MXPA06008712A - PYRROLE-DERIVATIVES AS FACTOR Xa INHIBITORS - Google Patents

Abstract

The present invention relates to compounds of the formulae (I) and (Ia), wherein R0;R1;R3;R4;R22, Q;V, G and M have the meanings indicated in the claims. The compounds of the formulae (I) and (Ia) are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formulae (I) and (Ia), their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Description

DERIVATIVES OF PIRROL AS INHIBITORS OF THE XA FACTOR The present invention relates to the compounds of the formulas I and where R °; R1; R3; R4; R22; Q, V, G and M have the meanings indicated below. The compounds of formulas I and II are valuable pharmacologically active compounds; they have a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders such as thromboembolic diseases or restenosis. They are reversible inhibitors of factor Xa (FXa) and / or factor Vlla (FVIla) of blood coagulation enzymes, and can be applied in general under conditions in which undesired factor Xa activity is present and / or of the factor Vlla or for the cure or prevention whose inhibition of factor Xa and / or factor Vlla is intended. The invention also relates to processes for the preparation of compounds of the formulas I and II, to their use, in particular as active ingredients in pharmaceutical products, and to the pharmaceutical preparations comprising them. Normal homeostasis is the result of a complex balance between the processes of clot initiation, the formation and dissolution of the clot. The complex interactions between blood cells, plasma-specific proteins and the vascular surface maintain fluidity of the blood unless a wound and blood loss occurs (EP-A-987274). Many significant pathological states refer to anomalous homeostasis. For example, local thrombus formation due to rupture of the atherosclerotic plaque is the main cause of acute myocardial infarction and unstable angina. Treatment of an occlusive coronary thrombus by thrombolytic therapy or percutaneous angioplasty may be accompanied by acute thrombolytic re-closure of the affected vessel. There continues to be a need for safe and effective therapeutic anticoagulants to limit or prevent thrombus formation. It is most desirable to develop agents that inhibit coagulation without directly inhibiting thrombin but inhibiting other steps in the coagulation cascade such as factor Xa activity and / or factor Vlla. It is now believed that factor Xa inhibitors involve a lower bleeding risk than thrombin inhibitors (A.E.P. Adang &J.B. Rewinkel, Drugs of the Future 2000, 25, 369-383). Low molecular weight, factor Xa specific blood clot inhibitors have been described, which are effective but do not produce unwanted side effects, for example, in WO-A-95/29189. However, in addition to being an effective inhibitor of blood coagulation, specific for factor Xa, it is desirable that said inhibitors also have additional advantageous properties, for example stability in the plasma and in the liver and selectivity against other serine proteases whose Inhibition is not intended, such as thrombin. There is a continuing need for more blood coagulation inhibitors specific for low molecular weight factor Xa, which are effective and also have the above advantages. Specific inhibition of factor Vlla / catalytic complex of tissue factor using monoclonal antibodies (WO-A-92/06711) or a protein such as factor Vlla inactivated by chloromethyl ketone (WO-A-96/12800, WO-A -97/47651) is an extremely effective means of controlling the formation of the thrombus produced by acute arterial injury or thrombotic complications related to bacterial septicemia. There is also experimental evidence to suggest that inhibition of Vlla factor / tissue factor activity inhibits restenosis after balloon angioplasty. Mandrel hemorrhage studies have been carried out and indicate that inhibition of factor Vlla / tissue factor complex has the widest safety interval with respect to therapeutic efficacy and bleeding risk of any anticoagulant method tested including inhibition of thrombin, of platelets and factor Xa. Certain inhibitors of factor Vlla have