MXPA00012966A - Sulfur substituted sulfonylaminocarboxylic acid n-arylamides, their preparation, their use and pharmaceutical preparations comprising them - Google Patents

Abstract

The present invention relates to compounds of formula (I), wherein A1, A2, R1, R2, R3, X and n are as defined in the claims, which are valuable pharmaceutically active compounds for the therapy and prophylaxis of diseases, for example of cardiovascular diseases such as hypertension, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of formula (I) are capable of modulating the body's production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of formula (I), to their use for the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of formula (I).

Description

SULFONYLAMINOCARBOXYLIC ACID N-ARILAMIDES WITH SUBSTITUTION OF SULFUR, ITS PREPARATION, ITS USE AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM SULPHONYLAMINOCARBOXYLIC ACID The present invention relates to compounds of the formula I wherein A1, A2, R1, R :, R3, X and n are in accordance with what is defined below, which are valuable pharmaceutically active compounds for the therapy and prophylaxis of diseases, for example, cardiovascular diseases such as hypertension, chest, heart failure, thrombosis or atherosclerosis. The compounds I of formula I are capable of modulating the body production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of diseases associated with an imbalance of cGMP. The invention also relates to processes for the preparation of compounds of the formula I, their use for the therapy and prophylaxis of the aforementioned diseases and for the preparation of pharmaceutical products for this purpose, and to pharmaceutical preparations comprising compounds i of formula I. 5 cGMP is an important intracellular messenger that triggers several different effects through the modulation of cGMP dependent protein kinases, phosphodiesterases and ion channels. Examples are relaxation of smooth muscles, inhibition of thrombocytosis activation and • Inhibition of the proliferation of smooth muscle cells and the adhesion of leukocytes. cGMP is produced by particulate and soluble guanylate cyclase in response to various extracellular and intracellular stimuli. In the case of the particular guanylate cyclase, the stimulation is performed essentially by peptide messengers such as atrial natriuretic peptide or the natriuretic peptide! cerebral. Soluble guanylate cyclase (sGC), which are • Cytosolic heterodynamic heme proteins, in contrast, are essentially regulated by the family of factors low molecular weight formed enzymatically. The most important stimulant is nitrogen monoxide (NO) or a closely related species. The function of other factors such as carbon monoxide or the hydroxyl radical still remains largely unclear. The Union of NO on heme with pentacoordinated hemo-nitrosyl complex formation is discussed as the activation mechanism of NO activation. The associated release of histidine that is bound in the basal state with iron converts the enzyme into active conformation. Active soluble guanylate cyclase consist of a unit a and a unit β. Several subunit subunits have been described that differ among them in relation to sequence, tissue-specific distribution, as well as expression at different stages of development. The di and ßi subtypes are expressed mainly in the brain and lung, whereas ß2 is found particularly in the liver and kidneys. The ß2 subtype is present in the human fetal brain. The subunits known as as and ß3 were isolated from the human brain and are homologous to ai i and ßi. More recent studies indicate an a2 and I subunit that contains an insert in the catalytic domain. All the subunits show greater homologies in the region of the catalytic domain. Enzymes probably contain one heme per heterodimer, which is linked through ide ß? ~ Cys-78 and / or ß? -His-105 and is part of the regulation center! Under pathological conditions, the formation of guanylate cyclase activation factors may be reduced, or their degradation may be promoted due to the increasing occurrence of free radicals. The resulting reduced activation of sGC leads, through a weakening of the cell response mediated by respective cGMP, to, for example, an increase in blood pressure, platelet activation or cell proliferation. • increased and greater cell adhesion. Due, 5 the result is the formation of an endothelial dysfunction, atherosclerosis, hypertension, stable or unstable angina, thrombosis, myocardial infarction, strokes, or erectile dysfunction. The pharmacological stimulation he sGC offers a possibility to normalize the production of cGMP and therefore makes possible the treatment and / or prevention of disorders of this type. For the pharmacological stimulation of sGC, until now almost exclusively compounds have been used whose activity is based on a release of intermediate NO, for example organic nitrates. The drawback of this treatment is the development of tolerance and a reduction in activity, and the higher dosage that is required due to this. Several stimulators of sGC that do not act through the release of NO were described by Vesely in a series of 20 publications. However, the compounds, most of which are hormones, plant hormones, vitamins, or natural compounds such as, for example, lizard poisons have predominantly only weak effects on the formation of cGMP in used cells (D.L.

Vesely, Eur. J. Clin. Invest. 15 (1985) 258; D. L. Vesely, Biochem. Biophys. Res. Comm. 88 (1979) 1244). 'A stimulation of guanylate cyclase without heme by protoporphyrin A IX was demonstrated by Ignarro et al. (Adv. Pharmacol., 26 (1994) 35). Pettibone et al. (Eur. J. Pharmacol. 116 (1985) 5 307) described an antihypertensive action of diphenyliodonium hexafluorophosphate and attributed this to the stimulation of sGC. According to Yu et al. (Brit. J. Pharmacol. (1995) 1587), isoliquiritigenin, which has a relaxing action on rat isolated aortas, also activates sGC. • 10 Ko et al. (Blood 84 (1994) 4226), Yu et al. (Biochem J. 306 (1995) 787) and Wu et al. (Brit. J. Pharmacol. 116 (1995) ¡1973) demonstrated a sGC stimulation activity of 1-benzyl-3- (5-hydroxymethyl-2-furyl) indazole and demonstrated an antiproliferative and thrombocyte inhibiting action. In the EP-A-908456 and DE-A19744027 disclose fused pyrazoles and pyrazoles that exhibit sGC stimulation activity. A number of 2-sulfonylaminobenzoic acid N-arylamides whose N-aryl group carries a thio substituent I 20 has been mentioned in the literature. These compounds in which the N-aryl group generally leads as additional substituent groups which are easily oxidizable, such as, for example, two hydroxy groups which are in the pojsition for relative to each other and which in this case can As hydroquinone derivatives, they are auxiliary for the preparation of photographic materials (see, for example, chemistry abstracts 119, 105757, 120, 41858, 123, 70224 or 126, 257007). If isolated structural elements are considered, then the N-aryl group in these known compounds corresponds to the group in formula I in the case where A1 refers to a residue of 1,4-phenylene which is in the 2-position. and 5 carries hydroxy groups (or oxy substituents), and the number n is 0. British patent publication 876526 (chemistry abstracts 56, 15432e) discloses N- (5-chloro-2- (4-chlorophenylmercapto) -phenyl) ) 3,5-dichloro-2-methylsulphonylaminobenzoic acid amide, which can be used for the protection of wool against moths. The compounds encompassed by GB-A-876526 correspond to compounds of the formula I if simultaneously the ring A1 comprising the carbon atoms carrying the groups C (= X) -NH- and NH S02R2, together with the residues R3, is a benzene ring carrying from one to four halogen atoms of the chlorine and bromine series, R is alkyl (C? ~ C), X is oxygen and the group Ri-S (0) n-A1- is a residue of phenylmercaptophenyl (= phenylthiophenyl) which is substituted by halogen and / or trifluoromethyl and which may also be substituted by methyl or (C? -C4) alkoxy, and the total number of halogen atoms and trifluoromethyl groups is greater than two. No pharmacological activities of these known N-arylamides of 2-sulfonylaminobenzoic acid are disclosed. Surprisingly, it has been found that the compounds of the present invention effect a strong activation of guanylate cyclase and are therefore suitable for the therapy and prophylaxis of disorders associated with a low level of cGMP. Thus, the present invention relates to compounds of the formula I wherein A1 is a divalent residue of the phenylene, naphthylene and heteroarylene series which may be substituted by one or more identical or different substituents selected from the series of halogen, alkyl (C? -C5), phenyl, tolyl, CF3 / N02, OH, -O-alkyl (C1-C5), -O-alkyl (C2-C4) -O-alkyl (C? -C3), alkylenedioxy (C? -C2), NH2, -NH- (C1-C3) alkyl -N ((Ci-C3) alkyl) 2, -NH-CHO, -NH-CO- (C1-C5) alkyl • ~ CN, -C0-NH2, ^ CO-NH- (C1-C3) alkyl, -CO-N (C1-C3) alkyl) 2, -CO-OH, -p? -0- (C1-C5) alkyl, heterocyclyl , CHO, -CO- (C1-C5I) alkyl, S (0) n- (C1-C4) alkyl, -S (0) n-phenyl and -S (0) r-tolyl; the A2 ring comprising the carbon atoms it carries - the C (= X) -NH- and NH-S02R ~ groups is a benzene ring, a naphthalene ring, a 3-7 membered saturated or partially unsaturated carbocycle, a saturated or partially unsaturated or aromatic monocyclic 5 to 7 membered heterocycle containing one or more ring heteroatoms selected from the N, 0 and S series, or a saturated 8 to 10 saturated or partially unsaturated or aromatic bicyclic heterocycle contains one or more ring heteroatoms selected from the series N, 0 and S; R1 is aryl, heterocyclyl or alkyl (Ci-Ciß) which can be substituted by one or more identical or different R4 residues, or, if the number n in the group R1-S (0) n-? Is 2, R1 can also be NR5R ° or, if the number n in the! group R ^ SIOJn- is 0, R1 can also be -CN; R2 is aryl, heterocyclyl, NR = R6 or alkenyl (Ci-Cio) which may be substituted by one or more identical or different R4 residues; , R3 refers to one or more identical or different residues selected from the series hydrogen, halogen, CF3, I OH, -O-C1-C7 alkyl, -O-C2-C alkyl-O-alkyl (C? - | C.), -O-aryl, (C1-C12) alkylenedioxy • N02, -CN -NR7R8, -CO-OH, pCO-O- (C1-C5) alkyl, heterocyclyl, -S (O) r-alkyl (C1-C5I) and (C1-C5) alkyl which may be substituted by one or several identical or different R4 residues; R4 is fluorine, OH, -O-(C1-C10) alkyl, -O-(C2-C4) alkyl-0-alkyl (C? -C ~), -O-aryl, -CN, NRRS, -CO- NH;, -CO-NH- (C1-C3) alkyl, -CO-N- ((C? -C3) alkyl) 2 # -CO-OH, -CO-O -alkyl (C? ~ C5), heterocyclyl or oxo; R5 is hydrogen, (C1-C10) alkyl which may be substituted by one or more identical or different R4 substituents and / or by aryl, or is aryl, heterocyclyl, -CO-NR7R8, -CO-aryl or -CO -alkyl (C1-C10), where the alkyl residue may be substituted by one or more identical or different R4 residues; R, 66 i; n_dJe "p_e" Vn, dJiJe.n-t? -e-m "e?" Nt? -e- dJe_ Rr > s5 has one of the indicated meanings for R 5, or R 5 and R 6 together with the nitrogen atom on which they are attached form a saturated or partially unsaturated 5 to 8 membered ring which, in addition to the nitrogen atom carrying the R 5 groups and R6 may contain one or more additional ring heteroatoms selected from the series N, O and S and which may be substituted by one or more substituents identical or different from the fluorine series, (C1-C5) alkyl, hydroxy-alkyl (C1-C3), alkyl (Ci-C3) -O-(C1-C4) alkyl, aryl, CF3, OH, -O-(C1-C7) alkyl, -0-aryl, -O-alkyl (C2- C4) -O- (C1-O7) alkyl, (C2-C3) alkylenedioxy, NR7R8, -CN, -CO-NH2, -CO-NH- (C1-C3) alkyl, -CO-N (alkyl (C? -C3)) 2, -CO-OH, -CO-O-alkyl (C1-C5) • CHO, -CO-alcjuyl I (Ci-Cs), -S (O) n-alkyl? (C? ~ C4), -S (0) n-NH2, -S (O) n-NH-alkyl? (C1-C3), -S (0) nN ((C? -C3) alkyl) 2 oxo, -CH2) m-NH2), - (CH2) m- NH- (C1-C4) alkyl and - (CH2) ) mN ((C: -C4) alkyl) 2 wherein in the substituent - (CH2) mN ((CX-C4) alkyl) 2 the two alkyl groups can be connected through a single bond and then together with the The nitrogen carrying them can form a 5- to 7-membered ring which, in addition to this nitrogen atom and the carbon atoms, can additionally contain an oxygen atom, a sulfur atom or a NR group as a ring member; R7 is hydrogen or (C1-C7) alkyl which may be substituted by one or more substituents identical or different from the OH series, -O-C1-C5 alkyl, NH2, -NH-alkyl (C? -fC4) and -N ((C?-C4) alkyl) 2 wherein the N (alkyl (C ?LC)) 2 substituent the two alkyl groups can be connected through a single bond and then together with the nitrogen atom it takes to form a ring of 5 to 7 members which, in addition to this nitrogen atom and the carbon atoms I may also contain an oxygen atom, a sulfur atom1 or a group NR5 as a ring member; R8 independently of R7 has one of the meanings] of R7 or is -CO- (C1-C4) alkyl; aryl is phenyl, naphthyl or heteroaryl which may be substituted by one or more substituents identical or different from the series of halogen, (C1-C5) alkyl, phenyl, tolyl, CF3, -0-CF3, N02, OH, -O -alkyl (C1-C5), -O-alkyl (C2-C4) -O-alkyl (C1-C3), alkylenedioxy (CC :), NH2, -NH- • (C1-C3) alkyl, -N (alkyl) (C1-C3)) 2, -NH-CHO, -NH-CO-acyl 5 (C1-C5) -CN, -CO-NH2, -CO-NH- (C1-C3) alkyl, -CO-N (alkyl (C? -C3)) 2, -CO-OH, -CO-O-alkyl (C1-C5), heterocyclyl, CHO, -CO- (C1-C5) alkyl, -S (O) n-alkyl (C1-C4), -S (0) n-phenyl S (0) n-tolyl; heteroaryl and heteroarylene are a residue of a heterocycle Aromatic 5 or 6-membered or an 8- to 10-membered bicyclic aromatic heterocycle each containing one or more ring heteroatoms of the N, 0 and S series; heterocyclyl is a residue of a saturated or partially unsaturated heterocycle of 5 to 11 monocyclic members or Polycyclic containing one or more ring heteroatoms of the series N, O and S and which may be substituted by one or more substituents identical or different from the series fluorine, (C1-C5) alkyl, OH, -O-alkyl ( C1-C5), -O-(C2-C4) alkyl-O-(C1-C3) alkyl, NH2, -NH- (C1-C3) alkyl, -N ((Ci- 20 C3) alkyl) 2, -CN , -CO-NH 2, -CO-NH- (C 1 -C 3) alkyl, -CO-N (C 1 -C 2 alkyl, -CO-OH and -CO-0-C 1 -C 5 alkyl; n is 0, either 2; m is 2, 3 or 4, X is 0 or NH or X is a nitrogen atom that is is found bound through a single bond with a ring carbon atom in the group A1, said ring carbon atom is directly adjacent to the carbon atom in A1 bearing the -NH-C (= X) - group of such that the group -NH- • C (= X) - together with the carbon atoms in A1 carrying it forms a fused imidazole ring; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts; where, however, the compound of formula I is excluded Wherein simultaneously the ring A2 comprising the carbon atoms bearing the groups C (= X) -NH- and NH-S02R2 gives them a benzene ring substituted in the 3-position and in the 5-position by chlorine, R2 is methyl, X is oxygen and R1-S (O) n-A1- is a residue of 5-chloro-2- (4-chlorophenylmercapto) -phenyl.

If groups or substituents can occur several times in the compounds of the formula I such as for example R3, R, 4, R5, aryl, heterocyclyl, alkyl, etc. or the numbers n and m can independently have the indicated meanings and can in each case be identical or different.

