzimidazol-2-yl ) ethylamine and triethylamine in N, N-dimethylformamide.
Yield: 23% (over 2 levels)
R _f value: 0.65 (silica gel, dichloromethane / isopropanol = 9: 1)
C ₂₈ H ₃₁ Cl ₂ N ₇ O ₃ (584.51)
Mass spectrum: (M + H) ⁺ = 584/586/588 (chloroisotopes) Example 6 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (2 aminomethyl-pyrrolidin-1-yl-carbonyl) -quinazoline

300 mg (0.51 mmol) of 6-chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2-tert-butoxycarbonylaminomethylpyrrolidin-1-ylcarbonyl) -quinazoline are dissolved in 5 ml of dioxane and treated with stirring at room temperature with 5 ml of 6 molar hydrochloric acid solution. The mixture is heated to 40 ° C for 2 hours. Thereafter, the mixture is stirred into ice-water and adjusted to pH 8 with ammonia solution. The mixture is then extracted three times with ethyl acetate, the combined organic phases are washed with sodium chloride solution, dried over sodium sulfate and the solvent is removed in vacuo. The residue is treated with ether, filtered off and dried.
Yield: 46%
R _f value: 0.10 (silica gel, dichloromethane / ethanol = 4: 1 + 1% acetic acid)
C ₂₃ H ₂₃ Cl ₂ N ₇ O (484.39)
Mass spectrum: (MH) ^- = 482/484/486 (chloroisotopes) Example 7 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (morpholine-4 yl-carbonyl) -quinazoline

Prepared analogously to Example 2c from 4,6-dichloroquinazoline-7-carboxylic acid chloride, morpholine and sodium hydroxide solution in dichloromethane and subsequent reaction analogously to Example 2d with 1- (5-chloro-1N-benzimidazol-2-yl) ethylamine and triethylamine in N, N-dimethylformamide.
Yield: 10.8% (over 2 levels)
R _f value: 0.60 (silica gel, dichloromethane / ethanol = 9: 1)
C ₂₂ H ₂₀ Cl ₂ N ₆ O ₂ (471.35)
Mass spectrum: (M + H) ⁺ = 471/473/475 (chloroisotopes) Example 8 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7 - (piperazin-3-on-2-yl-carbonyl) -quinazoline

(a) (S) -N'-tert-butoxycarbonyl-N- (2-amino-4-chloro) -phenyl-alaninamide and (S) -N'-tert-butoxycarbonyl-N- (2-amino-5-chloro) phenyl-alaninamide

6.64 g (35.1 mmol) of (S) -N-tert-butoxycarbonylalanine and 5.00 g (35.1 mmol) of 4-chloro-o-phenylenediene are dissolved in 150 ml of tetrahydrofuran, and at 0 ° C while stirring slowly 7.24 g (35.1 mmol) of N, N'-dicyclohexylcarbodiimide are added. After stirring for 16 hours at room temperature, it is filtered and the solvent removed in vacuo. The residue is recrystallized from 50 ml of ethyl acetate and dried at 50.degree.
Yield: 6.35 g (58%) (mixture of both title compounds)
R _f value: 0.66 (silica gel, dichloromethane / ethanol = 9: 1)
C ₁₄ N ₂₀ ClN ₃ O ₃ (313.79)
Mass spectrum: (M + H) ⁺ = 314/316 (chloroisotopes)

(b) (S) -N-tert-butoxycarbonyl-1- (5-chloro-1 H-benzimidazol-2-yl) ethylamine

The mixture (6.35 g) prepared in Example 8a is mixed with 75 ml of glacial acetic acid under argon atmosphere and heated to 55 ° C for 4 h. The acetic acid is distilled off in vacuo.
Yield: 6.80 g (94%)
R _f value: 0.70 (silica gel, dichloromethane / ethanol = 9: 1 + 1% ammonia solution)
Mass spectrum: (MH) ^- = 294/296 (chloroisotopes)

(c) (S) -1- (5-Chloro-1H-benzimidazol-2-yl) ethylamine-ditrifluoroacetate

1.50 g (5.07 mmol) of (S) -N-tert-butoxycarbonyl-1- (5-chloro-1H-benzimidazol-2-yl) -ethylamine are treated with a solution of 7 ml (92 mmol) of trifluoroacetic acid in 50 ml of dichloromethane and stirred for 70 minutes at room temperature. Volatile components are removed in vacuo, the residue is taken up twice in ethanol and dichloromethane.
Yield: 2.05 g (95%)
R _f value: 0.25 (silica gel, dichloromethane / ethanol = 9: 1 + 1% ammonia solution)
C ₉ H ₁₀ ClN ₃ × 2 C ₂ HF ₃ O ₂ (195.65 / 423.70)
Mass spectrum: (M + H) ⁺ = 196/198 (chloroisotopes)

(d) 6-Chloro-4- [1- (SL (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (piperazin-3-one-1-ylcarbonyl) quinazoline

Prepared analogously to Example 2d from 4,6-dichloro-7- (piperazin-3-on-1-ylcarbonyl) quinazoline, (S) -1- (5-chloro-1H-benzimidazol-2-yl) ethylamine ditrifluoroacetate and triethylamine in N, N-dimethylformamide.
Yield: 22%
R _f value: 0.30 (silica gel, dichloromethane / isopropanol = 9: 1)
C ₂₂ H ₁₉ Cl ₂ N ₇ O ₂ (484.35)
Mass spectrum: (M + H) ⁺ = 484/486/488 (chloroisotopes) Example 9 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7 - (2,5-dihydropyrrol-1-yl-carbonyl) -quinazoline

Prepared analogously to Example 2c from 4,6-dichloroquinazoline-7-carboxylic acid chloride, 2,5-dihydropyrrole and sodium hydroxide solution in dichloromethane and subsequent reaction analogously to Example 2d with (S) -1- (5-chloro-1H-benzimidazole-2 yl) ethylamine and triethylamine in N, N-dimethylformamide.
Yield: 22% (over 2 levels)
R _f value: 0.55 (silica gel, dichloromethane / ethanol = 9: 1)
C ₂₂ H ₁₈ Cl ₂ N ₆ O (453.33)
Mass spectrum: (M + H) ⁺ = 453/455/457 (chloroisotopes) Example 10 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (pyrrolidin-1-yl-carbonyl) quinazoline

