MXPA01000399A - Disubstituted bicyclic heterocycles having, in particular, a thrombin inhibitive effect - Google Patents

Abstract

The invention relates to disubstituted bicyclic heterocycles of general formula (I) Ra - Het - B - Ar - E, in which Ra, Ar, B, Het and E are defined as in Claim No. 1, to their tautomers, their stereoisomers, their mixtures, their salts, and to the production thereof. The invention also relates to the medicaments containing the pharmacologically active compounds and to their application. The compounds of the general formula (I), in which E represents a cyano group, depict valuable intermediate products for producing the remaining compounds of general formula (I), and the compounds of said general formula (I), in which E represents an RbNH-C(=NH) group, comprise valuable pharmacological properties, in particular, a thrombin inhibitive and thrombin time prolonging effect.

Description

BICICLIC HETEROCICLES D I REPLACED ITS PREPARATION AND ITS EMPLOYMENT AS A MEDICATION DESCRIPTION OF THE INVENTION The object of the present invention are new bicyclic di-substituted heterocycles of the general formula Ra-Het-B-Ar-E, (I) their tautomers, their stereoisomers, their mixtures and their salts, in particular their salts physiologically compatible with inorganic or organic acids or bases, which have valuable properties. The compounds of the general formula I above, in which E represents a cyano group, represent valuable intermediates for the preparation of the remaining compounds of the general formula I, and the compounds of the general formula I above in which E represents a grupc RbNH-C (= NH), as well as its tautomers and its eisomers, have valuable pharmacological properties, in particular an inhibitory effect of thrombin and thrombin time extender. Accordingly, the new compounds of formula I above, as well as their preparation, the medicaments containing the pharmacologically active compounds and their use are subject of the present application. In the above general formula, B means an ethylene group, optionally substituted with one or two two C? _3 alkyl groups, a methylene group of the ethylene group, which is linked to the Het or Ar radical, may be replaced by an oxygen atom or sulfur, by a sulfamyl, sulfonyl, carbonyl or -NRi group, Ri representing a hydrogen atom or a C? -6 alkyl group, or B also means a straight chain C3_5 alkylene group, in which a methylene group, which is not linked to the radical Het or to the radical Ar, is replaced by a group -NRX, in which Ri is defined as mentioned above, E means a cyano group or RbNH-C (= NH), in wherein Rb represents a hydrogen atom, a hydroxy group, a C1-3 alkyl group or an in vivo cleavable radical, Ar means a phenylene or naphthylene group, sometimes substituted with a fluorine atom, chlorine or bromine, with a group t r i f 1 u or r ome t 11 o, C3_3alkyl or C1-3alkoxy, means a thienylene, thiazolylene, pyridinylene, pyrimidine, pyridinylidene group, optionally substituted on the carbon skeleton with a C1_alkyl group; 3, Het means a bicyclic heterocycle of the f or rmu 1 to X represents a nitrogen atom or a methino group, optionally substituted with a C 1-3 alkyl group, and Y represents an imino group, optionally substituted with a C 1-5 alkyl or C 3-7 cycloalkyl group, An oxygen or sulfur atom or X represents a nitrogen atom and represents an imino group substituted with a C 1-5 alkyl or C 3-7 cycloalkyl group, the alkyl and cycloalkyl substituent being in each case substituted with a carboxy group or with a group transformable in vivo in a carboxy group, being able to be replaced in one of the above-mentioned heterocycles additionally a group .- «^ sa» a ^ & - ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^^^^^^^^^^^^^^^^ ~ & *. r. $ r # * > # ü & * non-angular methine for a nitrogen atom, or Het means a group of the formulas.

Ri being defined as mentioned above, and Ra, means a phenyl-C1-3 alkoxy group, an amino group, a C3_3-amino alkyl group which is substituted at the nitrogen atom additionally with a phenol group 1 - a 1 qu i 1 or C1-3, a group R3-CO-R4N c R3-SO2-R4N, wherein R3 represents a C1-5 alkyl group, phenylC1-3 alkyl, C3-7 cycloalkyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tetrahi dr oqu i no 1 i 1 ootetr ah i dr o 1 s oqu i no 1 i 1 oy R 4 represents a hydrogen atom, a C 1 _ 5 alkyl group of 1 to 1 1 to 1 to 1 to 3 to 3, which in each case is substituted on the alkyl part with a group which can be converted in vivo into a carboxy group; with a carboxy or tetrazolyl group, with an aminocarbonyl group or C 1 _ 3 -aminocarbonyl group, which in each case are additionally substituted on the nitrogen atom with a group which can be transformed in vivo into a carboxymethyl group; 1 qu i 1 o C? -3, or with a The carboxy group represents a C2-s alkyl group substituted in the terminal position with a di- (C1-3 alkyl) -araino group, or a C3-7 cycloalkyl group. By a group which can be converted in vivo into a carboxy group, it is to be understood, for example, The hydroxymethyl group, a carboxy group esterified with an alcohol in which the alcohol part is preferably a Ci-e alkanol, a 1-to-1-cycloalkanol C1-3, a cycloalkanol 03-9, and a C5-cycloalkanol may be substituted. -8 additionally with one or two C 1-3 alkyl groups, a C 5 -s cycloalkanol in which a methylene group in the 3 or 4 position is replaced by an oxygen atom or by an imino group, optionally substituted with a C 1-3 alkyl group, phenyl 1 - at 1 qu i 1 or C 1 _ 3, phenyl-C 1 _ 3 -25 alkoxycarbonyl or C 2-6 alkanoyl. and the part of The cycloalkanol may be further substituted with one or two C1-3 alkyl groups, a C1 1 or a 1 that is not 1 C4-7, a C3-5 alkenol, a f in i1-a1 which does not 1 C3-.5, a C3-5 alkynol of ofin 1 - a 1 qui not 1 C3-5, with the proviso that no bond in the oxygen atom starts from a carbon atom carrying a double or triple bond, a C3-C3-β-alkanol C1-3 cycloalkyl, a bicyclic 1 or a ca 1 with a total of 8 to 10 carbon atoms that in the bicyclic part 1 or 1 that is additionally substituted with one or two alkyl groups C1-3, a 1,3-dihydro or -3-oxo-1-is obe nzofura no 1 or an alcohol of the formula R 5 -CO-O- (R 6CR 7) -OH, wherein R 5 represents a group Ci-a alkyl, C 5 7 cycloalkyl, phenyl 1 to 1 a 1 to 1 to C 1 to 3 phenyl, Rg represents a hydrogen atom, a C 1-3 alkyl group, C 5-7 cycloalkyl or phenyl and R 7 represents a hydrogen atom or ur C 1 _ 3 alkyl group, or by a separable radical i The imino or amino group of uri is to be understood, for example, as a hydroxy group, an acyl group such as the benzoyl or pyridinoyl group or a C?-α6 alkanoyl group, such as the formyl, acetyl, propionyl group, »« Aanatfaem butanoyl, pentanoyl or hexanoyl, a group at 111 oxycarbon 11, or an alkoxy group C x _ j_ 6- car bon i 1 o such as the group me t ox i ca r bo n 11 o, et ox icar bo n 11 o, pr opox icar bon i 1 o, is op r opox icarb on i 1, butoxicar-bonyl, tert-bu t oxi car bon i 1, pen toxi-car bon i 1, he xo xi ca rb on i 1 o, oc ti 1 ox icar bon i 1 o, non i 1 ox icarbo -rulo, de ci 1 ox i ca rboni 1 o, unde ci 1 ox i ca rb on i 1, dode ci 1 oxi ca r bon i 1 oo hexade ci 1 ox i ca r bon i 1 o, a phenyl-alkoxy group C i? - ca r bon i 1 o such as the benzyloxycarbonyl group, f in i 1 et ox i-carb on i 1 oopheni lp r oppo xicar bon i 1, a C1-3 alkyl group-su 1 f on i 1 a 1 cox 1 C2-4 - ca r bon i 1, C 1 -C 3 alkoxy C 2-4 alkoxy C 2-4 alkoxy -carbonyl or R 5 CO-O- (R 6CR 7) -O-CO, wherein R 5 to R7 are defined as mentioned above. Furthermore, in the definition of the aforementioned alkyl and alkoxy saturated portions containing more than 2 carbon atoms, as well as the unsaturated alkanoyl and alkyl parts, containing more than 3 carbon atoms, are also included their branched isomers such as, for example, the isopropyl, tere-butyl, isobutyl group, etc. Preferred compounds of general formula I above are those in which £ ¿ Fe-B means an ethylene group, optionally substituted by one or two methyl groups, a methylene group of the ethylene group, which is linked to the radical Het or Ar, may be replaced by an oxygen or sulfur atom, by a carbonyl group or -NRi, Ri representing a hydrogen atom or a methyl group, or B also means an n-propylene group, in which the central methylene group is replaced by a group ~ NR ?, in which Ri is defined as mentioned above, E means a cyano group or RbNH-C (= NH), in which Rb represents a hydrogen atom, a C?-8 alkyloxy group, -carbonyl group, a cyc 1 or a 1 qu i 1 ox i C group 5 -7 - car bon i 1, benzoyl, nicotinoyl or 1 s on icoti no i 1, Ar means a phenylene group, sometimes substituted with a fluorine, chlorine or bromine atom, with a trifluoromethyl, methyl or methoxy group , or a thienylene group, optionally substituted with a methyl group, Het means a bicyclo heterocycle or colic of f r mu 1 • - XU * - * r * -, -, X represents a nitrogen atom or a methine group, optionally substituted with a methyl group, and Y represents an immo group optionally substituted with a C1-3 alkyl group or C3- cycloalkyl group 7, an oxygen or sulfur atom, or X represents a nitrogen atom and Y represents an amino group substituted with a C3-3 alkyl group, the alkyl part being substituted ad 1 c 1 on at the most with a carboxy group. C 1 - 3 alkyloxy-ca rb on 11 o, or Het means a group of the formulas & amp; & < > i with Ri being defined as mentioned above, and R2 represents a 'C3_3 alkyl group substituted with a carboxy or C1-3-alkoxycarbonyl group, and Ra, means a benzyloxy group, an amino group, an alkylC group? -3-amino which is substituted on the nitrogen atom ad 1 c 1 on at least with a benzyl group, a group R 3 -CO-R 4 N or R 3 -SO 2 -R 4 N, wherein R 3 represents a C 1-4 alkyl group , benzyl, C5-7 cycloalkyl phenyl, pyridyl, qumolyl, isoquinolyl, tetrahi dr oqu 1 not 111 ootetrah 1 drois oqu i no 1 i 1 o and R4 represents a hydrogen atom, a C1-3 alkyl group, which is substituted with a carboxy group, C 1 -3 alkoxycarbonyl or, tetrazolyl, ami nocar bon i 1 oo C 1-3 alkyl-ami no car bon 11 or, the aminocarbonyl and the C 1-3 alkylamino groups being substituted rbon 11 or, in each case at the nitrogen atom, ad 1 cyan ate with a carboxy-C 3 -C 3 alkyl or C 1 -C 3 -alkoxy 11-a 1 group or 11 or C1-3, or a C2-3 alkyl group substituted in terminal position with a di- (C1-3 alkyl) -am group, its isomers and its salts.

Particularly preferred compounds of general formula I above are those in which B means an ethylene group optionally substituted by one or two methyl groups, a methylene group of the ethylene group, which is linked to the radical Het, can be replaced. or Ar, for an oxygen or sulfur atom, for a carbonyl group or -NRlf representing Ri a hydrogen atom or a methyl group, or B also means an n-propylene group, in which the central methylene group is replaced by a group -NRi, in which Ri is defined as mentioned above, E means a group RbNH-C (= NH), in which R represents a hydrogen atom, an alkyloxy group CI-B, -carbonyl, a group cic 1 or 1 qu 11 axi Cs -? - ca r boni 1 oo benzoyl, Ar means a phenylene group, optionally substituted by a fluorine, chlorine or bromine atom, with a trif 1 or r or 111 group, methyl or methoxy, or a thienylene group, optionally substituted with a methyl group in the carbon skeleton, Het means a bicyclic heterocycle of the fo rmu 1 a X represents a nitrogen atom or a methino group, optionally substituted with a methyl group, and Y represents an imino group, optionally substituted by a C 1-3 alkyl or C 3-7 cycloalkyl group, an oxygen or sulfur atom, or X represents a nitrogen atom and Y represents an imino group substituted with a C.-3 alkyl group. the alkyl part being further substituted with a carboxy or C 1 -C 3 alkyloxycarbonyl group, and Ra means a benzyloxy group, an amino group, a C alqu-3-amino alkyl group which is substituted on the atom of nitrogen ad 1 c 1 ona lme nte with a benzyl group, a group R3-CO-R4N or R3-SO2-R4N, in which R3 represents a C 1 -4 alkyl, benzyl, C5.7 cycloalkyl group, phenyl, pyridyl, quinolyl, isoquinolyl, tetrahydroquio 1 i 1 octetrahidroiso qu ino 1 i 1 oy JBto ^ asac R4 represents a hydrogen atom, a C1-3 alkyl group, which is substituted with a carboxy group, C1-.3-alkoxycarbonyl, tetrazolyl, aminocarbonyl or C1-3 alkyl-ami no car bo ni 1 o, the aminocarbonyl and C ?3-aminocarbonyl alkyl groups being substituted, in each case at the nitrogen atom, additionally with a C3-3 carboxyalkyl group or C1-3 alkoxy-ca r bon i 1-a 1 qu i 1 o C1-3or a C2-3 alkyl group substituted in terminal position with di- (C 1-3 alkyl) -amino group, in particular those compounds of the above general formula, in which Ra in position 5 means a group R3-CO -R4N or R3-SO2-R4N, which R3 and R4 are defined as mentioned above, their isomers and their salts. Very particularly preferred compounds are those of the general formula wherein X means a methino group or a nitrogen atom, B means an ethylene group, the methylene group being replaced with Ar being replaced by an oxygen atom or an imino group, Ar means a group 1, 4-pheni 1 e not , E means an amidino group, Ri means a methyl group and Ra, means a group R3-CO-R4N or R3-SO2-R4N, R4 representing a methyl group substituted with a carboxy group, C 1-3 alkoxy - ca r boni 1, car box ime ti 1 ami non -carbonyl or C 1-3 alkoxy - ca rbon i lme ti 1 ami noca r bon i 1 o, and R represents an iso qu io group 11 n - 8 - i 1 o, in particular those compounds of the above-mentioned general formula, in which Ra represents a group R3-CO-R4N, their isomers and their salts. As particularly preferred compounds of the general formula I above, there can be mentioned, for example, the following: (a) l-methyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin- 8-Sulfonylamino] -benzimidazole, (b) l-methyl-2- [2- (4-amidinofenyl) -ethyl] -5- [N- (NT- (hydroxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole, (c) l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N - (hydroxy-carbonylmethyl) -quinolm-8-sulfonylamino] -benzimidazole and (d) 1 -me ti 1 - 2 - [N - (4-amidi no f eni 1) - aminome ti 1] - 5 - [N - (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -indol, as well as their salts. The new compounds can be prepared according to methods known per se, for example according to the following procedures: a. For the preparation of a compound of the general formula I, in which E means a group RbNH-C (= NH), in which Rb represents a hydrogen atom, a hydroxy group or C1_3 alkyl: reaction of a compound, eve tually formed in the reaction mixture, of the general formula Ra - Het - B - Ar - C (= NH) - Z lf (II) wherein B, Ar, Het and Ra are defined as mentioned at the beginning and Zi represents an alkoxy or aralkoxy group such as the methoxy, ethoxy, n-propoxy, isopropoxy or benzyloxy group, or an alkylthio or aralkylthio group such as the methylthio, ethylthio, n-propylthio or benzylthio group, with an amine of the general formula H2N-b ', (III) in which Rb' represents a hydrogen atom, a hydroxy group or C1-3 alkyl. The reaction is conveniently carried out in a solvent such as methanol, ethanol, n-propanol, water, methanol / water, tetrahydrofura or dioxane, at temperatures between 0 and 150 ° C, preferably at temperatures between 20 and 120 ° C, with a compound of the general formula III or with a corresponding salt by addition of acids such as, for example, ammonium carbonate. A compound of the general formula II is obtained, for example, by reaction of a compound of the general formula I, in which E represents a cyano group, with a corresponding alcohol such as methanol, ethanol, n-propanol, isopropanol and alcohol benzyl, in the presence of an acid such as hydrochloric acid, or by reaction of a corresponding amide with a trialkyxonium salt such as triethyloxonium tetrafluoroborate, in a solvent such as methylene chloride, tetrahydrofuran or dioxane, . soasaste * ..A-. ? temperatures between 0 and 50 ° C, but preferably at 20 ° C, or a corresponding nitrile with hydrogen sulfide, conveniently in a solvent such as pyridine or dimethylformamide and in the presence of a base such as triethylamine and subsequent alkylation of the thioamide formed with a corresponding alkyl or aralkyl halide. b. For the preparation of a compound of the general formula I, in which the group Ra and E are defined as mentioned at the beginning, with the proviso that the group Ra contains a carboxy group and E is defined as at the beginning, or the group Ra, is defined as at the beginning and E represents a group NH2-C (= NH), or the group Ra contains a carboxy group and E represents a group NH2-C (= NH): transformation of a compound of the formula general - Het B - Ar IV in which A, B, Ar and Het are defined as at the beginning and the group Ra 'and E' possess the meanings mentioned at the beginning for the group Ra, and E, with the condition that the group Ra ', contains a group transformable into a carboxyl group by hydrolysis, treatment with an acid or base, thermolysis or hydrogenolysis, and E is defined as at the beginning, or E 'represents a group which can be transformed into an NH2 -C (= NH) group by hydrolysis, treatment with an acid or base, thermolysis or hydrogenolysis and the group Ra »present the meanings mentioned at the beginning for the group Ra, or the group Ra ', contain a group which can be converted into a carboxyl group by hydrolysis, treatment with an acid or base, thermolysis or hydrogenolysis, and E' represents a group transformable in a NH2-C group (= NH) by hydrolysis, treatment with an acid or a base, thermolysis oh 1 dr ogenol isis, by hydrolysis, treatment with an acid or base, thermolysis oh 1 drogen or 1 is 1 s in a compound of the general formula I, in which the group Ra, and E are defined as mentioned at the beginning, with the proviso that the group Ra contains a carboxy group and E is defined as at the beginning, or the group Ra, present the meanings mentioned at the beginning and E represents a group NH2-C (= NH), or the group Ra, contain a carboxy group and E represents a group NH2-C (= NH).

As a group which can be converted into a carboxy group, for example, a carboxyl group protected by a protective radical, such as its functional derivatives, for example its amides, esters, thioesters, trimer esters, esters, ortho esters, can be used. or imino esters unsubstituted or substituted, conveniently, are transformed into a carboxyl group by hydrolysis, esters thereof with tertiary alcohols, for example the tert-butyl ester, which is transformed into a conveniently carboxyl group by treatment with an acid or thermolysis, and its esters with aralkanols, for example the benzyl ester, which are conveniently converted to a carboxyl group by means of hi drge or 1 isis. The hydrolysis is conveniently carried out in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid or mixtures thereof, or in the presence of a base such as lithium hydroxide, sodium hydroxide or potassium hydroxide in a suitable solvent such as water, water / water no. 1, water / ethanol, water / water, alcohol, ethanol, water / ethanol / dioxane, to - ff lte & aifeisá-jü *. temperatures between -10 and 120 ° C, for example at temperatures between room temperature and the boiling temperature of the reaction mixture. If the group Ra ', and / or E' in a compound of the formula IV contains, for example, the tere-butyl or tert-butyloxycarbonyl group; then these can also be separated by treatment with an acid such as trifluoroacetic acid, formic acid, p-to-1 acid, not its 1-ion, sulfuric acid, hydrochloric acid, phosphoric acid or po-phosphonic acid, optionally in an inert dioxane, preferably at temperatures between -10 and 120 ° C, for example at temperatures between 0 and 60 ° C, or also thermally, optionally solvent such as methylene chloride, chloroform, benzene, toluene, diethyl ether, tetrahydrofuran or in a inert solvent such as methylene chloride, chloroform, benzene, toluene, tetrahydrofuran or dioxane and preferably in the presence of a catalytic amount of an acid such as p -t 1 ue not its 1f ng ico, sulfuric acid, phosphoric acid or polyphosphoric acid, preferably at the boiling point of the solvent used, for example at temperatures between 40 and 120 ° C.

If the group Ra ', and / or E' in a compound of the formula IV contains, for example, the benzyloxy or be cycloxycarbonyl group, then these can also be separated by hydrogenation in the presence of a hydrogenation catalyst such as 1 a di / car bon in a suitable solvent such as methanol, ethanol, ethanol / water, glacial acetic acid, ethyl acetate, dioxane or dimethylene, preferably at temperatures between 0 and 50 ° C, for example at room temperature, and a hydrogen pressure of 1 to 5 bars. c. For the preparation of a compound of the general formula I, in which the group Ra contains one of the ester groups mentioned at the beginning in the definition of the group Ra: reaction of a compound of the general formula Ra "- Het - B - Ar - E, (V) in which B, E, Ar and Het are defined as at the beginning and the group Ra "has the meanings mentioned at the beginning for the group Ra, with the proviso that the group Ra" contains a carboxyl group or a group which can be converted into a corresponding ester group by an alcohol, with an alcohol of the general formula HO-R8, (VI) in which Rβ represents the alkyl part of one of the in vivo separable radicals mentioned at the beginning, exception of the group R5-C0-0- (R5 CR7) for a carboxyl group, or with its formamidoacetals or with a compound of the general formula Z2-R9, (VII) in which Rg represents the alkyl part of one of the in vivo separable radicals mentioned at the beginning, with the exception of the group R5-CO-O- (R5CR7) for a carboxyl group and Z2 represents a leaving group such as a halogen atom, for example a chlorine or bromine atom. The reaction with an alcohol of the general formula VI is conveniently carried out in a solvent or mixture of solvents such as methylene chloride, benzene, toluene, chlorobenzene or, tetrahydrofuran, benzene / tetrahydrofuran or dioxane, but preferably in an alcohol of the general formula VI, optionally in the presence of an acid such as hydrochloric acid in the presence of a water subtracting agent, for example in the presence of isobutyl ester of c 1 oroformate, thionyl chloride, tr ime ti 1 c 1 orosi 1 ano, hydrochloric acid, sulfuric acid, metanic acid, ionic acid, non-ionic acid, phosphorus trichloride, phosphorus pentoxide, N, N '- di cic 1 ohex i 1 ca rb odi imi da, N, N '-dicic 1 ohe xicarb odi imi da / N -hi dr ox is uc cin imi da, N, N'-carbonyldiimidazole or N, N' - ti on 11 di imi da zo 1, trifei 1 fosfi na / tetrac 1 oruro de carbon otrifeni 1 phosphine / diethyl ether of aza di car bo bo x 11 co, optionally in the presence of a base such as potassium carbonate, N-ethyl-di is op r op i 1 amine or N, N-dimime ti 1-ami not -pyridine, conveniently at temperatures between 0 and 150 ° C, preferably at temperatures between 0 and 80 ° C. With a compound of the general formula VII, the reaction is conveniently carried out in a solvent such as methylene chloride, tetrahydrofuran, dioxane, dimethyl ether, dimethylamine or acetone, optionally the presence of a reaction accelerator such as sodium or potassium iodide and, preferably, in the presence of a base such as sodium carbonate or potassium carbonate or in the presence of a tertiary organic base such as -e 1 1 -di is op r op i 1 amine or N-eti 1 -mo rfo 1 i na which, at the same time, can also serve as solvents, or possibly in the presence of silver carbonate or silver oxide, at temperatures between -30 and 100 ° C, but preferably at temperatures between -10 and 80 ° C. d. For the preparation of a compound of 0 the general formula I, in which Rb represents a radical that can be separated in vivo: reaction of a compound of the general formula Ra-Het-B-Ar-C (= NH) -NH2, (VII ) In which Ra, Het, B and Ar are defined as in the beginning, with a compound of the general formula Z3-Rio, (IX) wherein 0 Rio means a radical that can be separated in vivo and Z3 means a nucleophilic leaving group such as a halogen atom, for example a chlorine, bromine or iodine atom. The reaction is carried out advantageously in a solvent such as methanol, ethanol, chloride Methylene, tetrahydrofuran, toluene, dioxane, dimer, its 1-oxide or dimethylformamide, optionally in the presence of an inorganic base or a tertiary organic base, preferably at temperatures between 20 ° C and 20 ° C. boiling temperature of the solvent used. With a compound of the general formula IX, in which Z3 represents a nucleophilic leaving group, the reaction is preferably carried out in a The solvent, such as methylene chloride, aceton on 11 r 11, tetrahydrofuran, toluene, dimethylformamide or dimethylamine, optionally in the presence of a base such as sodium hydride, potassium carbonate, tert. bu 111 potassium or N - 15 and 111 - di 1 s op r op 11 ami na, at temperatures between 0 and 60 ° C. and. For the preparation of a compound of the general formula I, in which Ra represents an amino group and E represents a cyano group: reduction of a nitro compound of the general formula N02 - Het - B - Ar - CN, (X ) where B, Ar and Het are defined as mentioned at the beginning.