The alkyl residues can be straight chain or branched. This also applies when they are part of other groups, for example, in alkoxy groups, alkoxycarbonyl groups or amino groups, or when they are substituted. Examples of alkyl groups are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, the n-isomers of these residues, isopropyl, isobutyl, isopentyl, sec-butyl , tert-butyl, neopentyl, 3,3- 5 dimethylbutyl. The term "alkyl" also expressly includes unsaturated alkyl residues, that is, alkyl residues containing one or more double bonds and / or one or more triple bonds such as, for example, alkenyl residues and alkynyl residues. Obviously an unsaturated alkyl group contains at least two carbon atoms. Specific alkyl groups I whose number of carbon atoms can vary from up to a given upper limit, therefore also comprise unsaturated alkyl groups whose number of carbon atoms can vary from 2 up to the upper limit, given.

Examples of such residues are the vinyl residue, the 1-propenyl residue, the 2-propenyl residue (allyl residue), the 2-butenyl residue, the 2-methyl-2-propenyl residue, the 3-methyl-2 residue. -butenyl, the ethynyl residue, the 2-propynyl residue (propargyl residue), the 2-butynyl residue or the 3-butynyl residue. In addition, the term "alkyl" also expressly includes alkyl residues in which, through the closure of an internal ring within the alkyl group, a cyclic system is formed, that is, the term "alkyl" also includes saturated cycloalkyl residues and partially unsaturated and cycloalkyl-alkyl residues (alkyl substituted by cycloalkyl). Obviously, a monocyclic cycloalkyl group contains at least 3 atoms of carbon. Specific alkyl groups whose number of carbon atoms can vary from 1 to a given upper limit, therefore also comprise monocyclic cycloalkyl groups whose number of carbon atoms can vary from 3 up to the given upper limit, and appropriate cycloalkyl-alkyl groups. Examples of such cycloalkyl residues are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Cycloheptyl and cyclooctyl which may also be substituted by one or more identical or different (C 1 -C 4) alkyl residues, particularly methyl. Examples of such substituted cycloalkyl residues are 4-methylcyclohexyl, 4-tert-butylcyclohexyl or 2,3-dimethylcyclopentyl. Furthermore, unless otherwise indicated, the term alkyl also includes here expressly unsubstituted alkyl residues as well as alkyl residues substituted by one or more, for example one, two, three or four, identical or different aryl residues. He The term "alkyl" therefore also includes here expressly "arylalkyl" residues such as for example "(C 1 -C 4) arylalkyl", for example, benzyl residues, phenylethyl residues or indanyl residues. In substituted alkyl residues, for example, arylalkyl-hydroxyalkyl-as per Example-(C1-C3) -OH or alkoxyalkyl-such as for example- (Ci- C3) -O-(C1-C4) alkyl, the substituents may be present at any desired position. The 3 to 7 membered saturated or partially unsaturated carbocycle representing the ring can be derived from the monocyclic cyclopropane, cyclobutane, cyclopentane, cyclohexane or cycloheptane origin systems. If the carbocycle is unsaturated, it may contain, for example, a double bond or, in the case of a 5-membered ring, 6-membered ring or 7-membered ring, may contain * r 10 also two double bonds that can be isolated or conjugated. The double bonds can be present at any position relative to the groups C (= X) -NH- and NH-SO2-R, ie, for example, a double bond can also be present between the two ring carbon atoms. that 15 have these two groups. Unless otherwise indicated, phenyl residues, naphthyl residues and heterocyclic residues, for example, heteroaryl residues, may be unsubstituted or may carry one or more, for example one, two, three or four identical or different substituents which may be in any desired position. Unless otherwise indicated, in these residues, for example, substituents indicated 1 may be present as substituents of an aryl group. A preferred series of Substituents that may be present in the residue aryl are formed by the substituents halogen, alkyl (C | -Cs), phenyl, tolyl, CF3, N02, OH, -O-(C1-C5) alkyl, -O-alkyl ( Ci-C) -O-(C1-C3) alkyl, alkylenedioxy (C? -C2), NH2, -NH- (C1-C3) alkyl, -N ((C? -C3) alkyl) 2, -NH- CHO, -NHH-CO- (C1-C5) alkyl, CN, -CO-NH2, -CO-NH- (C1-C3) alkyl • ¡-CO-N (C1-C3) alkyl) 2, -CO -OH, -CO-0-(C1-C5) alkyl, heterocyclyl, CHO, -CO- (C1-C5) alkyl, -S (0) n-(C1-C4) alkyl, -S (0) n- phenolyl and -S (O) n-tolyl. If in compounds of the formula I nitro groups are present as substituents, in total only up to two nitro groups can be present in the molecules. If phenyl residues, phenoxy residues, benzyl residues or benzyloxy residues are present as substituents for example in aryl residues such as phenyl residues and / or in heterocyclic residues then in these substituents the benzene ring may also be unsubstituted or substituted by one or more , for example one, two, three or four identical or different residues, for example residues of the (C1-C4) alkyl, halogen, hydroxy, (C1-C4) alkoxy, trifluoromethyl, cyano, hydroxycarbonyl, (C1- C4)) carbonyl, aminocarbonyl, nitro, amino, alkylamino (C 1 -C 4), di- (C 1 -C 4) alkyl) amino and (C 1 -C 4) alkylcarbonylamino. In monosubstituted phenyl residues, the substituent can be in the 2-position, in the 3-position or in the 4-position, in disubstituted phenyl residues, the substituents can be in the position 2,3, position 2,4, position 2,5, position 2,6, position 3,4, or position 3. 5. in trisubstituted phenyl residues, the substituents may be in the 2-position, 3,4, position 2,3,5, position 2,3,6, position 2,4,5, position 2,3,6, position 2,4,5, position 2,4,6 or position 3, 4,5. Tolyl can be 2-tolyl, 3-tolyl or 4-tolyl. Naphthyl can be -naphthyl or 2-naphthyl. In monosubstituted 1-naphthyl residues, the substituent may be in position 2, position 3, position 4, position 5, position 6, position 7 or position 8, in monosubstituted 2-naphthyl residues, in position 1, position 3, position 4, position 5, position 5, position 6, position 7 or position 8. The above explanations as well as the following explanations regarding monovalent residues are applied correspondingly to the divalent residues feni ^ Leno, naphthylene and heteroarylene. The free bonds through which the divalent residues are bound over the adjacent groups may be present at any ring carbon atom. In the case of phenylene residue, they can be found in position 1,2 (ortho-phenylene), position 1,3 (meta-phenylene), or 1,4-position (para-phenylene). In the case of a naphthylene residue, the free bonds can be found in the 1,2-position (= 1,2-naphthylene or 1,2-naphthalenediyl) or in the 1,3-position, 1,4-position, 1-position, 5, position 1,6, position 1,7, position 1,8, position 2,3, position 2, 6 or position 2,7. In the case of 5-membered ring aromatics containing a heteroatom such as thiophene or furan, the two free bonds can be found in position 2,3, position 2,4, position 2,5, or position 3,4 . A divalent residue derived from pyridine can be a residue 2, 3-2, 4-2, 5-, 2, 6-, 3, 4- or 3,5-pyridinediyl. In the case of non-symmetrical divalent residues, the present invention includes all positional isomers, that is, in the case of a 2,3-pyridinediyl residue, for example, it includes the compound in which the adjacent group is present in the position 2 and the other adjacent group is present in position 3 as well as the compound in which the adjacent group is present in position 3 and the other adjacent group is present in position 2i. Heteroaryl residues, heteroarylene residues, heterocyclyl residues, heterocycles representing ring A2 and rings that are formed by two groups attached to a nitrogen atom together with this nitrogen atom are preferably derived from heterocycles containing one, two, four or four identical or different ring heteroatoms, more preferably heterocycles containing one, two or three in particular one or two identical or different heteroatoms. Unless otherwise indicated, the heterocycles can be monocyclic or polycyclic such as, for example, monocyclic, bicyclic or tricyclic. They are preferably monocyclic or bicyclic. The rings of preference are 5-member rings, 6-member rings | or rings of 7 members. Examples of heterocyclic, monocyclic and bicyclic systems from which residues occurring in the compounds of formula I can be derived are pyrrole, furan, thiophene, imidazole, pyrazole, 1,2,3-triazole, 1, 2,4-triazole, 1,3-dioxole, 1,3-oxazole (= oxazole), 1,2-oxazole (= isoxazole), 1,3-thiazole (= thiazole), 1,2-thiazole (= isothiazole) ), tetrazole, pyridine, pyridazine, pyrimidine, Pyrazine, pyran, thiopyran, 1,4-dioxin, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1 , 2,3-triazine, 1, 2,4-triazine, 1,3,5-triazine, 1,2,4,5-tetrazine, azepine, 1,2-diazepine, 1,3-diazepine, 1,4 - diazepine, 1,3-oxazepine, 1,3-thiazepine, indole, benzothiophene, benzofuran, benzothiazole, benzimidazole, quinoline, isoquinoline, quinoline, quinazoline, quinoxaline, phthalazine, thienothiophenes, 1,8-naphthyridine and other naphthyridines, pteridine, or phenothiazine, each of these in saturated form (perhydro form) or in partially unsaturated form (for For example, the dihydro form or the tetrahydro form) or i in the form of maximum unsaturation, insofar as the respective forms are known and stable. Thus, suitable heterocycles also include, for example, the saturated heterocycles pyrrolidine, piperidine, piperazine, morpholine and thiomorpholine. The degree of saturation of the groups • * * - "- * - '- + ^^^^^^^ heterocycles are indicated in their individual definitions Unsaturated heterocycles may contain, for example, one, two or three double bonds within the anjillo system. 5 members and 6-membered rings can, in particular, also be aromatic.Results derived from heterocyclic hedges can be attached through any suitable carbon atom.Nitrogen heterocycles which can carry a hydrogen atom as a substituent on a carbon atom. ring nitrogen, for example, pyrrole, imidazole, pyrrolidine, morpholine, piperazine, etc., can also be attached through a ring nitrogen atom, particularly if the heterocyclic residue in question is attached to a carbon atom., a thienyl residue may be present as 2-thienyl or 3-thienyl residue, a furyl residue may be present as 2-furyl residue or 3-furyl residue, a pyridyl residue may be present as 2-pyridyl residue, 3-pyridyl residue or 3-pyridyl residue or 4-pyridyl residue, a piperidinyl residue may be present as a 1-piperidinyl residue (= piperidino residue), 2-piperidinyl residue, 3-piperidinyl residue or 4-piperidinyl residue, a residue (thio) ) morpholinyl can be present as 2- I (thio) morpholinyl, residue 3- (thio) morpholinyl or residue 4- (thio) morpholinyl (= thiomorpholino residue). A residual of 1,3-thiazole or imidazole linked through a carbon atom can be bound through position 2, position 4 or position 5. _ ß? Unless otherwise indicated, heterocyclic groups may be unsubstituted or carry one or several, for example one, two, three or four identical or different substituents. Substituents in heterocycles may be present in any desired position, for example, in a 2-thionyl residue, or 2-furyl residue in the 3-position and / or in the 4-position and / or in the 5-position, in a 3-residue. - "thionyl or 3-furyl residue, in position 2 and / or in position 4 and / or in position 5, in a 2-pyridyl residue in position 3 and / or in position 4 and / or in position 5 and / or in position 6, in a 3-pyridyl residue, in position 2 and / or in position 4 and / or in position 5 and / or in position 6, in a 4-pyridyl residue, in the 2-position and / or in the 4-position and / or in the 5-position and / or in the 6-position. Unless stated otherwise, for example the substituents may be present as substituents in heterocyclic groups indicated in the definition of the group Aryl and, in the case of saturated or partially unsaturated heterocycles as additional substituents, also the t-oxo group and the thioxo group may be present. Substituents on a heterocycle as well as substituents on a carbocycle can also form a ring, i.e., a ring system. The rings may also be condensed from. such that, for example, cyclopenta-fused, cyclohexa-fused or benzo-fused rings may also be present. Suitable substituents on a suitable ring nitrogen atom of a heterocycle are, in particular,] for example, unsubstituted (C1-C5) alkyl residues and alkyl residues substituted by aryl, aryl residues, acyl residues such as -CO-alkyl (C1 -C5) or sulfonyl residues such as -S02- (C1-C5) alkyl. Suitable nitrogen heterocycles may also be present as N or 1 oxides as quaternary salts containing a counter-ion derived from a physiologically acceptable acid. Pyridyl residues, for example, may be present as N-pyridine oxides. Halogen is fluorine, chlorine, bromine, iodine, preferably fluorine or chlorine. Without limiting the present invention, in the formulas la, Ib, le, Id, le, If, Ig and Ih, examples of groups of compounds of the invention are shown in which A2 in the formula I has specific denotations. A1, R1, R2, R3, X and n in the formulas la, Ib, le, Id, le, If, Ig and Ih are in accordance with what is defined above for formula I, and the number k in formula Ib is 1 , 2,3,4 or 5, particularly 3 or 4.

In the benzene ring presented in the formula where i carries the groups C (= X) -NH-and-NHS02R2, four positions are present that can carry a residue R3. The compounds of the formula can therefore carry four residues R3 which, according to the definition R3, can all independently of one another be hydrogen or can have a different meaning of hydrogen, that is, in the compounds of the formula Presented benzene in the formula may be unsubstituted or may carry one, two, three or four substituents identical or different from the halogen series, CF3, OH, -O- (C1-C7) alkyl. -0-C2-C4 alkyl-O-(C1-C7) alkyl, -O-aryl, -O-alkylenedioxy (Ci-C2), N02, -NC, NRR8, -CO-NR7R8, -CO-OH , -CO-0-alkyl? (C1-C5), heterocyclyl, -S (0) n-(C1-C5) alkyl and (C1-C5) alkyl which may be substituted by one or more identical or different R4 residues. These explanations apply accordingly to the compounds of formulas Ib to Ih. The compounds of the formula I wherein X is a nitrogen atom that through a single bond is fixed on a ring carbon atom in the group A1 said ring carbon atom is directly adjacent to the carbon atom in A1 which carries the group -NH-C (= X) - in such a way that the group -NH-C (= X) - together with the carbon atoms in A1 carrying it forms a fused imidazole ring, I are represented by the formula Ii.