125 mg (0.28 mmol) of 6-chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) ethylamino] -7- (2,5-dihydropyrrol-1-ylcarbonyl ) -quinazoline are dissolved in 20 ml of methanol dissolved with 100 mg Raney nickel and treated at 5 bar pressure for 5 hours at room temperature with hydrogen. It is then filtered and the filtrate concentrated in vacuo. The residue is treated with 20 ml of a mixture of ethyl acetate and diethyl ether in the ratio 1: 1, filtered off and dried.
Yield: 82 mg (65 / °)
R _f value: 0.50 (silica gel, dichloromethane / ethanol = 9: 1 + 1% acetic acid)
C ₂₂ H ₂₀ Cl ₂ N ₆ O (455.35)
Mass spectrum: (M + H) ⁺ = 455/457/459 (chloroisotopes)

The following examples describe the preparation of pharmaceutical application forms which contain as active ingredient any compound of the general formula (I): Example I Dry ampoule containing 75 mg of active ingredient per 10 ml of composition: active substance 75.0 mg mannitol 50.0 mg Water for injections ad 10.0 ml

production:

Active ingredient and mannitol are in Water dissolved. After bottling is freeze-dried.

The solution to the ready-to-use solution is water for injections. Example II Dry ampoule with 35 mq active ingredient per 2 ml Composition: Active ingredient 35.0 mg Mannitol 100.0 mg Water for injections ad i.0 rn1

production:

Active ingredient and mannitol are in Water dissolved. After bottling is freeze-dried.

The solution to the ready-to-use solution is water for injections. Example III Tablet with 50 mg active ingredient Composition: (1) Active substance 50.0 mg (2) lactose 98.0 mg (3) corn starch 50.0 mg (4) polyvinylpyrrolidone 15.0 mg (5) magnesium stearate 2.0 mg 215.0 mg

production:

(1), (2) and (3) are mixed and with an aqueous solution of (4) granulated. The dried granules are admixed with (5). Out This mixture tablets are pressed biplan with bilateral Facet and one-sided part notch.

Diameter of the tablets: 9 mm. Example IV Tablet with 350 mq active ingredient Composition: (1) Active substance 350.0 mg (2) lactose 136.0 mg (3) corn starch 80.0 mg (4) polyvinylpyrrolidone 30.0 mg (5) magnesium stearate 4.0 mg 600.0 mg

production:

(1), (2) and (3) are mixed and with an aqueous solution of (4) granulated. The dried granules are admixed with (5). Out This mixture tablets are pressed biplan with bilateral Facet and one-sided part notch.

Diameter of the tablets: 12 mm. Example V Capsules with 50 mg active ingredient Composition: (1) Active substance 50.0 mg (2) dried corn starch 58.0 mg (3) lactose powdered mg 50.0 (4) magnesium stearate 2.0 mg 160.0 mg

production:

(1) is triturated with (3). This Trituration is the mixture of (2) and (4) under intense mixing added.

This powder mixture is filled on a capsule filling machine into size 3 hard gelatine capsules. Example VI Capsules with 350 mq active ingredient Composition: (1) Active substance 350.0 mg (2) dried corn starch 46.0 mg (3) powdered milk sugar 30.0 mg (4) magnesium stearate 4.0 mg 430.0 mg

production:

(1) is triturated with (3). This Trituration is the mixture of (2) and (4) under intense mixing added.

This powder mixture is filled in a capsule filling machine into hard gelatin capsule size 0. Example VII Suppositories containing 100 mg of active ingredient 1 suppository contains: active substance 100.0 mg Polyethylene glycol (MW 1500) 600.0 mg Polyethylene glycol (MG 6000) 460.0 mg polyethylene sorbitan monostearate 840.0 mq 2000.0 mg

production:

The polyethylene glycol will come together melted with Polyethylensorbitanmonostearat. At 40 ° C, the milled active substance in the melt homogeneously dispersed. It will at 38 ° C chilled and in slightly pre-cooled Suppository forms poured out.

Claims (11)

Substituted nitrogen-containing heterobicyclene of the general formula

in R ^1, an amino, C _1-5 alkylamino, C _3-7 cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each at the amine nitrogen atom by a phenylcarbonyl or phenylsulfonyl or by a in the alkyl portion optionally substituted by a carboxy group, a can be converted into a carboxyl group in viva group, an amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe substituted C _1-5 alkyl or C _{1- 5} alkylcarbonyl group may be substituted, wherein two nitrogen atoms are separated by at least two carbon atoms, a di- (C _{1- 5} alkyl) amino or N- (C _3-7 - cycloalkyl) -C _{1- 5} alkylamino group, wherein the C _{1- 5} alkyl moiety with the exception of the 1-position in each case by a hydroxy, C _1-3 alkoxy, amino, C _{1- 3} alkylamino, di - may be (C _1-3 alkyl) amino or substituted C _{3- 6} -Cycloalkyleniminogruppe, a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group wherein the cycloalkyleneimine moiety is represented by one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl C _1-3 alkylamino C _1-3 alkyl, di (C _1-3 alkyl) amino C _1-3 alkyl, C _1-5 alkyloxycarbonylamino C _1-3 alkyl, C _{3- 6} -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylamino-carbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl or di- _(C1-3 alkyl) aminocarbonyl group may be substituted or a non-adjacent imino group of the methyl group by a hydroxy, benzyloxy , C _{3- 6} -Cycloalkyleniminogruppe may be substituted _1-3 alkoxy, amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C and / or a methyl group in the 3 Position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulphinyl or sulphonyl group or a methylene group in the 4-position e iner 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom or by an -NH-, -NC _1-3 alkyl, -N (C _{2- 3} alkanoyl) -, sulfinyl or sulfonyl can be substituted and or a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) Optionally substituted by one or two C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl-, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl, C _{1- 6} -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl -, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl or C _{3- 6} -Cycloalkyleniminocarbonylgruppen substituted 5- to 7-membered Cycloalkenyleniminocarbonyl- or Cycloalkenyleniminosulfonylgruppe, wherein the double bond is not attached to a nitrogen atom is a optionally substituted by one or two C _{1- 5} alkyl aminocarbonyl or amino sulfonyl group, where the substituents may be identical or different and each one of the C_ ₅ alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxy-C _1-3 alkyl, amino C _{1- 3-} alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _{1 -3} alkyl, C _{1- 5-alkyloxycarbonylamino} C _1-3 alkyl, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- ( C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -cycloalkyleneiminocarbonyl may be substituted or a non-adjacent imino group of the methyl group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di- (C _{1- 3-} alkyl) -amino or C _3-6 -cycloalkyleneimino group, a C _1-7 -alkylcarbonyl or C _3-7 -cycloalkylcarbonyl group, wherein the methylene group in the 2-, 3- or 4-position in a C _3-7 - Cycloalkylcarbonylgruppe can be replaced by an oxygen or sulfur atom, a carbonyl, sulfinyl, sulfonyl or an -NH group in which the hydrogen atom of the -NH group by a C _1-3 alkyl or C _1-3 Alkylcarbonyl group, a phenylcarbonyl or heteroarylcarbonyl group which in the phenyl or heteroaryl moiety can be replaced by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, aminoC _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl- or C _1-3 alkoxy group, optionally substituted by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _1-3 -alkyl group, where the phenyl moiety is represented by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, amino C _1-3 -alkyl group , C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino C _1-3 alkyl, C _3-6 cycloalkyleneimino-C _1-3 alkyl or C _1-3 alkoxy and / or wherein a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO- group or a methylene group which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group, or a group of the formulas