The reduction is preferably carried out by hydrogenolysis, for example with hydrogen, in the presence of a catalyst such as pa 1 a di / / car bon, in a solvent such as methanol, ethanol, acetic acid ethyl ester, dimethylformamide, tell me The reaction is carried out with glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid, at temperatures between 0 and 50 ° C, but preferably at room temperature and at a hydrogen pressure of 1 to 7. Bars, but preferably from 3 to 5 bars. This can also be carried out with nascent hydrogen, for example with zinc / glacial acetic acid, zinc / hydrochloric acid or iron or their suitable salts with hydrochloric acid. f. For the preparation of a compound of the general formula I, in which Ra represents an amino group and E represents a cyano group: separation of a protective radical for an amino group of a compound of the general formula Ra "- Het - B - Ar - CN, (XI) in which B, Ar and Het are defined as mentioned at the beginning and «To adftaia & - < - r:, z. ^ 2; -j ?? "Ra" means an amino group protected by a protective radical, as the protective radical for an amino group, for example, the acetyl group, trifluoroacetyl, benzoyl, ethoxycarbonyl, tert-bu t ox i ca r boni 1 o, benzyloxycarbonyl, benzyl, me t ox i be nc i 1, 2, 4-d ime t ox ibenci 1 oof such ilo. The separation of a protective radical used is preferably carried out by hydrolysis in an aqueous solvent, for example in water, isop ripa no 1 / a gua, tetrahydrofuran / gua odi oxa no / a gu a, 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 such as lithium hydroxide, sodium hydroxide or potassium hydroxide, or by separation of the ether, for example in the presence of and with a temperature of 1 to 1, at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C, the separation d A benzyl radical, a methoxybenzyl radical, or an oxycarbon radical, is preferably carried out by hydrogenation, for example with hydrogen in the presence of a catalyst such as carbon dioxide, in a solvent such as methanol, ethanol, acetic acid ethyl ester, dimethylaminophenone, dime ti 1 fo rmami a / a cetane or glacial acetic acid, possibly with acidic acid such as 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 3 to 5 bar, the separation of a me t ox i be nci 1 group is also effected in the presence of an oxidizing agent such as nitrous (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 separation of a 2, 4-d-methyl or oxenc-11 radical is preferably carried out in trifluoroacetic acid in the presence of anisole, the separation of a radical tere -butyl orbit-1-butylated oxycarbonate is preferably carried out by treatment with an acid such as trifluoric acid or hydrochloric acid, optionally with the use of a solvent such as methylene chloride, dioxane or ether, the separation of a phthalyl radical is preferably carried out in the presence of hydrazine or of a primary amine such as methylamine, The solvent is obtained in a solvent such as methanol, ethanol, isopropanol, toluene / water or dioxane, at temperatures between 20 and 50 ° C, the separation of a radical from The oximetry is also carried out by treatment with a catalytic amount of tetrakis- (triphenylphosphma) -palladium (O), preferably in a solvent such as tetrahydrofuran and preferably in the presence of an excess of such a base. as morphol 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) -rod chloride or (I) in a solvent such as aqueous ethanol and, optionally, in the presence of a base such as 1, 4-diaz ab icic 1 or [2.2.2] or t, at temperatures between 20 and 70 ° C. g. For the preparation of a compound of the general formula I, in which Ra represents a group R3-CO-R4N or R3-SO2-R4N and E represents a cyano group: reaction of a compound of the general formula R4NH-Het-B - Ar - CN, (XII) in which .- «& mSn > aHS. *.-..- »< ,, R4, Het, B and Ar are defined as mentioned at the beginning, with a compound of the general formula R3-X-Z4, (XIII) wherein R3 is defined as mentioned at the beginning, X means a carbonyl or sulfonyl group and Z4 means a nucleophobic leaving group such as a halogen atom, for example a chlorine, bromine or iodine atom or, also, in the case where X represents a carbonyl group, means, together with another carbon atom. hydrogen of the contiguous nitrogen atom, another bond bond - n 11 r oge no. The reaction is preferably carried out in a solvent such as methanol, ethanol, methylene chloride, tetrahydrofuran, toluene, dioxane, dιme 111 its 1-fold or dime-111 foaming, optionally in the presence of of an inorganic base or a tertiary organic base, preferably at temperatures between 20 ° C and the boiling temperature of the solvent employed. With a compound of the general formula XIII, in which Z4 represents a nucleophobic leaving group, the reaction is preferably carried out in a solvent such as methylene chloride, acetonitrile, tetrahydrofuran, toluene, 1-methyl bromide or dimethyl ether. 111 its 1-oxime, 5 optionally in the presence of a base such as sodium hydride, potassium carbonate, pyridine, potassium tert-bu 111 potassium or N-eti 1-di is op r op 11 amine, a temperatures between 0 and 60 ° C. h. For the preparation of a compound of the General formula I, in which Ra represents a group R3-CO-R4N or R3-S02-R4N and E represents a cyano group, where R4 is defined as mentioned at the beginning, with the exception of the hydrogen atom: reaction of a compound of the general formula R3-X-NH-Het-B-Ar-CN, (XIV) wherein R3, Het, B, Ar and X are defined as mentioned at the beginning, with a compound of the formula general R4 '- Z5, (XV) in which R4' possesses, with the exception of the hydrogen atom, the meanings mentioned at the beginning for R4 and l ~ ^.? - fcfefe3aíÍÉfe-¿- ** - > Z5 means a nucleophilic leaving group such as a halogen atom, for example a chlorine, bromine or iodine atom. The reaction is preferably carried out in a solvent such as methylene chloride, acet on 11 r 11, acetone, tetrahydrofura no, toluene, dime 111 fo rmami da odime 111 su xix, suitably in the presence of a base such as sodium hydride, potassium carbonate, pyridine, 1, 8-diaz ab icic 1 or [5.4.0] unde c-7-ene, tert -bu 111 ato potassium or N-e 111-di is op r op 11 ami na, at temperatures between 0 and 60 ° C. i. For the preparation of a compound of the general formula I, in which R 4 represents a C alquilo-5 alkyl group ofen 11 - a 1 qu 11 or C _ 3, which is substituted in each case in the alkyl part with a group transformable in vivo in a carboxy group, with a tetrazolyl group, with a group ami no car bon 11 oo alkyl C 1-3 - ami ocar bon 11 or, which in each case are substituted at the nitrogen atom, di c 1 ona lme nte, with a group transformable in vivo in a ca box group 1 - to 1 qu 11 or C1-3, and E represents a cyano group: reaction of a compound of the general formula R3 - X - NR4 '- Het - B - Ar - CN, (XVI) e that R 3, Het, B, Ar and X are defined as mentioned at the beginning and R 'means a C 1-5 alkyl or phenyl-C 1 -C 3 alkyl group, which in each case is substituted the alkyl part with a group which can be transformed in vivo into a carboxy group, with a tetrazolyl group, with an aminocarbonyl group or C C-3-amino-carbonyl alkyl which, in each case, is substituted at the nitrogen atom, additionally with a group transformable in vivo in a car box group i-a 1 qu i 1 or C1-3, or its derivatives reactive with a compound of the general formula Rn-H, (XVII) in which R4 'possesses the of the abovementioned for R4, with the exception of the hydrogen atom, and R11 represents a substituent mentioned at the beginning in the definition of the radical R, of the C? _5 alkyl group ofeni 1 - a 1 qu i 1 or C1-3, which is bound with the radical Rxl through a carbonyl group. The reaction of a carboxylic acid of the general formula XVI is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, benzene / tetr ah i dr of ur ano or dioxane, optionally in the presence of a water-scavenging agent, for example in the presence of isobutyl ester of organic acid, orthocarbonate tetraethyl ester, ortho-acetic acid trimethyl ester, 2, 2 - tell me t oxip r opane, tetr ame t ox isi 1 a no, thionyl chloride, tr ime ti 1 c 1 orosi 1 ano, phosphorus trichloride, phosphorus pentoxide, N, N'-dicyclohexylcarbodiimide, N, N '- dicyclohexylcarbodi-imide / N-hydroxysuccinimide, N, N '-di-cyclohexylcarbo-d ?? m? da / 1-hydroxybenzotriazole, 2- (lH-benzatriazole-1-yl) -l tetrafluoroborate , 3, 3-tetramethyl-uronium, 2 - (1 H -be nzotriazo 1 - 1 -yl) -1, 1, 3, 3-tetram tetrafluoroborate ethyluronium / l-hydroxybenzotriazole, N, N'-ca r bon 11 di imi da zo 1 otrifeni 1 fosfino / tetrac 1 carbon oruro, and optionally with the addition of a base such as pyridine, 4 - d íme ti 1 ami nop iri di na, N -me ti 1 -mo rfo 1 inaotrie 111 ami na, conveniently at temperatures between 0 and 150 ° C, preferably at temperatures between 0 and 100 ° C. The reaction of a corresponding reactive compound of the general formula XVI such as its esters, imidazolides or halides with an amine of the general formula XVII is preferably carried out in a corresponding amine as solvent, optionally in the presence of another solvent such as methylene or ether and, preferably, in the presence of a tertiary organic base such as triethylamine, N-ethyl- d 11 s op r op i 1 amine or N -me thi 1 -mo rfo 1 i na, at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 100 ° C. j. For the preparation of a benzothiazolyl or benzoxazolyl benzothiazolyl or benzthiazolyl compound of the general formula I, in which B represents an ethylene group: reaction of a compound, optionally formed in the reaction mixture, of the formula general wherein Ra and Y are defined as mentioned at the beginning, with a compound of the general formula HO-CO-B '- Ar - E, (XIX wherein Ar and E are defined as mentioned at the beginning and B 'means an ethylene group, optionally substituted with one or two C? _3 alkyl groups. The reaction is conveniently carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuran, be nc ene / tetrahydrofura no or dioxane, optionally in the presence of a water subtracting agent, example in the presence of isobutyl ester of c 1 oroformic acid, tetraethyl ester of orthocarbonic acid, trimethyl ester of orthoacetic acid, 2,2-dimethoxypropionate, tetrimethoxane 11 to not, chloride Thionyl, triamote 1 c 1 orosi 1 a, phosphorus trichloride, phosphorus pentoxide, N, N'-dicyclohexylcarbodiimide, N, N'-dicyclohexicarbo-d i imi da / N - hi dr oxisuccin imi da, N, N'-dicyclohexylcarbodiimide / 1-hydroxy-benzotriazole, tetrafluoroborate of 2- (1 H -b in zotriazo 1 - 1 - i 1) -1, 1, 3, 3 - tetr ame ti 1 ur on io, tetrafluoroborate of 2- (lH-benzotriazol-1-yl) -1, 1, 3, 3-tetramethyluronium / l- Hydrogen ox i - benzotriazo 1, N, N '- car bon i ldi imi da zo 1 ctrifeni 1 fosfine / tetrac 1 or ur or carbon, and eventually under the addition of a base such as pyridine, 4 - d íme ti 1 ami nop iri dina, N -me ti 1 -mo rfo 1 i na or triethylamine, conveniently at temperatures between 0 and 150 ° C, preferably at temperatures between 0 and 100 ° C. The reaction of a corresponding reactive compound of the general formula XIX, such as its esters, imidazolides or halides with an amine of the general formula XVIII is preferably carried out in a solvent such as methylene chloride, ether or tetrahydrofuran and, preferably, in the presence of a tertiary organic base such as triethylamine, N-ethyl- 15 diis op r op 1 ami nao N -me ti 1 -mo rfo 1 i na which, at the same time, can serve as solvents, at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 100 ° C. k. For the preparation of a compound of the general formula I, which contains one of the radicals t e t r ah i dr o - qui no 1 i na or -isoquinoline mentioned at the beginning: hydrogenation of a compound of the general formula I which contains one of the radicals quinoline or isoquinoline mentioned at the beginning.

The hydrogenation is preferably carried out in the presence of an acid such as hydrochloric acid with hydrogen in the presence of a catalyst such as palladium or car bon or in a solvent such as methanol, ethanol, ethyl ester of acetic acid, dimethylformamide , d ime ti 1 fo rmami da / a ce t ona or glacial acetic acid, at temperatures between 0 and 50 ° C, but preferably at room temperature and at a pressure of hydrogen from 1 to 7 bar, but preferably from 3 to 5 bar. In the case of the reactions described above, reactive groups optionally present, such as hydroxy groups, The carboxy, amino, alkylamino or imino can be protected during the reaction by customary protective groups which, after the reaction, are separated again. For example, as a protective radical for a The hydroxy group comes into consideration the group trimeti 1 if 1 i 1, acetyl, benzoyl, tere-butyl, trifly, benzyl or tetrahydride or, as protective radicals for a carboxyl group, the trimide group is considered. 1 if 1 i 1, methyl, ethyl, tere-butyl or benzyl and as radical For an amino, alkylamino or imino group, the acetyl, hydroxy, trifluoride, or benzoyl, oxocar bon 11 or, tert-bu t oxicar bon i 1, ben ci 1 ox, benzyl, or oxocarbon group may be considered. icarb on 11 o, benzyl, 5 me t ox i be nc i 1 oo 2, 4 - dime t ox i be nci 1 o and, for the amino group, add the phthalyl group. The optionally subsequent separation of a protective radical used is effected, for example, by hydrolysis in an aqueous solvent, for example in water, is op rpa no 1 / a gua, tetrahydrofura no / a gua or di oxa no / a gua, in the presence of an acid such as trifluoric acid or hydrochloric acid or hydrochloric acid sulfuric acid, or in the presence of an alkali metal base such as hydroxide lithium, sodium hydroxide or potassium hydroxide, or by separation of the ether, for example in the presence of and at the same time 11 s, at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C . The separation of a hydroxy, benzyl, me t ox and benzyl radical or oxide is carried out, however, for example by hydrogenolysis, for example with hydrogen, in the presence of a catalyst such as p a 1 a d i o / ca r b on o, in a solvent such as methanol, lfcfe f ^ £ - S? aii- ^ H 'ethanol, acetic acid ethyl ester, tell me the title, tell me 1 / or amide / acet on or glacial acetic acid, possibly with the addition of an acid such as 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 3 to 5 bar. The separation of a non-oxidizable group can also be effected 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 separation of a hydroxy, benzyl, methyl or benzethyloxycarbonyl radical is carried out, however, for example by hydrogenolysis, for example with hydrogen, in the presence of a catalyst such as pa 1 a di o / car bon or, in a solvent such as methanol, ethanol, acetic acid ethyl ester, dimethylether, dimethylaminophenol, acetic acid or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid, temperatures between 0 and 50 ° C, but preferably at room temperature, and at a hydrogen pressure of 1 to 7 bar, but preferably 3 to 5 bar. The separation of a non-toxic group can also be carried out in the presence of an oxidizing agent such as nitrate (IV) ammonium nitrate in a solvent such as methylene chloride, acetonitrile or acetonitrile / water, at temperatures between 0.degree. and 50 ° C, but preferably at room temperature. The separation of a 2,4-d ime t oxibene radical is, however, preferably carried out in the presence of anisole. The separation of a tere-butyl radical of cterc-buyl-1-oxycarbide is preferably effected by treatment with an acid such as trifluoroacetic acid, hydrochloric acid, optionally with the use of a solvent such as methylene chloride, dioxane or ether. . The separation of a phthalyl radical is preferably carried out in the presence of hydrazine C of a primary amine such as methylamine, ethylamine or n-b u t i 1 amine, in a solvent such as methanol, This is ethanol, isopropanol, toluene / water or dioxane, at temperatures between 20 and 50 ° C. The separation of an allyloxycarbon radical is effected by treatment with a catalytic amount of t-t r a k i s - (t r i f in 11 f or s f i na) -palladium (O), preferably in a solvent such as tetrahydrofuran and, preferably, in the presence of an excess of a base such as morpholine or 1,3-dαmone, at temperatures between 0 and 100 ° C, preferably at room temperature and under an inert gas, or by treatment with a catalytic amount of tris- (tr? phen? lphosphine) -rod? chloride or (I) in a solvent such as aqueous ethanol and, optionally, in the presence of a base such as 1,4-d? azab? c? [2.2.2] octane, at temperatures between 20 and 70 ° C. The compounds of the general formulas I] to XIX, used as starting substances, which are partly known from the literature, are obtained according to methods known from the literature and, moreover, their preparation is described in the appendices. Thus, for example, a compound of the general formula II is obtained by reaction of a corresponding nitrile, which, for its part, is conveniently obtained according to the processes 3: ah, with a corresponding thioalcohol or alcohol, in the presence of sodium chloride. hydrogen or hydrogen bromide. 5 A compound of the general formulas IV, V, VIII, X, XI and XIX, used as starting material, is conveniently obtained according to a process of the present invention. In addition, the compounds of the formula General I obtained, can be separated into their enantiomers and / or diastereoisomers. Thus, for example, the compounds of the general formula I obtained, which are manifested in racemates, can be separated according to known methods: see Allinger NL and Eliel EL in "Topics in Stereochemistry", Vol. 6, Wiley Interscience, 1971) in their optical antipodes, and compounds of the general formula I with at least 2 asymmetric carbon atoms can be separated, in By virtue of their physico-chemical differences, according to methods known per se, for example by chromatography and / or fractional crystallization, in their diastereoisomers which, if they result in racemic form, can then be separated into The enantiomers, as mentioned above.

The separation into the enantiomers is preferably effected by column separation in chiral phases or by recrystallization in an optically active solvent, or by reaction with an optically active substance which forms with the racemic compound salts or derivatives such as, for example, esters or amides, in particular acids and their activated derivatives or alcohols, and separation of the mixture of salts or the diastereomeric derivative obtained in this way, for example by virtue of the different solubilities, it being possible to liberate the antipodal fibers from the pure salts or derivatives d i a s t e r e or i s orme s by the action of suitable agents. Optically acidic Particularly common active substances are, for example, the D and L forms of tartaric acid or dibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelic acid, camphorsulfonic acid, glutamic acid, aspartic acid or quinaic acid. Eat The optically active alcohol is, for example, (+) - or (-) - menthol, and as optically active acyl radical in amides, for example, the (+) - or (-) - menthyloxycarbonyl radical comes into consideration.

Furthermore, the compounds of the formula I obtained can be converted into their salts, in particular for the pharmaceutical application, into their physiologically compatible salts with inorganic or organic acids. Suitable acids are, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, maleic acid, benzoic acid, methacid not their f ón icoo acid to 1 ue not your 1 f óni co. In addition, the novel compounds of formula I, thus obtained, if they contain a carboxy group, can then be converted, if desired, into their salts with inorganic or organic bases, in particular for the pharmaceutical application, in their physiologically compatible salts. Suitable bases are, for example, sodium hydroxide, potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine. As already mentioned at the beginning, the new compounds of the general formula I and their salts have valuable properties. Thus, the compounds of the general formula I, in which E represents a cyano group or Ra represents an amino group and E represents a cyano group, represent valuable intermediate products for the preparation of the remaining compounds of the general formula I, and compounds of the general formula I, in which 1 E represents a group RbNH-C (= NH), as well as its tautomers, its stereoisomers, its physiologically compatible salts, have valuable pharmacological properties, in particular an inhibitory effect of thrombin, an extended thrombin time effect and an inhibitory effect on serine-related proteases such as, for example, trypsin, urokinase, factor Vlla, factor Xa, factor IX, factor XI and factor XII, also presenting some compounds such as, for example, the compound of Example 16, at the same time ur inhibiting effect of thrombocyte aggregation. For example, the compounds A = l-methyl-2- [(4-amid-n-phenyl) -oxymethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole, B = 1-methyl- 2 - [2 - (4-amidinofenyl) -e] - 5 - [N - ('- (hydroxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole, C = 1 -methyl 1 - 2 - [N- (4-midi not f in i 1) - ami no-metí 1] -5- [N- (hydroxy-carbonylmethyl) -quinolin-8-su 1 f on i 1 ami no] - be nc imi da zo 1 and 'D = l-methyl-2 - [N- (4-amidinofenyl) -aminomethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -indole were examined for their effect on thrombin time as follows: Material: plasma, human coded blood, test thrombin (bovine), 3C U / ml, Behringwerke, Marburg buffer barbiturate - diethyl acetate, ORWH 60/61, Be ringwer e, Marburg Biomatic BIO coagulometer, Sars tedt Realization: The determination of thrombin time was carried out with a Biom coagulometer BIO atic Sarstedt. The test substance was added to the test containers prescribed by the manufacturer1 with 0.1 ml of human coded plasma and 0.1 ml of diethyl barbiturate buffer (DBA buffer). The batch was incubated for one minute at 37 ° C. By adding 0.3 U test thrombin in 0.1 ml of: S- * A -j¡aaÉB agw ..

DBA buffer the coagulation reaction was started. Conditioned by the device, with the introduction of thrombin the measurement of the time until the clotting of the batch begins. As a control, batches were added to which 0.1 ml of DBA buffer was added. According to the definition, the concentration of effective substance at which the thrombin time was doubled with respect to the control was calculated by means of a curve of do s i - e f e c t o. The following table contains the values found: Substance T ostime of t r omb ina (DE2oo e n μM) A 0, 015 B 0, 016 C 0, 031 D 0, 054 For example, in rats no acute toxic side effects could be observed in the application of the compounds in the above dose range. Accordingly, these compounds. They are very compatible.

By virtue of their pharmacological properties, the novel compounds and their physiologically compatible salts are suitable for the prevention and treatment of venous and arterial thrombotic diseases such as, for example, the treatment of acute thrombosis of the leg veins, the prevention of reocclusions after arterial bypass operations or angioplasty (PT (C) A), as well as in the occlusion of peripheral arterial diseases such as pulmonary embolism, disseminated intravascular coagulation, prophylaxis of coronary thrombosis, stroke prophylaxis and Prevention of occlusion of vascular channels or Stents. Additionally, the compounds according to the invention are suitable for an anosomal support in the case of a thrombolytic treatment such as, for example, with rt-PA or streptokinase, to prevent long-term restenosis after of PT (C) A, to prevent metastasisation and the development of coagulation-dependent tumors and of fibrin-dependent inflammatory processes, for example in the treatment of pulmonary fibrosis.

The dosage necessary to achieve a corresponding effect is conveniently in the case of intravenous administration at 0.01 to 10 mg / kg, preferably 0.03 to 3 mg / kg and, in the case of oral administration at 0 , 1 to 10 mg / kg, preferably 0.3 to 5 mg / kg, in each case 1 to 4 times a day. For this purpose, the compounds of the formula I prepared according to the invention can be incorporated into conventional galenical preparations such as tablets, dragees, capsules, powders, suspensions or suppositories, optionally in combination with other active substances, together with one or more substances of support and / or customary inert diluents, for example with corn starch, lactose, sucrose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / g 1 icero 1, water / sor bi ta, a gua / po 1 ieti 1 e ng 1 ico 1, pr op 11 e ng 1 ico 1, alcohol ceti 1 es-teari 11 co, carboxymethylcellulose, or substances with fat content such as fat aura or mixtures thereof adequate. The following examples have to explain the invention in more detail: - s. ? ÁkSü r Preliminary observations In the case of the determination of the Rf values, 1-Polygram gel plates from E. Merck, Darmstadt, were always used, insofar as not indicated otherwise. The spectra of EKA tables (mass spectra of e 1 e c t r opu 1 ve r i z ation of cations) are described, for example, in Chemie unserer Zeit 6_, 308-316 (1991).