A2, R1, R2, R3 and n in the formula Ii are in accordance with that defined above in the formula I. The ring A3 which has resulted from the group A1 through the formation of a bond with the nitrogen atom representing X and said ring it comprises the two carbon atoms presented in formula Ii bearing the nitrogen atoms of the fused imidazole ring, is a benzene ring, a naphthalene ring or a heteroaromatic ring, wherein the explanations related to A1 above are applied correspondingly to these rings. The present invention includes all heteroisomeric forms of the compounds of the formula I. Asymmetry centers present in the compounds of the formula I can all independently of one another have the S configuration or the R configuration. The invention includes all the enantiomers and diastereomers and mixtures of ions or more heteroteomers, for example, mixtures of enantiomers and / or diastereomers in all proportions. Thus, enantiomers are a subject of the invention in enantiomeric and pure form, both as levorotatory antipodes and dextrorotatory, in the form of racemates and in the form of mixtures of two enantiomers in all proportions. In the case of a cis / trans isomerism, the invention includes both the cis / trans form as well as mixtures of these forms in all proportions. The preparation of individual stereoisomers can be effected, if desired, by separation of a mixture by customary methods, for example, by chromatography or crystallization, by the use of stereochemically uniform starting materials for synthesis or? well by stereoselective synthesis. Optionally, a derivation can be effected before a separation of stereoisomers. The separation of a mixture of stereoisomers can be carried out in the step of the formula I or the step of an intermediate product during the synthesis. The present invention also includes all tautomeric forms of the compounds of the formula I. If the compounds of the formula I contain one or more acidic or basic groups, the invention also includes the corresponding physiologically or toxicologically acceptable salts, particularly the pharmaceutically usable salts. . Thus, compounds of the formula I containing acidic groups can be present in these groups and can be used according to the present invention, for example, as alkali metal salts, ferrous alkali metal salts or ammonium salts. Examples of such salts are sodium salts, potassium salts, calcium salts, magnesium salts or salts with ammonia or organic amines such as, for example, ethylamine, ethanolamine, triethanolamine or amino acids. Compounds of the formula I which contain one or more basic groups, that is to say groups which can be protonated, can be present and I can be used according to the invention in the form of their acid addition salts with inorganic or organic acids, for example, as salts with hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid,! nitric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzokic acid, formic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, acid succinic, pimelic acid, fumaric acid, maleic acid, malic acid, sulfamic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid, etc. If the compounds of the formula I simultaneously contain acid groups and basic groups in the molecule, the invention also includes, in addition to the salt forms mentioned, internal salts or betaines (zwitterions). Salts can be obtained from the compounds, eg formula I, by customary methods known to the person skilled in the art, for example, by combining with an organic or inorganic acid or base in a solvent or dispersing agent, or by exchange of anions or exchange of cations of other salts. The present invention also includes all the salts of the compounds of the formula I which, due to their low physiological compatibility, are not directly suitable for use in pharmaceutical substances but which can be used; for example, as intermediates for chemical reactions or for the preparation of physiologically acceptable salts. The present invention also includes all the solvates of compounds of the formula I, for example hydrates or adducts I with alcohols and also derivatives of the compounds cfe ^ to formula I, such as esters, amides, prodrugs and active metabolites. A1 preferably a phenylene or a heteroarylene residue of 5 or 6 members, more preferably phenylene, where all these residues may be unsubstituted or may be substituted as indicated. If the group A1 is substituted, that is to say if it carries one or more substituents in addition to the group R1-S (0) n »'it is preferably substituted by one or two of the identical or different substituents indicated above. Preferably, a phenylene residue representing A1! it is unsubstituted, that is, in addition to the groups and G (= X) -NH carries four hydrogen atoms. The group R1-S (0) n is preferably linked to an atom in A1 that is not directly adjacent to the carbon atom carrying the group C (= X) -NH. If A1 is phenylene, the group R'-SIO) is particularly preferably located in the meta position or in the para position, more particularly in the para position, relative to the carbon atom carrying the C group (= X) -NH. The ring A2 comprising the two carbon atoms which carry the groups R -S02-NH and C (= X) -NH- is preferably an aromatic ring, more preferably a benzene ring or a thiophene ring, particularly an benzene ring, wherein all these rings may be unsubstituted or substituted by one or more residues R3 which are different from hydrogen. R1 is preferably (C1-C7) alkyl, NR5R6 or aryl, more preferably NR5R6, phenyl or 5-membered or 6-membered heteroaryl, most preferably NR5R6, where all these residues may be unsubstituted or substituted in accordance with indicated and where, according to what is stated above, R1 can be NR5R6 if the number n in the group is 2. R2 is preferably aryl, more preferably phenyl or either 5-membered or 6-membered heteroaryl, particularly phenyl or a residue of a 5-membered or 6-membered monocyclic aromatic heterocycle containing one or two heteroatoms identical or different from the N, O and S series such as, for example, phenyl, thienyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, pyridyl, etc., particularly phenyl or 2-thienyl, where all these residues may be unsubstituted or substituted in accordance with the indicated. Preferably, an aryl residue representing R2 is substituted aryl. If an aryl residue representing R2 is substituted aryl, it is preferably substituted by one, two or three, particularly one or two identical or different substituents. Substituents on an aryl residue representing R2 are preferably substituents selected from the series of halogen, CF3, -0-CF3, N02, -CN, alkyl (C? RC4) and -O- (C1-C4) alkyl, more preferably substituents of the series F, Cl, Br, CF3, -0-CF3, N02, -CN, CH3 and -OCH3. An especially preferred substituted aryl residue representing R 2 is aryl substituted by Cl, for example, by one or two chlorine atoms, particularly by a chlorine atom. The rings representing A2 can be unsubstituted or substituted rings as indicated. When they are unsubstituted rings, they carry only R3 residues that are hydrogen. When they are substituted rings, they carry one or more residues R that are different from hydrogen. These positions of substituents that do not carry a residue RJ that is different from hydrogen carry hydrogen atoms. If the ring A2 carries one or more residues R3 which are different from hydrogen, it preferably carries one or two of these residues.