in each of which one hydrogen atom in the heterocyclic moiety can be replaced by a methylsulfonylmethyl, aminoC _1-3 -alkyl or aminocarbonyl group and m is the number 1 or 2, R ^{2 is} a hydrogen, fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogens may be replaced by fluorine atoms totally or partially, a C _{2- 3} alkenyl, C _{2- 3} alkynyl, C _1-3 alkoxy or trifluoromethoxy, R ³ a hydrogen atom or a C _1-3 alkyl group, R ⁴ is a hydrogen atom or a linear or branched C _{1- 5} alkyl group optionally substituted by a hydroxy, C _1-3 -alkyloxy, mercapto, C _1-3 - Alkylsulfanyl, C _1-3 alkylsulfinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, C _{3 6} -Cycloalkyleniminocarbonyl-, amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino, C _{3- 6} -Cycloalkylenimino, C _1-3 alkylcarbonyl amino, C _3-6 Cycloalkylcarbonylamino, benzyloxycarbony lamino or guanidino group, a phenyl or heteroaryl, phenyl C _1-3 alkyl or heteroaryl C _1-3 alkyl group, optionally substituted by a hydroxy, C 1-10 alkyloxy, benzyloxy, hydroxycarbonyl-C _1-3 alkoxy, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di ( C _1-3 alkyl) -aminocarbonylC _1-3 alkyloxy, C _3-6 cycloalkyleneiminocarbonylC _1-3 alkyloxy carboxy, C _1-3 alkyloxycarbonyl group, a 4-7 membered Cycolalkylenimino-C _1-3 alkyl group, or a 4- to 7-membered cycloalkyl-C _1-3 alkyl group in which one or two methylene groups by a -NH- or -N (C _1-3 alkyl) - group and in which one or two of the -NH- or -N (C _1-3 -alkyl) group adjacent methylene groups may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as defined above, in the two -NH- or -N (C _1-3 -alkyl) groups precisely one -CH ₂ group are separated from each other, are excluded, R ⁵ represents a hydrogen atom or a C _1-3 alkyl group or R ⁴ and R ⁵ together with the carbon atom to which they are attached form a C _3-7 cycloalkyl wherein one of the methylene groups of the C _3-7 cycloalkyl group may be replaced by an imino, C _1-3 -alkylimino, acylimino or sulfonylimino group, B is a group of the formulas