already been described. EP-A-987274, for example, discloses compounds that contain a tripeptide unit, which inhibits factor Vlla. However, the characteristic profile of these compounds is still not ideal, and there is a continuing need for more blood coagulation inhibitors of the low molecular weight factor Vlla inhibitor. The present invention satisfies the above needs by providing new compounds of the formulas I and II, which have better inhibitory activity of factor Xa and / or factor Vlla and which are favorable agents with high bioavailability. Therefore, the present invention relates to compounds of the formulas I and R ° is 1) an aryl of 6 to 14 monocyclic or bicyclic elements, in which the aryl is mono-, di- or trisubstituted independently from each other by R8, 2) a heterocyclyl of 4 to 15 monocyclic or bicyclic elements of the group pyridinyl, pyrimidinyl, indolyl, isoindolyl, indazolyl, phthalazinyl, quinolyl, isoquinolyl, benzothiophene, quinazolinyl and phenylpyridyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R8, or 3) a heterocyclyl 4 to 15 monocyclic or bicyclic elements, containing one, two, three or four heteroatoms selected from nitrogen, sulfur or oxygen, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R8, and which is further substituted by a monocyclic or bicyclic 4 to 15-membered heterocyclyl, which contains one, two, three or four heteroatoms selected from nitrogen, sulfur or oxygen, wherein the heterocyclyl is unsubstituted or mono-, di-, or trisubstituted independently of each other by R8, R8 is 1) halogen, 2) -NO2, 3) -OH, 4) -O-CF3 5) an aryl of 6 to 14 monocyclic or bicyclic elements, in which the aryl is mono-, di- or trisubstituted independently from each other by halogen or -O- (C? -Cs) -alkyl, 6) - (C? -8) -alkyl, in that the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -OH or a methoxy, 7) -O- (C-? -8) -alkyl moiety, wherein alkyl is not substituted or mono-, di- or trisubstituted independently from each other by halogen, NH2, -OH or a methoxy moiety, 8) -SO2-CH3 or 9) -SO2-CF3 with the proviso that R8 is at least one halogen or a residue -O- (C? -Cs) -alkyl, if R ° is an aryl of 6 to 14 monocyclic or bicyclic elements, Q is - (C0-C2) -alkyliene-C (O) -NR10-, -NR10 -C (O) -NR10-, -NR 0-C (O) -, - (C C6) -alkylene, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - ( CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mS- (CH 2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) m-SO2-NR10- (CH2) n-, - (CH2) m-NR10-SO2- (CH2) n -, - (CH2) m-NR10-SO2-NR10- (CH2) n-, - (CH2) m-CH (OH) - (CH2) n-, - (CH2) mOC (O) -NR10- (CH2) ) n-, - (C2-C3) -alkylene-O- (C0-C3) -alkylene-, - (C2-C3) -alkylene-S (O) -, - (C2-C3) -alkylene-S ( O) 2-, - (CH2) m-NR10-C (O) -O- (CH2) n-, - (C2-C3) -alkyl-S (O) 2-NH- (R10) -, - (C2-C3) -alkylene-N (R10) - or - (C0-C3) -alkylene-C (O) -O- (CH2) m-, wherein R10 is as defined below, and in which n and m are, independently of each other, identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, in which the alkylene moieties which are formed by - (CH2) mo - (CH2) n- are unsubstituted or mono-, di- or trisubstituted, independently of one another, by halogen, -NH2 or -OH; or - (C3-C6) -cycloalkylene, wherein the cycloalkylene is unsubstituted or mono-, di- or trisubstituted, independently of one another, by halogen, -NH2 or -OH; R1 is a hydrogen atom, - (C? -C4) -alkyl, wherein alkyl is unsubstituted or substituted one to three times by R13; - (C -? - C3) -alkylene-C (O) -NH-R °, - (C -? - C3) -alkyl ene-C (O) -O-R10, an aryl of 6 to 14 elements monocyclic or bicyclic, wherein the aryl is mono-, di- or trisubstituted, independently of one another, by R8, wherein R8 is as defined above; a monocyclic or bicyclic 4 to 15-membered heterocyclyl which contains one, two, three or four heteroatoms selected from nitrogen, sulfur or oxygen; - (C-1-C3) -perfluoroalkylene; - (C? -C3) -alkylene-S (O) - (CrC4) -alkyl; ~ (CrC3) -alkylene-S (O) 2- (C? -C3) -alkyl; - (C? -C3) -alkylene-S (O) 2-N (R4 ') -R5'; - (C C3) -alkyllene-O- (C? -C) -alkyl; - (Co-C3) -acykylene- (C3-C8) -cycloalkyl or - (Co-C3) -alkylhene-het, wherein