R3, particularly one of these residues R3. The R3 residues that are different from hydrogen are preferably located at positions on the A2 ring that are not directly adjacent to the C (= X) -NH and R2-S02-NH groups. If A2 is a saturated or partially unsaturated carbocycle, residues R3 which are different from hydrogen are preferably (C 1 -C 4) alkyl, particularly methyl. If A2 is an aromatic ring, particularly if A2 is a benzene ring, residues R "which are different from hydrogen are preferably alkyl (Ci-C3), halogen, (C1-C3) alkoxy, or CF3, more preferably methyl, chloro or methoxy If A2 is an aromatic apillo, particularly a benzene ring, it is especially preferred if the ring bears one chlorine atom or two methoxy groups as substituents, that is, if a residue R3 is present which is chlorine or well if two residues R3 are present which are methoxy, and the other positions in the benzene ring carry hydrogen atoms If A2 a benzene ring, residues R3 which are different from hydrogen are preferably in positions 4 and / or 5 | (in relation to group C (= X) -NH in position 1 and with relation in group R2-S02-NH in position 2) If a group is substituted by one or more residues R4, it is preferably replaced by one, two or three, particularly one or two resi R or identical duos. R 4 is preferably hydroxy, (C 1 -C 4) alkyloxy, di (C 1 -C 4) alkyl, amino or heteroaryl R 5 and R 6 are preferably, independently of each other, hydrogen, (C 1 -C 9) alkyl, (C 1 -C 4) alkyl ) -O-alkyl (CHC3) or 5-membered or 6-membered aryl or together with the nitrogen atom carried by R5 and R6 form a 5-membered, 7-membered heterocycle which, in addition to the nitrogen atom carrying the groups R5 and R6 may contain an additional ring heteroatom of the series N, O and S, and may be substituted by one or more, for example one, two, three or four identical or different residues selected from the series consists of (Ci-C3) alkyl, hydroxy (C1-C3) alkyl, 5-membered or 6-membered aryl, carbamoyl, hydroxy and oxo, It is especially preferred if R and R together with the nitrogen atom carrying these residues form a heterocyclic of 5 members, 6 members or 7 members that, in addition to the nitrogen atom that carries s groups R5 and R6 may contain an additional ring heteroatom selected from the series consisting of N, 0 and S and which may be substituted by one or more, eg, one, two, three or four identical or different residues selected within the series consisting of (C 1 -C 3) alkyl, hydroxy (C 1 -C 3) alkyl, 5-membered or 6-membered aryl, carbamoyl, hydroxy, and oxo, particularly (C 1 -C 3) alkyl, such as, for example, methyl . Preferably a heterocycle formed from the groups R5 and R6 together with the nitrogen atom carrying these residues is a saturated heterocycle. Particularly preferably a heterocycle formed by R5 and Rd together with the nitrogen atom carrying these residues is derived from morpholine, thiomorpholine, 1,1-dioxo-thiomorpholine, 1-oxo-thiomorpholine, from 1 dialkylmorpholines such as dimethylmorpholines, from 2,6-dimethylmorpholine, cis-2,6-dimethylmorpholine, 1 3,5-dimethylmorpholine, cis-3,5-dimethylmorpholine, 1- (pyrimidin-2-yl) -piperazine, piperidine-4-carboxamide, 1- (2-hydroxyethyl) -piperazine, 1-methylpiperazine, 1-ethylpiperazine, from 1-arylpiperazines, from piperazine-1-carboxylate ethyl, piperidine, 2-methylpiperidine, 2,6-dimethylpiperine, cis-2,6-dimethylpiperidine, 3,5-dimethylpiperidine, cis-3,5-dimethylpiperidine, 4-hydroxypiperidine, from 4-oxopiperidine, or a of the same, such as 1,4-dioxa-8-aza-spiro [4.5] decane, from tetrahydropyridine, tetrahydropyrimidine, 1-methylhomopiperazine, thiazolidine, pyrroline, pyrrolidine, 3-hydroxypyrrolidine, 1,2,3, 4-tetrahydroisoquinoline or 2, 3-dihydro-lH-isoindole, where these rings are attached through the ring nitrogen atom or in the case of piperazine derivatives, through s nitrogen atom of unsubstituted ring. Particularly preferably a heterocycle formed by R and Rd together with the nitrogen atom carrying these residues is derived from morpholine, thiomorpholine, 1,1-dioxo-thiomorpholine, 1-oxo-thiomorpholine, 2,6-dimethylmorpholine, cis -2, 6-dimethylmorpholine, 3,5-dimethylmorpholine, cis-3,5-dimethylmorpholine, 1- (pyrimidin-2-yl) -piperazine, piperidine-4-carboxamide, 1, 2, 3, 4-tetrahydroisoquinoline or 2,3-dihydro-lH-isoindol, furthermore preferably morpholine, 2,6-dimethylmorpholine or cis-2,6-dimethylmorpholine, particularly morpholine or cis-2,6-dimethylmorpholine, where these rings are bound through the ring nitrogen Io or, in the case of the derivative of MuiÉteiliM. & * r * Ml * piperazine, through the nitrogen atom of unsubstituted ring. R7 is preferably hydrogen, (C1-C3) alkyl, ((Ci-C4) alkyl) 2-N-alkyl (C? -C3) or (C1-C4) alkyl -O-alkyl (C? -C3) . R8 is preferably hydrogen, (C? -C3) alkyl or acetyl. Aryl is preferably phenyl or heteroaryl, particularly phenyl or either 5-membered or 6-membered heteroaryl. Unless stated otherwise, preferred substituents on aryl residues are halogen, CF3, (C? -C) alkyl, aiano, nitro, and (C? -C3) alkyloxy, most preferred substituents are CF3, chloro, methyl, and methoxy . Heteroaryl and heteroarylene are preferably a residue of a 5-membered or 6-membered monocyclic aromatic heterocycle, particularly a residue derived from the heteroaromatics thiophene, pyrazole, thiazole, oxazole, isoxazole, pyridine, pyrimidine, pyridazine and tetrazole. The heterocyclic is preferably a residue derived from a saturated heterocycle, more preferably a residue of a saturated 5-membered or 6-membered monocyclic heterocycle, particularly a residue derived from pyrrolidine, piperidine, from N-alkylpiperazines, from morpholine, from dialkylmorpholines , of thiomorpholines or tetrahydrofuran. In addition, the above explanations for preferred heterocycles formed by the residues R5 and R6 together with the nitrogen atom carrying these residues are applied correspondingly to the heterocyclyl residues bound through a ring nitrogen atom. If a group S (0) n is attached to a nitrogen atom, the number n there is preferably 1 or 2, more preferably 2. The number n in the group R1-S (0) n is preferably 0 or 2, especially preferably 2. X is preferably 0, or a nitrogen atom which is bound via a single bond to a ring carbon atom in group A, said ring carbon atom is directly adjacent to the carbon atom in A1 which bears the group -NH-C (= X) - such that the group -NH-C (= X) - together with the carbon atoms in A1 that carry it form a fused imidazole ring. X is particularly preferably O. Preferred compounds of the formula I are the compounds in which one or more of the residues contained herein have preferred meanings, all combinations of definitions of preferred substituents is a subject of the present invention. Also, in relation to all preferred compounds of formula I, the present invention includes all stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. Preferred groups of compounds are also formed, for example, by means of the compounds of the formulas la, I b, le, Id, le, If, Ig and Ih where one or more residues have preferred meanings, in all their stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. A group of particularly preferred compounds is formed, for example, by compounds of the formula I wherein A1 is phenylene or heteroarylene wherein these residues may be unsubstituted or substituted by one or more substituents identical or different from the series consisting of halogen, alkyl (C? -C4), CF3, -O-alkyl (C? -C) and -CN; the ring A2 comprising the two carbon atoms carrying the groups R2-S02-NH and C (= X) -NH- is an aromatic ring; R1 is (C1-C7) alkyl which may be substituted by one or more identical or different R4 residues, or is aryl, or if the number n in the group R1-S (0) n- is 2, is also N R5R6; R2 is aryl; R3 indicates one or more identical or different residues selected from the series consisting of hydrogen, halogen, CF3, OH, -O-C1-C4 alkyl, -O-C2-C4 alkyl-0-alkyl (C ? -C4), -O-aryl, N02, -CN, NR R8, -CO-NR R8, -COFOH, -CO-0-alkyl (C? -C4), heterocyclyl, -S (O) n-alkyl (C1-C4) and (C1-C4) alkyl which may be substituted by one or more identical or different R residues; R "is fluorine, OH, -O-alkyl (Ci-Cio), -O-alkyl (C2-C4) -0-alkyl (C? -C), -O-aryl, -CN, NRR8, -CO- NH2, -CO-NH- (C1-C3) alkyl, -CO-N ((C? -C3) alkyl) 2, -CO-OH, -CO-O- (C1-C4) alkyl, heterocyclyl or oxo R5 and R6 independently of one another are hydrogen, (C1-C9) alkyl, (C1-C4) alkyl -O-(C1-C3) alkyl or aryl or together with the nitrogen atom carried by R5 and R6 form a 5-membered to 7-membered heterocycle which, in addition to the nitrogen atom carrying the R and R groups, may contain an additional ring heteroatom selected from the series consisting of N, O and S, and may be substituted by one or several identical or different residues selected from the series consisting of (C1-C3) alkyl, hydroxy (C1-C3) alkyl, aryl, carbamoyl, hydroxy and oxo; R 'is hydrogen, (C1-C3) alkyl, (alkyl (C? -C4)) 2-N-(C1-C3) alkyl- or (C1-C4) alkyl -O-(C1-C3) alkyl-; R is hydrogen, (C1-C3) alkyl or acetyl or, aryl is phenyl or heteroaryl which can all be substituted by one or more identical or different substituents selected from the series consisting of halogen, (C 1 -C 4) alkyl, phenyl, CF 3, N 2, -O-alkyl (C 1) -C4), (C1-C2) alkylenedioxy, NH2, -NH-CO-alkyl (Cx-C4), -CN, -CO-NH2, -CO-OH and -CO-0-alkyl (C1-C4); heteroaryl and heteroarylene are a residue of a 5-membered or 6-membered monocyclic aromatic heterocycle, containing one or more identical or different ring heteroatoms selected from the series consisting of N, 0 and S; heterocycle is a residue of a saturated 5-membered or 6-membered monocyclic heterocycle containing one or more identical or different ring heteroatoms selected from the series consisting of N, 0 and S and which may be substituted by one or more identical substituents or different selected within the series consisting of fluorine, alkyl (Ci-C), OH, -O-alkyl (C? -C4), NH2, -CN, -C0-NH2, -CO-OH and -CO- O-alkyl (C? -C4); n is 0, 1 or 2; X is oxygen; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. A group of more particularly preferred compounds is formed, for example, of the compounds of formula I wherein A1 is phenylene unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (C1-6) alkyl C4), CF3, -0- (C1-C4) alkyl and -CN; the ring A2 comprising the two carbon atoms carrying the groups R2-S02-NH and C (= X) -NH- is a benzene ring; R1 is NR5R6; R2 is aryl; R3 refers to one or more identical or different residues selected from the series consisting of hydrogen, halogen, CF3, -O-(C1-C4) alkyl, -CN and alkyl; R5 and R6 together with the nitrogen atom carrying R51 and R6 form a 5-membered or 6-membered saturated heterocycle which, in addition to the nitrogen atom carrying the groups R5 and R6, may contain an additional ring heteroatom selected from the series which consists of N, O and S, and which may be substituted by one or more identical or different residues selected from the series consisting of (C1-C3) alkyl, hydroxy (C1-C3) alkyl, alryl, carbamoyl, hydroxy and oxo; aryl is phenyl or 5-membered or 6-membered heteroaryl containing one or more identical or different ring heteroatoms selected from the series consisting of N, O and S, said residues may all be substituted by one or more identical substituents or different selected within the series consisting of halogen, (C1-C4) alkyl, CF3, N02, -O- (C1-C4) alkyl, -NH-CO- (C1-C4) alkyl and -CN; n is 2; X is oxygen; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. A group of especially preferred compounds consists, for example, of compounds of the formula I wherein A1 is an unsubstituted divalent phenylene residue; ring A2 consisting of the two carbon atoms 1 carrying the groups R2-S02-NH and C (= X) -NH- is a benzene ring; R1 is NR5R6; R2 is aryl; R3 indicates one or more identical or different residues selected from the series consisting of hydrogen, halogen, -O-(C1-C4) alkyl and (C1-C4) alkyl; R5 and R6 together with the nitrogen atom carrying R5 'and R6 form a saturated 6-membered heterocycle which, in addition to the nitrogen atom carrying the groups R5 and R6, may contain an additional ring heteroatom selected from the series consisting of of N, O and S, and which may be substituted by one or more identical or different residues selected from the series consisting of alkyl (Ci-C3), aryl, oxo and carbamoyl; aryl is phenyl or a 5-membered or 6-membered heteroaryl containing one or more identical or different ring heteroatoms selected from the series consisting of N, O and S, said residues may all be substituted by one or more identical substituents or different selected within the series consisting of halogen, (C 1 -C 4) alkyl, CF 3 and -O-(C 1 -C 4) alkyl; n is 2; X is oxygen; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. A group of additional preferred compounds consists, for example, of compounds of the formula I wherein A1 is a residue of 1,4-phenylene unsubstituted divalent; the A2 ring comprising the two carbon atoms bearing the groups R2-S0-NH and C (= X) -NH-, together with the residues R3 is a benzene ring bearing one or two substituents selected from the series consisting of chlorine and methoxy; R1 is NR5R6; R < is phenyl or thienyl, said residues are all substituted by one or two chlorine atoms; R5 and R6 together with the nitrogen atom bearing R5 and R6 form a saturated 6-membered heterocycle which, in addition to the nitrogen atom carrying the groups R5 and Rd, can contain ^^ U ^ b an additional ring heteroatom selected from the series consisting of 0 and S, and unsubstituted or substituted by one or two methyl residues; n is 2; X is oxygen; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. The present invention also relates to processes for the preparation of compounds of the formula I which are described below and through which the compounds of the present invention can be obtained. According to scheme 1, compounds of the present invention can be obtained, for example, by first reacting an aminocarboxylic acid of the formula II with a sulfonyl chloride of the formula R2-S02-C1 or a sulfonic acid anhydride in the presence of a base in a solvent such as, for example, water, pyridine or an ether. Suitable bases are inorganic bases such as for example sodium carbonate or organic bases, such as for example pyridine or triethylamine. The sulfonylaminocarboxylic acid of the formula III which is obtained can be activated, for example by reaction with a chlorination agent such as for example phosphorus pentachloride, phosphorus oxychloride or thionyl chloride in an inert solvent to provide an acid chloride of the Formula IV that reacts later with an arylamine. The activation of the carboxylic acid group in the compounds of the formula III can, however, also be carried out differently, for example, by one of several methods for the formation of amide bonds ep the chemistry of the peptides which are well known to those skilled in the art, for example, by conversion to a mixed anhydride or an activated ester or by the use of a carbodiimide such as dicyclohexylcarbodiimide. The reaction of activated sulfonylaminocarboxylic acid with an arylamine is favorably carried out in an inert solvent such as, for example, pyridine, tetrahydrofuran or toluene in the absence or in the presence of an inert auxiliary base such as, for example, a tertiary amine or pyridine. If the arylamine which is used in the reaction with the activated carboxylic acid already contains the desired substituent Rx-S '(0) n then the reaction directly provides the final compound of formula I. Compounds of the formula I wherein the number n in the group RS (0) n is 1 or 2 can also be obtained by the reaction of an activated carboxylic acid with a mercapto substituted arylamine of the formula R1-S-A1-NH2 and then by oxidation of the mercapto group in the compound of formula V under standard conditions such as for example with a peroxide such as for example hydrogen peroxide or a peracid such as for example 3-chloroperbenzoic acid or onoperoxyphthalic acid in a solvent such as for example methylene chloride or acetone. Activated carboxylic acids can also be reacted first with arylamines of the formula A'-NH ?. The product resulting from the reaction of formula VI can also be chlorosulfonated under standard conditions and the chlorosulfonyl group can then be converted under standard conditions into the group R1-S02, for example, by reaction with suitable amines in substance or in a solvent such as for example N-methylpyrrolidone, dimethylformamide, toluene or an ether, optionally in the presence of an auxiliary base. Auxiliary, the activated carboxylic acids can be reacted with fluorosulfonylar amines of the formula F-S02-AX-NH2 and the fluorosulfonylp intermediates of the formula VII which are obtained can be converted under standard conditions into the compounds of the formula I in accordance with the invention Scheme 1 lll The compounds of the formula I according to the present invention can also be obtained by the reaction of the activated sulfonylaminocarboxylic acids, for example, the acid chlorides of the formula IV illustrated in scheme 1, with a mercaptoarylamine of the formula H2N ^ A '-SH unsubstituted in the sulfur atom. In a nucleophilic substitution reaction, the product of the formula VIII which is obtained can be subsequently alkylated or arylated on the sulfur atom with an alkyl halide or an aryl halide or another reactive compound under the s The compounds of the formula I can also be obtained, for example, by first activating a suitably substituted nitrocarboxylic acid of the formula IX, for example by conversion to the respective acid chloride of the formula X or by another procedure, and then by its reaction with a substituted arylamine of the formula R1-S (0) n-A1-NH2 analogously to the procedures described above (see scheme 3). Also, as arylamines, fluorosulfonylar amines of the • formula F-SO.-A1 -! ^, And in the N- (fluorosulfonylaryl) -carboxamides of formula XI which are obtained, the fluorosulfonyl group can be converted under standard conditions into a group R ^ SO? according to the invention for example with an amine of the formula HNR R. Scheme 3 / 25 XJII i Before the nitro group of formula XII is subsequently reduced in the nitro group to an amino group, the activation effect of the nitro group on the A2 ring and a suitable R3 residue, for example a hydrogen atom, can be used. Halogen, can be replaced with a different R3 residue by reaction with a nucleophilol, for example, an amine. The reduction of the nitro group to provide an amino group can be effected, for example, by catalytic hydrogenation in the presence of a noble metal catalyst or, preferably, in the presence of Raney nickel in a solvent such as for example ethanol, glacial acetic acid or an ethanolic solution of hydrogen chloride or can be effected by reduction with a basic metal such as zinc, tin or iron in the presence of an acid. The reduction can also be carried out, for example, with tin (II) chloride or by reaction with sodium dithionite, preferably in a mixture of methanol, tetrahydrofuran and water as solvent. The sulfonylation of the amino group in the reduction product of formula XIII • With an activated sulfonic acid derivative, it can be carried out analogously to the reactions described above, for example, with a sulfonic acid chloride in pyridine, and finally provide the compound of the formula I. The compounds of the formula I in which X is a nitrogen atom attached to a ring carbon atom in the group A1 through a single bond, whose carbon atom is The ring is directly adjacent to the carbon atom in A1 bearing the group -NH-C (= X) -, ie the benzimidazole derivatives of the formula II, can for example be obtained by the reaction of an acid derivative activated sulfonylaminocarboxylate obtained in accordance with As described above according to scheme 1, for example, a carboxylic acid chloride of formula IV (or else, analogously to scheme 3, a nitrocarboxylic acid derivative) with a 1,2-diaminoarene in the presence of a dehydrating agent such as, for example, Thionyl or phosphorus pentachloride (see scheme 4) Scheme 4 XIV? The reaction is usually carried out in an inert solvent, for example, in a toluene or xylene hydrocarbon. The 1,2-diaminoarene may already contain the final group or a precursor group thereof, for example the group R ^ S. Subsequent steps, for example, reactions in the sulfur atom, can then be carried out in accordance with what is explained above. It can also be used 1, Unsubstituted 2-diaminoarenes and the resulting products of the formula XIV can be chlorosulfonated, for example with chlorosulfuric acid and the sulfonyl chlorides obtained can be converted into the final compounds containing the group R1-S02 for example, by reaction with a suitable amine. All reactions for the synthesis of the compounds of the formula I are well known per se by those skilled in the art and can be carried out under standard conditions according to the procedures described in the literature and / or through the activation of the soluble guanylate cyclase (sGC), and therefore are useful agents for the therapy and prophylaxis of disorders associated with a low level or • decreased cGMP either caused by said low level or well for which therapy or prophylaxis an increase in the present level of cGMP is desired. The activation of sGC by the compounds of formula I can be observed, for example, in the activity assay described below. Disorders and pathological conditions associated with a level • Low cGMP or in which an increase in cGMP is desired and for which therapies and prophylaxis it is possible to use compounds of the formula I are, for example, cardiovascular disorders such as for example endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, angina stable and unstable chest, thrombosis, restenosis, myocardial infarction, strokes, heart failure or pulmonary hypertension, or, for example, erectile dysfunction, bronchial asthma, chronic renal failure and diabetes. Compounds of the formula I can also be used in the therapy of liver cirrhosis and also to better r a restricted performance of memory or learning ability. The compounds of formula I and their physiologically acceptable salts can be administered to animals; from Preference is given to mammals, and particularly to humans, as pharmaceutical agents per se, in mixtures with each other or in the form of pharmaceutical preparations. An object of the present invention therefore also relates to the compounds of the formula I and their physiologically acceptable salts for use as pharmaceutical agents, their use for activating soluble guanylate cyclase, for normalizing a disturbed cGMP balance and particularly its use in the therapy and prophylaxis of the aforementioned syndromes as well as their use for the preparation of drugs for these purposes. In addition, an object of the present invention relates to pharmaceutical preparations (or pharmaceutical compositions) comprising as active component an effective dose of at least one compound of the formula I and / or a physiologically acceptable salt thereof and a pharmaceutically vehicle usual acceptable, ie |, one or more pharmaceutically acceptable vehicle substances and / or additives. An object of the present invention also relates to the compound of formula I already known per se and excluded by waiving the compounds defined above of formula I which are, per se, an object of the present invention, and their physiologically acceptable salts as activators of soluble guanylate cyclase. All the foregoing and the following statements regarding the pharmacological effects and the uses of the compounds of the formula I also apply accordingly to dtiftÜri ^ compound of the formula I where simultaneously the annulus A¿ comprising the carbon atoms bearing the groups C (= X) -NH- and NH-S02R2 is a benzene ring substituted at positions 3 and 5 by chlorine, R2 is methyl, X is oxygen and R1-SiOi-1- is a 5-chloro-2- (4-chlorophenylmercapto) -phenyl residue and its physiologically acceptable salts. Thus an object of the present invention therefore relates to said compound and its physiologically acceptable salts for use as a pharmaceutical agent, pharmaceutical preparations comprising as an active component an effective dose of said compound and / or a physiologically acceptable salt and a pharmaceutically vehicle usual acceptable, and the use of said compound and / or a physiologically acceptable salt thereof in the therapy or prophylaxis of the aforementioned syndromes as well as its use for the preparation of drugs for these purposes. The pharmaceutical agents according to the present invention can be administered orally, for example, in the form of pills, tablets, sugar-coated tablets, granules, hard and soft gelatine capsules, aqueous, alcoholic or oily solutions, syrups, emulsions or suspensions, or for rectal administration, for example, in the form of suppositories. The administration can also be carried out parenterally, for example, subcutaneously, intramuscularly or intravenously in the form of solutions for injection or infusion. Other suitable forms of administration are, for example, percutaneous administration < or topical, for example, in the form of ointments, dyes, sprays or transdermal therapeutic systems, or administration by inhalation in the form of nasal sprays, or mixtures of aerosols, or, for example, microcapsules, implants or rods. The preferred administration form depends, for example, on the disease to be treated and its severity. The amount of active compound of the formula I and / or its physiologically acceptable salts in the pharmaceutical preparations is usually 0.2 to 500 mg, preferably 1 to 200 mg, per dose, but depending on the type of the pharmaceutical preparation, it can also be greater, j The 15 pharmaceutical preparations usually comprise 0.5 to 90% by weight of the compounds of the formula I and / or their physiologically acceptable salts. The preparation of the pharmaceutical preparations can be carried out in a manner known per se. For this purpose, one or several compounds of the formula I and / or its physiologically acceptable salts, together with one or more solid and liquid substances and / or pharmaceuticals (or auxiliary substances) and, if desired, in combination with other pharmaceutically active compounds having a therapeutic action or prophylactic are combined in a suitable administration form or dosage form which can then be used as a pharmaceutical agent in human or veterinary medicine. For the production of pills, tablets, sugar-coated tablets, and hard gelatin capsules, it is possible to use, for example, lactose, starch, for example, corn starch, or starch derivatives, talc, stearic acid or its salts, etc. Vehicles for soft gelatine capsules and suppositories are, for example, fats, waxes, semi-solid and liquid polyols, natural or hardened oils, etc. Suitable carriers for the preparation of solutions, for example of solutions for injection, or of emulsions or syrups are, for example, water, physiological sodium chloride solution, alcohols such as ethanol, glycerol, polyols, sucrose, invert sugar, glucose , mannitol, vegetable oils, etc. It is also lyophilized the compounds of the formula I and their physiologically acceptable salts and using the resulting lyophilizates, for example, for the preparation of preparations for injection or infusion. Suitable carriers for microcapsules, implants or rods are, for example, copolymers of glycolic acid and lactic acid. In addition to the active compounds and carriers, the pharmaceutical preparations may also contain customary additives such as fillers, disintegrants, binders, lubricants, wetting agents, stabilizers, emulsifiers, dispersants, preservatives, sweeteners, colorants, flavors, aromatizers, thickeners, thinners. , buffer substances, solvents, solubilizers, agents to achieve a deposition effect, salts to alter the osmotic pressure, coating agents or antioxidants, The dosage of the active compound of the formula] I to be administered and / or of a physiologically acceptable salt of the It depends on the individual case and must, as usual, adapt to individual circumstances to achieve an optimal effect. Thus, it depends on the nature and severity of the disease to be treated, and also on the sex, age, weight and individual response of the human or animal to be treated, the efficacy and duration of action of the compounds used, whether the The therapy is water or chronic or prophylactic, or else if other active compounds are administered in addition to the compounds of the formula I. In general, a daily dose of about 0.01 to 100 mg / kg, preferably 0.1 to 10 mg / kg , particularly from 0.3 to 5 mg / kg (in each case mg per kg of body weight) is suitable for administration to an adult weighing approximately 75 kg to obtain the desired results. The daily dose may be administered in the form of a single dose or, in particular, when larger amounts are administered, it may be divided into several individual doses, for example, two, three or four individual doses. In some cases, depending on the individual response, it may be necessary to deviate towards • up or down of the daily dose provided. The compounds of the formula I activate guanylate cyclase soluble, mainly by binding in the heme-binding bag of the enzyme. Taking this property into account, apart from the use as pharmaceutically active compounds in human and veterinary medicine, they can also be used as a scientific tool or as research assistants biochemicals in which said effect is desired on guanylate cyclase, and also for diagnostic purposes, for example, in the in vitro diagnosis of cell samples or tissue samples. The compounds of the formula I and salts thereof can therefore be used as was mentioned above, as intermediates for the preparation of other pharmaceutically active compounds. The fwing examples of compounds of the formula I and of intermediates for their preparation illustrate the invention without limiting it. Examples 1.