in which n is the number 1 or 2, R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxyl, amino, C _1-3 -alkylamino group, R ^{7 is} a hydrogen, fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms are completely or a C _{2- 3} alkenyl or C _{2- 3} alkynyl, hydroxy, C may be replaced by fluorine atoms, partially, represent _1-3 alkoxy, trifluoromethoxy or cyano group, and X ¹ to X ³ are each independently a nitrogen atom or a CH group mean at least one and at most two of the groups X ¹ to X ³ represent a nitrogen atom, while, unless otherwise stated, the term "heteroaryl" is a in the carbon skeleton are optionally substituted by a C _{1 3-} alkyl, carboxy, C _1-3 alkoxycarbonyl or C _1-3 alkoxy-carbonylamino group is to be understood monocyclic substituted 5- or 6-membered heteroaryl group, wherein the 6-membered heteroaryl one, two or three nitrogen atoms and the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group, an oxygen or sulfur atom, or an optionally C _1-3 alkyl, amino-C _1-3 alkyl, C _1-3 alkylamino-C _1-3 alkyl, di (C _1-3 alkyl) amino C _1-3 alkyl, C _3-6 cycloalkylene imino C _1-3 alkyl or Phenyl-C _1-3 -alkyl group-substituted imino group or an oxygen or sulfur atom and additionally contains a nitrogen atom or an imino group optionally substituted by a C _1-3 -alkyl or phenyl-C _1-3 -alkyl group and two or three nitrogen atoms, and in addition to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms, a phenyl ring may be fused and the bonding is via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused phenyl ring, wherein the alkyl and alkoxy groups included in the definitions are more than have two carbon atoms, unless otherwise mentioned, may be straight-chain or branched, and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions wholly or partially may be replaced by fluorine atoms, the tautomers, the diastereomers, the enantiomers, the mixtures and salts thereof, wherein under a converted in vivo into a carboxy group, for example an esterified with an alcohol carboxy group in the alcoholic moiety is preferably a C _{1- 6} alkanol, a phenyl-C _1-3 -alkanol, a C _3-9 cycloalkanol, a C _5-7 -Cycloalkenol, C _{3- 5} alkenol, a phenyl-C _{3- 5} alkenol, a _{C3 - 5} -alkynol or phenyl-C _{3- 5} -alkynol, with the proviso that no bond to the oxygen atom starts from a carbon atom which carries a double or triple bond, a C _3-8 -cycloalkyl-C _1-3 -alkanol or an alcohol of the formula R ^{8 is} -CO-O- (R ⁹ CR ¹⁰ ) -OH, a C _{1- 8} alkyl, C cycloalkyl, phenyl or phenyl-C alkyl in which R ⁸ is _1-3, R ⁹ is a hydrogen atom, a C _1-3 alkyl, C _5-7 cycloalkyl - or phenyl group and R ^{10 represent} a hydrogen atom or a C _1-3 alkyl group, is to be understood. Substituted nitrogen containing heterobicycles of the general formula I according to claim 1, in which R ¹ is an amino, C _{1- 5} alkylamino, C _{3- 7} cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each of at the amine nitrogen atom by a phenylcarbonyl or phenylsulfonyl group or by an optionally substituted in the alkyl part by a carboxy group, a in vivo into a carboxy group, an amino, C _1-3 alkylamino, di (C _1-3 alkyl) - amino or C _{3- 6} -Cycloalkyleniminogruppe substituted C _{1- 5} alkyl or C _{1- 5} alkylcarbonyl group may be substituted, wherein two nitrogen atoms are separated by at least two carbon atoms, a di- (C _{1- 5} alkyl) amino or N- (C _3-7 cycloalkyl) C _{1- 5} alkylamino group, wherein the C _{1- 5} alkyl moiety with the exception of the 1-position in each case by a hydroxy, C _1-3 alkoxy, amino -, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C may be substituted _{3- 6} -Cycloalkyleniminogruppe, a 4- b is 7-membered or Cycloalkyleniminocarbonyl- Cycloalkyleniminosulfonylgruppe, wherein the alkyl Cycloalkyleniminoteil by one or two C _1-3 alkyl, C _1-3 alkoxy-C _1-3 amino-C _1-3 alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkyleneimino-C _1-3 -alkyl, C _{1- 5} alkyl-C _1-3 alkyloxycarbonylamino, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl ) -C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _{1- 3} alkyl) -aminocarbonyl or C _3-6 - Cycloalkyleniminocarbonylgruppe may be substituted or a non-imino group adjacent methylene group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino - or C _3-6 -Cycloalkyleniminogruppe and / or a methylene group in the 3-position of a 5-membered cycloalkyleneimino group by a sulfur atom, a sulfinyl or sulfonyl or a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom or by an -NH-, -NC _1-3 -alkyl-, or -N (C ₂ -C ₃ alkanoyl), sulfinyl or sulfonyl group and / or a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO -NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO- group may be replaced, optionally substituted by one or two C _1-3 alkyl, amino C _1-3 alkyl, C _1-3 alkylamino C _1-3 alkyl, di (C _1-3 alkyl) amino C _1-3 alkyl, C _3-6 cycloalkylene imino C _1-3 alkyl, C _1-6 cycloalkylamino-C _1-3 alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl groups substituted 5- to 7-membered Cycloalkenyleniminocarbonyl- or Cycloalkenyleniminosulfonylgruppe, wherein the double bond is not attached to a nitrogen atom, an optionally by one or two C _{1- 5} alkyl substituted amino carbonyl, or aminosulfonyl group, wherein the substituents may be identical or different and each one of the C _{1- 5} alkyl groups by e ine or two C _1-3 alkyl, C _1-3 alkoxyC _{1- 3} alkyl, amino-C _1-3 alkyl, C _1-3 alkylamino-C _1-3 -alkyl- , di (C _1-3 alkyl) amino-C _{1- 3} alkyl, C _3-6 -Cycloalkylenimino-C _1-3 alkyl, C _1-5 alkyloxycarbonylamino C _1-3 alkyl -, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- ( phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -cycloalkyleneiminocarbonyl may be substituted or a non-adjacent imino group of the methyl group by a Hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _3-6 cycloalkyleneimino group may be substituted C _1-7 -alkylcarbonyi or C _3-7 -cycloalkylcarbonyl group, wherein the methylene group is in the 2-, 3- or 4-position in a C _3-7 -cycloalkylcarbonyl group by an oxygen or sulfur atom, a carbonyl, sulfinyl, Sulfonyl or an -NH group e in which the hydrogen atom of the -NN group can be replaced by a C _1-3 -alkyl or C _1-3 -alkylcarbonyl group, a phenylcarbonyl or heteroarylcarbonyl group which in the phenyl or heteroaryl moiety is replaced by a fluoro, Chlorine or bromine atom, by a trifluoromethyl, C _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 alkyl, di (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -cycloalkylenimino-C _1-3 -alkyl or C _1-3 -alkoxy, may optionally be substituted by an amino, C _1-3 Alkylamino, di (C _1-3 alkyl) amino, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _1-3 alkyl group, where the phenyl moiety is substituted by a fluoro , Chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl-, di- (C _{1- 3} alkyl) amino-C _1-3 alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl or C _1-3 alkoxy group may be substituted and / or wherein a - CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO- Group or a methylene group which is adjacent to the nitrogen atom, may be replaced by a carbonyl group in a 5- to 7-membered cycloalkyleneimino group, or a group of the formulas