Example 1 l-Methyl-2- [2- (4-amidinofenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -methanesulfonylamino] -benzimidazole a. l-ethyl-2- [2- (4-cyanophenyl) -ethyl] -5-nitro-benzimidazole 2.3 g (0.014 mol) of 2-methyl-amino-5-nitro-aniline and 2.7 g ( 0.0154 mol) of 4-cyano-non-phenol-1-acetic acid are heated at reflux for 1 hour in 25 ml of phosphorus oxychloride. After cooling, it is mixed with water and alkalized with ammonia. The precipitate is filtered with suction, washed with water and dried. Yield: 3.8 g (89% of theory), R value: 0.28 (silica gel); dichloromethane / methanol b. l-Methyl-2- [2 - (4-cyanophenyl) -ethyl] -5-amino-benzimidazole 3.8 g (0.0124 mol) 'of 1-methyl-2 - [2 - (4-cyn. feni 1) - eti 1] - 5 - nitro-be nc imi da zo 1 dissolve 5 in 100 ml of methanol and 100 ml of di c 1 or ome ta and, after the addition of 0.5 g of palladium at 10% on active carbon, they are hydrogenated with water. Then, the catalyst is filtered off and concentrated by evaporation. 10 Yield: 3.2 g (93% of theory), R value: 0.38 (silica gel, dichloromethane / methanol = 9: 1) c. l-methyl-2- [2- (4-cyanophenyl) -ethyl] -5-methano-sulphonylamino-benzimidazole; 1.6 g (5.8 mmol) of 1 -me 111-2 - [2 - ( 4 - cyanopheni 1) - and 111] - 5 - ami non-benzimide zo 1 and 0.66 c (5.8 mmol) of methacrylate and not its 1-ion are stirred in 30 ml of pipdin for 3 hours at room temperature. Next, 1 ml is added water and concentrated by evaporation. The residue is diluted with ethyl acetate and water and the crystalline product is filtered off with suction and dried. Yield: 1.4 g (68% of theory), R value: 0.70 (silica gel, dichloromethane / methanol = 9: 1) d. l-Methyl-2 - [2- (4-cyanophenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -methylammonium] -benzimidazole 1.4 g (3.95 mmol) of 1-methyl - 2 - [2 - (4-cyano-phenyl) -ethyl] -5-methanesulfon-lane-benzimidazole, 0.73 g (4.4 mmol) of (ethyl ester of bromoacetic acid and 2.8 g (20 g. mmol) of potassium carbonate are dissolved in 200 ml of acetone and refluxed for 2 hours, then filtered off and the solution is concentrated by evaporation Yield: 1.6 g (92% of theory) , Rf value: 0.76 (silica gel; dichloromethane / methane) = 9: 1) e. l-methyl-2- [2- (4-amidinophen-1-yl) -ethyl] -5- [N- (ethoxy- • carbonylmethyl) -me tanosulfonylamino] -benzimidazole 1.6 g (3.63 mmol) of 1 -me 111-2- [2 - (4-cyano-phenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -methane-sulphomlamino] -benzipudazole are dissolved in 50 ml of saturated ethanolic hydrochloric acid and stirred for 5 hours at room temperature. Next, the solvent is distilled off, the residue is dissolved in 30 ml of absolute ethanol and 3.5 g (3.63 mmol) of ammonium carbonate are added. After 18 hours at room temperature, it is evaporated to dryness and the residue is chromatographed on silica gel (methylene chloride / me t a no = 5: 1). The corresponding fractions are concentrated and the mixture is mixed by trituration with ether and filtered with suction. Yield: 0.9 g (50% of theory), R value: 0.36 (silica gel, dichloromethane / methanol = 5: 1) C22H27N5O4S (457.55) 10 mass spectrum: (M + H) + = 458 (M + Na) + = 480 EXAMPLE 2 l-Methyl-2 - [2- (4-amidinophenyl) -ethyl] -5- [N- (ethoxy-15 carbonylmethyl) -benzenesulfonyl] amino] -benzimidazole to . l-methyl-2- 2- (4-cyanophenyl) -etill-5- [N- (ethoxy-carbonyl-methyl) -benzenesulfonyl] amino] -begaimide zol Prepared analogously to Example Id, starting from 1 -me 111 - 2 - [2 - (4 - c 1 to no phen 11) - and 111] - 5 - be nce not its 1 f on 11 ami no -bencimide zo 1, ethyl ester of bromoacetic acid and carbonate of potassium er acetone. Performance: 54% of the theoretical, R f value: 0.84 (silica gel, dichloromethane / methanol = 9: 1) b. l-methyl-2 - [2- (4-amidinophenyl) -ethyl] -5- N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole Prepared analogously to Example le, from l-met? l-2- [2- (4-c? Anophen?) -et? L] -5- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole, and hydrochloric acid / ammonium carbonate in ethanol. Yield: 59% of theory, Rf value: 0.38 (silica gel, dichloromethane / methane = 5: 1) mass spectrum: (M + H) + = 520 (M + Na) + = 542 EXAMPLE 3 l-Methyl-2- [2- (4-amidinophenyl) -ethyl] -5- N- (hydroxycarbonyl-methyl) -benzenesulfoni-lamino] -benzimidazole 0.52 g (0.93 mmol) of 1 -me 111 - 2 - [2 - (4-amidinophenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -be nce not su 1 f on 11 ami no] -ben c idem zo 1, and 0.4 g ( 0.01 mol) of sodium hydroxide are stirred in 5 ml of water and 10 ml of ethanol for three hours at room temperature. Then it is diluted with &-i-faith ... water and adjusted to pH 4 with glacial acetic acid. The crystalline precipitate is filtered off with suction and dried. Yield: 77% of theory, C25H25N504S (491.66) mass spectrum: (M + H) + = 492 (M + Na) + = 514 (M-H + 2Na) + = 536 (2M + H + Na) ++ = 503 Example 4 l-Methyl-2 - [2- (4-amidinophenyl) -ethyl] -5- [N- (hydroxycarbonylmethyl) -me tanosulfonylamino] -benzimidazole Prepared analogously to Example 3, from 1-methyl ti-2 - [2 - (4-ami di no f in 11) - and 111] - 5 - [N - (ethoxycarbonylmethyl) -methanesulfonylamino] -benzimidazole and soda lye. Yield: 97% of theory, C2oH23N5? 4S (429.5) mass spectrum: (M + H) + = 430 (M + Na) + = 452 (2M + H + Na 2 + = 441 (2M + 3Na) 3 + = 309 Example 5 1-Ethoxycarbonylmethyl 2 - [(4-amidinopheyl) -oxymethyl] -5- N- (2-dimethylaminoethyl) -benzenesulfonylamino] -benzimidazole a. Mixture based on 1-ethoxycarbonylmethyl -2 - (4-cyanophenyl) -oxymethyl] -5-n-ro-benzimidazole and l-ethoxycarbonylmethyl-2-f (4-cyano-phenyl) -oxymethyl] -6-nitro-benzimidazole Prepared analogously to Example Id, from 1 H-2 - [(4-cyano f in i 1) -ox ime ti 1] -5-nitro-benzimidazole, ethyl ester of bromoacetic acid and potassium carbonate in acetone. Yield: 3.6 g (95% of theory), R value: 0.56 (silica gel, dichloromethane / methanol = 19: 1) b. Mixture based on 1-e-toxicarbonylmethyl - 2 - [(4-cyanophenyl) -oxymethyl] -5-amino-benzimidazol and l-ethoxycarbonylmethyl-2 - [(4-cyanophenyl) -oxymethyl] -6-amino-benzimidazole 3.6 g (9.5 mmol) of the mixture based on 1-ethoxycarbonyl-methyl-2- [(.-Cyanophenyl) -oxymethyl] -5-nitro-benzimide zo 1 and l-ethoxycarbonylmethyl-2- [(4-cyanophenyl) -ox ime ti 1] -6-nitro-benz imi da zo 1 are dissolved in 20C ml of methanol and, after the addition of 0.5 g of 10% palladium on active carbon, Hydrogen with hydrogen. The catalyst is then filtered off and concentrated by evaporation. The residue is chromatographed on silica gel (methylene chloride + 1 to 5% ethanol). Yield: 1.2 g (36% of theory) of 1-ethoxycarbonylmethyl-2- [(4-cyanophenyl) -oxymethyl] -5-amino-benzimidazole R value: 0.10 (silica gel; dichloromethane / methanol = 19: 1) Yield: 1.0 g (30% of theory) of 1-ethoxycarbonylmethyl-2- [(4-cyanophenyl) -oxymethyl] -6-amino-benzimidazole Rf value: 0.32 (silica gel; dichloromethane / methanol = 19: 1) c. l-Ethoxycarbonylmethyl-2-r (4-cyanophenyl) -oxymethyl] -5-benzenesulfonyl-lamino-benzimidazole Prepared analogously to Example 1, from 1-ethoxycarboxymethyl 1 - 2 - [(4 - cia no feni 1) -ox ime ti 1] - 5 - ami no -benz imi da zo 1 and chloride of acid bence not its 1 ión ico in pyridine. Yield: 100% of theory, Rf value: 0.43 (silica gel, dichloromethane / methanol = 9: 1) d. 1-e-co-ylmethyl-2 - [(4-cyanophenyl) -oxymethyl] -5- [N- (2-dimethylaminoethyl) -benzenesul onyl-amino] -benzimidazole 1.65 g (3.4 mmol) 3 - et oxicar bo ni lme ti 1 -2- [(4-cyanophenyl-nil) -oxymethyl] -5-benzenesulfonylamino-benzimidazole and 518.4 mg (3.6 mmol) of 2-dimethyl chloride hydrochloride 1 ami no ti 1 or dissolve in 100 ml of acetone and, after the addition of 2.0 g of potassium carbonate and 737 mg (4.85 mmol) of 1,8-diazabicyclo [5.4.0] undec 7-ene, heated to reflux for 11 hours. It is then filtered off and concentrated by evaporation. The residue is chromatographed on silica gel (methylene chloride and not / 5-10% ethanol). Yield: 750 mg (39% of theory), Rf value: 0.21 (silica gel, dichloromethane / methanol = 9: 1) e. 1-E Toxycarbonylmethyl-2 - [(4-amidinophenyl) -oxymethyl] -5- [N- (2-dimethylaminoe-thi-1-benzenesulfonyl-amino] -benzimidazole Prepared analogously to Example 1, e from l-ethoxycarbonylmethyl -2- [(4-cyanophen? L) -oxymethyl] -5- [N- (2-dimethylaminoet? L) -benzenesulfonylamino] -benzimidazole, and c 1 orhydric acid / ammonium carbonate in ethanol. i ^ Áik ^ & iii &X ^ Yield: 85% of theory, C29H34N605S (578.7) mass spectrum: (M + H) + 579 (M + 2H) ++ 290 Example 6 l-Ethoxycarbonylmethyl-2- (4-amidinophenyl) -oxymethyl] -6- [N- (2-dimethylaminoethyl) -benzenesulfonylamino] -benzimidazole a. l-Ethoxycarbonylmethyl-2- (4-cyano-phenyl) -oxymethyl] -6-benzene sulfonyl-lamino-benzimidazole Prepared analogously to Example LE, from l-ethoxycarbonylmethyl-2 - [(4-c? anophen? I) -ox? methylene] -6-ammo-benzimidazole and 1-ionic acid chloride in pyridine. Yield: 80% of theory, Rf value: 0.72 (silica gel, dichloromethane / methanol = 9: 1) b. 1- ethoxycarbonylmethyl 2 - [(4-cyanophenyl) -oxymethyl] -6- [N- (2-dimethylamino-ethyl) -benzenesulfonylamino] -benzimidazole Prepared analogously to Example 5d, from l-ethoxycarbonylmethyl-2- [( 4-c? Anophen?) Oxymethyl] -6-benzenesul-fonylamino-imidazole, chloride - • f *? ' ? ¡»« A *: a »* 2 & ^ ^ .f tSM h drocloruro 2 - 111 ami tell noe t i1 or potassium carbonate and 1, 8 - di z ab i c i c 1 or [5.4.0] undec-7-ene in acetone. Yield: 24% of theory, R value: 0.34 (silica gel, dichloromethane / methanol = 9: 1) c. l-ethoxycarbonylmethyl-2-f (4-amidinophenyl) -oxime-tl] -6- [N- (2-dimethylamino-tyl) -banzene-sulfonyl-amino] -benzimidazole Prepared analogously to Example 1, from l-ethoxycarbonylmet? l-2- [(4-c? anophen? l) -oxymethyl] -6- [N- (2-dimethylamino] -benzenesulfon on 11 ami] - b ene imi da zo 1 and acid c 1 orhydric / ammonium carbonate in ethanol. Yield: 67% of theory, C29H3 N605S (578.7) mass spectrum: (M + H) + = 579 (M + 2H) ++ = 290 E j emplo July 1 -hidroxicarbonilmetil -2-f (4-amidinophenyl) -oximetil] -5- [N- (2 tilaminoe Tell me til) -benzenesulfonyl-amino] benzimidazole "A, ifi? --- &S5 Prepared analogously to Example 3, starting from 1-et ox i ca r bon i lme ti 1 - 2 - [(4-ami di no f in i 1) - oxymethyl] -5- [N- (2-dimethylaminoethyl) -benzenesulf on i 1 ami] -b ene imi da zo 1 and soda lye 5 Performance: 91% of theory, C27H30N6O5S (550, 65) mass spectrum (EKA): (M + H) + = 551 (M + 2H) ++ = 276 Example 8 1-Ethoxycarbonylmethyl -2-T (4-amidinophenyl) -oxymethyl] -5- [N- (2-dimethylaminoethyl) -me tanosulfonylamino] -benzimidazole Prepared analogously to Example 1, from 1-ethoxycarbonylmethyl. -2- [(4-cyanophenyl) -oxymethyl] -5- [N- (2-dimethylaminoetyl) -methanesulfonyl-ami no] -benzimide zo 1 with ethanolic hydrochloric acid and ammonium carbonate. Yield: 96% of theory, 20 C24H32N605S (516, 6) mass spectrum (EKA): (M + H) + = 517 (M + 2 H) + + = 2 5 9 E j emp l o 9 1 - . 1-ethoxycarbonylmethyl 2 - [(4-amidinophenyl) -oxymethyl] -6- [N- (2-dimethylaminoethyl) -me tanosulfonylamino] -benzimidazole Prepared analogously to Example le, from l-ethoxycarbonylmethyl-2- [ (4-cyanophenyl) -oxymethyl] -6- [N- (2-dimethylaminoetyl) -methanesulfonyl-ami no] -be nc idem 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 69% of theory, C24H32N605S (516.6) mass spectrum (EKA): (M + H) + = 517 (M + 2H) ++ = 259 Use 10 1 -hydroxycarbonylmethyl 2 - [(4-amidinophenyl) -oxymethyl] -6- [N- (2-dimethylaminoe ti 1) -me tanosulfonyl-amino] -benzimidazole Prepared analogously to Example 3, starting from 1 - oxy et ca rboni lme 111-2 - [(4 - amidi of in 11) -oximetil] -6- [N- (? 2-dimethylaminoeth l) -methanesulfonyl-ami no] -benzyl c imi da zo 1 and soda lye. Yield: 92% of theory, C22H28N605S (488, 67) mass spectrum (EKA): (M + H) + = 489 (M + 2H) ++ = 245 Example 11 1 -hydroxycarbonylmethyl 2- [(4 -amidinophenyl) -oxymethyl] -5- [N- (2-dimethylaminoethyl) -me tanosulfonyl-amino] -benzimidazole Prepared analogously to Example 3, from l-ethoxycarbonylmethyl-2- [(4-amidinophenyl) -oxymethyl ] -5- [N- (2-dimethylaminoethyl) -methanesulfonyl-ami no] -ne ncimide zo 1 and soda lye. Performance: 98% of the theoretical, 40 /// C22H28 6? 5S (488, 6) mass spectrum (EKA): (M + H) + = 489 (M + 2H) ++ = 245 Use 12 l-methyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (e-oxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, starting from 1 -me ti 1 - 2 - [(4-cyano f eni 1) -ox ime ti 1] - 5 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 70% of theory, C 29 H 28 N 6 O 5 S (572, 65) spectrum of EKA tables) M + H = 573 M + 2 H = 287 M + H + Na = 298 E j emplo 13 l-et l-2- [2- (4-amidinofenll) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin- 8 - sulfonylamino] - benzimidazole Prepared analogously to Example le, 10 from l-et l-2- [2- (4-c anofen l?) -ethyl] -5- [N- (etoxicarbonimetil) -quinolm-8-sulfon lam not?] - benzimidazole and hydrochloric acid ethanolic, ethanol and ammonium carbonate. Yield: 85% of theory, 15 C3? H32N604S (584, 71) R value: 0.32 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 585 (M + H + Na) ++ = 304 20 (M + 2H) ++ = 293 Example 14 l-Methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulphonyl] amino] benzimidazole & fc¿ * 'w = Mt ^. . = fc ^ > ^^ Xm. »• S ?? i, prepared analogously to Example le, starting from 1 -me 111-2 - [2 - (4-cyanof in 11) -e 111] - 5 - [N - (ethoxycarbonimethyl) qumolm-8-sulfon? lam? no ] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 71% of theory, C3oH3? 604S (570, 68) R value: 0.30 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 571 (M + H + Na) ++ = 297 (M + 2H) ++ = 286 Use 15 lc? Clopropyl-2- [2- (4-amidinofeni 1) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, from 1 - ci clop r opi 1 - 2 - [2 - (4-ami di no f in 11) -ethyl] -5- [N- (ethoxycarbonylmethyl) -qumol? N-8-su 1 f on 11 ami no] -Beginning of zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 76% of theory, C32H32N6? 4S (596.72) R value: 0.34 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) * = 597 (M + H + Na) ++ = 310 (M + 2H) ++ = 299 Example 16 l-Methyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (hydroxycarbonylmethyl) -gui-or-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, starting from l- methyl-2- [(4-amidinofenyl) -oxymethyl] -5- [N- (methoxycarbonyl-methyl) -quinolin-8-su-1-foni-amyl] -b ene imi da z ol and soda lye. Yield: 43% of theory, C27H24N605S (544.6) mass spectrum EKA M + H) + = 545 M + Na) + = 567 MH) "= 543 2M + 2Na + H 3 + = 378.7 XH-NMR (d6-DMS0): d = 3.90 (s, 3 H), 5.05 (s, 2 H), 5.73 (s, 2 H), 7.09 (dd, 1 H), 7, 38 (d, 2 H), 7.52 (d, 1 H), 7.57-7.74 (m, 2 H), 7.80 (dd, 1 H), 7.92 (d, 2 H) ); 8.13 (d, 1 H); 8.31 (d, 1H); 8.61 (dd, 1 H); 9.12-9.30 (m, 3H); 9.38 (s, 2H) ppm Ie 17 l-ethyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (hydroxycarbonyl-methyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, starting from from 1 - e 111 - 2 - [2 - (4-ami di nofe ni 1) - e 111] - 5 - [N - (ethoxycarbonylmethyl) -qumol? n-8-sulfon? lam? no] - benzimidazole and soda lye. Yield: 74% of theory, C29H28 604S (556, 65) mass spectrum (EKA): (M + H) + = 557 (M + Na) + = 579 Use 18 l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, from 1 - me 111 - 2 - [2 - (4-ami dinofen 11) - and 111] -5- [N- (ethoxycarbonylmetyl) -quinoline-8-sulfonamino-benzimidazole and bleach soda. Performance: 96% of the theoretical, C28H26N6? 4S (542.59) mass spectrum (EKA): (M + H) + = 543 (M + Na) + = 565 (2M + 3Na) 3"= 385 Use 19 l-cyclopropyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole. Prepared analogously to Example 3, starting from 1-cyc 1 op r op i 1 - 2 - [2 - (4-ami di nofeni 1) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8- su 1 f on i 1 ami no] - Be nc imi da z ol and lye of soda. Yield: 88% of theory, 15 C3oH28N604S (568, 66) mass spectrum (EKA): (M + H) + = 569 (M + Na) + = 591 2M + 3Na 3 + = 402 EXAMPLE 20 l-Ethyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (ethoxycarbonylmethyl) -quinone 8-sulfonylaminobenzimidazole Prepared analogously to Example 1, from -ethyl-2- [(4-cyanophen? l) -oxymethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 81% of theory, 5 C30H30 6O5S (586.7) mass spectrum (EKA): (M + H) + = 587 (M + H + Na) ++ = 305 (M + 2H) ++ = 294 Example 21 l-Ethyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (hydroxycarbonyl-methyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, starting from 1 - eti 1 - 2 - [(4-amidi no fe nor 1) - oxime ti 1] - 5 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and soda lye. Yield: 96% of theory, C28H26N605S (558, 6) 20 mass spectrum (EKA): (M + H) + = 559 (M + Na) + = 581 (M-H) ~ = 557 E j us 22 l ^^^^ v ^^^^^^ l-methyl-2- [2- (4-amidi-ofenyl) -oxymethyl] -5- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole Prepared analogously to Example le, from l-methyl-2- [(4-cyanophenyl) -oxymethyl] -5- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 48% of theory, C26H27N5O5S (521.6) mass spectrum (EKA): (M + H) + = 522 (M + H + Na) ++ = 272.8 Example 23 L-methyl-2- [2- (4-amidinophenyl) ethyl] -5- [N- (Nf- (ethoxycarbonylmethyl) -aminocarbonylmethyl 1) -quinolin-8-sulphonamino] -benzimidazole a. l-Methyl-2- [2- (4-cyanophenyl) -ethyl] -5- [N- (hydroxycarbonyl-ill -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, from 1-methyl-1 - 2 - [2 - (4 - cia no f in i 1) - eti 1] - 5 - [N - (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and sodium hydroxide in ethanol / water Yield: 92% of the theoretician, • jfe.

R f value: 0.24 (silica gel, dichloromethane / methanol = 9: 1) b. l-Methyl-2- [2- (4-cyanophenyl) -ethyl] -5- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonyl methyl) -quinolin-8-sulfonylamino] -becimidazole 2.1 g (0.004 mol) of l-methyl-2- [2- (4-cyanophenyl) -ethyl] -5- [N- (hydroxycarbonylmethyl) -quo 1 in-8-su 1 f on i 1 ami no] -be nc imi Zero 1 and 0.65 g (0.004 mol) of N, N'-ca r bon i 1 di imi da zo 1 are dissolved in 30 ml of dimethylformamide and stirred for 45 minutes at 80 ° C. Then, 0.71 g is added (0.0046 mol) of ester g 1 i c i ne t í 1 i co and 0.51 g (0.005 mol) of triethylamine and stir for another four hours at 80 ° C. The solvent is concentrated by evaporation and the residue is chromatographed on silica gel (methylene chloride / ano 1 = 50: 1). Yield: 44% of theory, R value: 0.74 (silica gel, dichloromethane / methanol = 9: 1) c_. l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 1, starting from 1 -me ti 1 - 2 - [2 - (4 - cia no fe ni 1) - eti 1] - 5 - [N - (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -qu? nolm-8-sulfonylamino ] -benzium zol and acid or ammonium hydrocarbon bonate in ethanol. Yield: 86% of theory, C32H33N705S (627, 73). Mass spectrum: (M + H) + = 628 (M + 2H) + = 314.8 (M + H + Na) ++ = 325.7 Example 24 l-Methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (N'- (e-toxycarbonylmethyl-N '-methyl-aminocarbonylmethyl) -quinolin-8-sulfonylamino ] -benzimidazole Prepared analogously to Example LE, starting from l-met? l-2- [2- (4-c? anophen? l) -et? l] -5- [N- ('-ethoxy? carbon? lmet? lN '-methyl-aminocarbonylmethyl) -quinolin-8-sulfonamino] -benz midazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate Yield: 63% of theory, C33H35N7O5S (641.76) value Rf: 0.30 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 642 (M + H + Na) ++ = 332.8 (M + 2H ) ++ = 321.7 Use 25 l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (N '- (hydroxycarbonylmethyl) -aminocarbonylmethyl) -quinoline- - aul foni lamino] -benzimidazole Prepared analogously to Example 3, starting from 1-methyl ti 2 - [2 - (4-ami di no f in i 1) - eti 1] - 5 - [N - (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) - qu i no 1 in - 8 - su 1 f oni 1 ami no] -be n ci da z o 1 and bleach soda Yield: 87% of theory, C3oH29N705S (599.68) mass spectrum EKA 'M + H) = 600 M + H + Na) + + = 311.8 15 M + Na) + + = 622 M + 2H) + + = 300.8 2M + H + 2Na) 3 + = 415 2M + 3Na 3 + = 422.7 XH-NMR (d6-DMS0 + DC1): 20 d = 3.29 (t, 2H), 3.51 (t, 2 H); 3.80 (s, 2 H); 3.87 (s, 3 H); 5, 01 (s, 2 H); 7, 10 (dd, 1H); 7, 56-7, 90 (m, 8 H); 8, 17 (d, 1 H); 3, 28 (d, 1 H); 8, 68 (dd, 1 H); 9, 26 (dd, 1H) ppm E n g ect 26 vattB l-methyl-2- [2- (4-midinophenyl) -ethyl] -5- [N- (N '-hydroxycarbonylmethyl-N' -methyl-1-aminocarbonylmethyl 1) -quinolin-8-sulfonylamino] - Benzimidazole Prepared analogously to Example 3, from 1 -me ti 1 - 2 - [2 - (4-ami di no pheni 1) - eti 1] - 5 - [N - (N '-ethoxycarbonylmethyl-N' -methyl-aminocarbonylmethyl) -quinolin- 8-sulfonylamino] -benzimidazole and soda lye. Yield: 97% of theory, C3? H3? N707s (613.71) mass spectrum (EKA) M + H) = 614 M + Na) + = 636 M + 2H) + + = 307.7 M + H + Na) + + = 318.6 M + 2Na = 329.6 Use 27 l-methyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (hydroxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole Prepared analogously to Example 3, starting from 1-methyl ti-2. - [(4-amidi no f eni 1) - oxime ti 1] - 5 - [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole and sodium hydroxide solution. Yield: 79% of theory, C24H23N5O5S (493, 6) mass spectrum (EKA M + H) = 494 M + Na) + = 516 M-H) "= 492 Example 28 l-Methyl-2- [N- (4-aminophenyl) -aminomethyl] -5- [N- (methoxycarbonylmethyl) -quinolin-8-sulfonilamino] -benzimidazole Prepared analogously to Example le, from 1 -me 111 - 2 - [N - (4 - c 1 anof in 11) - ami nome 111] -5- [N- (methoxycarbonyl-methyl) -qu? nol? n-8-su 1 f on 11 ami o ] -benzene, zo 1 and methanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 65% of theory, C28H27N7O4S (557, 64) Rf value: 0.33 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 558 (M + 2H) + + = 279.7 (M + H + Na) + = 290.7 E 299-methyl-2- [2- (4-amidinofeuyl) -ethyl] -5- [N- (methoxycarbonylmethyl)] -quinolin-8-sulfonylamino] benzimidazole Prepared analogously to Example LE, starting from 1-methyl 1-2 - [N - (4-cyn not f at 11) -e 111] - 5 - [N - (methoxycarbonylmethyl) -qu? nolin-8-sulfon? lamino] -benzimidazole and methanolic hydrochloric acid, methanol and ammonium carbonate. Yield: 78% of theory, C29H28N6? 4S (556, 65) R value: 0.29 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 557 (M + 2H) ++ = 579 (M + H + Na) ++ = 290.3 Use 30 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- 15 (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino-benzimidazole Prepared analogously to Example 3, starting from 1-methyl 1-2 - [N - (4-ami di no phen 11) -amomomethyl] -5- [N- ( ethoxycarbonylmethyl) -quinolin-8- 20 its 1 foni 1 ami no - be nc imi da zo 1 and soda lye. Yield: 91% of theory, C27H25N7O4S (543; 62) mass spectrum (EKA): (M + H) + = 544 (M + Na) + = 566 25 (M + H + Na) ++ = 283.8 - * .., c-faith. ^ a ^^ - »^ ^ - ^? aiW» ítfea - «88« - 1 -,. -, ^ m (M + 2Na) ++ = 294.6 XH-NMR (d6-DMSO): d = 3.70 (s, 3 H); 4.60 (broad s, 4 H); 6.45 (dd, 1 H); 6.72 (d, 2 H); 7.09 (d, 1 H); 7.30-7.60 (m, 5 H); 7.73 (dd, 1 H); 8.08 (d, 1 H); 8.11-8.35 (m, 3 H); 8.53 (dd, 1H); 9.18 (dd, 1 H); 11.55 (broad s, 2 H) ppm E n g lish 31 10 l-methyl-2- [2- (4- (N-ethoxycarbonylamino) phenyl) -ethyl] -5- [N- (mexycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole 0.8 g (1.34 mmol) of l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- (methoxycarbonylmethyl) -15 qu i not 1 in-8-su 1 f on i 1 ami no] -benz imi da zo 1 is dissolved in 50 ml of tetrahydrofuran and 10 ml of water and, after the addition of 0.55 g (4.0 mmol) of potassium carbonate, is stirred for 10 minutes at room temperature. room temperature. Then they are added 0.17 g (1.6 mmol) of ethyl ester of chloroformic acid and stir for another 60 minutes at room temperature. Then, the organic phase is separated, dried and concentrated by evaporation. The residue is chromatographed on silica gel (methylene chloride / methanol = 30: 1). The "JA¿" .- * - ~ A3¿ d «% ¿3a £ &toJÍ - ~» -,. At the end, the corresponding fractions are concentrated, mixed by trituration with ether and filtered with suction. Yield: 0.41 g (49% of theory), R value: 0.57 (silica gel, dichloromethane / methanol = 9: 1) C32H32N606S (628.71) mass spectrum: (M + H) + = 629 (M + Na) + = 651 10 (M + 2H) ++ = 315 Use 32 l-methyl-2- [1- (4-amidinophenoxy) -1-methyl-ethyl] -5- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -15-benzimidazole Prepared analogously to Example 1, from 1 -me ti 1 - 2 - [1 - (4 - cia no fe nox i) - 1 -me thi 1 - ethyl] -5- [N- (ethoxycarbonylmethyl) - be nce not su 1 f on i 1 ami no] -be c imi da zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 31% of theory, C26H3? N505S (549, 7) mass spectrum (EKA): (M + H) + = 550 25 (M + Na) + = 572 ** & L £ < For example 33 l-methyl-2- [N- (4-amidinophen-11) -aminomethyl] -5-benzyloxy-benzimidazole a. l-methyl-2- [N- (4-cyanophenyl) -aminomethyl] -5-benzyloxy-benz imidazole Prepared analogously to Example la, from 2-methyl-1-amino-5-benzyl-1-oxy-an i 1 inay 4-cia no feni 1 ami noa cé ti co in phosphorus oxychloride. Yield: 11% of theoretical, melting point: > 350 ° C value R f: 0.60 (silica gel, ethyl acetate) b. l-Methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5-benzyloxy-benzimidazole Prepared analogously to Example LE, from 1-methyl ti-2 - [N - (4-cyanal) 1) - ami nome ti 1] - 5 -be nci 1 ox i -be nc imi zo zo 1 and acid c 1 orh idico / ca r bona to ammonium in ethanol. Yield: 66% of the theoretical, RF value: 0.23 (silica gel, dichloromethane / methanol = 4: 1) C23H23N50 (385.47) mass spectrum: (M + H) + = 386 (M + 2H) + + = 193, 5 XSt5¿. K., »f JÉfcwi- A» ~ AE j emplo 34 l-methyl-2- [(4-amidinopheni 1) -oxymethyl] -5- [N- (me tolocarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, from 1 -me 111-2 - [(4-cyn not in 11) -oxime 111] -5 - [N- (methoxycarbonylmethyl) -quinolin-8-sulfonamino] -benzimidazole and methanolic hydrochloric acid, methanol and ammonium carbonate. Yield: 68% of theory, CsdHse gOsS (558, 6) mass spectrum (EKA): (M + H) + = 559 (M + 2H) ++ = 280 (M + H + Na) ++ = 291 EXAMPLE 35 l-Ethoxycarbonylmethyl-2- [(4-amidinophenyl) -oxymethyl] -5- (quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 1, starting from 1-et ox i ca r bon i lme ti 1 - 2 - [(4-cyanophen-11) -oxymethyl] -5- (quinolin-8-sulfonylamino) -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate Yield: 86% of theory, C28H26N6O5S (558, 6) mass spectrum (EKA): (M + H) + = 559. (M + Na) + = 581 (M + 2H) ++ = 280 Use 36 l-methyl-2- [(4- (N-ethoxycarbonylamido) phenyl) -oxim] -5- [N- (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, a from 1 -me ti 1 - 2 - [(-amidino f eni 1) - oxime ti 1] - 5 - [N- (methoxycarbonylmethyl) -quinol? N-8-sulfon? Lamino] -benz midazole and ethyl ester of acid c 1 oroformi co. Yield: 25% of theory, C3? H30N6O7S (630.7) 15 Rf value: 0.34 (silica gel, dichloromethane / ethanol = 19: 1) mass spectrum (EKA): (M + H) + = 631 (M + Na) + = 653 (M + H + Na) ++ = 327 20 Use 37 1- (3-ethoxycarbonylpropyl) -2- [(4-amidinophenyl) -oxymethyl] -5- (quinolin- 8) -sulfonylamino) - bbenzimidazole Prepared analogously to Example 1, from 1 - (3-ethoxycarb on i lp r op 11) - 2 - [(4-cyano-phenyl) -oxymethyl] -5- (quinol-n-8-sulfonylamino) -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 63% of theory, C3oH30N5? 5S (586.7) mass spectrum (EKA): (M + H) + = 587 (M + Na) + = 609 (M + 2H) ++ = 294 Example 1 1-Hydroxycarbonylmethyl 2 - [(4-amidinophenyl) -oxymethyl] -5- (quinolin-8-sulfonylamino) -benzimidazole Prepared analogously to Example 3, starting with 1-et ox i ca r bon i lme 111) - 2 - [(4-amino di-not-phenyl) -oxymethyl] -5- (quinoline-8-sulfonylamm) -benzimidazole and sodium hydroxide solution. Yield: 97% of theory, C26H22N6O5S (530, 6) mass spectrum (EKA): (M + H) + = 531 (M + Na) + = 553 E n gle 39 ** $ - '1- (3-hydroxycarbonylpropyl) -2- [(4-amidinophenyl) -oxymethyl] -5- (quinolin-8-sulfonilamino) -benzimidazole Prepared analogously to Example 3, starting with l- (3 -ethoxycarbonylpropyl) -2- [(4-amidinophenyl) -oxymethyl] -5 ^ (quinolin-8-su 1 foni 1 ami no) -benz imi da zo 1 and soda lye. Yield: 91% of theory, C28H26N605S (558, 6) mass spectrum (EXA): M + H) = 559 M + Na) + = 581 M + 2H) + + = 280 M + H + Na) + + = 291 M + H + K) + + = 299 Use 40 l-methyl-2- [(4- (N-cyclohexyloxycarbonylamino) phenyl) -oxymethyl] -5-N- (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, starting from of 1 -me ti 1 - 2 - [(4-ami di no-phenyl-1) -ox ime ti 1] - 5 - [N- (methoxycarbonylmethyl) -quinol? n-8-sulfonylamino) -benzimidazole and ester cic 1 oh ex ico acid chloride chloroform. Performance: 44% of the theoretical, "J S" a.