het is a cyclic nitrogen, sulfur or oxygen moiety, wherein said cyclic moiety is unsubstituted or mono-, di- or trisubstituted, independently of one another, by R14, R4 and R5 are independently of each other, identical or different and are a hydrogen atom or - (C? -C4) -akyl, or R1 and R22 together with the atoms to which they are attached can form a cyclic group of 6 to 8 elements, which contains 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of each other by R 14, or R 1 -NV can form a a cyclic group of 4 to 8 elements, containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, R14 is halogen, -OH, = O, - (C? -C8) -alkyl, - (C? -C4) -alkoxy, -NO2, - (C0-C4) -alkyl-C (O) -O-R18 , -CN, - (C0-C4) -alkyl-N (R18) -R21, - (C0-C4) -alkyl-O-R18, - (C0-C4) -alkyl-het, - (Co-C8) -alkyl-SO2- (C1-C4) -alkyl, - (C0-C8) -alkyl-SO2- (C? -C3) -perfluoroalkyl, - (C0-C8) -alkyl-SO2-N (R18) -R21 , - C (O) -NH- (C? -C8) -alkyl, -C (O) -N - [(C? -C8) -alkyl] 2, -NR18-C (O) -NH- (C ? -C8) -alkyl, -C (O) -NH2, -S-R18, or -R ^ -C ^ -H-Kd-Cs) -alkyl] 2, wherein R18 and R21 are independently of each other the hydrogen atom, - (C? -C3) - perfluoroaI- or - (Ci-CβJ-alkyl, V is 1) a cyclic residue of 3 to 7 elements, containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic moiety is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, or 2) a monocyclic or bicyclic heterocyclyl of 4 to 15 elements, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R14, G is a direct bond, - (CH2) m-NR10-SO2-NR 0- (CH2) n-, - (CH2) m-CH (OH) - (CH2) n-, - (CH2) m- , - (CH2) mO- (CH2) n-, - (CH2) mC (O) -NR10- (CH2) n-, - (CH2) -SO2- (CH2) n-, - (CH2) m-NR10 -C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mC (O) - (CH2) n-, - ( CH2) -S- (CH2) n-, - (CH2) m-SO2- NR10- (CH2) p-, - (CH2) m-NR10-SO2- (CH2) n-, - (CH2) m-NR10 -, - (CH2) mO-C (O) -NR10- (CH2) n- or - (CH2) m-NR10-C (O) -O- (CH2) p-, n and m are independently of each other identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, M is 1) an atom of hi phenogen, 2) - (Ci-Csy-alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, 3) -C (O) -N (R 11) -R 12, 4) - (CH2) m-NR10, 5) an aryl of 6 to 14 elements, in which the aryl is unsubstituted or mono-, di- or trisubstituted independently from each other by R14, 6) a heterocyclyl of 4 to 15 monocyclic or bicyclic elements, wherein the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, 7) - (C 3 -C 8) -cycloa-Icyl, wherein said cycloalkyl is unsubstituted or mono -, di- or trisubstituted independently from each other by R 14, or 8) a cyclic residue of 3 to 7 elements containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic moiety is not substituted or mono-, di- or trisubstituted independently from each other by R14, wherein R14 is defined above, R3, R4 and R22 are independent of each other, are identical or different and are 1) hydrogen atom, 2) halogen, 3) - (C? -C4) -alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C4) - alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (C -? - C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R13, or c) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, d) -CF3, oe) -CHF2, 7) -NO2, 8) -CN, 9) -SOs-R11, wherein s is 1 or 2, 10) -SOt-N (R1) -R12, wherein t is 1 or 2 11) - (C0-C4) -acylene-C (O ) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 15) -NR10-SO2-R10, 16) -S-R10, 17) - (C0-C2) alkylene-C (O) -O- (C2 -C4) ~ alkyne-OC (O) - (C? -C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-) C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (C? -C6) -alkyl, 20) -C (O) -OC (R15, R16) -OC ( O) -R17, 21) - (Co-C4) -alkylene- (C6-C? 4) -aryl, in which aryl is mono-, di- or trisubstituted independently from each other by R13, 22) - (Co-C4) -alkylene- (C -Ci5) -heterocyclyl, in which the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 23) - (Co-C4) -alkylene (C3-C8) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 24) - (Co-C) -alkylene-het, wherein het is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, 25) - (C0-C4) -alkylene-O-CH2- (C? -C3) -perfluoroalkylene-CH2-O- (Co- C) -alkyl, 26) -SOw-N (R11) -R13, wherein