in which one hydrogen atom in the heterocyclic moiety can be replaced by one methylsulfonylmethyl, aminoC _1-3 -alkyl or aminocarbonyl group and m is the number 1 or 2, R ^{2 is} a chlorine or bromine atom, a C _1-3 alkyl group wherein the hydrogen atoms may be replaced by fluorine atoms entirely or partially, or a C _{2- 3} alkenyl group, R ³ represents a hydrogen atom or a C _1-3 alkyl group, R ⁴ is a hydrogen atom or a linear or branched C _{1- 5} Optionally substituted by a hydroxy, C _1-3 alkyloxy, mercapto, C _1-3 alkylsulfanyl, C _1-3 alkylsulfinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl , C _1-3 -alkylaminocarbonyl-, di- (C _1-3 alkyl) aminocarbonyl, C _{3- 6} -Cycloalkyleniminocarbonyl-, amino, C _1-3 alkylamino, di- (C _1-3 - alkyl) -amino, C _{3- 6} -Cycloalkylenimino, C _1-3 alkylcarbonylamino, C _{3- 6} -Cycloalkylcarbonylamino-, benzyloxycarbonylamino or guanidino group is substituted, a phenyl or heteroar yl, phenyl-C _1-3 -alkyl or heteroaryl-C _1-3 -alkyl group optionally substituted by a hydroxy, C 1-6 alkyloxy, benzyloxy, hydroxycarbonylC _1-3 alkoxy, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _{1 3-} alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) aminocarbonylC _1-3 alkyloxy, C _3-6 cycloalkyleneiminocarbonylC _1-3 alkyloxy, carboxy , C _1-3 alkyloxycarbonyl group, a 4- to 7-membered Cycolalkyienimino-C _1-3 alkyl group or a 4- to 7-membered cycloalkyl-C _1-3 alkyl group in which one or two methylene groups by a -NH- or -N (C _1-3 -alkyl) - group may be replaced and in which one or two of the -NH- or -N (C _1-3 -alkyl) group adjacent methylene groups are each replaced by a carbonyl group with the proviso that a cycloalkyl group as defined above in which two -NH- or -N (C _1-3 -alkyl) groups are separated by exactly one -CH ₂ - group are excluded, R ⁵ Hydrogen atom or a C _1-3 alkyl group or R ⁴ and R ⁵ together with de m carbon atom to which they are attached, a C _3-7 cycloalkyl group, wherein one of the methylene groups of the C _3-7 cycloalkyl group may be replaced by an imino, C _1-3 alkylimino, acylimino or Sulfonyliminogruppe, B a group of formulas

in which n is the number 1, R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxy, amino, C _1-3 -alkylamino group, R ^{7 is} a hydrogen, fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be replaced by fluorine atoms totally or partially, a C _{2- 3} alkenyl or C _2-3 alkynyl, hydroxy, C _1-3 alkoxy, trifluoromethoxy or cyano group, and X ¹ to X ³ each independently represent a nitrogen atom or a CH group wherein at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom, wherein, unless otherwise mentioned, under the "Heteroaryl group" is to be understood as meaning a monocyclic 5- or 6-membered heteroaryl group which is optionally substituted in the carbon skeleton by a C _1-3 -alkyl, carboxy, C _1-3 -alkoxycarbonyl or C _1-3 -alkoxycarbonylamino group, wherein the 6-membered heteroaryl group has one, two or three nitrogen atoms and the 5-membered strength heteroaryl is an optionally alkyl group by a C _{1- 3} alkyl or phenyl-C _1-3 substituted imino group, an oxygen or sulfur atom or an optionally by a C _{1- 3} alkyl, amino-C _{1- 3} alkyl -, C _{1- 3} -alkylamino-C _{1- 3} alkyl, di (C _{1- 3} alkyl) amino-C _{1- 3} alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 - alkyl or phenyl-C _1-3 alkyl group substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or an optionally substituted by a C _1-3 alkyl or phenyl-C _1-3 alkyl group-substituted imino group and two or three nitrogen atoms and in addition to the monocyclic heteroaryl groups mentioned above via two adjacent carbon atoms a phenyl ring may be fused and the bonding is via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused phenyl ring, wherein the alkyl and alkoxy groups contained in the definitions, Unless otherwise stated, they may have more than two carbon atoms, may be straight-chain or branched, and the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms, their tautomers, their enantiomers, their diastereomers, their mixtures and their salts. Substituted nitrogen containing heterobicycles of the general formula I according to claim 1, in which R ¹ is an amino, C _{1- 5} alkylamino, C _3-7 cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each of at the amine nitrogen atom by a phenylcarbonyl or phenylsulfonyl group or by an optionally substituted in the alkyl part by a carboxy group, a in vivo into a carboxy group, an amino, C _1-3 alkylamino, di (C _1-3 alkyl) - amino or C _3-6 -Cycloalkyleniminogruppe substituted C _1-5 alkyl or C _{1- 5} alkylcarbonyl group may be substituted, wherein two nitrogen atoms are separated by at least two carbon atoms, a di- (C _{1- 5} alkyl) amino or N- (C _3-7 cycloalkyl) C _{1- 5} alkylamino group, wherein the C _{1- 5} alkyl moiety with the exception of the 1-position in each case by a hydroxy, C _1-3 alkoxy, amino , C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _3-6 cycloalkyleneimino group, a 4-7 -gliedrige Cycloalkyleniminocarbonyl- or Cycloalkyleniminosulfonylgruppe, wherein the cycloalkyleneimine moiety through one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _3-6 -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5} alkyloxycarbonylamino-C _{1- 3} alkyl-, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -cycloalkyleneiminocarbonyl may be substituted or a non-adjacent imino group of the Methylene group may be substituted by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _3-6 cycloalkyleneimino group and / or a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulphinyl or sulphonyl group or a methylene group in the 4-position of a 6- or 7-membered ring gen cycloalkyleneimino group by an oxygen or sulfur atom or by an -NH-, -NC _1-3 alkyl, -N (C _{2- 3} alkanoyl) -, sulphinyl or sulphonyl group may be replaced and / or a -CH ₂ -CH ₂ - replaced in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO, -CO-NH, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO- group optionally substituted by one or two C _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 alkyl, di (C _1-3 alkyl) -amino-C _1-3 alkyl, C _3-6 cycloalkyleneimino-C _1-3 alkyl, C _1-6 cycloalkylamino-C _1-3 alkyl, aminocarbonyl, C _1-3 -Alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 -cycloalkyleneiminocarbonyl-substituted 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulfonyl group, wherein the double bond is not bonded to a nitrogen atom, optionally by a or two C _{1- 5} alkyl substituted aminocarbonyl or aminosulphonyl group, with di e substituents may be the same or different and each represents an alkyl of C _{1- 5} alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxy-C _1-3 amino-C _1-3 alkyl, C _1-3 alkylamino C _1-3 alkyl, di (C _1-3 alkyl) amino C _1-3 alkyl, C _3-6 cycloalkyleneimino C _{1 3} alkyl, C _{1- 5-alkyloxycarbonylamino} C _1-3 alkyl, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 -alkyl) -aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl group may be substituted or a non-imino group adjacent methylene group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 -alkyl) -amino or C _3-6 -cycloalkyleneimino group, optionally substituted by an amino, C _1-3 -alkylamino, di- (C _1-3 -alkyl) -amino, hydroxy, phenyl -, heteroaryl or a 4- to 7-membered cycloalkyl enimino group monosubstituted C _1-3 -alkyl group, wherein the phenyl part is replaced by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, amino-C _1-3 -alkyl-, C _1-3 - alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl or C _1-3 Alkoxy group can be substituted and / or where a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N (CH ₃ ) -CO group or a methylene group which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group, or a group of the formulas