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxybenzoic acid 33.71 g (0.32 mol) of sodium carbonate was dissolved in 250 ml of water and heated to a temperature of 60 ° C. HE introduced 25.00 g (0.13 mole) of 2-amino-4,5-dimethoxy-benzoic acid in the solution, and 29.55 g (0.14 mole) of 4-chloro chloride were added in portions over a period of 15 minutes. -benzenesulfonyl. After cooling the mixture, it was filtered with suction, the residue was taken up in a 1% sodium hydrogencarbonate solution, the solution was filtered, and the product was precipitated by the addition of 1 N hydrochloric acid. 25.90 g was obtained (55%) of 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzoic acid with a melting point (mp) of 212-214 ° C. Analogously, the fwing were obtained: 2.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -benzoic acid, melting point: 210 ° C 3.) 5-chloro-2- (3,4-dichloro- phenylsulfonylamino) -benzoic acid . ) 2- (4-chloro-phenylsulfonylamino) -cyclopentanecarboxylic acid; melting point: 147 ° C 6.) 2- (4-chloro-phenylsulfonylamino) -5-methyl-benzoic acid, melting point: 201 ° C 7.) 3- (4-chloro-phenylsulfonylamino) -thiophenic acid 2-carboxylic; melting point: 180 ° C 8.) 3- (4-chloro-phenylsulfonylamino) -pyrazol-4-carboxylic acid; oil 9.) 2- (4-chloro-phenylsulfonylamino) -pyridine-3-carboxylic acid; melting point: decomposition (dec.) > 36¡0 ° C . ) 2- (4-chlorophenylsulphonylamino) -4,5-dimethoxy-benzoyl chloride 25.90 g (0.07 mol) of 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzoic acid were mixed with 75 ml of toluene . 17.30 g (0.08 mol) of phosphorus pentachloride was added and the mixture was stirred at a temperature of 4 C | -45 ° C for 2.5 hours. Then, the mixture was concentrated in vacuo to half its volume and the product that was precipitated was removed by filtration with suction and washed with a small amount of toluene. There were obtained 25.30 g (93%) of 2- (4-chloro-phenylsulphonylamino) -4,5-dimethoxy-benzoyl chloride with a melting point of 175-177 ° C. Analogously there were obtained: 11.) 5-chloro-2- (4-chloro-phenylsulphonylamino) -benzoyl chloride; melting point: 127 ° C 12.) 5-chloro-2- (3,4-dichloro-phenylsulfonylamino) -benzoyl chloride; melting point: 117 ° C 13.) 2- (4-chloro-phenylsulfonylamino) cyclopentanecarboxylic acid chloride; melting point: 107 ° C 14.) 2- (4-chloro-phenylsulfonylamino) -5-methyl-benzoyl chloride; melting point: 114 ° C 15.) 3- (4-chloro-phenylsulfonylamino) -thiophene-2-carboxylic acid chloride; melting point: 122 ° C 16.) 3- (4-Chloro-phenylsulfonylamino) -prazole-4-carboxylic acid chloride; melting point: 260 ° C 17.) 2- (4-chloro-phenylsulfonylamino) -pyridine-3-carboxylic acid chloride 18.) 4- ((2- (4-chloro-phenylsulfonylamino) -4,5-fluoride - dimethoxy-benzoyl) -amino) -benzenesulfonyl • 10.00 g (25.6 mmol) of 2- (4-chlorophenylsulfonylamino) -4,5-dimethoxy-benzoyl chloride were mixed with 300 ml of toluene, 4.49 g (25.6 mmol) of 4-aminobenzenesulfonyl fluoride were added and the mixture was heated under reflux condition for 4 hours. After cooling, the precipitated solid was removed by filtration with suction and washed with toluene. 11.71 g (87%) of the compound were obtained of the title that had a melting point of 2 16-219 ° C. Analogously there were obtained: 19.) 4- ((5-chloro-2- (4-chloro-phenylsulfonylamino) -benzoyl) -amino) -benzenesulfonyl fluoride; melting point 242 ° C 20.) N- (-aminosulfonyl-phenyl) -5-chloro-2- (4-chloro-phenylsulfonylamino) -benzamide; melting point 260 ° C 21.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- ((4- (4-nitro-phenyl) -mercapto) -phenyl) -benzamide; melting point: 255 ° C 22.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (phenylmercapto) -phenyl) -benzamide; melting point 169 ° C 20 23.) 5-chloro-2- (4-chlorophenylsulphonylamino) - N- (4-methylmercapto-phenyl) -benzamide; melting point: 220 ° C 24.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-methyl-benzothiazol-5-yl) -benzamide; melting point: 251 ° C 25.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (3-diethylamino-2-hydroxy-propyl-mercapto) -phenyl) -benzamide; MELEMELI melting point: 102 ° C 26.) 4- ((5-chloro-2- (3,4-dichloro-phenylsulfonylamino) -benzoyl) -amino) -benzenesulfonyl fluoride; melting point: 232 ° C 27.) 4- (2- (4-chloro-phenylsulfonylamino) -cyclopentanecarbonylamino) -benzenesulfonyl fluoride; melting point: 211 ° C 28.) 4- ((2- (4-Chloro-phenylsulfonylamino) -5-methyl-benzoyl) -amino) -benzenesulfonyl fluoride; melting point: 224 ° C 29.) 4- ((3- (4-chloro-phenylsulfonylamino) -thiof | en-2-carbonyl) -amino) -benzenesulfonyl fluoride; melting point: 255 ° C . ) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4-mercapto-phenyl) -benzamide; melting point: 202 ° C 31.) 4- ((3- (4-chloro-phenylsulfonylamino) -pyrazol-4-carbonyl) -amino) -benzenesulfonyl fluoride; melting point: 251 ° C 32. ) 3- ((5-Chloro-2- (4-chloro-phenylsulphonylamino) -benzoyl) -amino) -benzenesulfonyl fluoride; melting point: 224 ° C 33.) 4- (2- (4-Chloro-phenylsulfonylamino) -pyridine-3-carbonyl) -amino) -benzenesulfonyl fluoride; Melting point: 263-2? 65 ° C 34.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4-met: il-5- (thiomorpholin-4-sulfonyl) -thiazol-2-yl) -benzamide; melting point: 265-267 ° C 35.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-methylmercapto-phenyl) -benzamide 36.) 5-chloro-2- (4-chloro phenylsulfonylamino) - | N- (3-methylmercapto-phenyl) -benzamide 37.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (5-methyl- Isoxazol-3-ylsulfamoyl) -phenyl) -benzamide 38.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4-nitro-5-phenylsulfonyl) -phenyl) -benzamide 39 .) 5-Chloro-2- (4-chloro-phenylsulfonylamino) N- (5-ethyl-sulphon-2-hydroxy-phenyl) -benzamide 40.) N- (3-Butylsulfamoyl-phenyl) -5-chloro-2- (4-chloro-phenylsulfonylamino) -benzamide 10 41.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-nipro-5-propylmercapto-phenyl) -benzamide 42.) 5-chloro-2 - (4-Chloro-phenylsulphonylamino) -N- (4-thiocyanato-phenyl) -benzamide 43.) N- (4-acetylsulfamoyl-phenyl) -5-chloro-2- (4-pyrro-phenylsulfonylamino) -benzamide 44 .) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-phenylmercapto-phenyl) -benzamide 45.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-chloro) -5- (2- cyano-ethylsulfamoyl) -phenyl) -benzamide 20 46.) N- (5-Butylsulfamoyl-2-methoxy-phenyl) -5-chloro-2- (4-chloro-phenylsulfonylamino) -benzamide 47. ) N- (4-benzoylsulfamoyl-phenyl) -5-chloro-2- (4? Chlorophenylsulfonylamino) -benzamide 48.) 5- chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-chloro-4-methylsulfonyl-phenyl) -benzamide 49.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- ( 4- (hexadecylsulfonyl) -phenyl) -benzamide • 50.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (butylaminocarbonylaminosulfonyl) -phenyl) -benzamide 5 51.) 5-chloro-2 - (4-chloro-phenylsulfonylamino) -N- (2-sulfamoyl-phenyl) -benzamide 52.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (2-methylmercapto-5-trifluoromethyl-phenyl) -benzamide 53.) 5-chloro-2- (4-chloro-phenylsulfonylamino) - - (3-methylsulfonyl-phenyl) -benzamide 54.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- ( 3- (2-hydroxyethylsulfonyl) -phenyl) -benzamide 55.) (4- (5-Chloro-2- (4-chloro-phenylsulphonylamino) -benzoylamino) -phenylmercapto) -acetic acid 15 56.) 5-chloro -2- (4-Chloro-phenylsulfonylamino) -N- (4- (3, 4-dimethyl-isoxazol-5-ylsulfamoyl) -phenyl) -benzamide 57.) 5-Chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (thiazol-2-ylsulfamoyl) -phenyl) -benzamide 58.) 5-chloro -2- (3,4-dichloro-phenylsulfonylamino) -N- (4- 20 ethylmercapto-phenyl) -benzamide; melting point: 171 ° C 59.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-4- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide 500 mg (0.95 mmol) were dissolved 4- (- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzoyl) -amino) -25-benzenesulfonyl fluoride in 1 ml of thiomorpholine and heated at a temperature of 90 ° C for 30 minutes. For comparison, the mixture was poured into 50 ml of ice / 1N hydrochloric acid, the precipitate was removed by suction filtration, dried in a vacuum drying chamber in phosphorus pentoxide and recrystallized from hexane / ethyl acetate. 378 mg (65%) of the title compound having a melting point of 241 ° C were obtained. Analogously there were obtained: 60.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (cis-2,6-dimethyl-1-morpholin-4-sulfonyl) -phenyl) -pyridine-3-carboxamide; melting point: 256-258 ° C 61.) N- (4- (4-carbamoyl-piperidin-1-sulfonyl) -phenyl) -2- (4-chloro-phenylsulfonyla) -pyridine-3-carboxamide; melting point: 273-276 ° C 62.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (piperidin-1-sulfonyl) -phenyl) -pyridine-3-carboxamide; melting point: 180-183 ° C 63.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 246 ° C 64. ) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4-methyl-piperazin-1-sulfonyl) -phenyl) -benzamide; melting point: 219 ° C 65.) 5-chloro-2- (4-chloro-f-phenylsulfonylamino) -N- (4 -? (2,6-dimethyl-morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 259 ° C 66.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (cis-2, 6-dimethyl-morpholin-4-sulfonyl) -phenyl) -benzamide; melting point j: 251 ° C 67.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4-hydroxy-piperidin-1-sulfonyl) -phenyl) -benzamide; melting point: 255 ° C 68.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (1,4-dioxa-8-aza-spiro [4.5] decan-8-sulfonyl) -phenyl) - benzamide; melting point: 256 ° C 69.) 5-chloro-2- (3,4-dichloro-phenylsulfonylamino) -jN- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 253 ° C 70.) 5-chloro-2- (3,4-dichloro-phenylsulfonylamino) -N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 222 ° C 71.) 5-chloro-2- (3,4-dichloro-phenylsulfonylamino) -N- (4- (4-methyl-piperazin-1-sulfonyl) -phenyl) -benzamide; melting point i: 246 ° C 72.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxyN- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 172 ° C 73.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4- (2-hydroxy-ethyl) -piperazin-1-sulfonyl) -phenyl) -benzamide; melting point: 277 ° C 74.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (morpholon-4-sulfonyl) -phenyl) -cyclopentanecarboxamide; melting point: • 180 ° C 75.) 5-chloro-2- (4-chloro-phenylsulfonylamino) - - (4-5-diethylsulfamoyl-phenyl) -benzamide; melting point: 226 ° C 76.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (piperidin-1-sulfonyl) -phenyl) -benzamide; melting point: 240 ° C 77.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (2-methoxy-ethylsulfamoyl) -phenyl) -benzamide; melting point: 209 ° C 10 78.) 2- (4-chloro-phenylsulfonylamino) -5-methyl-N- (4-morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 203 ° C 79.) 3- (4-chloro-phenylsulfonylamino) -N- (4-morfol: in-4-sulfonyl) -phenyl) -thiophene-2-carboxamide; melting point: 220 ° C 80.) 3- (4-chloro-phenylsulfonylamino) -N- (4- (morphol: in-4-sulfonyl) -phenyl) -lH-pyrazole-4-carboxamide; oil 81.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (3- (morphol; in-4-sulfonyl) -phenyl) -benzamide; melting point: 238 ° C 82.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -1 N- (3- I (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point 20 202 ° C 83.) 5-Chloro-2- (4-chloro-phenylsulfonylamino) -N- (3- (4-methyl-piperazin-1-sulfonyl) -phenyl) -benzamide hydrochloride; fusion point: 245 ° C 84.) 3- (4-chloro-phenylsulfonylamino) -N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -thiophene-2-carboxamide; melting point: 229 ° C 85.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 228 ° C • 86.) 2- (4-chloro-phenylsulfonylamino) -5-methyl? N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 5 234 ° C 87.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (4-methyl-piperazin-1-sulfonyl) -phenyl) -benzamide; melting point 172 ° C 88.) 2- (4-Chloro-phenylsulfonylamino) -N- (4- (cis-2,6-dimethyl-10-morpholin-4-sulfonyl) -phenyl) -4,5-dimethoxy- benzamide; melting point: 208 ° C 89.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (4-hydroxy-piperidin-1-sulfonyl) -phenyl) -4,5-dimethoxy-benzamide; melting alum: 244 ° C 15 90.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (piperidin-3-sulfonyl) -phenyl) -benzamide; melting point: 258 ° C 91.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (thiazolidin-3-sulfonyl) -phenyl) -benzamide; melting point: 20 261 ° C 92.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (2,5-dihydro-lH-pyrrol-1-sulfonyl) -phenyl) -4,5-dimethoxy -benzamide; melting point: 262 ° C 93.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (1,2,3,6-tetrahydro-pyridin-1-sulfonyl) -phenyl) -4,5 -dimethoxy-benzamide; melting point: 252 ° C 94.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (2-methyl-piperidin-1-sulfonyl) -phenyl) -benzamide; melting point: 227 ° C 95.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (piperazin-1-sulfonyl) -phenyl) -benzamide; melting point: 243 ° C 96.) 'ethyl 4- (4- (2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzoylamino) -phenylsulfonyl) -piperazine-1-carboxylic acid ethyl ester; melting point: 245 ° C 97.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (4-methyl-piperidin-1-sulfonyl) -phenyl) -benzamide; melting point 267 ° C 98.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (4-methyl-perhydro- [1,4] diazepin-1-sulfonyl) -phenyl) - benzamic.a; melting point: 274 ° C 99.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (4-ethyl-piperazin-1-sulfonyl) -phenyl) -4,5-dimethoxy-benzamide; melting point: 191 ° C 100.) 2- (4-chloro-phenylsulfonylamino) -N- (4- ((2-dimethylamino-ethyl) -ethyl-sulfamoyl) -phenyl) -4,5-dimethoxy-benzamide; melting point: Dec. > 119 ° C 101.) 2- (4-Chloro-phenylsulfonylamino) -N- (4- (1, 4, 5, 6-tetrahydro-pyrimidin-1-sulfonyl) -phenyl) -4,5-dimethoxy- ^^ benzamide; melting point: Dec. > 237 ° C 102.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (4- (pyrimidin-2-yl) -piperazin-1-sulfonyl) -phenyl) -benzamide; melting point: Dec. > 194 ° C 103.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (4- (4-chloro-phe-n-yl) -piperazin-1-sulfonyl) -phenyl) -4,5-dimethoxy -benzamide; melting point: Dec. > 243 ° C 104.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (indan-1-ylsulfamoyl) -phenyl) -4,5-dimethoxy-benzamide; melting point: 161 ° C 105.) 2- (4-chloro-phenylsulfonylamino) -N- (4- ((2- (lH-indol-3-yl) -ethyl) -methyl-sulfamoyl) -phenyl) - 4,5-dimethoxy-benzamide melting point: 182 ° C 106.) 1- (4- ((2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzoyl) -amino) -phenylsulfonyl) -piperidine -4-carboxamide; mp 252 ° C 107.) 2- (4-chloro-phenylsulfonylamino) | N- (4-cyclopropylsulfamoyl-phenyl) -4,5-dimethoxy-benzamide; melting point: 222 ° C 108.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (3-hydroxy-pyrrolidin-1-sulfonyl) -phenyl) -4,5-dimethoxy-benzamide; melting point: 272 ° C 109.) N- (4- (allyl-cyclohexyl-sulfamoyl) -phenyl) -2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzamide; injection point: 182 ° C 110.) 1- (4- ((2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-benzoyl) -amino) -phenylsulfonyl) -pyrrolidine-2-carboxylic acid; melting point: 240 ° C (sintering) 111.) 5-chloro-2-nitro-benzoyl chloride 100.00 g (0.50 mol) of 5-chloro-2-nitrobenzoic acid were mixed with 72.20 g (0.61 mol) of chloride of thionyl and the mixture was heated under reflux condition for 2 hours. The excess thionyl chloride was removed in vacuo. 106.50 g (approximately 98%) of 5-chloro-2-nitro-benzoyl chloride was obtained as an oil. Analogously there were obtained: 112.) 5-methyl-2-nitro-benzoyl chloride; oil 113.) 4- (5-chloro-2-nitro-benzoylamino) -benzenesulfonyl fluoride 86.00 g (0.39 mol) of 5-chloro-2-nitro-benzoyl chloride were dissolved in 300 ml of toluene, drop was added dropwise a solution of 62.00 g (0.35 mol) of 4-aminobenzenesulfonyl fluoride, and the mixture was heated at reflux for 4 hours. Subsequently it was cooled and concentrated in vacuo to half its volume, cooled and the precipitated solid was removed by suction filtration. There were obtained 121.60 g (86%) of the title compound having a melting point of 182-184 ° C. Analogously, the following were obtained: 114.) 4- (5-methyl-2-nitro-benzoylamino) -benzenesulfonyl fluoride; melting point: 179 ° C 115.) 5-chloro-N- (4-ethylmercapto-phenyl) -2-nitro-benzamide 116.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) ) -2-nitro-benzamide 120.00 g (0.33 mol) of 4- (5-chloro-2-nitro-benzoylamino) -benzenesulfonyl fluoride, 29.10 g (0.83 mol) of morpholine and 33.85 g (0.33 mol) were stirred. ) of triethylamine in 1200 ml of toluene at a temperature of 60 ° C for 2 days. The precipitated solid was removed by suction filtration and recrystallized from acetone / n-hexane. Obtained 102.10 g (71%) of the title compound having a melting point of 243-245 ° C. Analogously there were obtained: 117.) 5-chloro-2-nitro-N- (4- (thiomorpholin-4-sulfonyl) -phehyl) -benzamide; melting point: 120 ° C 118.) 5-methyl-N- (4- (morpholin-4-sulfonyl) -phenyl) -2-nitro-benzamide; melting point: 249 ° C 119.) N- (4- (morpholin-4-sulfonyl) -phenyl) -5- (morpholin-4-yl) -2-nitro-benzamide. 20.00 g (0.56 mol) of 4- (5-chloro-2-nitro-benzoylamino) -benzenesulfonyl fluoride in 48.5 g (0.557 mol) of morpholine under reflux condition for 1 hour. Subsequently, the mixture was cooled, poured into ice / hydrochloric acid and filtered with suction. 26.0 g (98%) of the title compound having a melting point of 252 ° C was obtained. 120.) 2-amino-5-chloro-N- (4- (morpholin-4-sulfonyl) -phepyl) -benzamide 11.10 g (26.1 mmol) of 5-chloro-N- (4- (morpholin-4) were dissolved. -sulfonyl) -phenyl) -2-nitro-benzamide in 440 ml of tetrahydrofuran / methanol (1: 1) and a solution of 27.23 g (156.4 mmol) of sodium dithionite in 330 ml of water was added dropwise. After stirring for 1 hour at room temperature, the organic solvents were removed on a rotary evaporator, and the precipitated product was removed by suction filtration and purified by chromatography on silica with methylene chloride / methanol (9: 1). 5.68 g (55%) of the title compound having a melting point of 229-231 ° C were obtained. Analogously there were obtained: 121.) 2-amino-5-chloro-N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 177 ° C 122.) 2-amino-N- (4- (morpholin-4-sulfonyl) -phenyl) - (5-morpholin-4-yl) -benzamide; melting point: 228 ° C 123.) 2-amino-5-chloro-N- (4-ethylsulfonyl-phenyl) -benzamide; melting point: 159-161 ° C 124.) 5-chloro-2- (5-chloro-l, 3-dimethyl-lH-pyrazole-4-sulfonyl-amino) -N- (4- (thiomorpholin-4-) sulfonyl) -phenyl) -benzamide were dissolved 250 mg (0.60 mmol) of 2-amino-5-chloro-N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide in 10 ml of dry pyridine and added dropwise a solution of 195 mg (0.85 mmol) of 5-chloro-1,3-dimethyl-1H-pyrazol-4-sulfonyl chloride in 5 ml of pyridine at a temperature of 0 ° C. After 2 hours, the mixture was poured on ice, the precipitated solid was removed by suction filtration and purified by chromatography on silica gel with methylene chloride / methanol (98: 2). 250 mg (69%) of the title compound having a melting point of 215-216 ° C was obtained. Analogously there were obtained: 125.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (4-phenyl-phenylsulfonylamino) -benzamide; melting point: 214 ° C 126.) 5-chloro-2- (3,4-dimethoxy-phenylsulfonylamino) -jN- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 245 ° C 127.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (4-trifluoromethoxy-phenylsulfonylamino) -benzamide; melting point: 195 ° C 128.) 2- ((4-acetylamino-phenyl) -sulfonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point 198 ° C 129.) 5-chloro-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 112 ° C 130.) 5-chloro-2- (5-chloro-l, 3-dimethyl-pyrazol-4-sulfonyl-amino) -N- (4- (morpholin-4-sulfonyl) -phenyl) ) -benzamide; melting point: 161 ° C 131.) 5-chloro-2- ((1-methyl-imidazole-4-sulfonyl) -amino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point 141 ° C 5 132.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (pyridin-3-sulfonylamino) -benzamide; melting point: 222 ° C 133.) 2- (4-benzyloxy-phenylsulfonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 245 ° C • 10 134.) 5-chloro-2- (ethylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 274-276 ° C 135.) 2- ((2-acetamido-4-methyl-thiazole-5-sulfonyl) -amino) -5-chloro-N- (4- (morpholin-4-sulfonyl) phenyl) -benzamide; melting point: 257 ° C 15 136.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (thiophen-2-sulfonylamino) -benzamide; melting point: 216 ° C 137.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (4-trifluoromethyl-phenylsulfonylamino) -benzamide; melting point: 264 ° C 20 138.) 2- (4-bromo-phenylsulfonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 232 ° C 139.) 2- (3,5-bis-trifluoromethyl-phenylsulfonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 209 ° C 25 140.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (4-nitrophenylsulfonylamino) -benzamide; melting point: 239 ° C 141.) 5-chloro-2- (4-cyano-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 238 ° C 142.) 5-chloro-2- (4-methylsulfonyl-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 181 ° C 143.) 5-chloro-2- (4-isopropyl-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 105 ° C 144.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- ((2-phenyl-ethenyl) -sulfonylamino) -benzamide; melting point: 278 ° C 145.) 5-chloro-2- (4,5-dibromo-thiophene-2-sulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 232 ° C 146.) 5-chloro-2- (4-fluoro-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 245 ° C 147.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (5-phenylsulfonyl-thiophen-2-sulfonylamino) -benzamide; melting point: 103 ° C 148.) 5-chloro-2- (3-chloro-4-methoxy-phenylsulfonylamino) - | N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 274 ° C 149.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (quinolin-8-sulfonylamino) -benzamide; melting point: 262 ° C 150.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (2 |, 4,6-71 trimethyl-phenylsulfonylamino) -benzamide; melting point 240 ° C 151.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (3-nitro-phenylsulfonylamino) -benzamide; melting point: 220 ° C 152.) 5-chloro-2- (4-methoxy-phenylsulfonylamino) -N- (4- (morphplin-4-sulfonyl) -phenyl) -benzamide; melting point: 269 ° C 153.) 5-chloro-2-methylsulfonylamino-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 248 ° C 154.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2-phenylmethylsulfonylamino-benzamide; melting point: 106 ° C 155. ) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (2,2,2-trifluoroethylsulfonylamino) -benzamide; melting point: 208 ° C 156.) 2- (butylsulphonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 102 ° C 157.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (3-trifluoromethyl-phenylsulfonylamino) -benzamide; melting point: 212 ° C 158.) 2- (4-bromo-2, 5-dichloro-thiophen-3-sulfonylamino) -5-sloro-N- (4- (morpholin-4-sulfonyl) -phenyl) - benzamide; melting point: 267 ° C 159.) 5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -2- (2-trifluoromethyl-phenylsulfonylamino) -benzamide; melting point: 234 ° C 160.) 5-chloro-2- (3-chloro-phenylsulfonylamino) -N- (4- (morphblin-4-sulfonyl) -phenyl) -benzamide; melting point: 206 ° C 161.) 2- (4-Bromo-2-methoxy-phenylsulfonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 260 ° C 162.) 5-chloro-2- (2,6-dichloro-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 244 ° C 163.) 5-chloro-2- (2-cyano-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 200 ° C 164.) 2- (4-butoxy-phenylsulfonylamino) -5-chloro-N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 225 ° C 165.) 5-chloro-2- (7,7-dimethyl-2-oxo-bicyclo [2.2.1] heptan-1-sulfonylamino) -N- (4- (morpholin-4- sulfonyl) -phenyl) -benzamide; melting point: 120 ° C 166.) 5-chloro-2- (3-fluoro-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 204 ° C 167.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -5- (morpholin-4-yl) -benzamide; melting point: 264 ° C 168.) 5-chloro-N- (4-ethylsulfonyl-phenyl) -2- (4-r.ethyl-phenylsulfonylamino) -benzamide; melting point: 188-192 ° C 169. ) 5-chloro-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (ethylsulfonyl-phenyl) -benzamide; melting point: 195-197 ° C 170.) 5-chloro-2 - (4-chloro-3-nitro-phenylsulfonylamino) -N- (4-ethylsulfonyl-phenyl) -benzamide; melting point: 196-198 ° C 171.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4-ethylsulfonyl-phenyl) -benzamide; Melting point: 180-185 ° C 172. 5-chloro-2- (3, 5-dimethyl-io-soxazole-4-sulfonylamino) -N- (4-ethylsulfonyl-phenyl) -benzamide; melting point: Dec > 249 ° C 173. 5-chloro-2-ethylsulphonylamino-N- (4-ethylsulfonyl-phenol) -benzamide; melting point: 103 ° C 174.) 4-Chloro-N- (2- (1H-benzimidazol-2-yl) -4-chloro-phenyl) -benzenesulfonamide 1.00 g (2.7 mmol) of 5- chloro-2- (4-chloro-phenylsulphonylamino) -benzoyl and 296 mg (2.7 mmol) of o-phenylenediamine in 150 ml of toluene under reflux conditions for 1 hour. A small amount of liquid was removed by filtration with suction and the filtrate was evaporated.