C35H36N607S (684.8) mass spectrum (EKA (M + H) + = 685 (M + Na) + = 707 (M + H + Na) + '= 354 Use 41 l-methyl-2- [(3-amidinophenyl) -oxymethyl] -5-benzenesulfonyl-lamino-benzimidazole Prepared analogously to Example 1, from 1-me 111-2 - [(3-cyan of 11) -oxime 111] - 5 - (be n ce nosu 1 f on 11 ami no) -benzium zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 65% of theory, C22H2? N503S (435, 52) mass spectrum (EKA): (M + H) + = 436 (M + Na) + = 458 Example 42 l-methyl-2- [(3-amidinophen? L) -oxymethyl] -5- (quin lin -8-sulfonylamino) -benzimidazole Prepared analogously to Example le, starting from 1-me 111-2 - [(3 - cyan f eni 1) - oxime 111] - 5 - (which is 11 n - 8 - its 1 f on 11 ami) -benzyme zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 89% of theory, C25H22N603S (486.57) R value: 0.16 (silica gel, dichloromethane / ethanol = 4: 1) mass spectrum (EKA): (M + H) + = 487 (M + Na) + = 509 Example 43 l-methyl-2- [N- (4-amidinophenyl) -N-methyl-aminomethyl] -5- [N- (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 1, starting from 1 -me ti 1 - 2 - [N - (4-cyano-phen 11) -N -me-111-aminomethyl] -5- [N- (methoxycarbonylmethyl) -quinolin-8- su 1 f on i 1 ami no) -benc imi da zo 1 and methanolic hydrochloric acid, methanol and ammonium carbonate. Yield: 32% of theory, C29H29N7O4S (571, 67) Rf value: 0.28 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 572 (M + H + Na) ++ = 297.7 ! 3W ^ &f? TiS? S3 &62g: «? & Yes?. ~ ** 'a .. < «-« ^ E ju 44 L-methyl-2- [N- (4- (Neocarbonylamidoino) -phenyl) -aminomethyl] -5- [N- (me-oxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, starting from l-methyl-2- [N- (4-amidinofenyl) -aminomethyl] -5- [N- (methoxycarbonylmethyl) -quinolin-8- su 1 f on i 1 ami no] - be nc imi da z ol and ethyl ester of acid c 1 orof órmi co. 0 Yield: 71% of theory, C3iH3? N706S (629.70) R value: 0.62 (silica gel, dichloromethane / methanol = 9: 1) mass spectrum (EKA): (M + H) + = 630 15 (M + H + Na) ++ = 326.6 (M + 2H) ++ = 315.6 E g 45 l-methyl-2- [N- (4- (N-cyclohexy lo i carboni 1 amidi-0 no) phenyl) -aminomethyl] -5- [N- (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, starting from 1-methyl ti-2 - [N - (4-ami di no f in i 1) -aminomethyl] -5- [N- (methoxycarbonylmethyl) -quinolin-8- sulphide lamino] -benzimide zol and ester c i c 1 oh e x i 11 c o of acid c 1 o r or f ormi c. Yield: 59% of theory, C35H37N7O6S (683, 79) R value: 0.66 (silica gel, dichloromethane / methanol = 9: 1) mass spectrum (EKA): (M + H) + = 684 (M + H + Na) ++ = 353, 7 (M + 2H) ++ = 342, 6 10 E xample 46 2- [2- (4-amidinophenyl) -ethyl] -6- [N- (motoxicarbonylmethyl ) -quinolin-8-sulfonylamino] -benzoxazole a. 2- [(4-aminocarbonylphenyl) -ethyl] -6-nitro-15-benzoxazole 2.64 g (15 mmol) of 4- c 1 to non-phenyl-1-pr op 1-ony and 2.31 g (15 mmol) of 2-amino-5-n-11 -three-1 are stirred for three hours at 130 ° C in 50 ml of po-1-acid under a nitrogen atmosphere. It is then poured into water, the precipitate is filtered off with suction, dissolved in methylene chloride / methanol and filtered on activated carbon. The filtrate is concentrated by evaporation in a vacuum, the crystalline residue is filtered off with suction and dried.

~ * «* I» " • '-'iM &' ji & H ', Jfe * 33_Sfífe' t > »£ * Ü» »ta * í * ÍMI Yield: 3.0 g (64% of theory), R value: 0.43 (silica gel, dichloromethane / methanol = 19: 1) b. 2- [2- (4-C? Anophenyl) -ethyl] -6-n? Tro-benzoxazole 2.0 g (6.43 mmol) of 2- [(4-aminocarbonylphenyl) -ethyl] -6-n? tro-benzoxazole is heated for 60 minutes at reflux in 50 ml of phosphorus oxychloride. Then, it is distilled off in vacuo, the residue is mixed with ice / water, the crystalline product is filtered off with suction, washed and dried. The residue is chromatographed on silica gel (methylene chloride and no a 1 = 99.5: 0.5). The corresponding fractions are concentrated, mixed by triturating with ether, filtered with suction and dried. Yield: 1.25 g (66.5% of theory), Rf value: 0.40 (silica gel; dichloromethane / ethanol = 50: 1) c. 2- [2- (4-C? Anophenyl) -ethyl] -6-am-no-benzoxazole Prepared analogously to Example Ib, starting from 2 - [2 - (4-cyanophen-11) -e 111] -6 - n 11 ro - benzoxazole and palladium on active carbon in methanol / methylene chloride. Performance: 100% theoretical, Rf value =: 0.59 (silica gel, dichloromethane / ethanol = 19: 1) d. 2 - [2- (4-cyano-phenyl) -ethyl] -6- (N-quinolin-8-sulfonylamino) -benzoxazole Prepared analogously to Example le, starting from 2 - [2 - (4-cyano-pheni-1) - eti 1] - 6 - ami non-benzoxazole and acid chloride 8 - qu i no 1 insu 1 f ón i co in pyridine. Yield: 57% of theory, Rf value: 0.61 (silica gel, dichloromethane / ethanol = 19: 1) e. 2 - [2- (4-cyanophenyl) -ethyl] -6- [N- (methoxycarbonylmethyl) -guiñol in-8-sulfonylamino] -benzoxazole Prepared analogously to Example Id from 2 - [2 - (4-cyano) f in i 1) - eti 1] - 6 - [N - qu i no 1 in - 8 - su 1 f on i 1 ami no] - b in z oxa zo 1, bromoacetic acid methyl ester and potassium carbonate in acetone Yield: 88.5% of the theoretical, Rf value: 0.30 (silica gel, ethyl ether or ethyl acetate = 1: 1) f. 2 - [2 - (4-Amidino-enyl) -ethyl] -6- [N- (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzoxazole HjS & r Prepared analogously to Example le, starting from 2 - [2 - (4-cia no fen 11) -e 111] - 6 - [N- (methoxycarbonylmethyl) -qu? Nol? N-8-sulfon? Lam ? no] - benzoxazole and ammonium chloride acid ammonium in methanol. Yield: 82% of theory, R value: 0.32 (silica gel, dichloromethane / ethanol = 4: 1) C28H25N5O5S (543.61) 10 mass spectrum: (M + H) + = 544 (M + 2H ) ++ = 272.7 (M + H + Na) ++ = 283.7 Use 47 15 2 - [2 - (4-amidinophenyl) -ethyl] -6- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzoxazole Prepared analogously to Example 3, from 2- [2- (4-am? D? Nofen? L) -et? L] -6- [N- (methoxycarbonylmethyl) -qu? Nolm-8-sulfon? Lam] -20-benzoxazole and soda lye. Yield: 64% of theory, C27H23N5? 5S (529.59) R value: 0.11 (silica gel, dichloromethane / methanol = 4: 1) 25 mass spectrum (EKA): (M + H) + = 530 M + Na) + = 552 M + 2H) + + = 265.7 M + H + Na) + + = 276.7 2M + 3Na = 376 EXAMPLE 48 2- [(4-Amidinophenyl) -oxymethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -lH-benzimidazole Prepared analogously to Example le, starting from 2- [(4-cyanophen ?) -ox? met? l] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -1H-benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 79% of theory, 15 C28H26N6? 5S (558, 63) R value: 0.26 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 559 (M + 2H) ++ = 280 20 (M + H + Na) ++ = 291 Example 49 l-methyl-2- [N- (4-amidinobene i 1) -aminomethyl] -5 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -25-benzimidazole -i ¿¿¿w.i .. l ^ 4 ....- ^ s & a ^ S »¡. ~. , ... «MU ...,.« ... - ^ - ». , - -á -? ^ -M ¿^ ^ it S £ ^ z & it. ^^, .jeJ &SSi Prepared analogously to Example le, from 1 -me 111 - 2 - [N- ( 4-cia nobe nc 11) - ami nome 111] -5- [N- (ethoxycarbonyl-methyl) -qu? Nol? N-8-sulphon? L-ami no] -benz bound zol and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 82% of theory, C3oH3iN704S (585.70) R value: 0.30 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 586 (M + 2H) ++ = 293.7 E 3 emplo 50 l-methyl-2- [N- (4-amidinobenzyl) -aminomethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, from 1 -me 111 - 2 - [N - (4-amyl di nobenc 1) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -qu? nol? n-8-su 1 f on i 1 ami no] -ben c I'm in zo 1 and soda lye. Yield: 94% of theory, C28H27N7O4S (557, 64) mass spectrum (EKA): (M + H) + = 558 (M + Na) + = 580 .-, k- &!?? .. ..- .. ,, A¡¡ ^ E j emplo 51 2 - [2 - (4-amidinophenyl) -ethyl] -5- [ N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzoxazole a. 2- [2- (4-Cyanophenyl) -ethyl] -5-nitro-benzoxazole 5 Prepared analogously to Example 46b, starting from 2 - [(4-amino-car bon-11-phe-11) -e 111] -5-n 11 ro - benzoxazole and phosphorus oxychloride. Yield: 36% of theory, value R f: 0.90 (silica gel; dichloromethane / methanol 10 = 19: 1) b. 2- [2- (4-C? Anophenyl) -ethyl] -5-amino-benzoxazole Prepared analogously to Example Ib, starting from 2 - [2 - (4-cynophen-11) -e 111] - 5 - n 11-benzoxazole and palladium on active carbon in methanol / methylene chloride. Yield: 100% of theory, R value: 0.36 (silica gel, dichloromethane / methanol = 19: 1) c. 2- [2- (4-cyanophenyl) -ethyl] -5- (N-quino-lin-8-sulphonylamino) -benzoxazole Prepared analogously to Example le, from 2 - [2 - (4-cyanophen-11) - and 111] -5-amino-benzoxazole and acid chloride 8-qui not 11 nsu 1 f ón i co in pyridine. 25 Performance: 27% of the theoretical, t Rf value: 0.70 (silica gel, dichloromethane / methanol = 19: 1) d. 2- [2- (4-cyano-phenyl) -etill-5- [(N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzoxazole Prepared analogously to Example Id, from 2 - [2 - (4-anophenol eni 1) -eti 1] - 5 - (N-quino 1 in-8 - su 1 f on i 1 ami no) -ben z oxa zo 1, ethyl ester of bromoacetic acid and potassium carbonate in acetone Yield: 100 % of theory, value R f: 0.78 (silica gel, dichloromethane / methanol = 50: 1) e 2- [2- (4-amidinophenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin - 8 -silynylamino] -benzoxazole Prepared analogously to Example le, starting from 2 - [2 - (4 - cyano f in i 1) - eti 1] - 5 - [N - (et oxycarbonylmethyl) - quinolin-8-sulfonamino] -benzoxazole and acidic ammonium chloride in ethanol yield: 98% of theory, R value: 0.44 (silica gel, dichloromethane / methanol = 5: 1) C29H27 5O5S (557, 63) mass spectrum (EKA): (M + H) + = 558 (M + 2H) ++ = 279.7 (M + H + Na) ++ = 290, 7 Example 52 2- [2- (4-amidinophenyl) -ethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzoxazole Prepared analogously to Example 3, from 2- [2- ( 4-amidinophenyl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzoxazole and sodium hydroxide solution. Yield: 77% of theory, C27H23N5O5S (529.58) mass spectrum (EKA M + H) + = 530 M + Na) + = 552 M + H + Na) ++ = 276.6; M-H + 2Na ) + = 574; M + 2Na) ++ = 287.6 The solution was 53 L-methyl-2- [2- (2-amidinothiophen-5-yl) -ethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, from 1 -me ti 1 - 2 - [2 - (2-cy without thiof en-5-i 1) - eti 1] - 5- [N- (ethoxycarbonylmethyl) -quinol? n-8- su 1 foi 1 ami no] - be nc imi da zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Performance: 42, of the theoretician, -.--. "«: • »" ,, - »¿8Wft¿.,. ^, -.g-aS ^ Jed ^ á ^^ ga ^^ - ^^^ a ^ é ^^ »^: .. '.,' - ^ a¡ bb? B.

C28H28 6? 4S2 (576, 71) R f value: 0.36 (silica gel; dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 577 (M + 2H) ++ = 289 (M + H + Na) ++ = 300 E 3 emplo 54 l-met? L-2- [2- (2-a idinotiof en-5-? L) -ethyl] -5- [N- (hydroxycarbonylmethyl) quinolin-8-sulfoni lamino] -benzimidazole Prepared analogously to Example 3, from 1 -me 111-2 - [2 - (2-amidino 11 of en-5-l, 11) -ethyl] -5- [N- (ethoxycarbonyl-methyl) -qu? nol? n- 8- su 1 f on 11 ami no - be nc ími da zo 1 and lye of soda. Yield: 98% of theory, C26H24N604S2 (548, 66) mass spectrum (EKA): (M + H) + = 549 (M + Na) + = 571 E -j 55 l-met? L-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- (etoxycarbonylmethyl) -benzenesulfanthylamino] -benzimidazole Prepared analogously to Example LE, starting from 1-methyl ti 2 - [N - (4-cyanof in i 1) - ami nome ti 1] - 5- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole and acid ethanolic hydrochloride, ethanol and ammonium carbonate. Yield: 50% of theory, C26H28 6? 4S (520.62) R value: 0.34 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 521 Use 56 l-methyl-2- [N- (4-aminophenyl) -aminomethyl] -5- [N- (hydroxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole Prepared analogously to Example 3, starting from 1-methyl-1 2 - [N - (4-amidino f eni 1) - aminomethyl] -5- [N- (ethoxycarbonylmethyl) -benzene sulphon i ami no] -be nc imi da zo 1 and soda lye. Yield: 97% of theory, C2.H24N6O4S (492.56) mass spectrum (EKA): (M + H) + = 493 (M + Na) + = 515 (M-H + 2Na) + = 537 (M + 2Na) ++ = 269 Example 57 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- (N-benzyl-N-methylamino) -benzimidazole Prepared analogously to Example le, starting from 1-me 111 - 2 - [N- (4 - cia no fen 11) - ami n ome 111] - 5 - (- be nc 11 - -me 111 ami no) -be nc ím id zo 1 and ethanolic hydrochloric acid, ethanol and carbonate of ammon io. Yield: 85% of theory, 10 C2 H26N6 (398.51) R value: 0.27 (silica gel; dichloromethane / methanol = 4: 1) mass spectrum (EKA): (M + H) + = 399 (M + 2H) ++ = 200 15 E jmplo 58 l-methyl-2- [N- (4-amidinophenyl) ) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -n-bu-tanosulfonylamide] - benzyl zol Prepared analogously to Example LE, from 1 -me 111-2 - [N - (4-cynophen 11) - ami nome 111] - 5- [N- (ethoxycarbonylmethyl) -n-butanesulfonylammo] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. 25 Performance: 71% of the theoretical, C24H32N604S (500, 63) Rf value: 0.32 (silica gel; dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 501 M + H + Na 262 Example 59 l-Methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -benzoylamino] -benzimidazole Prepared analogously to Example le, from 1-methyl-1 - 2 - [N - (4 - cia no feni 1) - ami nome ti 1] -5- [N- (ethoxycarbonylmethyl) -benzoylamino] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 56% of theory, C27H28N603 (484.57) R value: 0.34 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 485 (M + H + Na) ++ = 254 Example 60 l-Methyl-2-tN- (4-amidinophenyl) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -pyridin-2-yl-carbonylamino] benzimidazole Prepared analogously to Example le, starting from 1-me ti 1 - 2 - [N- (4-cyano f in i 1) - ami nome ti 1] - 5- [N- (ethoxycarbonylmethyl) -pyridin-2-ylca rboni 1 amino] -benz imide zol and acid ethanolic hydrochloride, ethanol and ammonium carbonate. Yield: 64% of theory, Rf value: 0.31 (silica gel, dichloromethane / methanol = 5: 1) mass spectrum (EKA): (M + H) + = 486 (M + H + Na) ++ 254.7 Example 61 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- (hydroxycarbonyl-yl) -n-bu-tannesulfonylamino] -benzimidazole. Prepared analogously to Example 3, starting from 1-methyl ti 2 - [N- (4-ami diene f eni 1) -aminomethyl] -5- [N- (ethoxycarbonyl-methyl) - n - bu tanosu 1 f on i 1 ami no] -be nc imi da zo 1 and lye of soda. Yield: 98% of theory, C22H28N6O4S (472.57) mass spectrum (EKA): (M + H) + = 473 (M + Na) + = 495 (M + 2Na) ++ = 259 The reaction was carried out using 62 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- (hydr oxy carbome ti 1) -ben zoi lamino] -benzimidazole. Prepared analogously to Example 3, starting from of 1 -me 1 1 - 2 - [N - (4-ami di no f in 11) -aminomethyl] -5- [N- (ethoxycarbonyl-methyl) -benzo 11 ami no] -b ene z and z soda lye. Yield: 69% of theory, C25H24N603 (456.51) mass spectrum (EKA): (M + H) + = 457 (M + 2Na) ++ = 251 (M + Na) + = 479 Use 63 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- (hydroxycarbonylmethyl) -pyr idin-2-yl-carbonylamino] -benzimidazole Prepared analogously to Example 3, starting from of 1 -me 111-2- [N - (4-ami di no-phen-11) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -p? r? d? n-2-? lc ar bon 11 ami no ] - benc imi da zo 1 and soda lye. Yield: 96% of theory, C2 H23 703 (457.50) mass spectrum (EKA): (M + H) + = 458 (M + Na) + = 480 e > 'I83íM £? R¿, S < rf¿3flte. ^ aMfefe ^ »M + H + Na = 240.6 M + 2Na = 251.6 EXAMPLE 64 l-Methyl-2- [(4-amidinophenyl) -oxymethyl] -5- (N-cyclohexyl-me tanosulfonylamino) -benzimidazole Prepared analogously to Example le, from 1-methyl 111 - 2 - [(4 - ci anus fen 11) -oxime 111] -5- (N-cyclohexyl-methanesulfonyl) -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 79% of theory, C23H29N503S (455.59) R value: 0.21 (silica gel, dichloromethane / ethanol = 4: 1) mass spectrum (EKA): (M + H) + = 456 (M + Na) + = 478 Example 65 l-methyl-2- [(4-amidinophenyl) -oxymethyl] -6- [N- (ethoxycarbonylmethyl) -benzenesulfoni-lamino-benzimidazole Prepared analogously to Example le, starting from l-met? L-2 [(4-C? Anophen? L) -oxymethyl] -6- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzimidazole and hydrochloric acid, ethanolic, ethanol and ammonium carbonate. Yield: 45% of theory, C26H27N5O5S (521.6) mass spectrum (EKA): (M + H) + = 522 (M + H + Na) ++ = 272.7 Use 66 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- (N-cyclopentylmethanesulfonylamino) -benzimidazole Prepared analogously to Example le, starting from 1 -me 111-2 - [N- (4 - c 1 ano f eni 1) - ami nome 111] -5- (N-cyclopentyl-methanesulfonyl) -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 89% of theory, C22H28N602S (440, 58) Rf value: 0.17 (silica gel, dichloromethane / ethanol = 4: 1) mass spectrum (EKA): (M + H) + = 441 (M + Na) + = 463 E j psa 67 l-methyl-2- [(4-amidinophenyl) -oxymethyl-5- [ N- (N '- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole »9 * a¡» -.