w is 1 or 2.27) - (C0-C4) -alkylene-C (O) -N (R11) -R13, 28 ) - (C0-C) -alene-N (R11) -R13, or 29) a remainder of the following list if two residues -OR19 are attached to adjacent atoms can form together with the atoms to which they are attached to a ring of 5 or 6 elements, which is unsubstituted or substituted one, two, three or four times by R13, R11 and R12 are independently of one another identical or different and are 1) hydrogen atom, 2) - (Ci-Cι-alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, 3) - (Co-C6) -alkyl- (C3-C8) -cycloalkyl, 4) -SOt-R10, wherein t is 1 or 2.5) - (Co-C6) -alkyl- (C6-Ci4) -aryl, wherein alkyl and aryl independently one of the other are unsubstituted or mono-, di- or trisubstituted by R13, 6) - (CrC3) -perfluoroalkyl, 7) -O-R17, or 8) - (Co-C6) -alkyl- (C4-Ci5) -heterocyclyl, in which alkyl and heterocyclyl independently of one another are unsubstituted or mono-, di- or trisubstituted by R13, or R11 and R12 together with the nitrogen atom to which they are attached can form a monocyclic heterocyclic ring of 4 to 8 elements which in addition to the nitrogen atom may contain one or two identical or different ring heteroatoms selected from oxygen, sulfur and nitrogen; wherein said heterocyclic ring is unsubstituted or mono-, di- or trisubstituted independently of each other by R13, R4 and R22 in formula I or in the formula together with the carbon atoms to which they are attached can form a phenyl residue, R13 is halogen, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C3-C8) -cycloalkyl, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3) -N (R10) -S (O) u-R10, in that u is 1 or 2, -S- R10, -SOrR10, wherein r is 1 or 2, -S (O) VN (R10) -R20, where v is 1 or 2, -C (O ) -R10, - (CrCsJ-alkyl, - (CrCsValkoxy, phenyl, phenyloxy-, -O-CF3, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) - R17, - (C -? - C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -O-R17, - (C? - C3) -perfluoroalkyl, -O-R15, -NH-C (O) -NH-R10, -NH-C (O) -O-R10 or a remainder of the following list R10 and R20 are independently from each other hydrogen, - (d-CβJ-alkyl, - (C0-C) -alkyl-OH, - (C0-C4) -alkyl-O- (C? -C4) -aryl or - (d-C3) - perfluoroalkyl, R15 and R16 are independently of each other hydrogen, - (Ci-CβJ-alkyl, or together with the carbon atom to which they are attached can form a carbocyclic ring of 3 to 6 elements which is not substituted or substituted one to three times by R10, and R17 is - (C -C6) -alkyl, - (d-C6) -alkyl-OH, - (d-C6) -alkyl-O- (d-C6) ) -alkyl, - (C3-C8) -cycloalkyl, - (d-C6) -alkyl-O- (d-C8) -alkyl- (C3-C8) -cycloalkyl, - (C? -C6) - (C3-C8) alkyl-cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (C? -C4) -Iquine or R10, in all its forms stereoisomers and their mixtures in any proportion, and their physiologically tolerable salts. 2) The present invention also relates to the compounds of formula I, wherein: R ° is 1) an aryl of 6 to 14 monocyclic or bicyclic elements, wherein aryl is mono-, di- or tri-substituted independently one from another by R8, 2) a monocyclic or bicyclic monocyclic or bicyclic heterocyclyl of the benzothiophene, indazolyl, indolyl, isoindolyl, isoquinolyl, phenylpyridyl, phthalazinyl, pyridyl, pyridinyl, pyrimidinyl, quinolyl and quinazolinyl group, wherein said heterocyclyl is substituted or mono-, di- or trisubstituted independently from each other by R8, or 3) a monocyclic or bicyclic 4 to 15-membered heterocyclyl, which contains one, two, three or four heteroatoms selected from nitrogen, sulfur or oxygen, in the that said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R8, and that it is further substituted by a monocyclic or bicyclic 4 to 15-membered heterocyclyl, containing one, or three or four heteroatoms selected from nitrogen, sulfur or oxygen, in which the heterocyclyl is unsubstituted or mono-, di-, or trisubstituted independently of one another by R8, R8 is 1) halogen, 2) -NO2, 3) -OH, 4) -O-CF3 5) an aryl of 6 to 14 monocyclic or bicyclic elements, in which the aryl is mono-, di- or trisubstituted independently from each other by halogen or -O- (C? -C8) -alkyl, 