The residue was taken up in 50 ml of toluene, 600 mg of thionyl chloride were added and the mixture was heated again under reflux conditions for 10 hours.

Subsequently, it was cooled and the precipitated solid was removed by suction filtration. 280 mg were purchased (25%) of the title compound having a melting point of 225-228 [deg.] C. 175.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (1-, 1- dioxo-thiomorpholine-4-sulfonyl) -benzamide 176.) 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (1-oxo-thiomorpholin-4-sulfonyl) -benzamide. mg (0.82 mmol) of 2- (4-chloro-phenylsulfonylamino) -4,5-dimethoxy-N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide in 50 ml of acetone at a temperature of 0 ° C. A solution of 371 mg (1.23 mmol) of 50% m-chloroperbenzoic acid in 20 ml of acetone was added and the mixture was stirred at room temperature overnight, for the preparation it was poured into water / ice and the precipitate It was removed by filtration with suction The two products obtained as a mixture were separated by chromatography on silica with methylene chloride-methanol (97: 3) Analogously obtained: 177.) 5-chloro-2- (4) -chloro-phenylsulfonylamino-N- (4- (1,1-dioxo-thiomorpholin-4-sulfonyl) ) -phenyl) -benzamide; melting point: 182 ° C. 178.) 5-Chloro-2- (4-chloro-phenylsulfonylamino-N- (4- (1-oxo-thiomorpholin-4-sulfonyl) -phenyl) -benzamide, melting point: 233 ° C. 179.) 5-chloro-2- (3,4-dichloro-phenylsulfonylamino-N- (4-ethylsulfonyl) -phenyl) -benzamide; melting point: 240 ° C. 180.) 5-chloro-N- (4-ethylsulfonyl) -phenyl) -2-nitro-benzamide 181.) 4-chloro-N- (4-chloro-2- (morpholine- 4-sulfonyl) -1H-benzimidazol-2-yl) -phenyl) -benzenesulfonamide. 200 mg (0.5 mmol) of 4-chloro-N- (2? - (1H-benzimidazol-2-yl) -4-chloro were added. phenyl) -benzenesulfonamide at a temperature of 0 ° C to 1 ml of chlorosulfuric acid and heated to a temperature of 60 ° C for 30 minutes.