in which one hydrogen atom in the heterocyclic moiety can be replaced by one methylsulfonylmethyl, aminoC _1-3 -alkyl or aminocarbonyl group and m is the number 1 or 2, R ^{2 is} a chlorine or bromine atom, a C _1-3 alkyl group wherein the hydrogen atoms may be wholly or partially replaced by fluorine atoms, or a C _{2- 3} alkenyl group, R ³ represents a hydrogen atom, R ⁴ is a hydrogen atom or a linear or branched C _{1- 5} alkyl group optionally substituted by a hydroxy , C _1-3 -alkyloxy, mercapto, C _1-3 -alkylsulfanyl, C _1-3 -alkylsulfinyl, C _1-3 -alkylsulfonyl, carboxy, Aminocarbonyl, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 alkyl) aminocarbonyl, C _{3- 6} -Cycloalkyleniminocarbonyl-, amino, C _1-3 alkylamino, di- (C _{1- 3-alkyl)} -amino, C _{3- 6} -Cycloalkylenimino-, C _1-3 alkylcarbonylamino, C _{3- 6} -Cycloalkylcarbonylamino-, benzyloxycarbonylamino or guanidino group is substituted, a phenyl or heteroaryl, phenyl-C _{1- 3} alkyl or heteroaryl C _1-3 alkyl group optionally substituted by a hydroxy, C _{1- 4} alkyloxy, benzyloxy, hydroxycarbonyl-C _1-3 alkoxy, C _1-3 alkyloxycarbonyl-C _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) aminocarbonyl C _1-3 alkyloxy, C _{3- 6} -Cycloalkyleniminocarbonyl-C _1-3 alkyloxy, carboxy C _1-3 alkyloxycarbonyl group is substituted, a 4- to 7-membered Cycolalkylenimino-C _1-3 alkyl group, or a 4- to 7-membered cycloalkyl-C _1-3 -alkyl group in which one or two methylene groups are replaced by an -NH- or -N (C _1-3 -alkyl) group t and in which one or two of the -NH or -N (C _1-3 alkyl) group adjacent methylene groups may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as defined above, in the two -NH- or -N (C _1-3 -alkyl) groups are separated by exactly one -CH ₂ -group, excluding R ^{5 is} a hydrogen atom or R ⁴ and R ⁵ together with the carbon atom to which they are attached are a C _3-7 cycloalkyl group wherein one of the methylene groups of the C _3-7 cycloalkyl group may be replaced by an imino, C _1-3 alkylimino, acylimino or sulfonylimino group, B is a group of the formulas