Prepared analogously to Example le, starting from l-methyl-2- [(4-cyanophenyl) -oxymethyl] -5- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -qu i not 1 in-8-su 1 f on i 1 ami no] -b ene imi da zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 49% of theory, C3iH3? N706S (629.7) mass spectrum (EKA): (M + H) + = 630 (M + 2H) ++ = 315.7 M + H + Na = 326.7 Example 68 l-methyl-2- [(4-amidinophenyl) -oxymethyl] -5- [N- (N '- (hydroxycarbonylmethyl) -aminocarbonylmethyl) -guinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, from 1 -me ti 1 -2 - [(4 -ami di no f eni 1) -oxime ti 1] - 5 - [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -quo 1 in-8 - his 1 f oni 1 ami no] -be nc imi da zo 1 and soda lye. Yield: 79% of theory, C29H27N706S (601.7) mass spectrum (EKA): (M + H) + = 602 (M + Na) + = 624 ^ ZS ^. . ^? ^ ?. »-, J & amp; & & J8 .- ^ ----.« -.-. ¿-? Í-SM + 2H) ++ = 301,7 (M + H + Na) + + = 312.7 Example 69 5 l-methyl-2- [(4-amidinophenyl) -oxymethyl] -5- (N- (2-ethoxycarbonyl-ethyl) -qunolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, from 1 -me 111-2- [(4-cyanophenol) -oxime 111] -5- (N-10 (2-ethoxycarbonyl-ethyl) -quinol-n-8-sulfon Lamino] - benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate Yield: 62% of the theoretical, C3oH3oN605S (586.7) 15 mass spectrum (EKA): (M + H) + = 587 (M + 2H) ++ = 294 (M + H + Na) ++ = 305 E xample 70 20 2 - [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -1, 2, 3, 4- tetrahydroquinone 1 in-8-sulfonylamino ] -benzofuran Prepared analogously to Example le, starting from 2 - [N - (4-cyano f in 11) - ami nome 111] - 3 -me 111-25 - [N- (ethoxycarbonylmethyl) -1, 2, 3, 4-tetrahydro- '' .. qumolm-8-sulfon? Lam? No] -benzofuran (prepared analogously to Example 107) and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 55% of theory, C3oH33N505S (575.70) R value: 0.25 (silica gel, dichloromethane / ethanol = 4: 1) mass spectrum (EKA): (M + H) + = 576 (M + H + Na) ++ = 299.7 E xemplo 71 2- [N- (4-amidinophenyl) -aminomethyl] -3-meth? L-6- [N- (hydroxycarbonylmethyl) -1, 2, 3, 4 -tetrahydro -quinolin-8-sulfonylamino] -benzofuran Prepared analogously to Example 3, starting from 2 - [N- (4-amide f in 11) -ammome 111] -3-meth? l-6- [N- (ethoxycarbonylmethyl) - 1, 2, 3, 4-tetrahydrochlor 11 n - 8 - su 1 f on 11 ami no] -ben zofur ano and soda lye. Yield: 94% of theory, C28H29N5O5S (547, 65) mass spectrum (EKA): (M + H) + = 548 (M + Na) + = 570 (M + 2Na) ++ = 296.7 Example 72 2- [2- (amidinofentl) -ethyl] -4-methyl-7- [N-e-toxicarbonylmethyl) -quinolin-8-sulfonylamino] -quinol ina Prepared analogously to Example le, from 2 - [2 - (4 - cia no f in i 1) - eti 1] - 4 - me thi 1 - 7 - [N - (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline (prepared analogously to Example 102) and acid ethanolic hydrochloric acid, ethanol and carbonate amon i o. Yield: 50% of theory, C32H31N504S (581.6) R value: 0.18 (silica gel, dichloromethane / ethanol = 4: 1) 15 mass spectrum (EKA): (M + H) + = 582 ( M + 2H) ++ = 291.7 (M + H + Na) ++ = 302.7 Use 73 20 2- [2- (4-amidinophenyl) -ethyl] -4-methyl-7- [N- (hydroxycarbonylmethyl] -quinol in- 8-sulfonylamino] -quinoline Prepared analogously to Example 3, a starting from 2 - [2 - (4-amidi not f eni 1) - eti 1] - 4 -me 111 - 7 - [N - (ethoxycarbonylmethyl) -quinolin-sulfonylamino] quinoline and soda lye. Yield: 38% of theory, C30H27N5? 4S (553.60) mass spectrum (EKA): (M + H) 554 (M + Na '= 576 (M + 2H + = 277.7 Example 74 1-methyl-1 - 2 - [2 - (4-amidinophen-1) -ethyl] -5- (N-quinoline-8-sulfonylamino) -indole hydrochloride a. (E) -4- [2- (1-methyl-indole-2-yl) ethenyl] benzonitrile 3.2S g (approximately 67 mmol) of a suspension of 50% sodium hydride in mineral oil is heated for 45 minutes up to 80 ° C in 70 ml of d ime ti 1 s ul f ox i do. After cooling to room temperature, an additional 140 ml of dimethyl ether and 1% of the mixture are added, and in portions, 18.2 g (44 mmol) of 4-cyanobenzene bromide 11 rifon 11 phosphonium. it is stirred for 90 minutes at room temperature. Then, 7.0 g (44 mmol) of 1-methyl-1-yl-1-carbale hydroxide (44%) were added dropwise (J. Org. Chem. 5, 2, 104 (1987). )) in 70 ml of 1-methyl ester and allowed to stir for 30 minutes at room temperature, for 20 minutes at 40 ° C and for 16 hours again at room temperature. The crude product is diluted with 200 ml of ethyl acetate, washed with 400 ml of 14% sodium chloride solution and the aqueous phase is extracted with 2 x 300 ml of ethyl acetate. The combined organic phases are dried with sodium sulphate, the solvent is distilled off in vacuo and the crude product is purified by flash chromatography (silica gel, petroleum ether, ethyl acetate = 9). :1) . Yield: 2.4 g (21% of theory), R value: O, 52 (silica gel, ethyl acetate / petroleum ether = 3: 7) b.4- [2- (l-methyl -indol-2-yl) ethyl] benzonitrile 2.3 g (8.9 mmol) of (E) -4 - [2 - (1-methyl) 1 -i do 1 - 2 - i 1) eteni 1] be The mixture is dissolved in 150 ml of methanol and 50 ml of methylene chloride and hydrogenated with 0.20 g of 10% palladium on carbon at a hydrogen pressure of 3 bar. vacuum and the white residue obtained is washed with a little diethyl ether and acetone Yield: 1.8 g (78% of theory), R value: 0.50 (silica gel, ethyl acetate / petroleum ether = 3 7) a - * - i ^ -a &-? ^ * ^ k ^ c.4- [2- (l-Methyl-5-nitro-indol-2-yl) ethyl] benzonitrile In the space of 2 hours dissolve 1.7 g (6.53 mmol) of 4 - [2 - (1-methyl) 1-i ndol-2 -i 1) eti 1] be nz on itri 1 or in 20 ml of concentrated sulfuric acid at 15 ° C and then cooled to 2 ° C. Then, 0.66 g (6.53 mmol) of potassium nitrate are added in portions (increase in temperature to about 10 ° C). Stirring is continued for 30 minutes at 2-5 ° C and then poured on ice. The resulting yellowish precipitate is filtered off and washed with water. Yield: 2.0 g (100% of theory), Rf value: 0.24 (silica gel, ethyl acetate / petroleum ether = 3: 7) d.4- [2- (l-methyl-5 - amino-indol-2-yl) ethyl] benzonitrile 2.0 g (6.55 mmol) of 4 - [2 - (1-methyl-1 -5-nitr o-indol-2-y1) eti 1] benzonitri 1 or are dissolved in 200 ml of methanol and 200 ml of methylene chloride and hydrogenated with 0.20 g of 10% palladium on carbon at a hydrogen pressure of 3 bar. Next, the solvent is separated by S &tissk distillation under vacuum and the residue is washed with a little methanol. Yield: 1.67 g (93% of theory) of an amorphous solid from beige to yellow, R value: 0.38 (silica gel, methylene chloride 1 ene / e t a nol = 19: 1) e. l-methyl-2- [2- (4-cyanophenyl) -ethyl] -5- (N-quino lin -8-sulfonylamino) -indole A solution of 1.57 g (5.7 mmol) of 4- [ 2- (1-me 111-5-ammo-i ndol-2-11) -e 111] ben z on 11 ri and 1.42 g (6.2 mmol) of qumol? N-8- acid chloride Sulfonic acid in 30 ml of pipdma is stirred for 1 hour at room temperature. The solvent is then removed in vacuo, the residue is taken up in 50 ml of methylene chloride, washed with 50 ml of saturated sodium hydrogen carbonate solution, dried with sodium sulfate and purified by flash chromatography. (silica gel, me 111 chloride and no / eta no 1 = 99: 1). Yield: 0.77 g (49% of theory), R value f: 0.39 (silica gel, me 111 chloride and no / e t a n 1 = 50: 1) F. Hydrochloride of 1 -me t i 1 - 2 - [2 - (4-amidinofeni 1) -ethyl] -5- (N-quinolin-8-sulfoni l m no) - indole - ^ 4SL & amp; amp; *. L ** > ^. ^. ^ '^ ^ S ^^ b ^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ - [2 - (4 - cia no feni 1) - eti 1] - 5 - (N -qu ino 1 in - 8 - su 1 f on i 1 ami no) - step 1 and ethanolic hydrochloric acid, ethanol and carbonate of ammonium. Yield: 39% of theory, C2 H25N502S (483, 6) Rf value: 0.29 (silica gel, me 111 ene / eta chloride no 1 = 4: 1 + some drops of acetic acid) mass spectrum (SKA ): (M + H) + = 484 Use 75 l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5-fN- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -indole Prepared analogously to Example le, starting from 1 -me ti 1 - 2 - [2 - (4 - cia no f in i 1) - and 111] - 5 - [N - (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -i ndo 1 and ethanolic hydrochloric acid, ethanol and carbonate of ammonium. Yield: 53% of theory, C31H3? N504S (569, 69) R value: 0.19 (silica gel, dichloromethane / ethanol = 4: 1) mass spectrum (EKA 'M + H) + = 570 M + 2H 235.7 (M + H + Na 296.6 Use 76 5 l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5-fN- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino) -indole Prepared analogously to Example 3, starting from 1 - me ti 1 - 2 - [2 - (4-amidi no f eni 1) -eti 1] - 5 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -indole 10 and soda lye. Yield: 96% of theory, C29H27 5O4S (541.63) mass spectrum (EKA): (M + H) + = 542 (M + Na) + = 564 15 (M + 2H) ++ = 271.7 ( MH) "= 540 Example 77 l-Methyl-2- (4-amidinobenzylamino) -5- (quinoline-8-20-sulphonylamino) -benzimidazole Prepared analogously to Example 1, from 1-methyl ti 2 - (4 - cian ob enci 1 ami no) - 5 - (qu i no 1 in - 8 - su 1 f on i 1 ami) -benc imi da zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate.

Performance: 85% of the theoretical, C25H23N7O2S (485, 57) Rf value: 0.40 (silica gel, e 111 o / ethane 1 / ammon 1 aco = 50: 45: 5) mass spectrum (EKA): (M + H) + = 486 (M + H + Na) ++ = 254.7 Example 78 l-methyl-2- (4-midinobenzylthio) -5- (quinol? N-8-sulfonylamino) -benzimidazole Prepared analogously to Example le, starting from 1-me 111-2 - (4-cyanob) enc 1111 o) - 5 - (qu 1 not 11 n-8 - su 1 f on 11 ami no) -be nc ia 1 z and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 69% of theory, C25H22N6O2S2 (502, 62) R value: 0.45 (silica gel, e 111 o / eta acetate 1 / ammon 1 to co = 50: 45: 5) mass spectrum ( EKA): (M + H) + = 503 (M + Na) ++ = 525 EXAMPLE 79 2 - [(4-Amidinophenyl) methyl thio] -5- (N-qu i no lin-8-sulfoni lamino) -benzothiazole hydrochloride a. 2 ~ \ (4-cyanophenyl) methylthio] -6-nitro-benzathiazole . ^ - ». Kt-eaBSI uJfo: «- ** - * > - To a solution based on 1.5 g (7.06 mmol) of 2-me rc ap to -6-nitroben-zothiazo 1 0.37 g (7.7 mmol) of sodium hydride are added in portions. (50% in mineral oil) and then stirred for 30 minutes at 50 ° C. Then 1.45 g (7.4 mmol) of 4-b r omome t i lbe n z on i t r i 1 o is added dropwise and the mixture is stirred at 50 ° C. for a further hour. The reaction mixture is combined with 30 ml of ethyl acetate and 70 ml of 14% sodium chloride solution, after which precipitates a large part of the compound of the statement in the form of a beige precipitate. The organic phase is concentrated in vacuo, the precipitated crude product is triturated with diethyl ether and the aqueous phase is separated. The solid obtained meets with the beige precipitate. Yield: 1.3 g (56% of theory), Rf value: 0.52 (silica gel, ethyl acetate / petroleum ether = 3: 7) b. 2 - \ (4-cyanophenyl) -methylthio] -6-amino-benzothiazole 20 A suspension of 1.0 g (3.05 mmol) of 2- [(4-cyanophenyl) methylthio] -6-nitro-benzathiazole heat to boiling in 60 ml of acetic acid until a clear solution results. Next, 2.0 g (36 g) are added in two portions mmol) of iron powder and boiled for 5 hours. reflux minutes. It is filtered and the filtrate is concentrated in vacuo. The crude product is made alkaline by the addition of concentrated ammonia and purified by flash chromatography (silica gel, ethyl acetate / petroleum ether = 20:80 to 35:65). Yield: 0.22 g (24% of theory) of a beige amorphous solid, R value: 0.44 (silica gel, ethyl acetate / petroleum ether = 4: 6) c. 2- [(4-cyanophenyl) methylthio] -6- (N-quinolin-8-sulfonylamino) -benzothiazole A mixture based on 2.3 g (7.74 mmol) of 2 - . 2 - [(4-c? Anophen? L) methotthyl] -6-ammo-benzoth? Azole and 15 1.85 g (8.1 mmol) of cholino-8-sulfonic acid chloride stir for 2 hours at room temperature in 30 ml of pyridine. At room temperature, the solvent is distilled off in vacuo and the crude product is purified by flash chromatography (silica gel, methylene chloride / ethanol = 99: 1). Yield: 3.15 g (83% of theory) melting point: 106-108 ° C R value: 0.33 (silica gel; ethyl acetate / petroleum ether = 4: 6) X & Ma ^ r ^^^^^^ b? I ^ & i ^ k! ^ h? ^) ^ i ^ X'í £ í. d. 2 - [(4-Amidinopheni 1) methyl thio] -5- (N-quinolin-8-sulfonyl-lamino) -benzothiazole hydrochloride Prepared analogously to Example 1, from 2 - [(4-cyano-fe-ni-1) ) me ti 11 io] - 6 - (N - qu i no 1 in - 8 - su 1 f on i 1 ami no) - ben zotiazo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 91% of theory, C24H? 9N502S, (505.64) R value: 0.34 (silica gel; me t i 1 e no / e t a 1 = 4: 1 + some drops of acetic acid) Mass spectrum (SKA): (M + H) + = 506 EXAMPLE 80 15 Me z cy based on 2- (4-amidinophen-1) -ethyl] -1-methyl-6 - (quinoline-8-sulfonyl-1-amino) -imidazo hydrochloride. b] pyridine and 2- [2- (4-amidinophenyl) -ethyl] -3-methyl-6- (quinolin-8-sulfoni-lamino) -imidazo [4, 5-b] pyridine hydrochloride 20 a. 3 - (4-Cyanophenyl) -N- (3,5-di-tro-pyrid-2-yl) -propionic acid amide A solution based on 1.8 g (10 mmol) of 2-ami no-3, 5-din 11 ro -pyridine, 2.4 g (12 mmol) of 3- (cyanophenyl) propionyl chloride, 2.0 ml of triethylamine and 0.1 g of dimethylamine in 35 ml of Chlorobenzene is heated to 150 ° C for 3 hours. The solvent is then removed by distillation in vacuo and the residue is taken up in 50 ml of ethyl acetate. It is washed with 50 ml of water and 50 ml of saturated sodium chloride solution, dried with sodium sulfate and, after distilling off the solvent, purified by flash chromatography (silica gel, methylene chloride). . Yield: 2.2 g (65% of theory), Rf value: 0.67 (silica gel; me t i 1 e t i 1 c e t ona / xi 1 eno = 1: 1) b. 2 - [2 - (4-Cyanophenyl) ethyl] -6-phthalimido-imidazo [4, 5-b] pyridine A suspension based on 2.1 g (6.15 mmol) of 3 - ( 4 - ci an of in i 1) -N - (3, 5 -di nitro-pyrid-2-i 1) -pr op i ion icoy 0.50 g of 10% palladium on carbon in 50 ml of acetic acid glacial is reacted at 80 ° C at a hydrogen pressure of 3 bar. After cooling, the catalyst is filtered off, 1.1 g (7.4 mmol) of phthalic acid anhydride are added and the mixture is heated to boiling for 1 hour. The solvent is distilled off in vacuo and the crude product is taken up in 50 ml of methylene chloride, washed twice with saturated sodium hydrogen carbonate solution and purified by flash chromatography (silica gel; ileno / e tanol = 40: 1 to 19: 1). Yield: 0.95 g (41% of theory), Rf value: 0.50 (silica gel; acetate e t i 1 o / e t a no 1 / amo - ni a co = 90: 10: 1) c. Mixture of isomers based on 2 - \ 2 - (4-cyano-enyl) -ethyl] -l-methyl-6-f-talimido-imidazo [4, 5-b] pyridine and 2 - [2- (4-cyano-phenyl) -ethyl] -3-methyl-6-f amido-imidazo [4, 5-b] pyridine A mixture based on 0.80 g (2.0 mmol) of 2- [2- (4-cyano-phenyl) -ethyl] -6-phthalamido-imidazo [4, 5 - b) pyridine, 0.25 g (2.2 mmol) of potassium tert-butylate and 0.32 g (2.2 mmol) of methyl iodide are stirred in 10 ml of dimethylsulfox. i do for 1 hour at room temperature. It is then poured onto ice / water, extracted with 100 ml of ethyl acetate, dried over sodium sulphate and the solvent is distilled off in vacuo. Yield: 0.80 g (98% of theory), R value f: 0.56 (silica gel; acetate of t i 1 o / e t a n 1 / amo - n i a c o = 90: 10: 1) d. Mix of isomers based on 2- [2- (4-cyanophen-1) -ethyl] -l-methyl-6-imidazo [4,5-b] pyridine and 3iüfc > , & & St. «*. 2- [2- (4-cyanophenyl) -ethyl] -3-methyl-6-imidazo [4, 5-b] pyridine 0.80 g (2.0 mmol) of the mixture of isomers based on 2- [2- (4-c? Anophen? L) -et? L] -l-met? L-6- 5 phta 1 iodide of zo [4, 5-b] pi ri di na and 2- [ 2- (4-cyanophenyl) -ethyl] -3-met? L-6-? M? Dazo [4, 5-b] pipdine are stirred in 5 ml of 40% aqueous me 111 amine solution and 20 ml of ethanol for 1 hour at 40-60 ° C. Then, the solvent is separated by After vacuum distillation, the crude product is taken up in 40 ml of ethyl acetate / ethanol (9: 1) and, subsequently, washed with water and saturated sodium chloride solution. After removing the solvent in vacuo, the residue is collected in The reaction is carried out, and analogously to Example 79c, with 0.41 g (1.8 mmol) of the acid chloride qui no 11 n-8-suphonic acid, is processed and purified by chromatography. rapid resolution (silica gel, methylene chloride to chloride me 111 e no / e t a no 1 = 19: 1). Yield: 0.50 g (54% of theory), Rf value: 0.63 + 0.50 (silica gel, e 111 e / e t a no 1 / ammon a co = 90: 10: 1) «- &« - .. i.-jiAsar J e. Mixture of isomers based on 2- [2- (4-amidinophenyl) -ethyl] -l-methyl-6- (quinolin-8-sulfonylamino) imidazo [4, 5-b] pyridine hydrochloride and hydrochloride of 2 - 2 - (4-amidinopheni 1) -e ti 1] - 3 -me thi -6- (quinolin-8-sulfonylamino) -imidazo [4,5-b] -pyridine Prepared analogously to Example le, from mixture of isomers based on 2- [2- (4-cyanophenyl) -ethyl] -l-methyl-6- (quinolin-8-sulfonyl-ami no) -imido zo [4,5-b] pyridine and 2 - [2 - (4-cyano f eni 1) -ethyl] -3-methyl-6- (quinoline-8-sulfonyl-amino) -imino zo [4,5-b] pyridine and hydrochloric acid methanol, methanol and ammonium carbonate. Yield: 80% of the theoretical, C25H23N702S (485.57) RF value: 0.25 + 0.21 (silica gel; ethyl acetate 1 o / eta no 1 / amoni a co = 50: 45: 5) Spectrum of masses (SKA): (M + H) +, 486 Example 81 2- (4-amidinobenzyl thio) -6- [N- (methoxycarbonylmethyl) -guiny lin-8-sulfonyl lamino] -benzothiazole Prepared analogously to Example le, from 2 - (4-cyanobenzene) io) - 6 - [N - (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] - n ^ .. -r • benzathiazole and ethanolic hydrochloric acid, ethanol ammonium carbonate. Yield: 28, of the theoretical, C27H23 5? 4S3 (577.41) Rf value = 0.21 (silica gel; dichloromethane / ethanol = 4: 1) Mass spectrum (EKA): (M + H) + = 578 M + H + Na = 300.7 E j us 82 Hydrochloride of 2 - [(4-amidinophenyl) oxime ti 1] - 5 - [N- (Toxiccarbonylmethyl) -quinolin-8-sulfonylamino] -benzothiazole a. Amide of (4-cyanophenyl) oxy-H- (5-nitro-2-mercapto-phenyl-1-acetic acid) A solution based on 1.05 g (6.5 mmol) of carb on i 1 di i -mi da The reaction mixture is heated to 50 ° C. for 30 minutes at 50 ° C. for 1 minute and 1.15 g (6.5 mmol) of tetrahydrofuran (4-cyanphene-1-oxyacetic acid). 1.0 g (5.9 mmol) of 2-methyl r cap-5-ni tr or i i na and heating for another 3 hours at 50 ° C. Filter, filter the filtrate in vacuo and extract the The crude product is purified by flash chromatography (silica gel, methylene chloride 1 and no / eta not 1 = 19: 1 to 4: 1).

"* -! *** Yield: 1.05 g (54% of theory), melting point: 274-276 ° C R value: 0.54 (silica gel; / ethane 1 = 19: 1 + some drops of ammonia 5 concentrate) b. 2- [(4-Cyanophenyl) oxymethyl-5-nitro-benzothiazole A solution based on 2.1 g (6.4 mmol) of amide of acid (4-cyano-phenyl-1-ox) is heated. - nitro - 2 -me rc ap tof in i 1) - a cetico in 20 ml of acid glacial acetic acid for 1 hour at 80 ° C, diluted with ice / water and the precipitated crude product separated by filtration. After flash chromatography (silica gel, methylene chloride 1 e no / e t a no 1 = 99: 1), an amorphous solid is obtained beige. Yield: 0.77 g (37% of theoretical), RF value: 0.56 (silica gel, me 111 chloride e no / e t a no 1 = 50: 1) c. 2 - \ (4-cyanophenyl) oxymethyl] -5-amino-benzothiazole A solution based on 0.62 g (2.0 mmol) of 2- [(4-Cyano-phenyl) oxymethyl] -5-nitro-benzothiazole in 20 ml of pyridine is mixed successively with 1.0 g (5.7 mmol) of sodium dithionite and 4 ml of water and stirred for 2 hours at 95 ° C. Then, the The solvent is removed by distillation under vacuum and the The residue is diluted with ice / water. It is filtered, and the filter residue is washed several times with a little cold water. Yield: 0.44 g (79% of theory), RF value: 0.37 (silica gel, methylene chloride 1 e n o / e t a no 1 = 50: 1) d. 2- [(4-cyanophenyl) oxymethyl] -5- (quinolin-8-sulfonylamino) -benzothiazole Prepared analogously to Example 79c, starting from 0.40 g (1.42 mmol) of 2- [(4-cyanopheni 1 ) ox ime ti 1] - 5 - ami no -be nzotiazo 1 and 0.34 g (1.5 mmol) of acid chloride qu i no 1 i n - 8 - s or 1 f ón i c o.