6) - (C? -C8) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -OH or a methoxy moiety, 7) -O- (C? -Cd) -alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, NH2, -OH or a methoxy moiety, 8) -SO2- CH3 or 9) -SO2-CF3 with the proviso that R8 is at least one halogen or a residue -O- (C? -8) -alkyl, if R ° is a 6 to 14 monocyclic or bicyclic aryl, Q is - (C0-C2) -alene-C (O) -NR10-, -NR10-C (O) -NR10-, -NR10-C ( O) -, - (C? -C6) -alkylene, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O) - (CH2) ) n-, - (CH2) mS- (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) m-SO2-NR10- (CH2) n-, - (CH2) ) m-NR10-SO2- (CH2) n-, - (CH2) m-NR10-SO2-NR10- (CH2) n-, - (CH2) m-CH (OH) - (CH2) p-, - ( CH2) mOC (O) -NR10- (CH2) n-, - (C2-C3) -acycline-O- (Co-C3) -alkyllene-, - (C2-C3) -alkylene-S ( O) -, - (C2-C3) -alkylene-S (O) 2-, - (CH2) m-NR10-C (O) -O- (CH2) n-, - (C2-C3) -alkylene- S (O) 2-NH- (R10) -, - (C2-C3) -alkylene-N (R10) - or - (C0-C3) -alkylene-C (O) -O- (CH2) m-, wherein R10 is as defined below, and wherein n and m are independently of one another identical or different are the integers zero, 1, 2, 3, 4, 5 or 6, wherein the alkylene moieties that are formed by - (CH2) m- or - (CH2) n- are unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; or - (C3-C6) -cycloalkyl, wherein the cycloalkylene is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; R1 is a hydrogen atom, - (C? -C4) -alkyl, in which alkyl is unsubstituted or substituted one to three times by R13; - (d-C3) -alkylene-C (O) -NH-R °, - (d-C3) -alkylene-C (O) -O-R15; an aryl of 6 to 14 monocyclic or bicyclic elements, wherein the aryl is mono-, di- or trisubstituted independently from each other by R8, wherein R8 is as defined above; a monocyclic or bicyclic 4 to 15-membered heterocyclyl which contains one, two, three or four heteroatoms selected from nitrogen, sulfur or oxygen; - (C? -C3) -perfluoroalkylene; - (C? -C3) -aikylno-S (O) - (C? -C4) -alkyl; - (C -? - C3) -alkylene-S (O) 2- (d-C3) - alkyl; - (C? -C3) -alkylene-S (O) 2-N (R ') -R5'; - (d-C3) -alkyl-O-O- (C? -C4) -alkyl; - (C0-C3) -alkylno- (C3-C8) -cycloalkyl or - (C0-C3) -alkylhene-het, in which het is unsubstituted or mono-, di- or tri-substituted independently one of another by R14, R4 and R5 are independent of each other identical or different and are a hydrogen atom or - (C? -C) -alkyl, or R1 and R22 together with the atoms to which they are attached can form a cyclic group from 6 to 8 elements, containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, or R 1 -NV can form a cyclic group of 4 to 8 elements, containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic group is unsubstituted or mono-, di- or tri-substituted independently one from another by R14, R14 is halogen, -OH, = O, - (C? -C8) -alkyl, - (C? -C4) -alkoxy, -NO2, - (C0-C) -alkyl-C (O ) -O-R18, -CN, - (Co-C4) -alkyl-N (R18) -R21, - (C0-C4) -alkyl-O-R18, - (C0-C4) -alkyl-het, - (Co-d -alkyl-SOHd ^ -alkyl, - (C0-C8) -alkyI-SO2- (C ? -C3) -perfluoroalkyl, - (C0-C8) -alkyl-SO2-N (R18) -R21, -C (O) -NH- (C? -8) -alkyl, -C (O) -N- [(C? -C8) -alkyl] 2, -NR18-C (O) -NH- (d-C8) -alkyl, -C (O) -NH2, -S-R18 or -NR18-C (O) -NH - [(d-C8) -alkyl] 2, in which R18 and R21 are independently of each other the hydrogen atom, - (C? -C3) -perfluoroalkyl or - (C? -C6) - where, V is 1) a cyclic moiety of 3 to 7 elements, containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic moiety is unsubstituted or mono-, di- or or trisubstituted independently from each other by R 14, or 2) a monocyclic or bicyclic heterocyclyl of 4 to 15 elements, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted, independently of one another by, R 14, G is a direct bond, - (CH2) m-NR10-S? 2-NR10- (CH2) n-) - (CH2) m -CH (OH) - (CH2) n-, - (CH2) m-, - ( CH2) mO- (CH2) n-, - (CH2) mC (O) -NR10- (CH 2) n-, - (CH2) -SO2- (CH2) n-, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O ) - (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) -S- (CH2) n-, - (CH2) m-SO2- NR10- (CH2) n -, - (CH2) m-NR10-SO2- (CH2) n-, - (CH2) m-NR10-, - (CH2) mO- C (O) -NR10- (CH2) n- or - (CH2) m-NR10-C (O) -O- (CH2) n-, n and m are independently identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, M is 1) an atom of hydrogen, 2) - (C? -C8) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R14, 3) -C (O) -N (R11) -R12, 4) - (CH2) m-NR10, 5) - (C6-C? 4) -aryl, wherein the aryl is unsubstituted or mono-, di- or trisubstituted independently of each other by R14, ) - (C4-Ci5) -heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R14, 7) - (C3-C8) -cycloa-I, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R14, or 8) a re cyclic element of 3 to 7 elements containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur or oxygen, wherein said cyclic moiety is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, in that R14 is defined above, R3, R4 and R22 are independent of each other, are identical or different and are 1) hydrogen atom, 2) halogen, 3) - (C? -C4) -alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C4) - alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (C? -C) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, or c) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) -CF3, oe) -CHF2, 7) -NO2, 8) -CN, ) -SOs-R11, where s is 1 or 2, 10) -SOt-N (R11) -R12, where t is 1 or 2 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - ( C0-C4) -achiol-N (R11) -R12, 15) -NR10-SO2-R10, 16) -S-R10, 17) - (C0-C2) alkylene-C (O) -O- (C2-) C4) -alkylene-OC (O) - (C? -C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (C0-C2) alkylene -C (O) -O- (C2-C4) -alkylene-OC (O) - (d-C6) -alkyl, 20) -C (O) -OC (R15, R16) -OC (O) -R1 7, 21) - (Co-C4) -alkylene- (C6-Ci4) -aryl, in which aryl is mono-, di- or trisubstituted independently from each other by R13, 22) - (Co-C4) -alkylene- (C4-Ci5) -heterocyclyl, in which the heterocyclyl is unsubstituted or mono-, di- or trisusituituido independently of each other by R13, 23) - (Co-C4) -alkylene- (C3-C8) -cycloalkyl, in which the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 24) - (Co-dJ-alkylene-het, in which het is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, ) - (C0-C4) -alkylene-O-CH2- (C? -C3) -perfiuoroalkyl-CH2-O- (Co-C4) -alkyl, or 26) -SOw-N (R11) -R13, in wherein w is 1 or 2, 27) - (C0-C4) -acylene-C (O) -N (R11) -R13, 28) - (C0-C4) -alkylene-N (R11) -R13, or 29) a remainder of the following list if two residues -OR19 are attached to adjacent atoms can form together with the atoms to which they are attached to a ring of 5 or 6 elements, which is unsubstituted or substituted one, two, three or four times by R13, R11 and R12 are independently of one another identical or different and are 1) hydrogen atom, 2) - (C? -C6) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 3) - (Co-C6) -alkyl- (C3-C8) -cycloalkyl, 4) -SOt-R10, wherein t is 1 or 2.5) - (Co-C6) -alkyl- (C6-C14) ) -aryl, wherein alkyl and aryl independently of one another are unsubstituted or mono-, di- or trisubstituted by R 13, 6) - (C? -C3) -perfluoroalkyl, 7) -O-R17, or 8) - (Co-C6) -alkyl- (C4-Ci5) -heterocyclyl, wherein alkyl and heterocyclyl independently of one another are unsubstituted or mono-, di- or trisubstituted by R13, or R11 and R12 together with the The nitrogen atom to which they are attached can form a monocyclic heterocyclic ring of 4 to 8 elements which in addition to the nitrogen atom can contain one or two identical or different ring heteroatoms selected from oxygen, sulfur and nitrogen; wherein said heterocyclic ring is unsubstituted or mono-, di- or trisubstituted independently of each other by R13, R4 and R22 in formula I or in the formula together with the carbon atoms to which they are attached can form a phenyl residue, R13 is halogen, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10 ) -R20, - (C3-C8) -cycloalkyl, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, -N (R10) -S (O) u-R10, wherein u is 1 or 2, -S- R10, -SOrR10, wherein r is 1 or 2, -S (O) VN (R10) -R20, wherein v is 1 or 2, -C ( O) -R10, - (d-C8) -alkyl, - (C? -C8) -alkoxy, phenyl, phenyloxy-, -O-CF3, - (Co-C4) -alkyl-C (O) -OC ( R15, R16) -OC (O) -R17, - (C? -C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) - O-R17, - (d-C3) -perfluoroalkyl, -O-R15, -NH-C (O) - R10 