in which n is the number 1, R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxy, amino, C _1-3 -alkylamino group, R ^{7 is} a fluorine, chlorine or bromine atom, a C _1-3 alkyl group in which the hydrogen atoms may be replaced by fluorine atoms totally or partially, a C _{2- 3} alkenyl, C _1-3 alkynyl or a hydroxy group, and X ¹ to X ³ each independently represent a nitrogen atom or a CH group mean at least one and at most two of the groups X ¹ to X ³ represent a nitrogen atom mean while, unless otherwise stated, the term "heteroaryl" is a in the carbon skeleton are optionally substituted by a C _1-3 -alkyl Carboxy, C _1-3 alkoxycarbonyl or C _1-3 alkoxy-carbonylamino substituted monocyclic 5- or 6-membered heteroaryl group is understood, wherein the 6-membered heteroaryl one, two or three nitrogen atoms and the 5-membered heteroaryl group an optionally by a C _1-3 -Al kyl or phenyl-C _1-3 alkyl group substituted imino group, an oxygen or sulfur atom or an optionally substituted by a C _1-3 alkyl, amino-C _1-3 alkyl, C _1-3 alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 alkyl, C _{3- 6} alkyl or C _1-3 -Cycloalkylenimino-phenyl-C _1-3 - alkyl group substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or an optionally substituted by a C _1-3 alkyl or phenyl-C _1-3 alkyl group imino group and two or three nitrogen atoms, and also to the abovementioned monocyclic Heteroaryl groups can be fused via two adjacent carbon atoms, a phenyl ring and the bond via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused phenyl ring, wherein the alkyl and alkoxy groups contained in the definitions having more than two carbon atoms, as far as others s, may be straight-chain or branched, and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms, their tautomers, their enantiomers, their diastereomers, their mixtures and their salts. Substituted nitrogen containing heterobicycles of the general formula I according to claim 1, in which R ¹ is an amino, C _{1- 5} alkylamino, C _3-7 cycloalkylamino or (phenyl-C _1-3 alkyl) amino group, each of at the amine nitrogen atom by a phenylcarbonyl or phenylsulfonyl group or by an optionally substituted in the alkyl part by a carboxy group, a in vivo into a carboxy group, an amino, C _1-3 alkylamino, di (C _1-3 alkyl) - amino or C _{3- 6} -Cycloalkyleniminogruppe substituted C _{1- 5} alkyl or C _{1- 5} alkylcarbonyl group may be substituted, wherein two nitrogen atoms are separated by at least two carbon atoms, a di- (C _{1- 5} alkyl) amino or N- (C _3-7 cycloalkyl) C _{1- 5} alkylamino group, wherein the C _{1- 5} alkyl moiety with the exception of the 1-position in each case by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di- (C _1-3 alkyl) amino or C _3-6 cycloalkyleneimino group, a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulphonyl group, wherein the cycloalkyleneimine moiety is substituted by one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 alkylaminoC _1-3 alkyl, di (C _1-3 alkyl) aminoC _1-3 alkyl, C _3-6 -Cycloalkylenimino-C _1-3 alkyl, C _{1- 5-alkyloxycarbonylamino} C _1-3 alkyl, C _3-6 -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _{1 -3} alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} -alkyiaminocarbonyl-, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, di- (C _1-3 alkyl) -aminocarbonyl or C _3-6 cycloalkyleneiminocarbonyl group or a methylene group adjacent to the imino group by a hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 Alkylamino, di (C _1-3 -alkyl) -amino or C _3-6 -cycloalkyleneimino group and / or a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulfur atom, a sulphinyl or sulphonyl group or a methylene group in 4 be replaced sulphinyl or sulphonyl group - _{(2- 3} alkanoyl C) by an oxygen or sulfur atom or by an -NH-, -NC _1-3 alkyl, -N-position of a 6- or 7-membered cycloalkyleneimino may be and / or a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or a -N ( CH ₃ ) -CO group may be replaced, optionally substituted by one or two C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _{3- 6} -Cycloalkylenimino-C _1-3 alkyl, C _{1- 6} -cycloalkylamino-C _1-3 -alkyl- , aminocarbonyl, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl or C _{3- 6} -Cycloalkyleniminocar bonylgruppen substituted 5- to 7-membered Cycloalkenyleniminocarbonyl- or Cycloalkenyleniminosulfonylgruppe, wherein the double bond is not attached to a nitrogen atom, an optionally by one or two C _{1- 5} alkyl substituted aminocarbonyl or aminosulphonyl group, wherein the substituents may be identical or different and each one of the C _1-5 alkyl groups by one or two C _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl, aminoC _1-3 alkyl, C _1-3 -alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 -alkyl, C _{3- 6} -Cycloalkylenirnirio-C _1-3 alkyl, C _{1- 5-alkyloxycarbonylamino} C _1-3 alkyl, C _{3- 6} -cycloalkylamino-C _1-3 -alkyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, N- (C _3-7 cycloalkyl) C _{1- 5} alkylaminocarbonyl, N- (phenyl-C _1-3 -alkyl) -C _{1- 5} alkylaminocarbonyl, be di (C _1-3 alkyl) aminocarbonyl or substituted C _{3- 6} -cycloalkyleneiminocarbonyl may or may not be adjacent to the imino group adjacent methylene group by e ine hydroxy, benzyloxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino or C _{3- 6} -Cycloalkyleniminogruppe may be substituted, an optionally substituted by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, mono-, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group monosubstituted C _{1- 3-} alkyl group, wherein the phenyl part is replaced by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 -alkyl, amino-C _1-3 -alkyl, C _1-3 -alkylamino-C _{1- 3} alkyl-, di- (C _1-3 -alkyl) -amino-C _1-3 alkyl, C _{3- 6} alkyl or -Cycloalkylenimino-C _1-3 C _1-3 alkoxy group may be substituted and / or wherein a -CH ₂ -CH ₂ - group in a 5- to 7-membered cycloalkyleneimino group by a -NH-CO-, -CO-NH-, -CO-N (CH ₃ ) - or an -N ( CH ₃ ) -CO group or a methylene group which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group, or a group de r formulas

in which one hydrogen atom in the heterocyclic moiety can be replaced by one methylsulfonylmethyl, aminoC _1-3 -alkyl or aminocarbonyl group and m is the number 1 or 2, R ^{2 is} a chlorine or bromine atom, a C _1-3 alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C _{2- 3} alkenyl group, R ³ is a hydrogen atom, R ⁴ is a hydrogen atom or a linear or branched C _{1- 5} alkyl group optionally substituted by a hydroxy, C _1-3 -alkyloxy, mercapto, C _1-3 alkylsulphanyl, C _{1- 3} alkylsulfinyl, C _1-3 alkylsulfonyl, carboxy, aminocarbonyl, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 alkyl) aminocarbonyl, C _{3- 6} -Cycloalkyleniminocarbonyl-, amino -, C _1-3 alkylamino, di- (C _1-3 -alkyl) -amino, C _{3- 6} -Cycloalkylenimino-, C _1-3 alkylcarbonyl amino, C _{3- 6} -Cycloalkylcarbonylamino-, benzyloxycarbonylamino - or guanidino group is substituted, a phenyl or heteroaryl, phenyl-C _1-3 alkyl or heteroaryl C _1-3 alkyl group optionally substituted by a hydroxy, C-alkyloxy, benzyloxy, hydroxycarbonyl-C _{1 3} -alkoxy, C _1-3 alkyloxycarbonylC _1-3 alkyloxy, aminocarbonylC _1-3 alkyloxy, C _1-3 alkylaminocarbonylC _1-3 alkyloxy, di (C _1-3 alkyl) aminocarbonyl-C _1-3 alkyloxy, C _{3- 6} -Cycloalkyleniminocarbonyl-C _1-3 alkyloxy, carboxyl, C _1-3 - Alkyloxycarbonylgruppe is substituted, a 4- to 7-membered Cycolalkylenimino-C _1-3 alkyl group or a 4- to 7-membered cycloalkyl-C _1-3 -alkyl group in which one or two methylene groups by a -NH- or -N (C _1-3 -alkyl) group may be replaced and in which one or two of the -NH- or -N (C _1-3 -alkyl) group may be substituted by a carbonyl group, with the proviso that are as defined above that a cycloalkyl group, are separated from each other in the two -NH- or -N (C _{1- 3} alkyl) groups by precisely one -CH ₂ group is excluded, R ⁵ represents a hydrogen atom, B is a group of formulas