The further purification is carried out by flash chromatography (silica gel, methylene chloride 1 and no / e t 1 = 99: 1). Yield: 0.41 g (61% of theory), R value: 0.49 (silica gel, methylene chloride 1 e no / e t a no 1 = 50: 1) e. 2 - [(4-cyanophenyl) oxymethyl] -5- [N- (ethoxycarbonyl-methyl) -quinone in-8-sulfonylamino] -benzothiazole A suspension based on 0.39 g (0.83 mmol) of 2- [(4-cyanophenyl) oxymethyl] -5- (quinolin-8-su 1 f on i 1 ami) -ben zothiazo 1, 0.23 ml (0.35 g, 2.1 mmol) of ethyl ester of acid br brn a cé ti co, 0.14 ml (0.14 g, 0.94 mmol) of 1.8- fc. i £? 3á £: tt fcc. - > ~ - ^ fesafe ^ »^ diaz ab icic 1 or [5, 4, 0] unde c - 7 - e no and 0.60 g (4.1 mmol) of potassium carbonate in 30 ml of acetone s heated for 3 hours hours until boiling. It is then filtered, the solvent is distilled off in vacuo and the residue is purified by flash chromatography (silica gel, methylene chloride / t a no 1 = 99: 1). Yield: 0.41 g (61% of theory), Rf value 0.54 (silica gel; me 111 e no / e t a no 1 = 50: 1 + some drops of ammonia) F. 2 - [(4-Amidinophenyl-toxime-tl] -5- [N- (methoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzathiazole hydrochloride Prepared analogously to Example le, starting from 2 - [(4-cyanophen-11) oxy] me 111] - 5 - [N - (ethoxycarbonylmethyl) -qu? nol? n-8-sulfon? lam? no] -benzothiazole and methanolic hydrochloric acid, methanol and ammonium carbonate 20 Yield: 67% of theory, C27H23N505S2 ( 561.64) Rf value = 0.36 (silica gel, me 111 chloride and no / ethane 1 = 4: 1) Mass spectrum (SKA): (M + H) + = 562 25 (M + H + Na) ++ = 292.7 s.-3Ü? si & S > - JákwHJS & bkA. > ** < -Ject 83 l-methyl-2- (4-amidinobenzylthio) -5-fN- (methoxycarbonylmethyl) -quin 1 in-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, from 1-me 111-2 - (4 - cia nobe nc 1111 o) - 5 - [- (methoxycarbonylmethyl) -qumol? N-8-sulfon? Lammo] -benzimidazole and methanolic hydrochloric acid, methanol and ammonium carbonate. Yield: 50% of theory, C28H26 604S2 (574.69) Rf value = 0.35 (silica gel, e 111 o / eta acetate 1 / ammonia co = 50: 45: 5) Mass spectrum (EKA ): (M + H) + = 575 (M + H + Na) ++ = 299 Example 84 1-methyl -2 - [4- (N-ethoxycarbonyl-amidino) -benzylthio] -5-N- (methoxycarbonylme il) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, starting from 1 -me 111-2- (4-amidi nobenc 1111 o) -5- [N- (methoxycarbonylmethyl) -qumo-l-n-8-sulfonamino] -benzimidazole and ethyl ester of citric acid 1 . Performance: 62% of the theoretical, . ~ * v JS = .. .aA »A» ?. -1 C31H3oN606S2 (646.75) Rf value = 0.55 (silica gel; ethyl acetate 1 o / et ano 1 / ammonia = 50: 45: 5) Mass spectrum (EKA): (M + H) + = 647 (M + Na) + = 669 E j emplo 85 l-methyl-2- (4-amidinobenciltio) -5- [N- (hydroxycarbonylmethyl) quinolin-8- sulf onilamino] benzothiazole Prepared analogously to Example 3 from 1 'I ti 1 - 2 - (4-ami di nobe nc i 11 io) - 5 - [N - (methoxycarbonylmethyl) -quinino-8-sulfonylamino] -benzimidazole and sodium hydroxide solution. Yield: 61.5% of theory, C27H2 604S (560, 66) Rf value = 0.20 (silica gel; ethyl 1 or eti: eta 1: amon ia co = 50: 45: 5) Mass spectrum (EKA): (M + H) + = 561 (M + Na) + = 583 E xample 86 2- [(4-amidinofenyl) -oxymethyl] -5-fN- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzothiazole Prepared analogously to Example 3, starting from 2- [(4-amidinophenyl) ) -oxymethyl] -5- [N- (methoxycarbonylmethyl) -qu? nolm-8-sulfon? lammo] -benzothiazole and soda lye. Yield: 93% of theory, C26H21 5O5S2 (547.62) value Rf = 0.13 (silica gel; dichloromethane / ethanol = 4: 1) Mass spectrum (EKA): (M + H) + = 548 (M + 2H) ++ = 274, 6 M + H + Na = 285, 6 (M + 2Na = 296, 6 Example 87 l-methyl-2- (4 - amidinobenci 1 thio) - 5 -benzoylamino -benzimidazole Prepared analogously to Example le, from 1 'I ti 1 - 2 - (4 - c 1 Anob Jan 1111 o) - 5 -b in zo 11 ami no - be nc imi da zo 1 and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 54.8% of the theoretical, C23H2? N5OS (415.52) value Rf = 0.35 (silica gel; acetate of e 111 o / et ano 1 / ammon 1 to co = 50: 45: 5) Spectrum Mass (EKA): (M + H) + = 416 88 - • * ^ aS ^ - ^ J ^ -S-¿^ & '' the £ ¿gto »2-FN (4 - enyl amidinof) aminomethyl] -5-FN (ethoxycarbonylmethyl) quinolin- 8 -sulfoni lamino] benzothiazole Prepared analogously to Example le, from 2 - [N- (4 - ci f year eni 1) -ammome 111] - 5 - [N- (ethoxycarbonylmethyl) -qu non-l n? -8-sulphonyl] -benzothiazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 80% of theory, C28H26Nd? 4S2 (574, 69) Rf value = 0.24 (silica gel, dichloromethane / ethanol = 4: 1) Mass spectrum (EKA): (M + H) + = 575 ( M + H + Na) ++ = 299 EXAMPLE 89 2- [N- (4-amidinophenyl) -aminomethyl] -5-fN- (hydroxy-carbonylmethyl) -quinolin-8-sulfonylamino] -benzothiazole Prepared analogously to Example 3, starting from 2 - [- ( 4 - ami di no f in 11) - ami nome 111] - 5 - [- (ethoxycarbonylmethyl) -qu? -nolm-8-sulfonamino] -benzothiazole and soda lye. Yield: 94% of theory, C26H = N6? 4S2 (546, 63) value Rf = 0.15 (silica gel; dichloromethane / ethanol 1) Mass spectrum EKA M + H) = 547 M + Na) + = 569 M + 2H) t = 274 M + H + Na = 285 M + 2Na) = 296 2M + 3Na 3 + = 387 Example 90 l-methyl-2- (4-amidinobenciltio) - 5 - [N- (ethoxycarbonyl-10-methyl) -benzoylamino] benzimidazole Prepared analogously to Example le, from 1 'I 111-2 - (4 - ci anobencyl 111 o) - 5 - [N- (ethoxycarbonylmethyl) -benzoylamino] -benzimidazole and ethanolic hydrochloric acid, ethanol and carbonate of ammonium. Yield: 68.8% of theory, C3 H27N5? S (538.08) value Rf = 0.27 (silica gel, e-acetate 111 o / et an o 1 / amoni a co = 50: 45: 5) 20 Mass spectrum (EKA): (M + H ) + = 502 (M + H + Na) ++ = 262.8 Ie 91 l-methyl-2- (4-amidinobenzylthio) - 5 - [N- (hydroxycarbonylmethyl) -benzaylamino] -benzimidazole Prepared analogously to Example 3, starting from 1 -me 111-2 - (4 -amy di nobenc 1111 o) - 5 - [N - (ethoxycarbonylmethyl) -benzoyl-ammo] -benzimidazole and sodium hydroxide solution. Yield: 79% of theory, C25H23N503S (473.53) Rf value = 0.21 (silica gel; ethyl acetate / ethanol / ammonia = 50: 45: 5) Mass spectrum (EKA): (M + H) + = 474 (M + Na) + = 496 EXAMPLE 92 2- [2- (4-Amidinophenyl) -ethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -quinol in-8-sulfonylamino] -imidazole [4,5-b] pyridine a. 3, 5-di- [3- (4-cyanophenyl) propionylamido] -2 • -methyl-pyridine A solution of 3.8 g (19 mmol) of 3,5-din 11 ro - 2 -me 111 - ammo-p iri di na is hydrogenated in e-space of 2 hours in 90 ml of ethanol / methylene chloride (2: 1) at a hydrogen pressure of 5 bar with 1, 0 g of 10% palladium on carbon. The catalyst is separated by filtration and the solvent is distilled off in vacuo. The black oily crude product is dissolved in 50 ml of pyridine and mixed at 0 ° C with 7.0 g (36 mmol) of 3- (4-cyanophenyl) propionic acid chloride. After 2 hours, the solvent is distilled off in vacuo, the residue is taken up in 100 ml of ethyl acetate and washed with water and saturated sodium chloride solution. It is dried with sodium sulfate, the solvent is distilled off and the residue obtained is purified by flash chromatography (silica gel, methylene chloride / ethanol = 49: 1 to 19: 1). Yield: 4.8 g (59% of theoretical), R value f: 0.40 (silica gel; acetate of t i 1 o / e t a no 1 / amon a co = 90: 10: 1) b_. 3-Methyl-2- [2- (4-cyano-phenyl) -ethyl] -6- [3- (4-cyano-phenyl) -propioni-lamido] -imidazo [4, 5-b] -pyridine A solution of 1 is heated 6 g (3.5 mmol) of 3,5-di- [3- (4-cyanophenyl) propionylamido] -2-methylamino-pyridine in 30 ml of glacial acetic acid for 1 hour up to 100 ° C. The solvent is distilled off in vacuo, the residue is taken up in 80 ml of methylene chloride and neutralized with sodium bicarbonate solution. The organic phase is dried with sodium sulphate, the solvent is distilled off in vacuo and the crude product is evaporated. it is purified by chromatography «1 rapid resolution (silica gel, methylene chloride / -ethanol = 49: 1 to 19: 1). Yield: 0.90 g (60% of theory), Rf value: 0.46 (silica gel; acetate ds eti 1 o / et ano 1 / ammonia co = 90: 10: 1) c.6-amino- 3-Methyl-2- [2- (4-cyanophenyl) -ethyl] -imidazo [4, 5-b] -pyridine 0.80 g (1.8 mmol) of 3-methyl-1 - 2 - [2 -] (4-cyano-phenyl) -ethyl] -6- [3- (4-cyanofenyl) propionyl-amido] -imidazo [4,5-b] -pyridine are heated for 2 hours to 100 ° C in 20 ml of hydrochloric acid 0.5 N. After cooling, it is made alkaline with ammonia and extracted with ethyl acetate. The organic phase is washed with saturated sodium chloride solution and the solvent is distilled off. Yield: 0.42 g (84% of theoretical), Rf value: 0.30 (silica gel, acetate of 111 o / e t ano 1 / amoni acó = 90: 10: 1) d. 2- [2- (4-cyanophenyl) -ethyl] -3-methyl-6- (quinolin-8-sulfonylamino) -imidazo [4, 5-b] pyridine Prepared analogously to Example 79c, from 0.40 g (1.4 mmol) of 6-ami no-3-methyl-1-2 - [2 - (4-cyanophen-1) -ethyl] -imidazo [4,5-b] pyridine with 0.39 g (1 , 6 mmol) of quinoline-8-sulfonic acid chloride. - a ^^ b- AA ^ Silá & t2 »^. r¿ -».? l ^ Í. «. ^ Yield: 0.60 g (90% theoretical), R value: 0.74 (gel silica; ethyl acetate 1 o / et ano 1 / ammonia co = 90: 10: 1) e. 2- [2- (4-cyanophenyl) -ethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino) -imidazo [4,5- b] pyridine Prepared analogously to Example 82e, a from 0.60 g (1.3 mmol) of 2- [2- (4-cyanophenyl) -ethyl] -3-methyl-6- (quinolin-8-sulfonylamino) -imi da zo [4, 5-b] ] pyridine with 0.33 g (1.5 mmol) of ethylester of ethylene broth. Yield: 0.70 g (98% of theory), R f value: 0.80 (silica gel; acetate of e t i 1 o / e t a o 1 / ammon i a c o = 90: 10: 1) f_. 2- [2- (4-amidinophenyl) -ethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -quinolin-8-sullynylamino] -imldazo [4,5-b] pyridine Prepared analogously to the Example , from 2 - [2 - (4-cyano-en-1) -eti-1] -3-methyl-1-6 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino) -imi da zo [4, 5 -b] pir idina and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 91% of the theoretical, C29, H29N7O4S (571, 66) value Rf = 0.22 (silica gel; acetate e 111 o / eta no 1 / ammonium co = 50: 45: 5) Mass spectrum (SKA): (M + H) + = 572 (M + H + Na) ++ = 297, E n gn 93 93 2- [2- (4-amidinophenyl) -ethyl] -3-methyl-6- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonilamino] -imidazo [4,5-b] pyridine Prepared analogously to Example 3, starting from 2 - [2 - (4-ami di no phen 11) -e 111] - 3 -me 111-6 - [N - (ethoxycarbonylmethyl) -qu? nol? n-8-sulfon ? lam? no) -ími da zo [4, 5 - b] piri di na and lye of soda. Yield: 77% of theory, C27H25N7O4S (5 3.59) Rf value = 0.16 (silica gel; ethanol acetate / ammonia = 50: 45: 5) Mass spectrum (EKA): (M + H) + = 544 (M + H + Na) + + = 283.8 Use 94 l-methyl-2- [N- (4-amidinophenyl) -am nomethyl] -5- [N- (etoxycarbonylmethyl) -quinolin-8-sulfonylamino] -indole Prepared analogously to Example le, e from 1 -me 111-2 - [N - (4 - c 1 anophen 11) - am n ome 111] - 5 - [N- (ethoxycarbonylmethyl) -qu? nol? n-8-sulfon? lam? no ] - indole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 55% of theory, C30H30N6? 4S (570.68) R value: = 0.22 (silica gel, dic 1 or ometa no / eta no 1 = 4: 1) Mass spectrum (EKA): (M + H) + = 571 (M + 2H) ++ = 286 (M + H + Na) ++ = 297 Use 95 l-methyl-2- [N- (4-amidinophenyl) -aminomethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -indole Prepared analogously to Example 3, from 1 -me 111 - 2 - [N- (4 -amidi no f eni 1) - ami nome 111] - 5- [N- (ethoxycarbonylmethyl) -qu? nolm-8-sulphon? lane] - indole and bleach soda. Yield: 97% of theory, C28H26N604S (542.62) mass spectrum (EKA): (M + H) + = 543 (M + Na) + = 565 (M + 2H) ++ = 272 (M + H + Na ) ++ = 283 (M + 2Na) ++ = 294 XH-NMR (d6-DMSO): d = 3.61 (s, 3 H); 4.50 (d, 2 H); 4.67 (s, 2 H); 6.20 (s, 1 H); 6.30 (d, 1 H); 6.70 (d, 2 H); 7.01 (d, 1 H); 7.29 (t, 1H); 7.38 (s, 1 H); 7.40-7.65 (m, 3 H); 7.77 (dd, 1 H); 8.03 (d, 1 H); 8.20 (d, 1 H); 8.42 (broad s, 2H); 8.55 (dd, 1H); 9.20 (dd, 1H) ppm Use 96 l-methyl-2- [(4-amidinophenyl) -thiomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example le, starting from l-methyl- 2- [(4-cyanophenyl) -thiomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 84% of the theoretical, C29H28N6? 4S2 (588.71) R value: = 0.35 (silica gel; ethyl acetate 1 o / et ano 1 / amoni a co = 50: 45: 5) Spectrum of masses (EKA): (M + H) + = 589 (M + H + Na) ++ = 306 Example 97 »JS- & -. ".Ai.i?: - l-Methyl-2- [(4-amidinophenyl) -thiomethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 3, a from l-methyl-2- [(4-amidinofenyl) -thiomethyl] -5 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and sodium hydroxide solution. Yield: 76% of theory, C27H2 604S (560, 66) R value: = 0.21 (silica gel, ethyl acetate / ethanol / ammonia = 50: 45: 5) spectrum. tables (EKA): (M + H) + = 56? (M + Na) + = 583 EXAMPLE 98 l-Methyl-2- [(4-amidinophenyl) -thiomethyl] -5- (quinolin-8-sulfonylamino) -benzimidazole Prepared analogously to Example LE, from 1-methyl-2 - [(4 - ci year f in 11) - 11 ome 111] - 5 - (qu i no 1 in - 8 - su 1 f on i 1 ami no) -be nc ia 1 z and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 70% of theory, C25H22N602S2 (502, 62) R value: = 0.29 (silica gel, e 111 o / et ano 1 / amoni a co = 50: 45: 5) Mass spectrum ( EKA): (M + H) + = 503 Example 99 2- [(4-Amidinophenyl) -acetyl] -7- (quinoline-8-sulfonylamino) -1,2,4,4-tetrahydro-isoquinoline a.2- [(4-cyanophenyl) -acetyl] hydrochloride -7-nitro-l, 2, 3, 4- 10 tetrahydro-isoquinoline 4.0 g (22.5 mmol) of 7-n? Tro-l, 2, 3, 4- tetrahi dr o - iso - qu i Do not dissolve in 100 ml of chlorobenzene or mix with 4.24 g (25 mmol) of 4-cyanoalkyl chloride and dilute to heat.

Reflux for 2 hours. After cooling to room temperature, it is diluted with 1 liter of petroleum ether and filtered. The residue is dissolved in ethyl acetate and chromatographed on silica gel, eluting at the beginning with Methylene and then with methylene chloride 1 e no / e t a no 1 (50: 1 and 25: 1). The desired fractions are combined and concentrated by evaporation. Yield: 3.80 g (53% of theory), R value f: = 0.50 (silica gel; me 111 e no / e t a no 1 = 19: 1) b.2- [(4-cyanophenyl) -acetyl] -7-amino-1,2,3-tetrahydro-isoquinoline Prepared analogously to Example Ib, starting from 2- [(4-cyanophenyl) -acetyl-7- nitro-l, 2,3,4-tetrahi dr o -iso qui no 1 i na ehi dr ge no no pa 1 a di o. Yield: 27% of theory, melting point: 186-188 ° C c. 2- [(4-cyanophenyl) -acetyl] -7- (quinolin-8-sulfonylamino) -1,2,4,4-tetrahydro-isoquinoline Prepared analogously to Example 1, from 2 - [(4-cyano) feni 1) - a ce ti 1] - 7 - ami not -1, 2, 3, 4 - tetr ah i dr o - is oqu i no 1 i na and quinolin-8-sulfonyl chloride. Yield: 80% of the theoretical, Rf value: = 0.55 (silica gel, chloride, methylene, ene / e, 1 = 19: 1) d. 2 - [(4-Amidinophenyl) -acetyl] -7- (quinoline-8-sulfonylamino) -1,2,4,4-tetrahydro-isoquinoline hydrochloride Prepared analogously to Example le, starting from 2 - [(4 - ci ano f in i 1) - aceti 1] - 7 - (qu i no 1 in - 8 - sulphonylamino) -1,2,3,4 - tetrahydro - isoquinoline and acid c 1 orh i dri co / ca r bona of ammonium in ethanol. Yield: 35% of theoretical, melting point: sintered from 173 ° C C27H25 503S (499.50) Mass spectrum: (M + H 500 EXAMPLE 100 2 - [(4-Amidinophenyl) -acetyl] -7-fN- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -1,2,3,4-e-trahydro-isoquinoline Prepared analogously to Example LE, starting from 2 - [(4 - cyan f eni 1) - a ce 111] - 7 - [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -1, 2, 3, 4 - tetrahi dr o - is oq i no 1 i na and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 35% of the theoretical, C31H31N505S (585.68) Rf value: = 0.20 (silica gel, dic 1 or ome t an / et ano 1 = 4: 1) Mass spectrum (EKA): (M + H) + = 586 (M + 2H) ++ = 293.6 (M + H + Na) ++ = 304.6 Example 101 2- [(4-amidinophenyl) -acetyl] -7- [N- (hydroxycarbonyl-yl) -quinolin-8-sulfonylamino] -1,2,3,4-tetrahydro-o-isoquinoline Prepared analogously to Example 3 , from 2 - [(4-ami di no phen 11) -ace 111] -7 - [N - (ethoxycarbonylmethyl) -qu? nolm-8-sulfon? lam? no] -1, 2, 3, 4 - tetrahi dr o - is oqu i nol i na and soda lye. Yield: 49% of theory, C29H27N5O5S (557, 6) R value: = 0.17 (silica gel, dichloromethane / ethanol = 3: 2) Mass spectrum (EKA): (M + H) + = 558 ( M + Na) + = 580 (M + 2 H) ++ = 279.7 (M + H + Na) ++ = 290.7 (2M + H + Na) + + = 569 Example 102 2 - [(4-Amidinophenyl) -oxymethyl] -4-methyl-7- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline hydrochloride a. 7-amino-2,4-dimethyl ti 1 -quinol ina 54.8 g (0.36 mol) of 3-a-111 amino-n-111 n, 38.0 g (0.38 mol) of a 111 to acetone and 32.5 ml of glacial acetic acid are stirred for 2 hours at 80 ° C. After cooling, the reaction mixture is poured onto ice / water and neutralized with sodium hydrogen carbonate solution.

After extraction for three times with ethyl acetate, the combined organic phases are washed with sodium chloride solution, dried over sodium sulfate and concentrated by evaporation. The crude product, thus obtained, is heated for 1 hour to 105 ° C with 200 ml of concentrated sulfuric acid. After cooling, the reaction mixture is poured onto ice / water and neutralized with ammonia solution.

After extraction with ethyl acetate three times, the combined organic phases are washed with sodium chloride solution, dried over sodium sulfate and concentrated by evaporation. The crude product is chromatographed on silica gel, eluting at the beginning with methylene chloride and then with methylene chloride 1 e no / e t a n o 1 (50: 1, 25: 1, 19: 3 and 9: 1). The desired fractions are combined, concentrated by evaporation and mixed by triturating with petroleum ether. 20 Yield: 24.15 g (39% of theory), CnH12N2 (172.20) Mass spectrum: M + = 172 b. 7-f talimido-2,4-dimethyl-quinol ina 6.90 g (40 mmol) of 7-ami no-2,4-di me t 11-25 quinoline, 5.95 g (42 mmol) of anhydride of acid Phthalic acid and 100 ml of glacial acetic acid are heated for 2 hours under reflux. After cooling, the reaction mixture is poured onto ice / water, the precipitated product is filtered with; 5 suction, wash with water and dry. Yield: 8.85 g (73% of theory), melting point: 203-205 ° C c .7-phthalimido-2,4-dimethyl-quinolin-1-oxide 4.25 g (14 mmol) of 7 - phta 1 imi do - 2, 4 - 10 d ime ti 1 - qu i no 1 i na dissolve in 500 ml of boiling methylene chloride After cooling to room temperature, 4.80 g of 3 - aq. c 1 or opbenbenic (approximately 50%). After 3 hours at room temperature, the The reaction solution is washed in each case 1 × with sodium hydrogen chloride solution and sodium chloride solution, dried over sodium sulfate and concentrated by evaporation and recrystallized from ethanol. 20 Yield: 2.45 g (55% of theory), melting point: > 250 ° C d. 2-chloromethyl-4-methyl-phthalimido-quinoline 4.30 g (13.5 mmol) of 7-phtha 1 i mi-2, 4-d ime ti 1-qu i no 1 i-1-ox i do and 4.20 g (22 mmol) of p-toluene sulfochloride are heated during refluxing in 300 ml of methylene chloride. After cooling to room temperature, the reaction solution is washed once with sodium hydrogencarbonate solution and sodium chloride solution, dried over sodium sulfate and concentrated by evaporation. The residue is chromatographed on silica gel, eluting initially with methylene chloride and then with methylene chloride / ethanol (50: 1). The fractions The desired compounds are combined, concentrated by evaporation and mixed by triturating with ether. Yield: 3.15 g (70, theoretical), melting point: 212-215 ° C e.2- [(4-cyanophenyl) -oxymethyl] -4-methyl-f-talimido-15-quinoline 895 mg (6, 2 mmol) of potassium tert-butethiol are dissolved in 50 ml of dimethyl ether 1 ml, mixed with 740 mg (6.2 mmol) of 4-hydroxybenzonitrile and stirred for 30 minutes. minutes to the room temperature. After the addition of 2.0 g of 2-c 1 or ome thi 1 -4-methyl thi-7-phtha-1-imi do not, the reaction mixture is stirred for a further 12 hours at the room temperature. After the addition of ice / water, it is filtered with suction of the precipitate formed, washed with water and dried. ? ~ j¡?) »> M8Sf? A & - t * .itá £ - »« • «. < H.H? l8§i .. ig & ¡ñÁá¡í? .f. d Yield: 2.20 g (89% of theory); melting point: 231-233 ° C f. 2- [(4-Cyanophenyl) -oxymethyl] -4-methyl-7-amino-quinoline 21.5 g (5.1 mmol) of 2- [(4-c? Anophen? L) -oxyethyl] -4 -met? l-7-phtal? could-qu? nol? na dissolve in 75 ml of 1 to no 1 (2: 1), mix with 7.5 ml of methylamine aqueous solution 40% and stir for 2 hours at room temperature. Then, the solution is concentrated by evaporation in a vacuum, the residue is stirred with 2N acetic acid, filtered with suction and dried. The crude product is chromatographed on silica gel, eluting initially with methylene chloride and then with methylene chloride and no / e t a n 1 (50: 1). The desired fractions are combined, concentrated by evaporation and mixed by triturating with ether. Yield: 1.05 g (71 'of theory), melting point: 192-194 ° C g. 2- [(4-cyanophenyl) -oxymethyl] -4-methyl-7- (quinino-8-sulfonylamino) -quinoline Prepared analogously to Example le, starting from 2 - [(4-cyano f-eni 1) - oxime 111] - 4 -me 111 - 7 -nanequino 1 inay and chloride of qu io 1 in - 8 - su 1 fon 11 o.