and R20 are independently from each other hydrogen, - (d-Cß) -alkyl, or - (C? -C3) -perfluoroalkyl, R15 and R16 are independently of each other hydrogen, - (d-Cß) -alkyl, or together with the carbon atom to which they are attached can form a carbocyclic ring of 3 to 6 elements which is unsubstituted or substituted one to three times by R10, and R17 is - (d-C6) -alkyl, - (d-C6) -alkyl-OH, - (d-C6) -alkyl-O- ( d- C6) -acyl, - (C3-C8) -cycloalkyl, - (d-CsJ-alkyl-O-id-Cs) - (C3-C8) alkyl- cycloalkyl, - (d-C6) -alkyl- (C3-C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (C? -C4) -alkyl or R10, in all its stereoisomeric forms and their mixtures in any proportion, and their physiologically tolerable salts. 3) Therefore, the present invention relates to the compounds of formula I in which R ° is 1) a monocyclic or bicyclic aryl of 6 to 14 elements of the phenyl, naphthyl, biphenylyl, anthryl or fluorenyl group, in the wherein aryl is mono-, di- or trisubstituted independently of one another by R8, 2) a heterocyclyl group of benzimidazolyl, 1,3- benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl is unsubstituted or mono- -, di- or trisubstituted independently from each other by R8, or 3) a heterocyclyl, in which the heterocyclyl is selected from the group of acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azeti dinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxathiolyl, benzothiazolyl, benzotriazolyl, benzotetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, 1,3- dioxolanyl, 1,3-dioxolenyl, 6H-1, 5,2-ditiacinilo, dihydrofuro [2,3-b] - tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, indolyl, 3H-indolyl, isobenzofuranyl, isocromanyl, isoindazolyl, isoindolinyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2, 3- oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,4-oxadiazoyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1, 4-oxazepanyl, 1, 4-oxazepinyl, 1, 2-oxazinyl, 1,3-oxaziniIo, 1, 4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, piridooxazolilo, pyridoimidazolyl, piridotiazolilo, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydro-quinolinyl, 1, 4,5,6-tetrahydropyridazinyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolium, thiantrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinium thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,4-triazinyl, 1,3,5-triazinyl, 1,2,3-trizolyl, 1,2,4-trizolyl, 1, 2,5-triazolyl, 1, 3,4-triazolyl and xanthenyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R8, and which is further substituted by a heterocyclyl, wherein the heterocyclyl selected from the group acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, benzotetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5- dihidrooxazoIiniIo, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1, 5,2-ditiacinilo, dihydrofuro [2,3-b] -tetrahidrofuraniIo, furanyl, furazanyl, imidazolidinyl, imidazolinyl, midazolilo, 1H-indazolyl, indolinyl, indolizinyl, indolyl, indolyl, 3H-indolyl, isobenzofuranyl, isocromanyl, isocholinyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl , oxadiazolyl, 1, 2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1, 3,4-oxadiazolyl, 1-oxa-thiepanyl 2, 1, 2-oxathiolanyl, 1 , 4-oxazepanyl, 1,4-oxazepinyl, 1, 2-oxaziniIo, 1, 3-oxazinyl, 1, 4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl , piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, piridooxazolilo, pyridoimidazolyl, piridotiazolilo, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinoIizinilo, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1, 2,5-thiadiazinyl, 1,2, 3-thiadiazoyl, 1,2,4-thiadiazoyl, 1, 2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1, 2-thiazinyl, 1, 3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, tiofenolilo, thiophenyl, thiopyranyl, 1, 2,3-triazinyl, 1,2,4- triazinyl, 1, 3,5-triaziniIo, 1, 2,3-triazolyl, 1, 2,4-trizolyl, 1, 2,5-triazolyl, 1, 3,4-triazolyl and xanthenyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R8, R8 is 1) halogen, 2) -NO2, 3) -OH, ) -O-CF3 5) an aryl of 6 to 14 monocyclic or bicyclic elements, in which the aryl is mono-, di- or trisubstituted