in which n is the number 1, R ^{6 is} a hydrogen atom or a C _1-3 -alkyl, hydroxyl, amino, C _1-3 -alkylamino group, R ^{7 is} a fluorine, chlorine or bromine atom, a C _{1-6 3} alkyl group in which hydrogen atoms which may be substituted by fluorine atoms totally or partially, a C _{2- 3} alkenyl, C _{2- 3} alkynyl or a hydroxy group, and X ¹ to X ³ each independently represent a nitrogen atom or a CH group where at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom, wherein, unless otherwise stated, by the term "heteroaryl group" in the carbon skeleton optionally by a C _1-3 alkyl , Carboxy, C _1-3 alkoxycarbonyl or C _1-3 alkoxy-carbonylamino group is to be understood as meaning monocyclic 5- or 6-membered heteroanegroup, the 6-membered heteroaryl group having one, two or three nitrogen atoms and the heteroaryl group which is optionally substituted by a C _1-3 Alkyl or phenyl-C _1-3 -alkyl substituted imino group, an oxygen or sulfur atom or an optionally by a C _1-3 alkyl, amino-C _1-3 alkyl, C _1-3 alkylamino-C _1-3 -alkyl, di- (C _1-3 -alkyl) -amino-C _1-3 alkyl, C _{3- 6} alkyl or C _1-3 -Cycloalkylenimino-phenyl-C _1-3 - alkyl group substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or an optionally substituted by a C _1-3 alkyl or phenyl-C _1-3 alkyl group imino group and two or three nitrogen atoms, and also to the abovementioned monocyclic Heteroaryl groups can be fused via two adjacent carbon atoms, a phenyl ring and the bond via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused phenyl ring, wherein the alkyl and alkoxy groups contained in the definitions having more than two carbon atoms, as far as nothing else res, may be straight-chain or branched, and wherein the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms, their tautomers, their enantiomers, their diastereomers, mixtures thereof and their salts. Substituted nitrogen-containing heterobicyclene of the general formula I according to claim 1, in which R ^{1 is} a 2,5-dihydro-1H-pyrrol-1-yl-carbonyl, pyrrolidin-1-yl-carbonyl, 2- (aminomethyl) -pyrrolidine 1-yl-carbonyl, 2- (N-tert-butoxycarbonylaminomethyl) -pyrrolidin-1-yl-carbonyl-3-oxo-piperazin-1-yl-carbonyl or morpholin-4-yl-carbonyl, R ^{2 is} hydrogen , Chlorine or bromine atom or a C _1-3 -alkyl group in which the hydrogen atoms may be wholly or partly replaced by fluorine atoms, R ^{3 is} a hydrogen atom, R ^{4 is} a hydrogen atom or the methyl group, R ^{5 is} a hydrogen atom, B is a group of the formulas

in which R ^{6 is} a hydrogen atom, R ^{7 is} a chlorine atom and X ¹ to X ³ are each independently a nitrogen atom or a CH group, where at least one and at most two of the groups X ¹ to X ^{3 represent} a nitrogen atom, their tautomers, their enantiomers, their diastereomers, their mixtures and their salts. The following compounds of general formula I according to claim 1: (1) 4 - [(5-chloro-1H-benzimidazol-2-yl) -methylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinoline (2) 6-chloro-4- [C- (5-chloro-1H-benzimidazol-2-yl) -methyl-amino] -7- (pyrrolidin-1-yl-carbonyl) -quinazoline, (3) 4- [C- (5-Chloro-1H-benzimidazol-2-yl) methylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinazoline, (4) 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2,5-dihydropyrrol-1-yl-carbonyl) -quinazoline, (5) 6-Chloro-4- [1- (5-chloro-1N-benzimidazol-2-yl) -ethylamino] -7- (2-tert-butoxycarbonyl-aminomethylpyrrolidin-1-ylcarbonyl) - quinazoline, (6) 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2-aminomethylpyrrolidine-1-yl-carbonyl) -quinazoline, (7) 6-Chloro-4- [1- (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (morpholin-4-yl-carbonyl) -quinazoline, (8th) 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (piperazin-3-on-1-yl-carbonyl) -quinazoline, (9) 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (2,5-dihydropyrrol-1-yl-carbonyl) -quinazoline, (10) 6-Chloro-4- [1- (S) - (5-chloro-1H-benzimidazol-2-yl) -ethylamino] -7- (pyrrolidin-1-yl-carbonyl) -quinazoline and their salts. Physiologically acceptable salts of the compounds according to claims 1 to 6th Medicament containing a compound after at least one of the claims 1 to 6 or a physiologically acceptable salt according to claim 7 next to optionally one or more inert carriers and / or diluents. Use of a compound after at least one the claims 1 to 6 or a physiologically acceptable salt according to claim 7 for the preparation of a medicament with an inhibitory Effect on factor Xa and / or an inhibitory effect on vennrandte Serine proteases. Process for the preparation of a medicament according to claim 8, characterized in that non-chemical way a compound according to at least one of the claims 1 to 6 or a physiologically acceptable salt according to claim 7 incorporated in one or more inert carriers and / or diluents becomes. A process for the preparation of the compounds according to claims 1 to 7, characterized in that (a) for the preparation of compounds of the general formula

in which R ³ to R ^{5 are} as defined in claim 1 and Z ^{1 is} the hydrogen atom or a protective group and B 'is a group of the formula

wherein R ⁶ and R ^{7 are} as defined in claim 1 and X is the nitrogen atom or the CH group, a compound of the general formula optionally formed in the reaction mixture

in which R ³ to R ^{7 are} as defined in claim 1, X is the nitrogen atom or the CH group and Z ^{1 is} the hydrogen atom or a protective group is cyclized, with subsequent deprotection of any protecting group is released, or (b) for the preparation a compound of the general formula

in which B, X ¹ to X ³ and R ⁵ to R5 are as defined in claim 1, a compound of the general formula

in which R ¹ , R ² and X ¹ to X ^{3 are} as defined in claim 1 and Z represents a leaving group, with a compound of the general formula

in which B and R ³ to R ^{5 are} as defined in claim 1, or (c) for preparing a compound of the general formula

in which R ¹ and R ^{2 are} as defined in claim 1, X ¹ and X ^{3 are} each a nitrogen atom and Z is a leaving group, a compound of the general formula

in which R ¹ and R ^{2 are} as defined in claim 1 and X is a hydroxy or C _1-4 alkoxy group or a halogen atom, cyclized with formamide and then the resulting compound of the general formula

in which R ¹ and R ^{2 are} as defined in claim 1, is reacted with a halogenating agent and a protecting residue used during the reactions for the protection of reactive groups is split off and / or so obtained a compound of the general formers I is separated into their stereoisomers, and / or a compound of the general formula I thus obtained in its salts, in particular for the pharmaceutical application in its physiologically acceptable salts with an inorganic or organic acid or base, is converted.