Yield: 67% of theory, melting point: 240-242 ° C h.2- [(4-cyanophenyl) -oxymethyl] -4-methyl-7- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] - quinoline Prepared analogously to Example Id, starting from 2 - [(4-cyano-en-1) -oxymethyl] -4-methyl-1 -7- (qu i no 1 in-8-su 1 f on i 1 ami no) - qu i no 11 na and ethyl ester of br omoa cé ti co acid. Yield: 92% of theoretical, melting point: sintered from 85 ° C i. 2 - [(4-Amidinophenyl) -oxime-tyl] -4-methyl-7- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline hydrochloride Prepared analogously to Example le, starting from 2- [(4 -cyanophenyl) -ox? methyl] -4-methyl-7- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline and hydrochloric acid / ammonium carbonate in ethanol. Yield: 49% of theoretical, melting point: sintered from 78 ° C C3? H29N505S (583.62) Mass spectrum: (M + H) + = 584 (M + H + Na) + = 303.7 (2M + H) + = 1167 3t? -Example 103 2 - [(4-amidi ofenyl) -oxymethyl] -4-methyl-7- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline Prepared analogously to Example 3, from 2- [ (4-amidinophen? L) -oxymethyl] -4-methyl-7- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline and soda lye. Yield: 19% of theory, C29H25 5OSS (555, 6) Mass spectrum (EKA): (M + H) + = 556 (M + Na) + = 578 (M + 2Na) ++ = 300 (M-H + 2Na) + = 600 EXAMPLE 104 2- [(4-amidinophenyl) -oxymethyl] -4-methyl-7- (quinolin-8-sulfonyl-amino) -quinoline Prepared analogously to Example le, starting from 2 - [(4-cyano-phenol 1 ) - oxime 111] - 4 -me ti 1 - 7 - (qu ino 1 in - 8 - su 1 f on i 1 ami no) - qu i no 11 na and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 22% of the theoretical, C27H23N503S (97, 55) R value: 0.23 (silica gel, dichloromethane / ethanol = 4: 1) melting point: smtepza from 195 ° C Mass spectrum (EKA) : (M + H) + = 498 Example 105 2 - [N- (4-Aminophenyl) -aminomethyl] -6- (quinolin-8-sulfonylamino) -imidazo [1,2-a] pyridine hydrochloride a. 2-chloromethyl-5-nitro-imidazo [1,2-a] pyridine 12.6 g (0.1 mol) of 1,3-di c 1 or to ketone are heated to 105 ° C and mixed in portions with 8.25 g (60 mmol) of 2-ami no-5-n 11 ro -piri di na. After 10 minutes at 105 ° C, the reaction mixture is cooled, combined with 11 ene / eta no 1 (8: 2) chloride and chromatographed on silica gel, eluting at the beginning with methylene chloride and then with me 111 chloride and no / eta no 1 (25: 1, 19: 1 and 9: 1). The desired fractions are combined, concentrated by evaporation and mixed by triturating with ether. Yield: 4.35 g (34% of theory), melting point: 124-127 ° C b .2- [N- (4-cyanophenyl) -aminomethyl] -6-nitro-im dazo [1, 2-a] ] pyridine 3.0 g (25.4 mmol) of 4-ami nobe nz on itri 1 o melt at 120 ° C and mix in portions with 1.30 g (6.3 mmol) of 2-c 1 or ome ti 1 - 5 - nitro-imi da zo [1,2-a] pipdin. After 30 minutes at 120 ° C, the reaction mixture is cooled, combined with methylene chloride 1 ene / eta no 1 (8: 2) and chromatographed on silica gel, eluting at the beginning with methylene chloride. and then with methylene chloride 1 and no / eta no 1 (50: 1, 25: 1 and 15: 1). 10 The desired fractions are combined and concentrated by evaporation. Yield: 0.71 g (39% of theory), R value: 0.50 (silica gel, methylene chloride 1 and no / ethane 1 = 19: 1) 15 c .2- [N- (4 -cyanomethyl) -aminomatill-6-amino-imidazo [1, 2-a] -pyridine Prepared analogously to Example Ib, starting from 2 - [N - (4-cyanophen-1) -ami nome ti 1] - 6 - nitro-imidazo [1,2-a] pyridine and hydrogen or palladium. 20 Yield: 75% of the theoretical, R f value: 0.20 (silica gel, methylene chloride 1 e n o / e t a n o 1 = 9: 1) d. 2- [N- (4-cyanophenyl) -aminomethyl] -6- (quinolin-8-sulfonylamino- = imidazo [1,2-a] pyridine Prepared analogously to Example 1, from 2 - [N - (4-cyano-phenyl-1) - ami-nome-thi] - 6 -amino-noniimido [1,2-a] pyridione and chloride quinolin-8-sulfonyl. Yield: 35% of theory, value R f: 0.78 (silica gel, chloride of me t i 1 e no / e t a n o 1 = 4: 1 + glacial acetic acid) e. 2- [N- (4-amidinophenyl) -aminomethyl] -6- (quinoline-8-sulfonylamino) -imidazole [1,2-a] pythine hydrochloride Prepared analogously to Example le, starting from 2 - [N- ( 4-cyclohexphi 1) - ami nome ti 1] - 6 - (quinolin-8-sulfonylamino) -imidazo [1,2-a] pyridine and c 1 -hydrochloride / ammonium cation. Yield: 51% of theory, Rf value: 0.15 (silica gel, methylene chloride 1 and no / eta no 1 = 4: 1 + glacial acetic acid) C24H27N7O2S (471.48) Mass spectrum: (M + H) = 472 Example 106 2- [N- (4-amidinophenyl) -aminomethyl] -6- [N- (ethoxycarbonylmethyl] -quinolin-8-sulfonylamino] -imidazo 1,2-] pyridine Prepared analogously to Example LE, starting from 2 - [N - (4-cyano-phenyl-1) -amino-111] -6- [N - (ethoxycarbonylmethyl] -qumol? N-8-sulphon? Lane] -imino-zo [1, 2-a 1 pyridine and ethanolic hydrochloric acid, ethanol and ammonium carbonate Yield: 11% of theory, C28H2 N7O4S (557, 65) Mass spectrum: (M + H) + = 558 (M + Na) + = 580 EXAMPLE 107 2 - [N- (4-Amidinophenyl) -aminomethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzofuran hydrochloride a. 4-Acetylamino-2-hydroxy-acetophenone 16.5 g (0.10 mol) of 3-methyl-1-acetyl anhydride are dissolved in 40 ml of dichloroethane and, after the addition of 19.6 g. (0.25 mol) of acetyl chloride are mixed in portions at 5 ° C with 42.0 g (0.32 mol) of aluminum chloride. After 2 hours at room temperature, the reaction mixture is heated at reflux for a further 2 hours. After cooling to room temperature, ice is added, A ^ MS ^ f ^^^ fl ^ ^ itetaaaaa - ^. A ^. ^ BK ^ > .

The formed precipitate is filtered off with suction, washed with water and dried. Yield: 14.8 g (77% of theory), R value: 0.40 (silica gel, ether of 5 p e t r o 1 e o / a c e t t o of ethyl = 1: 1) b. 4-amino-2-hydroxy-acetic acid 10.0 g (52 mmol) of 4-acetyl-1-ami-2-hydroxy-1-hydroxypropyl ester and 100 ml of 18% hydrochloric acid are heated for 15 minutes. reflux minutes.

After cooling to room temperature, the formed precipitate is filtered off with suction, washed with ice / water and dried. The filtrate is concentrated by evaporation, taken up in water and mixed with concentrated ammonia. He The precipitate formed is filtered off with suction, washed with ice / water, dried and combined with the first precipitate. Yield: 7.6 g (97% of theory), R value: 0.65 (silica gel; pe t r o 1 eo / a ce t a t o de etil = 1: 1) c. 4-phthalimido-2-hydroxy-acetophenone Prepared analogously to Example 102b, starting from 4-ami no-2-h i dr ox i-a c e t or fona none and phthalic acid anhydride. 25 Performance: 75% of the theoretical, R f value: 0.55 (silica gel; ethyl ether / ethyl acetate = 1: 1) d. 4- [(2-carboxy) -benzoylamino] -2-carboxymethyloxy-acetophenone 18.9 g (67 mmol) of 4-phtha1-im-2-hydroxy-1-acetophenone, 16.5 g (99 mmol) of ethyl bromoacetic acid ester and 40.0 g (0.3 mol) of potassium carbonate are taken up in 100 ml of acetone and refluxed for 6 hours. After cooling to room temperature, the formed precipitate is filtered off with suction and dried. The filtrate is concentrated by evaporation, taken up in water and extracted 3 times with ethyl acetate. The combined organic extracts are washed with water and dried. The combined crude products are dissolved in 50 ml of ethanol, mixed with 50 ml of 3N sodium hydroxide solution and stirred for 30 minutes at room temperature. After addition of 100 ml of water and acidification with 6N hydrochloric acid, the precipitate formed is filtered off with suction, washed with cold water and dried. Yield: 19.4g (81% of theory), Rf value: 0.30 (silica gel, methylene chloride / ethanol = 7: 3) e. 3-methyl-6-phthalimido-benzofuran A mixture of 36.0 g (0.1 mol) of 4- [(2-carboxy) -benzoylamino] -2-carboxymethyloxy-acetophenone, 30 g (0.37 mol) of acetate of sodium, 5 770 ml of acetic acid and 153 ml of glacial acetic acid are heated at reflux for 2.5 hours. The reaction mixture is concentrated by evaporation, the residue is triturated with water, filtered with suction, washed with water and dried.

Yield: 21.6 g (77% of theory), Rf value: 0.85 (silica gel, methylene chloride + 2.5% ethanol) f .2- [N- (4-cyanophenyl) -aminomethyl) 1] -3-methyl-6- f such imido-benzofuran 15 5.68 g (20 mmol) of 3-methyl-1-6-phtha-1-imidobenzofuran are dissolved in 150 ml of methylene chloride, mixed with 5.0 g of hydrofluoride 1 and 20 g of thionyl chloride and stir for 60 hours at room temperature. The mixture of The reaction is concentrated by evaporation, dissolved twice in methylene chloride and concentrated again by evaporation to dryness. The crude product is dissolved in 150 ml of toluene, mixed with 5.1 g (43 mmol) of 4-ami nobe n z on i t r i 1 and 20 g of aluminum oxide and heated to reflux SHkA «= iáíÉiafe I for 6 hours. The reaction mixture is concentrated by evaporation, the residue is taken up in methylene chloride and chromatographed on silica gel. (methylene chloride). The desired fractions are combined, concentrated by evaporation and mixed by triturating with ether of oil or 1 ml of methanol. Yield: 6.0 g (68% of theory), R value: 0.30 (silica gel, methylene chloride) 10 g. 2- [N- (4-cyanophenyl) -aminomethyl] -3-methyl-6-aminobenzofuran. Prepared analogously to Example 102f, starting from 2 - [N - (4 - cyano f in i 1) - ami nome 111] - 3 -me 111 - 6 - phta 1 imi do -be nzof ur ano and methylamine. 15 Yield: 65% of theory, value R f: 0.25 (silica gel; methylene chloride) h. 2- [N- (4-cyano-phenyl) -aminomethyl] -3-methyl-6- (quinolin-8-sulphonylamino) -benzofuran Prepared analogously to Example le, starting from 2 - [N - (4-cia) eni 1) - ami nome ti 1] - 3 -me ti 1 - 6 - ami no -be nzofur anus and quinolin-8-sulfonyl chloride. Yield: 97% of the theoretical, Rf value: 0.65 (silica gel, 25 me t i 1 chloride and no / e 1 = 95: 5) i. 2- [N- (4-cyanophenyl) -aminomethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzofuran. Prepared analogously to Example Id, from 2 - [N - ( 4 - ci ano f eni 1) - ami nome 111] - 3 -me 111 -6 - (qu i no 11 n - 8 - su 1 f on 11 ami no) - benzofur anus and ethyl ester of bronze a cé you co Yield: 99, of the theoretical, Rf value: 0.70 (silica gel; chloride of me 111 e no / e t a no 1 = 95: 5) j. 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (ethoxycarbonylmethyl) -q-inol-8-sulfonylamino] -benzofuran hydrochloride Prepared analogously to Example 1, from 2 - [N - (4 - ci ano f eni 1) - ami nome 111] - 3 -me 111 -6- [N- (ethoxycarbonylmethyl) -qu? Nol? N-8-su 1 f on i 1 ami no ] -be nzofur ano and acid c 1 orhi dr ico / car bona to ammonium. Yield: 32% of the theoretical, R f value: 0.21 (silica gel, methylene chloride 1 ene / et ano 1 = 4: 1 + glacial acetic acid) C30H29N5? 5S (571.67) Mass spectrum: (M + H) + = 572 (M + 2H) ++ = 286.7- z & ^ &r? &% (M + fi + N a) + + = 2 9 7, 7 E n g lish 1 0 8 2- [N- (4-amidinophenyl) -aminojttte tl] -3-methyl-6- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzofuran Prepared analogously to Example 3, from 2 - [N - (4-ami di no phen 11) - ami nome 111] - 3 -met? l-6- [N- (ethoxycarbonylmethyl) -qumol? n-8-su 1 f on i 1 ami no] - b in zof ur ano and soda lye. Yield: 94% of theory, C28H25N5O5S (543.61) Rf value: 0.12 (silica gel; d chloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum: (M + H) + = 544 ( M + 2H) ++ = 272.7 (M + H + Na) ++ = 283.6 (M + 2Na) ++ = 294.7 Example 109 2- [N- (4-amidinofenyl) -am nomethyl] -3-methyl-6- (quinolin-8-sulfonium lamino-benzofuran) Prepared analogously to Example le, starting from 2 - [N - (4 - c 1 year f in 11) - ami nome 111] - 3 -me 111 -6 - (qu 1 not 11 n - 8 - su 1 f on 11 - ami no) - be nzofuranoy acid jf JSLjh reo ethanolic hydrochloride, ethanol and ammonium carbonate. Yield: 17% of theory, C26H2 N503S (485.58) • "* Rf value: 0.17 (silica gel, me 111 eno / et 1 = 4: 1 + glacial acetic acid) Mass spectrum ( EKA): (M + H) + = 486 Example 110 2 - [(4-amidinophenyl) -oxymethyl] -4-methyl-7- [N- (ethoxycarboni 1-methyl] -ben zoi lamino] -quinoline Prepared analogously to Example le, starting from 2- [(4 -cyanophenyl) -ox? met? l] -4-met? l-7- [N- (ethoxycar bon i lme ti 1] -ben zo 11 ami no] - qui no nay ethanolic hydrochloric acid, ethanol and carbonate of ammonium Yield: 64% of theory, C29H28N O4S (496, 6) Mass spectrum: (M + H) + = 497 (M + H + Na) ++ = 260 S J & amp; amp; amp; amp; Use 111 2 - [N- (4-amidinophenyl) -amomethyl] -4-methyl-7- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline Prepared analogously to Example 1, from 2 - [N - (4 - ci ano f in 11) - ami nome 111] - 4 -me 111 -7- [N- (ethoxycarbonylmethyl) -qumolm-8-su 1 f on 11 ami no] - qu i no 1 i na and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 63% of the theoretical, C31H3oN604S (582.69) Rf value: 0.15 (silica gel, dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) + = 583 (M + H + Na) ++ = 303 Example 112 2- [N- (4-amidinophenyl) -aminomethyl] -4-methyl-7- [N- (hydroxycarbonylmethyl) -quinolin-8-sulfonylamino] -quinoline Prepared analogously to Example 3, starting from 2 - [ N - (4-ami di no phen 11) - ami nome 111] - 4 -met? L-7- [N- (ethoxycarbonylmethyl) -qu? Nol? N-8-su 1 f on i 1 ami no] - What a nol i na and lye of soda. Yield: 49% of theory, C29H26N6O4S (554, 64) Mass spectrum (EKA M + H) = 555 M + Na-) + = 577 M + 2Na) ++ = 300 2M + 3Na 3 + 392.6 Example 113 2 - [(4-Amidinophenyl) -oxymethyl] -4-methyl-7- [N- (hydroxycarbonylmethyl] -benzoyl inol -quinoline Prepared analogously to Example 3, starting with 2- [(4-am? dmofen? l) -ox? met? l] -4-met? l-7- [N- (ethoxycarbonylmethyl) -benzoylamino] -quinoline and sodium hydroxide. Yield: 26% of theory, Mass Spectrum (EKA): ( M + H) + = 469 E xample 114 2- [2- (4-amidinophenyl) -ethyl] -3-methyl-6- [N- (ethoxycarbonylme il) -quinolin-8-sulfonilamino] -benzofuran Prepared analogously to Example le, from 2 - [2 - (4 - c 1 ano f in 11) - e 111] - 3 -me 111 - 6 - [N - (ethoxycarbonylmethyl) -qumol? N-8-sulphon? Lammo] -benzofuran and ethanolic hydrochloric acid , ethanol and ammonium carbonate. Yield: 84% of theory, C3? H30N4? 5 (570, 68) R value: 0.24 (silica gel, dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) + = 571 (M + H + Na) ++ = 297 EXAMPLE 115 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (ethoxycarbonyl-benzenesulfonylamino] -benzofuran) Prepared analogously to Example le, starting from 2 - [N - (4 - cyan f in 11) - amy nome 111] - 3 -me 111 - 6- [N- (ethoxycarbonylmethyl) -benzenesulfonylamino] -benzofuran and ethanolic hydrochloric acid, ethanol and ammonium carbonate Yield: 36% of the Theoretical value R f: 0.22 (silica gel, dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) + = 521 iBi j »aj & < B6 ¿Sa * fe.- 'Jfe ¿xe? *! ÉsB? Example 116 vff 2- [2- (4-amidinophenyl) -ethyl] -3-methyl-6- [N- (hydroxycarbonyl-methyl) -quinolin-8-sulfonylamino] -benzofuran Prepared analogously to Example 3 , from 2 - [2 - (4-ami di no pheni 1) - eti 1] - 3 -methyl 1-6 - [N - (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzofuran and soda lye . Yield: 87% of theory, C29H26N4O5S (5 2, 63) Rf value: 0.13 (silica gel, dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) + = 543 (M + Na) + = 565 E xample 117 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (hydryloxycarbonylmethyl) -benzenesulfonylamino] -benzofuran Prepared analogously to Example 3, starting from 2 - [ - (4-ami di no feni 1) - ami n ome ti 1] - 3 - methyl-6- [N- (ethoxycarbonylmethyl) -benzene not its 1 f on i 1 ami] -be nzofuranoy lye of soda. Yield: 79% of theory, C25H24N4O5S (492.57) Rf value: 0.12 (silica gel, dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) + = 493 (M + Na) + = 515 M + 2Na 269 Example 118 2 - [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sullynylamino] -benzofuran Prepared analogously to the Example , from 2 - [N - (4 - cyano f in i 1) - ami nome 111] - 3 -me ti 1 -6- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -quo n-8 - its 1 f on i 1 ami no] -ben zofura and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 81% of theory, C32H32N606S (628, 72) Mass spectrum (EKA): (M + H) + = 629 (M + H + Na) ++ = 326 E xemployment 119 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (Nf (1 H - te trazol - 5 - i 1) -aminocarbonylmethyl) -quinolin-8-sulfoni lamino] -benzofuran • te * ft > .t ». ^ Ta-gay -j? -aia = -agfc- ". to . 2- [N- (4-cyanophenyl) -aminomethyl] -3-methyl-6- [N- (N '(1 H -tetrazol-5-yl) -amcarbonylmethyl) -quinolin-8-sulfonylamino] - benzofuran 0.53 g (1.0 mmol) of 2 - [N - (4-cyano-phen-1) -5-ammomethyl] -3-meth? -6-carbox? met? l-qu? nolm-8- its 1 f on i 1 ami no] - be nzof ur ano dissolve in 20 ml of tetrahydrofuran, mix with 0.2 5 g (1.2 mmol) of car bon 11 di i zo zo 1 and 0, 1 g (1.0 mmol) of 5-ami non-tetrazole 1 and heated at reflux for 5 hours. hours. The reaction mixture is concentrated by evaporation, the residue is dissolved in ethanol and chromatographed on silica gel (methylene chloride + 2.5, ethanol). The desired fractions are combined and concentrated by evaporation.

Yield: 0.11 g (19% of theory), C29H23N9O4S (593, 64) R value: 0.18 (silica gel, me 111 chloride and no / eta no 1 = 9: 1) Mass spectrum : (MH) "= 592 20 b. 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (N '- (1H-tetrazol-5-yl) -aminocarbonylmethyl) - quinoline-8-sulfonylamino] -benzofuran Prepared analogously to the Example le, a from 2 - [N - (4 - c 1 ano f in 11) - ami nome 111] - 3 -me 111 - < ¡& amp; * B ~ M. *, .s-Á¡ & «J8.-V 6- [N- (N '- (lH-tetrazo-5-yl) -aminocarbonylmethyl) - qu i not 11 n - 8 - su 1 f on i 1 ami nó] -be nzofura no and acid c 1 orhidri co / car bona to de ammonium. Yield: 97% of theory, C29H26N10? 4S (610, 67) Mass spectrum (EKA): (M + H) + = 611 (M + Na) + = 633 (M + H + Na) ++ = 317 EXAMPLE 120 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (1 H -tetrazol-5-yl) -methyl] -quinolin-8-sulfonylamino] -benzofuran a. 5-Bromomethyl-1- (2-cyanoethyl) -tetrazole 1.50 g (7.85 mmol) of bromoacetic acid (2-cyan oe ti 1) -amide are dissolved in 50 ml of methylene chloride and mixed with 508 mg (7.85 mmol) of sodium acidide. At 0 ° C a solution of 2.20 g (7.85 mmol) of trifluoroacetic acid anhydride in 5 ml of methylene chloride is added dropwise. After 22 hours at room temperature, add a saturated sodium hydroxide solution and extract 3 times with methylene chloride. The combined organic phases are dried over sodium sulfate and concentrate by evaporation. The crude product is chromatographed on silica gel, eluting initially with methylene chloride and then with methylene chloride 1 and no 1 (50: 1). The desired fractions are combined and concentrated by evaporation. Yield: 505 mg (30% of theory), C5H6BrN3 (216.06) Mass spectrum (EKA): M + = 215/217 (Br) b .2- [N- (4-cyanophenyl) -aminomethyl] -3- methyl-6- [Nl- (2-cyano-ethyl) -tetrazol-5-yl) -methyl) -quinolin-8-sulfonylamino] -benzofuran. Prepared analogously to Example Id, starting from 2 - [N - (4 - cyano f in i 1) - ami n ome ti 1] - 3 -me ti 1 -6 - (qu ino 1 in - 8 - su 1 f on i 1 ami no) -be nzofur anus and 5-bromomethyl-1- (2-cyanoethyl) -tetrazole. Yield: 98% of the theoretical, R f value: 0.45 (silica gel; methylene chloride 1 ene / eta no 1 = 95: 5) c .2- [N- (4-cyanophenyl) -aminomethyl] - 3-Methyl-6- [N- (1H-tetrazol-5-ylmethyl) -quinolin-8-sulfounilamino] -benzofuran 0.5 g (0.83 mmol) of 2 - [N - (- cyano) f eni 1) -aminomethyl] -3-methyl-6- [N- [1- (2-cyanoethyl) -tetrazol-5-yl-methyl] -qu? nolin-8-sulfonylamino] -benzofuran are dissolved in 50 ml of methylene chloride, it is 9 mix with 0.28 g (2.5 mmol) of potassium tert-butoxide and stir for 90 minutes at room temperature. The reaction mixture is concentrated by evaporation, the residue is dissolved in water and acidified with glacial acetic acid. The precipitate formed is separated by filtration, washed with water and dried. The crude product is chromatographed on silica gel (methylene chloride + 1-2% ethanol). The desired fractions come together and concentrate by evaporation. Yield: 110 mg (24% of theory), R value: 0.43 (silica gel, dichloromethane / ethanol = 9: 1) d. 2- [N- (4-amidinophenyl) -15-aminomethyl] -3-methyl-6- [N- (lH-tetrazol-5-yl) -methyl] -quinolin-8-sulfonylamino] -benzofuran hydrochloride Prepared analogously to Example 1, from 2 - [N - (4-cyano-phenyl-1) - ami nome ti 1] - 3 -me 111 -6- [N- (l-tetrazol-5-yl-methyl) -qu? nolin-8- 20 su 1 f on i 1 ami no] - ben zof ur ano and acid 1 ammonium bicarbonate. Yield: 97% of theory, C28. H25N9, 03S (567.66) Mass spectrum (EKA): (M + H) + = 568 25 (M + Na) + = 590 M + H + Na 295, 6 M + 2 Na) + + = 306.7 EXAMPLE 121 2- [2- (4-amidinophenyl) -ethyl] -3-methyl-6- [N- (N '- (and oxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sulfonylamino] -benzofuran Prepared analogously to Example le, from 2- [2- (4-c? anophen? l) -et? l] -3-met? l-6- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -quot; 11 n - 8 - su 1 f on 11 ami no] -ben zofur ano and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 61% of the theoretical, C33H33N506S (627.73) R value: 0.25 (silica gel, dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) + = 628 (M + 2H) ++ = 314.7 (M + H + Na) ++ = 325.7 Example 122 2- [N- (4-amidinophenyl) -aminomethyl] -3-methyl-6- [N- (N '(hydroxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sulfonyl] -benzofuran *., & x &jJ &tJe'i j. ~ "*, ia / k ~~ Prepared analogously to Example 3, starting from 2 - [N - (4 - ami di no feni 1) - ami ome ti 1 ] - 3 - met? L-6- [N- (N '- (ethoxycarbonylmethyl) -aminocarbonylmethyl) -quinolin-8-sulfonylamino] -benzofuran and sodium hydroxide solution Yield: 69% of theory, C30H28N6O6S (600.67) Mass spectrum EKA M + H) + = 601 M + Na) + = 623 10 M + 2 H) ++ = 301 M + H + Na 312 M + 2 Na = 323 Example 123 15 2- [2- (4-amidinophenyl) -ethyl] -4-methyl-7- [N- (lH-tetrazol-5-yl-methyl) -quinolin-8-sulfonylamino] -quinoline Prepared analogously to Example LE, starting from 2 - [2 - (4-cyano-phenyl-1) -eti-1] -4-methyl-1-7 - [N-20 (lH-tetrazol-S-yl-methyl) -quinolin -8-sulfonylamino] -quinoline and c 1 or hydride i co-eta n 1 i co, ethanol and ammonium carbonate. Yield: 31% of theory, C30H27N9O2S (577.67) Rf value: 0.15 (gel itself.) me * ce; dichloromethane / ethanol = 4: 1 + glacial acetic acid) Mass spectrum (EKA): (M + H) - + = 578 (M + Na) + = 600 (MH) "= 576 Example 124 L-methyl-2- [N- (4- (Nn-exoxyloxycarbonyl amidino) phenyl) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31 , from 1 -me 111-2 - [N - (4-ami diene f in 11) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -qu? nol? n-8-su 1 f on 11 ami no] - benzium zo 1 and n-hexyl ester of acid c 1 orofo rmi co. Yield: 61% of theory, C36H4iN706S (699.84) Rf value: 0.60 (silica gel, dichloromethane / methanol = 9: 1) Mass spectrum (EKA): (M + H) + = 700 (M + Na) + = 722 (M + H + Na) ++ = 361, 8 Example 125? l-methyl-2- [N- (4- (Nn-octyloxycarbonylamido) phenyl) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, from 1 -me ti 1 - 2 - [N - (- amidí no f eni 1) - aminomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8- su 1 f on 11 ami no] -b ene imi da zo 1 and sternium-octyl 1-acidic acid. Yield: 65% of theory, C38H45N706S (727.89) Rf value: 0.58 (silica gel, dichloromethane / methanol = 9: 1) 15 Mass spectrum (EKA): (M + H) + = 728 (M + Na) + = 750 (M + H + Na) ++ = 375.8 E n g lish 126 20 l-methyl-2- [N- (4- (Nn-bu ti loxycarbonylamino) phenyl) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfoni lamino] -benzimidazole Prepared analogously to Example 31, starting from 1 -me ti 1 - 2 - [N - (4-ami di no f in i 1) - .S »£ j & & "tS £ L᧠.. ^ .: SSík. Itesgí aminomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8- its 1 f on i 1 ami no] -benz imi da zo 1 and é Sulfuric acid ionic acid cyclophosphoric acid yield: 64% of theory, C34H37N706S (671, 78) R value: 0.57 (silica gel, dichloromethane / methanol = 9: 1) Mass spectrum (EKA): (M + H) + = 672 (M + Na) + = 694 10 (M + H + Na) ++ = 347.8 Example 127 L-methyl-2- [N- (4-amidino-2-methyl-toxophenyl) -aminomethyl] -5- (N-methyl-benzenesulfonylamino) -benzimidazole Prepared analogously to Example le, starting from 1-methyl 1 - 2 - [N - (4-cyano-2-methoxy-1-pheny1) -ammomethyl] -5- (N-methyl-benzenesulfonylamino) -benzimidazole and ethanolic hydrochloric acid, ethanol and ammonium carbonate. 20 Yield: 57% of theory, C24H26N603S (478.6) Mass spectrum (EKA): (M + H) + = 479 (M + Na) + = SOI .i88S3 »< muk > EXAMPLE 128 l-Methyl-2- [N- (4-amidinophenyl) -ammomethyl] -5- (N-methyl-phenyl-acetylamino) -benzimidazole Prepared analogously to Example le, from 1 - I 111 - 2 - [N - (4 - cia no fen 11) - ami nome 111] - 5 - (N -me 111 - fen 11 - a ce 111 ami no) - be nc ími da zo 1 and ethanolic hydrochloric acid , ethanol and baby carbonate. Yield: 54% of theory, C25H26N60 (426.53) R value: 0.27 (silica gel, dichloromethane / methanol = 5: 1) Mass spectrum (EKA): (M + H) + = 427 (M + 2H) + + = 214 Example 129 L-Methyl-2- [N- (4- (N-benzoy-lamidino) -phenyl) -aminomethyl] -5- [N- (ethoxycarbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, from 1 -me 111-2 - [N - (4-amidi not f eni 1) -ammomethyl] -5- [N- (ethoxycarbonylmethyl) -qu? nol? n-8-su 1 f on i 1 ami no] -beneficium zo 1 and benzoyl chloride. Yield: 54% of theory, C36H33 705S (675.77) '? ^% .. ^, - ^ * -, ^ - ** ¿,. . ^ ..t ^ üfe ifeáw .. *** -. »Mass spectrum: (M -?) + = 676 (M + Na) + = 698 EXAMPLE 130 1-methyl-2 - [N- (4 - (N-benzoylamidino) -phenyl) -aminomethyl] -5- [N- (n-propyloxycarbonylmethyl) -quinino-8-sulfonylamino] -benzimidazole Prepared analogously to Example 31, from 1 -me 111-2 - [N - (4-ami di-phen-11) -aminomethyl] -5- [N- (n-propyloxycarbonylmethyl) -qumolm-8-sulfon-lammo] - benzimidazole and benzoyl chloride. Yield: 52% of theory, C37H35N705S (689.77) Mass spectrum: (M + H) + = 690. (M + Na) + = 712 E-use 131 Dry ampoule with 75 mg of active ingredient per 10 ml C ompo s i c on: Active ingredient 75.0 mg Mannitol 50.0 mg Water for injection purposes up to 10.0 ml Preparation *. ^? ^ X2r ^, - The active principle and mannitol dissolve in water. After filling, it is lyophilized. The solution for making the solution ready for use is made with water for injection purposes.