Subsequently the mixture was drained in water / ice, I and the solid was removed by suction filtration, dried and added at a temperature of 0 ° C to one ml of morpholine. After stirring at room temperature for 1 hour, the mixture was poured into ice / hydrochloric acid and extracted with ethyl acetate. The extracts were evaporated and the residue was purified by chromatography on silica with hexane / ethyl acetate (1: 1). 20 mg (7%) of the title compound was obtained with a melting point of 225-228 ° C, XH-NMR (D6-DMSO): d (PPM) = 2.9 (m, 4H, morpholine-H), 3.6 (m, 4H, morpholine-H), 7.5 8dd, 4H, phenylene-H), 7.4-8.2 (m, 6H, benzo-H, phenyl-H) 182.) 5-chloro-N- (4-morpholine- 4-sulfonyl) -phenyl) -2- (2- (pyrrolidin-1-yl) -ethylsulfonylamino) -benzamide The compound was prepared by the use of 2-chloro-ethylsulfonyl chloride. The 1- (2- (4-chloro-2- (4- (morpholine-4-sulfonyl) -phenylcarbamoyl) -phenylsulfamoyl) -ethyl) -pyridinium chloride which was isolated as an intermediate reacted with pyrrolidine to provide the Title. XH-NMR (Dβ-DMSO): 6 (PPM) = 1.8 (m, 4H, pyrrolidin-H), 2.65 (m, 4H, pyrrolidin-H), 3.0 (m, 4H, morpholin-H), 3.1 ( t, 2H, ethylene-H), 3.35 (t, 2H, ethylene-H), 3.75 (m, 4H, morpholin-H), 7.50 (dd, 1H, H-4), 7.7 (d, 1H, H- 3), 7.75 (dd, 1H, JH-6), 7.85 ("dd", 4H, phenylene-H) 1.00 g (2.21 mmol) of 5-chloro-2- (4-chlorophenylsulfonylamino) -N was dissolved. - (4-mercaptophenyl) -benzamide in 25 ml of dimethylformamide and 0.25 g (2.21 mmol) of potassium tert-butylate was added. The mixture was stirred at room temperature for 15 minutes, then 0.27 g 82.21 mmol) of isopropyl bromide was added dropwise, and the mixture was heated to a temperature of 60 ° C for 8 hours. For the preparation it was poured into water and it was extracted with ethyl acetate. The combined extracts were evaporated and the residue was purified by chromatography on silica with hexane / ethyl acetate (3: 1). 420 mg (39%) of the title compound having a melting point of 168~-169 C were obtained. 184. Analogously obtained) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- ( 4-cyanomethyl ercapto-phenyl) -benzamide; melting point: 104 ° C 185.) Ethyl (4- ((5-chloro-2- (4-chloro-phenylsulphonylamino) -benzoyl) -amino) -phenylmercapto) -acetic acid ethyl ester; melting point: 133 ° C 186.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (2- (morpholin-4-yl) -ethylmercapto) -phenyl) -benzamide; melting point: 95 ° C 187.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4-2- (2-methoxy-ethoxy) -ethylmercapto) -phenyl) -benzamide; oil 188.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (prbp-2-ynyl) -mercapto-phenyl) -benzamide; melting point: 185 ° C | 189.) 5-chloro-2- (4-chloro-phenylsulfonylamino) N- (4-isopropylmercapto-phenyl) -benzamide; melting point: 169 ° C 190.) Sodium salt of 5-chloro2- (5-chloro-thiophene-2-sulfonylamino) -N- (4-morpholine-4-sulfonyl) -phenyl) -benzamide A mixture of 0.48 g of sodium hydroxide powder and 7 g of 5-chloro-2- (5-chloro-thiophene-2-sulfonylamino) ~ N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide in 250 ml of Ethanol was prepared in solution by short heating. After the mixture was evaporated in vacuo, 50 ml of water was added] and evaporated again in vacuo to dryness. This procedure was repeated twice. The resulting product was dried under vacuum at a temperature of 50 ° C. Melting point: 343"(decomposition) Analogously to the above compounds, the following example compounds were obtained: 191.) Hydrochloride of 4, 5 dimethoxy-2 (5-chloro-thiophene-2-sulfonylamino) -N- (4- (N-methyl-N- (pyridin-3-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; melting point: 214 ° C 192.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (morpholin-4-sulfonyl) -3-methyl-phenyl-9-benzamide; melting point: 192 ° C 193. ) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (cis-2,6-dimethyl-morpholin-4-sulfonyl) -3-methyl-phenyl) -benzamide; melting point: 254 ° C 194.) 5-Chloro-2- (4-chloro-phenylsulfonylamino) -N- (4 (3,5-dimethyl-piperidine-1-sulfonyl) -3-methyl-phenyl) -benzamide;] melting point: 242 ° C 195.) 5-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (piperidin-1-sulfonyl) -3-methyl-phenyl) -benzamide; melting point: 189 °, C 196.) 4, 5-dimethoxy-2- (3, 5-dimethyl-isoxazole-4-sulfonylamino) -N- (4- (N- (pyridin-3-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; melting point: 213 ° C. 197.) 4, 5-dimethoxy-2- (3,5-dimethyl-isoxazole-4-sulfonylamino) -N- (4- (N- (pyridin-3-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; melting point: 216 ° C. 198.) 5-chloro-2- (2,4-dimethyl-thiazole-5-sulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 190 ° C 199. 4,5-dimethoxy-2- (4-chloro-phenylsulfonylamino) -N- (4- (3,5-dimethyl-piperidin-1-sulfonyl) -phenyl) -benzamide; melting point: 249 ° C (decomposition) 200.) 2- (4-chloro-phenylsulfonylamino) -N- (4- (N-methyl-N- (pyridin-3-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; resin 201.) 3, 4-dimethoxy-2- (4-chloro-phenylsulfonylamino) -N- (4- (N-methyl-N- (pyridin-3-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; melting point: 241 ° C 202.) 5-bromo-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (morpholin-4-sulfonyl) -3-methyl-phenyl) -benzamide.; melting point: 249 ° C 203.) 5-bromo-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (cis-2,6-dimethyl-morpholin-4-sulfonyl) -phenyl) ) -benzamide; melting point: 244 ° C 204. ) 5-bromo-2- (5-chloro-thiophen-2-sulfonylamino) -N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 197 ° C 205.) 4, 5-dimethoxy-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (1, 2, 3, 4-tetrahydro-isoquinoline-2-sulfonyl) -phenyl) ) -benzamide; melting point: 213 ° C 206.) 4, 5-dimethoxy-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 232 ° C 207.) 4, 5-dimethoxy-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (cis-2,6-dimethyl-piperidin-1-sulfonyl) phenyl) -benzamide; melting point: 213 ° C 208.) 5-Chloro-2- (3, 5-dimethyl-isoxazole-4-sulfonylamino) -N- (4- (1, 2, 3, 4-tetrahydro-isoquinolin-2- sulfonyl) -phenyl) -benzamide; melting point: 260 ° C 209.) 5-Chloro-2- (3,5-dimethyl-isoxazole-4-sulfonylamino) -N- (4- (N-methyl-N-pyridin-3-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; melting point: 65 ° C (sintering) 210.) 6-Methyl-2- (4-chloro-phenylsulfonylamino) -N- (4- (perhydroazepin-1-sulfonyl) -phenyl) -benzamide; melting point: 151 ° C 211. ) 6-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (pyrrolidin-1-sulfonyl) -phenyl) -benzamide; melting point: 217 ° C ^ i it J ^^ um 212.) 6-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4-hydroxybutylamino) -sulfonyl) -phenyl) -benzamide: resin 213.) 5-chloro -2- (4-chloro-phenylsulfonylamino) -N- (4- (N-ethyl-N- (pyridin-4-yl-methyl) -aminosulfonyl) -phenyl) -benzamide; resin 214.) 2- (4-chloro-phenylsulfonylamino) -N- (4-thiomorpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 209 ° C 215.) 3-methyl-2- (4-chloro-phenylsulfonylamino) -N- (4- (N-methyl-N- (2- (pyridin-2-yl) -ethyl) -aminosulfonyl ) -phenyl) -benzamide; melting point: 193 ° C 216.) 4, 5-difluoro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4-aminocarbonyl-piperidin-1-sulfonyl) -phenyl) -benzamide; melting point: 227 ° C 217.) 4, 5-difluoro-2- (4-chloro-phenylsulfonylamino) -N- (4- (4- (2-hydroxyethyl) -piperazin-1-sulfonyl) -phenyl) - benzamide; resin 218.) 5-chloro-4-methoxy-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; oil 219.) 5-chloro-4-methoxy-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (cis-2,6-dimethyl-morpholin-1-sulfonyl) -phenyl) - benzamide; melting point: 89 ° C 220.) 5-Chloro-4-methoxy-2- (5-chloro-thiophene-2-sulfonylamino) -N- (4- (N-pyridin-3-yl) -N-methyl) -aminosulfonyl) -phenyl) -benzamide; melting point: 135 ° C 221. ) Sodium salt of 4,5-dimethoxy-2- (4-c-loro-phenylsulfonylamino) -N- (4-cis-2,6-dimethyl-morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 330 (decomposition) 222.) 5-Chloro-2- (3, 5-dimethyl-ioxazole-4-sulfonylamino) -N- (4- (cis-2,6-dimethyl-morpholin-4-) sulfonyl) -phenyl) -benzamide; melting point: 230 ° C 223.) 5-Chloro-2- (3, 5-dimethyl-isoxazole-4-sulfonylamino) -M- (4- (3,5-dimethylpiperidin-1-sulfonyl) -phenyl) - benzamide; melting point: 61 ° C 224.) 5-chloro-2- (3, 5-dimet? l-isoxazole-4-sulfonylamino) -N- (4- (morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 286 ° C 225.) 5-chloro-2- (5-chloro-thiophen-2-sulfonylamino) -N- (4-phenylsulfonyl) -phenyl) -benzamide; melting point: 227 ° C 226.) 4-chloro-2- (4-chloro-phenylsulfonylamino) -N- (4- (cis-2,6-dimethyl-morpholin-4-sulfonyl) -phenyl) -benzamide; melting point: 103 ° C Pharmacological investigations 1) Activation of soluble guanylate cyclase The activation of soluble guanylate cyclase (sGC) which catalyzes the conversion of guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP) and pyrophosphate, through The compounds according to the invention were quantified with the help of an enzyme immunoassay (EIA) from Amersham. For this purpose, the substances to be tested were initially incubated with sGC in microtrituration plates, and the amount of cGMP that was formed was determined. The sGC that was used had been isolated from bovine lung (see Methods in Enzymology, volume 195, page 377) "The test solutions (100 μl per well) contained 50 mM of triethanolamine (TEA) buffer (pH 7.5), 3 mM of MgCl2, 3mM of reduced glutathione (GSH), 0.1mM of GTP, 1mM of 3-isobutyl-1-methylxanthine (IBMX), an adequately diluted enzyme solution and the substance to be tested or, in the control experiments, the solvent. The substances to be tested were dissolved in dimethyl sulfoxide (DMSO) and the solution was diluted with DMSO / water, so that the final concentration c of the substance to be tested in test solution I had the value indicated in the table. The concentration of DMSO in the test solution was 5% (volume / volume). The reaction was initiated by addition of the sGC. The reaction mixture was incubated at a temperature of 37 ° C for 15 to 20 minutes and then suspended by cooling with ice and addition of the suspension reagent (50 mM EDTA, pH 8.0). a 50 μl aliquot was taken and used to determine the cGMP content using the acetylation protocol of the cGMP-EIA kit Amersham. The absorption of the samples was measured at 450 nm (reference wavelength 620 nm) in a microtiter plate reader. The concentration of cGMP was determined using a standard curve that was obtained under the same test conditions. The activation of sGC by a test substance is provided as the stimulation times of the basal enzymatic activity that was found in the control experiments (using solvent instead of test substance) (calculated using the stimulation formula n times = [cGMP] test substance / [cGMP] control). The following results were obtained: Example compound concentration c no stimulation, [μM] n times 23 50 14.7 59 50 34.8 63 50 33.9 64 50 23.9 65 50 24.6 66 50 33 67 50 29.6 68 50 12.1 69 50 28.3 70 50 25.1 71 50 13.4 72 50 27 73 50 16.5 75 50 5.1 76 50 10.6 77 50 5.9 79 50 15.4 84 50 23.7 86 50 32.9 87 50 12.5 88 50 24.4 89 50 11.6 124 50 31.2 129 50 8.6 130 50 35.3 132 50 9.9 134 50 7.2 136 50 24.2 137 50 4.6 139 50 21.9 145 50 8 146 50 10.2 148 50 15.5 150 50 15.3 151 50 19.9 155 50 7.8 156 50 7.8 157 50 4.6 175 50 21.1 176 50 13.9 191 10 27.5 192 10 26.7 193 10 31.1 194 10 20.0 195 10 16.2 196 10 21.9 206 10 19.3 208 10 23.1 209 10 28.5 222 10 29.5 223 10 27.1 224 10 27.8 225 10 13.4 226 25 3.3 2) Relaxation of the aorta For this test, male Wistar-Kyoto rats with normal tension were sacrificed by a blow to the neck. The abdominal cavity and thorax were opened by mid-stereotomy. The descending aorta was subsequently removed, which was released from connective tissue and divided into 8 sections of a length of approximately 4 mm. The tip of a pair of forceps was inserted into the lumen of 4 of the 8 segments. The endothelium was removed by careful rolling of the segments at the tip of the pair of forceps. The 8 segments of the aorta (4 with endothelium and 4 without endothelium) were subsequently suspended in an organic bath (Schuler-Organbad, Hugo Sachs Elektronik) at a constant temperature of 37 ° C for the isometric determination of the contraction tone. For 30 minutes, the segments were calibrated at a resting tension of 1 g in a Krebs-Henseleit solution (composition: Na + 144.0 mM; K + . 9 mM; Cl "126.9 mM; Caz + 1.6 mM; Mg2 + 1, 1.2 mM; H2PO4, 1.2 mM; SO4 1. 2 mM; HC03"25.0mM; D-glucose 11.1mM) carbopated (95% 02; 5% C02) with a pH of 7.4. In addition, 1 umol / 1 of indomethacin was added to the Krebs-Henseleit solution to inhibit prostaglandin biosynthesis. The segments were subsequently precontracted by the addition of phenylephrine (concentration in the solution: 1 uM) and the endothelium-dependent relaxation or functional loss of the endothelium was tested by the addition of acetylcholine (concentration in the solution: 1 uM). After a 30 minute washout period, the segments were precontracted again by the addition of phenylephrine (1 μM), and the relaxation action of the test substance of formula I was determined by administration of accumulated doses of the latter. The data was evaluated by standard methods. The IC50 concentration is given through which 50% shrinkage (50% relaxation) is inhibited. The following results were obtained: Compound of IC50, No 59 segment without endothelium 0.27 uM 59 segment with endothelium 0.52 μM 88 segment without endothelium 0.29 μM 88 segment with endothelium 0.67 μM 129 segment without endothelium 0.31 μM 129 segment with endothelium 0.46 μM 3) Hemodynamic effect in the pig Anesthetized (ketamine 20 mg / kg im metomidate 8 mg / kg ip, xylazine 2.5 mg / kg im and pentobarbital 25 mg / kg iv in the form of a bolus plus 0.16 mg / kg per minute) three pigs ( Germán landrace). The trachea was intubated and the animals received artificial respiration with air. Oxygen was added to maintain the gas parameters in the blood within the normal range. To record blood pressure (BP; BP (s) = systolic blood pressure, BP (d) = diastolic blood pressure) through a Statham 23Db pressure transducer a catheter was inserted into the right femoral artery. Left ventricular pressure (LVP), left ventricular end diastolic pressure (LVEDP), contraction capacity (dP / dt) and heart rate (HR) were determined with a Millar PC 350"gauge point" gauge inserted into the the right ventricle. After a period of stabilization of hemodynamic parameters of 30 minutes, the test substance was administered at the indicated dose in the exposed duodenum through a catheter. The data obtained were evaluated according to standard methods. The mean and standard deviations (M ± SEM) of the initial values and the maximum changes of the individual parameters are provided (= maximum effects). The following results were obtained: Compound of example 88 (dosage 10 mg / kg i.d.) Parameter initial value alteration maximum duration of action (min) BP (s) (mm Hg) 123126 -23 ± 6 > 180 BP (d) (mm Hg) 83 ± 24 -20 ± 8 > 180 LVEDP (mm Hg) 4 ± 0.6 -1.3 ± 0.3 > 180 dP / dtmax (mm Hg 18001289 -633133> 180 / sec)) HR (beats / min) 98 ± 2 -8 ± 2 > 180

Claims (11)