Example 132 Dry ampule with 35 mg of active ingredient per 2 Compo s i c on: 10 Active ingredient 35.0 mg Mannitol 100.0 mg Water for injection purposes up to 2.0 ml Preparation: 15 The active principle and mannitol dissolve in water. After filling, it is lyophilized. The solution for giving the ready-to-use solution is made with water for injection purposes.

E n g lis 133 Tablet with 50 mg of active ingredient Compo s i c ons: 25 (1) Active ingredient 50.0 mg 2) Lactose • 98.0 mg 3) Corn starch 50.0 mg 4) Po 11 vi n i lp i r r 11 11 dona 1 15 15 mg 5) Magnesium stearate 2.0 mg 215.0 mg Preparation: (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granulate is added by mixing (5). Compressed, biplanes, faceted on both sides and dividing notch on one side are pressed from this mixture. Diameter of the tablets: 12 mm.

E xemplode 134 Tablet with 350 mg of active ingredient C ompo sition: (1) Active ingredient 350.0 mg (2) Lactose 136.0 mg (3) Corn starch 80.0 mg (4) Po 11 vi ni lp irro 11 don 30.0 mg (5) Magnesium stearate 4.0 mg 600.0 mg Preparation ? Íjí &t; Ot? Is & ? i (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granulate is added by mixing (5). Compressed, biplanes, faceted on both sides and dividing notch on one side are pressed from this mixture. Diameter of the tablets: 12 mm.

E n g lis 135 Capsule with 50 mg of active ingredient C ompo sition: (1) Active ingredient 50.0 mg (2) Dried corn starch 58.0 mg (3) Powdered lactose 50.0 mg (4) Stearate magnesium 2, 0 mg 160.0 mg Preparation: (1) mix by grinding with (3). This crushed mixture is added, under intense mixing, to the mixture based on (2) and (4). This powder mixture is introduced into a capsule packing machine into hard gelatin plug-in size 3 capsules. eÜStueste fcSfe & assss E 3 emplo 136 Capsules with 350 mg of active ingredient C omp osition: (1) Active ingredient 350.0 mg (2) Dried corn starch 46.0 mg (3) Powdered lactose 30.0 mg (4) Magnesium stearate 4.0 mg 430.0 mg Preparation: 10 (1) is mixed by grinding with (3). This crushed mixture is added, under intense mixing, to the mixture based on (2) and (4). This powder mixture is introduced into a capsule filling machine in plug-in capsules of size 0 gelatin aura.

E -jus 137 Suppositories with 100 mg of suppository active ingredient contains: 20 Active ingredient 100.0 mg Polyethylene glycol (MW 1500) 600.0 mg Polyethylene glycol (MW 6000) 460.0 mg Polyethylenesorbitan monostearate 840.0 mg 25 2 0 0 0, 0 mg -;;, - - at at at at at at at at at at at at at at at Preparación Preparación Preparación Preparación:::::::::::: at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at at At 40 ° C, the milled active substance is dispersed homogeneously in the melt. It is cooled to 38 ° C and poured into weakly cooled suppository molds beforehand.

* VkM¡tHÍ¡ ÍL

Claims (12)

1. Bicyclic disubstituted heterocycles of the general formula Ra-Het-B-Ar-E, (I) wherein B means an ethylene group, optionally substituted with one or two C? -3 alkyl groups, a methylene group may be replaced of the ethylene group, which is linked with the radical Het or Ar, by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, carbonyl or -NRi group, Ri representing a hydrogen atom or a C? -6 alkyl group, or B also means a linear chain C al5 alkylene group, in which a methylene group, which is not linked to the radical Het or to the radical Ar, is replaced by a group NRi, in which Ri is defined as mentioned above, E means a cyano group or RbNH-C (= NH), wherein Rb represents a hydrogen atom, a hydroxy group, a C i _ 3 alkyl group or a radical cleavable in vivo, Ar means a phenylene group or naphthylene, optionally substituted with a fluorine, chlorine or bromine atom, with a trifluoromethyl group, C 1 -C 3 alkyl or C 1 -C 3 alkoxy, means a thienylene, thiazolylene, pyrid, and not pyrimidine group, pyridinylene or pyridinium, optionally substituted on the skeleton of carbons with an alkyl group C i -. , Het means a bicyclic heterocycle of the f or rmu 1 a wherein X represents a nitrogen atom or a methino group, optionally substituted with a C? _3 alkyl group, and Y represents an amino group, optionally substituted with a C 1-5 alkyl or C3_7 cycloalkyl group, an oxygen or sulfur atom or X represents a nitrogen atom and Y represents a group im not substituted with a C 1-5 alkyl or C 3-7 cycloalkyl group, the alkyl and cycloalkyl substituent being substituted in each case with a carboxy group or with a transformable group m alive in a group carboxy, being able to be replaced in one of the above-mentioned heterocycles ad 1 c 1 on a non-angular methine group by a nitrogen atom, or Het means a group of the f or rmu la. Rx being defined as mentioned above, and Ra, means a phenyl-C3-alkoxy group, an amino group, a C3_3-amino alkyl group which is substituted at the nitrogen atom additionally with a phenyl group 1 - to 1 qu and 1 or C? -3, a group R3-CO-R4N or R3-SO2-R4N, in which R3 represents a C1-5 alkyl group, phenyl 1 - a 1 qu i 1 or C? _3, C3-7 cycloalkyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tetr ah i dr oqu i no 1 i 1 ootetr ah i dr ois oqu i no 1 i 1 o and R4 represents a hydrogen atom, a C1- alkyl group. 5 or phenyl-C 1 _ 3 alkyl, which in each case is substituted on the alkyl part with a group which can be transformed in vivo into a carboxy group, with a carboxy or tetrazolyl group, with an ami nocarbon on 11 oo alkyl C? The ammonia is either substituted, or in each case substituted at the additional nitrogen atom with a transformable group m in a carboxy-C C-3 alkyl group, or with a carbohydrate group. xi represents a C2-5 alkyl group substituted in terminal position with a di- (C3_3) alkyl group -amino, or a C3_7 cycloalkyl group, their tautomers, their stereoisomers and their salts.

2. Bicyclic heterocycles di sust 1 tu 1 do s of the general formula I according to claim 1, wherein B means an ethylene group, optionally substituted with one or two methyl groups, and a methylene group of the ethylene group, which is linked, can be replaced. with the radical Het or Ar, by an oxygen or sulfur atom, by a carbonyl group or -NRi, Ri representing a hydrogen atom or a methyl group, or B also means an n-propylene group, in which the methylene group central is replaced by a group ~ NR ?, in which R1 is defined as mentioned above, E means a cyano group or RbNH-C (= NH), in which R represents a hydrogen atom, an alkyloxy group C? -B, -carbonyl, a cyc 1 or a 1 qu group 11 oxyC 5 _ -carbon 11 o, benzoyl, nicotinoyl or 1 s on 1 co 11 not 11 o, Ar means a phenylene group, optionally substituted with a fluorine, chlorine or bromine atom, with a tr 1 f 1 or ome 111 or, methyl or methoxy, or a thienylene group, optionally substituted with a methyl group, Het means a bicyclic heterocycle of formula X represents a nitrogen atom or a methine group, optionally substituted with a methyl group, and Y represents an amino group optionally substituted by a C 1-3 alkyl or C 3-7 cycloalkyl group, an oxygen or sulfur atom, or X represents a nitrogen atom and Y represents a group imino substituted with a C 1-3 alkyl group, the alkyl part being substituted ad 1 c 1 ona with a carboxy or C 1 -C 3 alkyloxy group or, or Het means a group of the formulas I Ri being defined as mentioned above, and R2 represents an alkyl group C1-3 substituted with a carboxy or C ?3-carbonyl alkoxy group, and Ra, means a benzyloxy group, an amino group, a C alqu --.-3-amino alkyl group which is further substituted at the nitrogen atom with a group benzyl, a group R3-CO-R4N or R3-S02-R4N, in which R3 represents a C4_4 benzyl, C5.7 cycloalkyl, phenyl, pyridyl, quinolyl, isoquinolyl, tetr ah idr oqu i no 1 i 1 alkyl group ootetrahydroiso qu i no 1 i 1 o and R4 represents a hydrogen atom, a C1-3 alkyl group, which is substituted with a carboxy group, C1-3 alkoxycarbonyl, tetrazolyl, aminocarbonyl or Ci -3 alkyl-ami noc ar bon i 1, the aminocarbonyl and C 1-3 alkyl amyl groups being unsubstituted or, in each case at the nitrogen atom, additionally substituted with a car box group i - a 1 qui 1 or C1-3 or C 1 -3-alkoxy-carbon-1-C 1 -alkyl, or a C 2-3 alkyl group substituted in terminal position with a di- (C 1-3 -alkyl) -amino group, its isomers and us salts.

3. Bicyclic di substituted heterocycles of the general formula I according to claim 1, wherein B means an ethylene group optionally substituted with one or two methyl groups, a methylene group of the ethylene group, which is linked to the radical Het, can be replaced. or Ar, for an oxygen or sulfur atom, for a group < ¡Ft »sS5?» Afe - ..,., »-. ,, & < The carbonyl or -NRlf representing Ri a hydrogen atom or a methyl group, or B also means an n-propylene group, in which the central methylene group is replaced by a group - NRi, in which Ri is defined as mentioned above, E means a group R NH-C (= NH), in which R represents a hydrogen atom, an alkyloxy group Ci-β, -carbonyl, a group 1 or 1 i i axi C 5 -7 - carboni 1 oo benzoyl, Ar means a phenylene group, optionally substituted by a fluorine, chlorine or bromine atom, with a tr 1 f 1 or r ome th 1 or methyl group or methoxy, or a thienylene group, optionally substituted with a methyl group in the carbon skeleton, Het means a bicyclic heterocycle of the formula X represents a nitrogen atom or a methine group, optionally substituted with a methyl group, and Y represents an imino group, optionally substituted with a C1-3 alkyl group or C-7 cycloalkyl, an oxygen or sulfur atom, or X represents a nitrogen atom and Y represents an imino group substituted with a C 1-3 alkyl group, the alkyl part being further substituted with a carboxy or C 1-3 alkyloxy group, and R a benzyloxy group, an amino group, a C 1 -C 3 alkyl group -amino which is substituted at the nitrogen atom by addition with a benzyl group, a group R3-CO-R4N or R3-SO2-R4N, wherein R3 represents a C1-4 alkyl group, benzyl, C5-7 cycloalkyl, phenyl, pyridyl, quinolyl, isoquinolyl, tetrahi dr oqu i no 1 i 1 oo 10 tetrahi dr ois oqu i no 1 i 1 o and R4 represents a hydrogen atom, a C? -3 alkyl group, which is substituted with a carboxy group, C 1 _ 3 -carbonyl, tetrazolyl, aminocarbonyl or C 1 alkyl alkoxy - ami no car bon i 1 o, the groups being replaced 15 ami ocar bon 11 oy alkyl C 1 - 3 - ami nocarboni 1 or, in each case at the nitrogen atom, additionally with a carboxy - a 1 qu i 1 or a C1-3 or a C 1 --3 alkoxycarbonyl group - C1-3 alkyl, or a C2-3 alkyl group substituted terminally with di- (C 1-3 alkyl) -amino group, 20 and its isomers and their salts.

4. Bicyclic heterocycles di s t i t u i s of the general formula I according to claim 3, in which Ra in position 5 means a group R3-CO-25 R4N or R3-SO2-R4N, which R3 and R4 are defined - é® & amp; amp; as mentioned above, their isomers and their salts.

5. Bicyclic heterocycles di s t i t u i t s of the general formula wherein X means a methino group or a nitrogen atom, B means an ethylene group, the methylene group being replaced by Ar being replaced by an oxygen atom or an imino group, Ar means a group 1, 4-fe ni 1 e no, E means an amidino group, Rx means a methyl group and Ra, means a group R3-CO-R4N or R3-SO2-R4N, R4 representing a methyl group substituted with a carboxy group, C 1 -3 alkoxy - car bon i 1, carox ime ti 1 ami no - ca r bon i 1 oo alkoxy Ciscar bon i lme ti 1 ami no ca rbon i 1, and R3 represents a group is oqu i no 1 in - 8 - i 1 o, and its isomers and their salts.

6. Bicyclic heterocycles di s t i t u i s of the general formula according to claim 5, in which Ra represents a group R 3 -CO-R 4 N, its isomers and its salts.

7. The following di-substituted bicyclic heterocycles of the general formula according to claim 5 are: (a) 1-methyl 1 - 2 - [(4-ami di no f in i 1) -oxymethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-su 1 foni 1 ami no] -be nc imi da z ol, (b) l-methyl-2- [2- (4-amidinophenyl) -ethyl] -5- [N- ( NT- (hydroxycarbonylmethyl) -aminocarbonylmethyl) -qui no 1 in-8-su 1 f on i 1 ami no-be nc imi da zo 1, (c) 1-met? L-2- [N- (4 -amidinofenyl) -aminomethyl] -5- [N - (hydroxy-carbonylmethyl) -quinolin-8-sulfonylamino] -benzimidazole and (d) 1 -methyl-2 - [N- (4 -amino dino f eni 1 ) -ammomethyl] -5- [N- (hydroxycarbonylmethyl) -quinolin-8-su 1 f on i 1 ami] - i ndo 1, as well as its salts.

8. Physiologically compatible salts of the compounds according to claims 1 to 7.

9. A medicament containing a compound according to at least one of claims 1 to 7, in which E represents a group R NH-C (= NH), or a salt according to claim 8 together with optionally one or more support substances and / or inert diluent agents.

10. Use of a compound according to at least one of claims 1 to 7 in which E represents a group RbNH-C (= NH), or a salt according to claim 8 for the preparation of a medicament with a thrombin time-prolonging effect , an inhibitory effect of thrombin and a 10 inhibiting effect on related problems.

11. Process for the preparation of a medicament according to claim 9, 15 characterized by the fact that, by non-chemical route, a compound according to at least one of claims 1 to 7, in which E represents a group RR NH-C (= NH), or a salt according to the rei indication 8 is incorporated in one or several 20 support substances and / or inert diluents.

12. Process for the preparation of the compounds according to claims 1 to 8, 25 characterized in that a. for the preparation of a compound of the general formula I, in which E means a group RbNH-C (= NH), in which Rb represents a hydrogen atom, a hydroxy group Or C1-3 alkyl, a compound, optionally formed in the reaction mixture, of the general formula Ra-Het-B-Ar-C (= NH) -Z 1, (II) wherein B, Ar is reacted , Het and Ra are defined as mentioned in claims 1 to 7 and Zi represents an alkoxy, aralkoxy, alkylthio or aralkylthio group, with an amine of the general formula H2N-Rb ', (III) in which Rb' represents a hydrogen atom, a hydroxy group or C1-.3 alkyl or, b. for the preparation of a compound of the general formula I, in which the group Ra and E are defined as in claims 1 to 7, with the proviso that the group Ra contains a carboxy group and E is defined as in the claims 1 to 7, or the group Ra is defined as in the claims 1 to 7 and E represents a NH2-C group (= NH), or the group Ra contains a carboxy group and E represents a group NH2-C (= NH), a compound of the general formula is transformed Ra '- Het - B - Ar - E', (IV) in which A, B, Ar and Het are defined as in claims 1 to 7 and the group Ra 'and E' possess the meanings mentioned in the claims 1 to 7 for the group Ra, and E, with the proviso that the group Ra ', contains a group transformable in a carboxyl group by hydrolysis, treatment with an acid or base, 10 thermolysis or hydrogenolysis, and E is defined as in claims 1 to 7, or E 'represents a group which can be transformed into an NH2-C group (= NH) by hydrolysis, treatment with an acid or base, thermolysis or hydrotreatment. isisy the group Ra, present The meanings mentioned in claims 1 to 7 for the group Ra, or the group Ra ', contain a group which can be converted to a carboxyl group by hydrolysis, treatment with an acid or base, thermolysis or hydrothogen i i s, and E' 20 represents a group which can be converted into an NH2-C group (= NH) by hydrolysis, treatment with an acid or a base, thermolysis or hydrogenolysis, by hydrolysis, treatment with an acid or base, thermolysis or hydrogenolysis in a compound 25 of the general formula I, in which the group Ra, and E a »& 3SSg-S« ^ ja are defined as mentioned in claims 1 to 7, with the proviso that the group Ra contains a carboxy group and E is defined as in claims 1 to 7, or the group Ra, present the meanings mentioned in claims 1 to 7 and E represents a group NH2-C (= NH), or the group Ra, contains a carboxy group and E represents a group NH2-C (= NH) or c. for the preparation of a compound of the general formula I, in which the group Ra contains one of the ester groups mentioned in claims 1 to 7 in the definition of the group Ra a compound of the general formula Ra "- Het - is reacted B - Ar - E, (V) in which B, E, Ar and Het are defined as claims 1 to 7 and the group Ra "has the meanings mentioned in claims 1 to 7 for the group Ra, with the proviso that that the group Ra "contains a carboxyl group or a group transformable in a corresponding ester group by an alcohol, with an alcohol of the general formula HO-R8, (VI) in which Rs represents the alkyl part of one of the said in vivo cleavable radicals claim 1, with excision of the group R5 -CO-0- (R5CR7) for a-, carboxyl group, or with their formamidoacetals or with a compound of the general formula Z2-R9, (VII) wherein Rg represents the alkyl part of one of the radicals in vivo separable mentioned claims 1 to 7, with the exception of the group R5-CO-O- (R5CR7) for a carboxyl group and Z2 represents a leaving group, or d. for the preparation of a compound of the general formula I, in which Rb represents an in vivo cleavable radical, a compound of the general formula Ra-Het-B-Ar-C (= NH) -NH2 is reacted, (VII ) wherein Ra, Het, B and Ar are defined as claims 1 to 7, with a compound of the general formula Z3-Rio, (IX) wherein R10 means an in vivo cleavable radical and Z3 means a leaving group nucleofuge, or e. for the preparation of a compound of the general formula I, in which Ra represents an amino group and E represents a cyano group, a nitro compound of the general formula N02 - Het - B - Ar - CN, (X) is reduced wherein B, Ar and Het are defined as mentioned in claims 1 to 7, of. for the preparation of a compound of general formula I, in which Ra represents an amino group and E represents a cyano group, a protective radical for an amino group of a compound of the general formula Ra "'- Het - is removed B - Ar - CN, (XI) 10 in which B, Ar and Het are defined as mentioned in claims 1 to 7 and Ra "? means an amino group protected by a protective radical, or g. for the preparation of a compound of the general formula I, in which Ra represents a group R3-CO-R4N or R3-S02-R4N and E represents a cyano group, a compound of the general formula R4NH-Het is reacted - B - Ar - CN, (XII) in which R4, Het, B and Ar are defined as mentioned in claims 1 to 7, with a compound of the general formula R3 - X - Z4, (XIII) wherein R3 is defined as mentioned in claims 1 to 7, X means a carbonyl or sulfonyl group and Z4 means a gi ^ íg | ^^ jgttKgte nucleophilic labile group or also, in the case that X represents a carbonyl group, means, together with another hydrogen atom of the contiguous nitrogen atom, another bond car bond - n 11 r oge no, or h. for the preparation of a compound of the general formula I, in which Ra represents a group R -CO- R 4 N or R 3 -SO 2 -R 4 N and E represents a cyano group, wherein R 4 is defined as mentioned above; 7, except for the atom Hydrogen, a compound of the general formula R3-X-NH-Het-B-Ar-CN is reacted, (XIV) wherein R3, Het, B, Ar and X are defined as mentioned 15 claims 1 to 7, with a compound of the general formula R4 '- Z5, (XV) in which R4' possesses, with the exception of the hydrogen atom, the meanings mentioned 20 claims 1 to 7 for R4 and Z5 means a nucleophilic leaving group, or i. for the preparation of a compound of the general formula I, in which R 4 represents a C 1-5 alkyl group or f e n i 1 - a 1 q i 1 or C 1-3, which is substituted in each case in the 25 of alkyl with a group which can be converted into a ^^? ítJSs «? ¿¿i¡ ^ & üs¡h. carboxy group, with a tetrazolyl group, with an aminocarbonyl group or an optionally substituted C.sub.1 -C.sub.3 -amino group, which in each case are substituted on the nitrogen atom, additionally, with a transformable group m alive in a group car box i - a 1 qu i 1 or C? -3, and E represents a cyano group, a compound of the general formula R3-X-NR4 '- Het - B - Ar - CN, (XVI) is reacted in wherein R3, Het, B, Ar and X are defined as mentioned in claims 1 to 7 and R4 'means a C1-5 alkyl group of 1 to 1 to 1 to 1 to 1 to 3 in each case, is substituted on the alkyl part with a group which can be converted in vivo into a carboxy group, with a tetrazolyl group, with an aminocarbonyl group or a C 1 -3-amino alkyl group or which, in each case, is substituted at the nitrogen atom, additionally, with a group transformable in vivo in a car box group i-a 1 qu i 1 or C 1-3, or its derivatives reactive with a compound of the formula Rn-H, (XVII) in which R4 'has the meanings mentioned in claims 1 to 7 for R4, with the exception of the hydrogen atom, and Rn represents a substituent mentioned in claims 1 to 7 in the definition of the radical R4, of the alkyl group C5.5 ofen 11 - to 1 qu1 1 or C3_3, which is linked to the radical Rn through a carbonyl group, oj. for the preparation of a benzothiazolyl or benzoxazolyl benzothiazolyl compound of the general formula I, in which B represents an ethylene group, a compound, optionally formed in the reaction mixture, is reacted the general formula in which (XVIII) Ra and Y are defined as mentioned in claims 1 to 7, with a compound of the general formula HO-CO-B '-Ar-E, (XIX) in which Ar and E are defined as mentioned claims 1 to 7 and B 'means an ethylene group, optionally substituted with one or two C1-3 alkyl groups, or k. for the preparation of a compound of the general formula I, which contains one of the tetrahydric or non-1-one or isoquinoline radicals mentioned in claims 1 to 7, a compound of the general formula I containing one is hydrogenated. of the quinolha or isoquinoline radicals mentioned in claims 1 to 7 and, if necessary, then a protection is separated for reactive groups optionally present, used in the reactions described above, and / or if desired, then a compound of the General formula I, thus obtained, is separated into its stereoisomers and / or a compound of general formula 1, thus obtained, is transformed into its salts, in particular into its physiologically compatible salts.