1. CLAIMS 1. A compound of formula I, where A1 is a divalent residue of the phenylene, naphthylene and heteroarylene series which may be substituted by one or several monocyclic saturated or partially unsaturated or aromatic containing one or more ring heteroatoms selected from the series N, O and S, or a bicyclic saturated or partially unsaturated or aromatic bicyclic heterocycle containing one or more ring heteroatoms selected within of the series N, 0 and S; R1 is aryl, heterocyclyl or alkyl (Ci-Ciß) which may be substituted by one or more identical or different R4 residues, or, if the number n in the group R1-S (0) n- is 2, R1 may be also be NR5R6 or, if the number n in the group R1-S (0) n- is 0, R1 may also be -CN; R is aryl, heterocyclyl, NRR or alkyl (Ci-Ci) which may be substituted by one or more identical or different R4 residues, R3 refers to one or more identical or different residues selected from the series hydrogen, halogen, CF3, OH, -O-alkyl (C? ~ C.), -O-C2-C4 alkyl-O-alkyl (Ci-C.), -O-aryl, (C1-C12) alkylenedioxy, N02, -CN -NR7R8, -CO-OH, -co-o-alkyl (C1-C5), heterocyclyl, -S (O) n-alkyl (Ci-G5) and (C1-C5) alkyl which may be substituted by one or more identical or different R4 residues: R4 is fluorine, OH, -O-alkyl (Ci-Cio), -O-alkyl (C2-C4) -0-alkyl (C? -C7), -O-aryl, -CN, NR7R8, -CO-NH2 / -CO-NH- (C1-C3) alkyl, -CO-N- (C1-C3) alkyl) 2, -CO-OH, -CO-O- (C1-C5) alkyl , heterocyclyl or oxo;
2. R5 is hydrogen, (C1-C10) alkyl which may be substituted by one or more identical or different R4 substituents and / or by aryl, or is aryl, heterocyclyl, -CO-NR7R8, -C0-aryl or -CO- alkyl (d-Cio), wherein the alkyl residue may be substituted by one or more identical or different R4 residues; Rd independently of R 5 has one of the meanings indicated for R 5, or R 5 and R 6 together with the nitrogen atom on which they are attached form a saturated or partially unsaturated 5 to 8 membered ring which, in addition to the nitrogen atom that it carries the groups R5 and R6 may contain one or more additional ring heteroatoms selected from the series N, 0 and S and which may be substituted by one or more substituents identical or different from the series fluorine, (C1-C5) alkyl, hydroxy (C 1 -C 3) alkyl, (C 1 -C 3) alkyl-OC (C 1 -C 4) alkyl, aryl, CF 3, OH, -O-(C 1 -C 7) alkyl, -0-aryl, -O-alkyl (C 2) -C4) -O- (C1-C7) alkyl, (C2-C3) alkylenedioxy, NRR8, -CN, -CO-NH2, -CO-NH- (C1-C3) alkyl, -C0-N (alkyl (C ? -C3)) 2, -CO-OH, -CO-O-alkyl (C? -Cs), CHO, -CO-alkyl (Ci-C5), -S (0) n-alkyl (C1-C4) , -S (0) n-NH2, -S (0) n-NH-alkyl (Ci-C3), -S (0) nN ((C1-C3) alkyl) 2, oxo, -CH2) m-NH2 ), - (CH2) m-NH- (C1-C4) alkyl and - (CH2) mN ((C1-C4) alkyl):? where in the substituent - (CH2) mN ((C? -C4) alkyl) 2 the two alkyl groups can be connected through a single bond and then together with the nitrogen atom carrying them can form a ring of 5 to 7 members which, in addition to this nitrogen atom and the carbon atoms may also contain an oxygen atom, a sulfur atom or a group NR "as a ring member, R7 is hydrogen or (C1-C7) alkyl which can be be substituted by one or more identical or different substituents of the OH, -O- (C1-C5) alkyl, NH2, -NH- (C1-C4) alkyl and - (alkyl (C? -C4)) 2 group where the substituent N ((C 1 -C 4) alkyl) 2 the two alkyl groups can be connected through a single bond and then together with the nitrogen atom carrying them form a ring of 5 to 7 members which, in addition to this Nitrogen atom and carbon atoms may also contain an oxygen atom, a sulfur atom or a NR5 group as a ring member R8 independently of R7 has one of the meanings of R 'or is -CO- (C1-C4) alkyl; aryl is phenyl, naphthyl or heteroaryl which may be substituted by one or more substituents identical or different from the halogen series, (C1-C5) alkyl, phenyl, tolyl, CF3, -0-CF3, N02, OH, -O-alkyl (C? -C5), -O-alkyl (C2-C4) -O-alkyl (C1- C3), alkylenedioxy (C? ~ C2), NH2, -NH- (C1-C3) alkyl, -N ((C1-C3) alkyl) 2 / -NH-CHO, -NH-CO- (C1-C5) alkyl ) -CN, -CO-NH2, -CO-NH- (C1-C3) alkyl -CO-N ((C? -C3) alkyl) 2, -CO-OH, -CO-O-alkyl (C1- C5), heterocyclyl, GHO, -CO- (C1-C5) alkyl, -S (O) n-(C1-C4) alkyl, -S (O) n ~ phenyl, and -S (0) n-tolyl; heteroaryl and heteroarylene are a residue of a 5- or 6-membered aromatic heterocycle or of a bicyclic aromatic heterocycle of 8 to 10 members each of which contains one or more ring heteroatoms of the N, O and S series; heterocyclyl is a residue of a saturated or partially unsaturated heterocycle of 5 to 11 monocyclic or polycyclic members containing one or more ring heteroatoms of the series N, O and S and which may be substituted by one or more substituents identical or different from the fluorine series, (C1-C5) alkyl, OH, -O- (C1-C5) alkyl, -O- (C2-C4) alkyl -O- (C1-C3) alkyl, NH2, -NH-alkyl (C1- C3), -N ((Ci-C3) alkyl) 2, -CN, -CO-NH2, -CO-NH- (C1-C3) alkyl, -CO-N ((Ci-C3) alkyl) 2, - CO-OH and -CO-0-alkyl (C? -C5); n is 0, 1 or 2; m is 2, 3 or 4; X is O or NH or X is a nitrogen atom that is bound through a single bond with a ring carbon atom in group A1, said ring carbon atom is directly adjacent to the carbon atom in A which the group -NH-C (= X) carries - in such a way that the group NH-C (= X) - together with the carbon atoms in A1 that takes it forms an imidazole ring; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts; where, however, the compound of formula I is excluded • where simultaneously the ring A2 comprising the carbon atoms carrying the groups C (= X) -NH- and NH-SO2R2 is a benzene ring substituted in the 3-position and in the 5-position by chloro, R2 is methyl, X is oxygen and Rx-S (0) n-A1- is a residue of 5-chloro-2- (4-chlorophenylmercapto) -phenyl. 2. A compound of the formula I according to claim 1, wherein A1 is a phenylene residue or a • 5 or 6 membered heteroarylene residue, where all these residues may be unsubstituted or substituted, in all their stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts.
3. 3. A compound of the formula I according to claim 1 and / or 2, wherein the ring A2 comprising the carbon atoms carrying the groups R2-S02-NH and C (= X) -NH- is a aromatic ring, in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts.
4. 4. A compound of formula I according to one or more of claims 1 to 3, wherein X is oxygen in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts.
5. 5. A compound of formula I according to one or more of claims 1 to 4, wherein R2 is unsubstituted or substituted aryl, in all its forms • stereoisomers and mixtures thereof in all proportions, and their physiologically acceptable salts.
6. 6. A compound of formula I according to claim 1 or claim 1, wherein R1 is (C1-C7) alkyl, aryl or NR5R6, where these residues may be unsubstituted or substituted, all its stereoisomeric forms and mixtures thereof in all proportions and their physiologically acceptable salts.
7. 7. A compound of formula I according to one or more of claims 1 to 6, wherein R1 is NR5Rd and R5 and Rd, independently of each other are hydrogen, alkyl (Ci- Cg), (C1-C4) alkyl- O-C 1 -C 3 -alkyl or either 5-membered or 6-membered aryl or together with the nitrogen atom carrying R 5 and R form a 5-membered, 7-membered heterocycle, which in addition to the nitrogen atom carrying the groups R5 and R6 may carry an additional ring heteroatom selected from the series consisting of N, 20 O and S and which may be substituted by one or more identical or different residues selected from the series consisting of alkyl (C1 -C3), hydroxyalkyl (C1-C3), 5-membered or 6-membered aryl, carbamoyl, hydroxy and oxo, in all their stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts. ..
8. 8. A compound of formula I according to one or more of claims 1 to 7, wherein A1 is phenylene or heteroarylene wherein these residues may be substituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (C? -C4) alkyl, CF3, -O-(C3-C4) alkyl and -CN; the ring A2 comprising the two carbon atoms carrying the groups R2-S02-NH and C (= X) -NH- is an aromatic ring; R1 is (C1-C7) alkyl which may be substituted by one or • 10 several identical or different R4 residues, either it is aryl, or if the number n in the group R1-S (0) n- is 2, it is also NR5R € R is aryl; R3 indicates one or more identical or different residues selected from the series consisting of hydrogen, halogen, CF3, OH, -O-C1-C4 alkyl, -O-C2-C4 alkyl-0-alkyl? (C? -C4), -O-aryl, N02, -CN, NR7R8, -C0-NRR8, -CO-OH, -? CO-0- (C1-C4) alkyl, heterocyclyl, -S (0) n -alkyl (C1-C4) and (C1-C4) alkyl which may be substituted by one or more 20 identical or different R residues; R4 is fluorine, OH, -O-(C1-C10) alkyl, -O-alkyl (C2-c4) -o- (C1-C7) alkyl, -O-aryl, -CN, NR'R0, -C0- NH2, -CO-NH- (C? -C3) alkyl, -CO-N ((C? -C3) alkyl) 2, -CO-OH, -CO-O- (C1-C4) alkyl, heterocyclyl or oxo; R5 and R6 independently of each other are hydrogen, alkyl (Ci-Cg), alkyl (C1-C4) -O-alkyl (C1-C3) or aryl c together with the nitrogen atom carrying R5 and R6c • form a 5-membered, 7-membered heterocycle which, in addition to the nitrogen atom carrying the groups R5 and Rd, may contain an additional ring heteroatom selected from the series consisting of N, O and S, and which may be substituted by one or more identical or different residues selected from the series consisting of (C1-C3) alkyl, hydroxy (C1-C3) alkyl, aryl, carbamoyl, • 10 hydroxy and oxo; R 'is hydrogen, (C 1 -C 3) alkyl, (C 1 -C 4) alkyl) 2-N- (C 1 -C 3) alkyl- or (C 1 -C 4) alkyl -O-(C 1 -C 3) alkyl-; R8 is hydrogen, (C1-C3) alkyl or acetyl; aryl is phenyl or heteroaryl that can all be 15 substituted by one or more identical or different substituents selected from the series consisting of halogen, (C 1 -C 4) alkyl, phenyl, CF 3, N 0 2, -O-(C 1 -C 4) alkyl, alkylenedioxy (C 1 -C 2) , NH2, -NH-CO- (C1-C4) alkyl, -CN, -CO-NH, -CO-OH and -CO-O- (C1-C4) alkyl; Heteroaryl and heteroarylene are a residue of a 5-membered or 6-membered monocyclic aromatic heterocycle, containing one or more identical or different ring heteroatoms selected from the series consisting of N, O and S; The heterocycle is a residue of a saturated 5-membered or 6-membered monocyclic heterocycle containing one or more identical or different ring heteroatoms selected from the series consisting of N, O and S and which may be substituted by one or several substituents identical or different selected within the series consisting of fluorine, alkyl (C? -C4), OH, -O-alkyl (C1-C4), NH2, -CN, -CO-NH2, -CO-OH and -CO -O-C1-C4 alkyl; n is 0, 1 or 2; X is oxygenate in all its stereoisomeric forms and mixtures thereof in all proportions, and physiologically acceptable salts thereof
9. 9. A compound of formula I according to one or more of claims 1 to 8, wherein A1 is unsubstituted or substituted phenylene. by one or more identical or different substituents selected from the series consisting of halogen, (C 1 -C 4) alkyl, CF 3, -O-(C 1 -C 4) alkyl and -CN; the ring A2 comprising the two carbon atoms carrying the groups R2-S02-NH and C (= X) -NH- is a benzene ring; R1 is NR5Rd; R2 is aryl; R3 refers to one or more identical or different residues selected from the series consisting of hydrogen, halogen, CF3, -O-(C1-C4) alkyl, -CN and alkyl; R5 and R6 together with the nitrogen atom carrying R: and R € form a saturated 5-membered or 6-membered heterocycle which, in addition to the nitrogen atom carrying the R groups and R ° may contain an additional ring heteroatom selected from the series consisting of N, O and S, and which may be substituted by one or more identical or different residues selected from the series consisting of (C 1 -C 3) alkyl , hydroxy (C? -C3) alkyl, aryl, carbamoyl, hydroxy and oxo; aryl is phenyl or 5-membered or 6-membered heteroaryl containing one or more identical or different ring heteroatoms selected from the series consisting of N, O and S, said residues may all be substituted by one or more identical substituents or different selected within the series consisting of halogen, (C1-C4) alkyl, CF3, N02, -O-(C1-C4) alkyl, -NH-CO-alkyl (C? -C4) and -CN; n is 2; X is oxygen; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiologically acceptable salts.
10. 10. A compound of formula I according to one or more of claims 1 to 9, wherein A1 is an unsubstituted divalent phenylene residue; the ring A2 consisting of the two carbon atoms bearing the groups R2-S02-NH and C (= X) -NH- is a benzene ring; R1 is NR5R6; R2 is aryl; R3 indicates one or more identical or different residues selected from the series consisting of hydrogen, halogen, -O-(C1-C4) alkyl and (C1-C4) alkyl; R5 and R6 together with the nitrogen atom carrying R and Re form a saturated 6-membered heterocycle which, in addition to the nitrogen atom carrying the groups R5 and Rd, may contain an additional ring heteroatom selected from the series consisting of N, O and S, and which may be substituted by one or more identical or different residues selected from the series consisting of alkyl (Ci-C3), aryl, oxo and carbamoyl; aryl is phenyl or a 5-membered or 6-membered heteroaryl containing one or more identical or different ring heteroatoms selected from the series consisting of N, O and S, said residues may all be substituted by one or more identical substituents < eos or different selected within the series consisting of halogen, (C 1 -C 4) alkyl, CF 3 and -O-(C 1 -C 4) alkyl; n is 2; X is oxygen; in all its stereoisomeric forms and mixtures thereof in all proportions, and their physiological salts • acceptable.
11. 11. A compound of the formula I according to claim 1 or claim 1, wherein A1 is an unsubstituted divalent 1,4-phenylene residue; the ring A2 comprising the two carbon atoms carrying the groups R2-S02-NH and C (= X) -NH-, together with the residues R3 is a benzene ring carrying one or two substituents selected from the series consisting of eloxy methoxy; R1 is NR5Rd; R 2 is phenyl or thienyl, said residues are all substituted by one or two chlorine atoms; R5 and R6 together with the nitrogen atom bearing R5 and R? form a saturated 6-membered heterocycle which, in addition to the nitrogen atom carrying the groups R5 and R6, may contain an additional ring heteroatom selected from the series consisting of O and S, and unsubstituted or substituted by one or two residues methyl; n is 2; X is oxygen; 25 in all its stereoisomeric forms and mixtures thereof soluble guanylate cyclase activator. 16. A compound of formula I according to claim 1 in one or more of claims 1 to 11 and / or its salt is physiologically acceptable for use in the therapy or prophylaxis of cardiovascular diseases, lendothelial dysfunction, diastolic dysfunction, atherosclerosis , hypertension, angina pectoris, thrombosis, restenosis, myocardial infarction, strokes, heart failure, pulmonary hypertension, erectile dysfunction, bronchial asthma, chronic renal insufficiency, diabetes or liver cirrhosis or to improve the limited performance of memory or learning capacity