independently from each other by halogen or -O- (C? -Cd) -alkyl, 6) - (C -? - C8) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -OH or a methoxy moiety, 7) -O- (C? -C s) -alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, NH2, -OH or a methoxy moiety, 8) -SO2-CH3 or 9) - SO2-CF3 with the proviso that R8 is at least one halogen or a residue -O- (C? -C8) -alkyl, if R ° is an aryl of 6 to 14 monocyclic or bicyclic elements, Q is - (C0-) C2) -acylene-C (O) -NR10-, -NR10-C (O) -NR10-, -NR10-C (O) -, - (C6) -alkylene, - (CH2) m-NR10-C (O) -NR10- (CH2 ) n-, - (CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mS- (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) m-SO2-NR10- (CH2) n-, - (CH2) m-NR10-SO2- (CH2) n-, - (CH2) m-NR 0 -SO2-NR10- (CH2) n- , - (CH2) m-CH (OH) - (CH2) n-, - (CH2) mOC (O) -NR10- (CH2) n-, - (C2-C3) -alkylene-O- (Co-C3 ) -alkylene-, - (C2-C3) -alkylene-S (O) -, - (C2-C3) -alkylene-S (O) 2-, - (CH2) m-NR10-C (O) -O - (CH2) n-, - (C2-C3) -aikylene-S (O) 2-NH- (R10) -, - (C2-C3) -alkinene-N (R10) - or - (C0-C3) -alkylene-C (O) -O- (CH2) m-, wherein R10 is as defined below, and wherein n and m are independently identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, in which the alkylene radicals which are formed by - (CH2) mo - (CH2) n- are unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; or - (C3-C6) -cycloalkylene, wherein the cycloalkylene is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -NH2 or -OH; R1 is a hydrogen atom, - (C? -C4) -alkyl, in which alkyl is unsubstituted or substituted one to three times by R13; - (d-C3) -alkylene-C (O) -NH-R °, - (C? -C3) -alene-C (O) -O-R15, an aryl of 6 to 14 monocyclic or bicyclic elements, in that the aryl is mono-, di- or trisubstituted independently of one another by R8, wherein R8 is as defined above; a monocyclic or bicyclic 4 to 15 element heterocyclyl, which is as defined above; - (C? -C3) -perfluoroalkylene; - (C? -C3) -aikino-S (O) - (C? -4) -alkyl; - (C1-C3) -alkylene-S (O) 2- (C1-C3) -alkyl; - (d-C3) -alkylene-S (O) 2-N (R4 ') - R5'; - (C? -C3) -alkylene-O- (d-C4) -aiol; - (Co-C3) -alkylene- (C3-C8) -cycloalkyl or - (Co-C3) -alkylhene-het, in which het is a residue selected from the group azepine, azetidine, aziridine, azirine, 1, 4- diazepane, 1, 2-diazepine, 1,3-diazepine, 1, 4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1, 3-dioxolene, 1, 3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, soxazol, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, 1, 4-oxazepane, 1, 2-oxatiepano, 1, 2-oxathiolane, 1, 2-oxazine, 1,3-oxazine , 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazine, thiadiazole , 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietane, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2 , 4-triazine, 1,3,5-triazine, 1,2,3-tria zol or 1, 2, 4-triazole, in which het is unsubstituted or mono-, di- or trisubstituted independently of each other by R 14, R 4 and R 5 are independently of each other identical or different and are a hydrogen atom or - (C -C ) -alkyl, or R1 and R22 together with the atoms to which they are attached can form a cyclic moiety of 6 to 8 elements selected from the group azocano, azocano-2-one, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4] diazocan, [1,2] diazocan-3-one, [1,3] diazocan-2-one, dioxazine, [1,4] dioxocan, dioxole, cetopiperazine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxocane, oxocan-2-one, piperazine, piperidine, pyran, pyrazine, pyridazine, pyrimidine or 5,6,7,8-tetrahydro-1 H azocin-2-one, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14, or R 1 -NV can form a cyclic group of 4 to 8 elements selected from the azepine group, azetidine, dioxazole, diazirine, 1,2-diazepine, 1,3-diazepine , 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoine, cetopiperazine, morpholine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine , pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine, 1,4-triazine, 1,3,5-triazine , 1,2,3-triazole or 1,2,4-triazole, wherein said group is unsubstituted or mono-, di- or trisubstituted independently of each other by R 14, R 14 is halogen, -OH, = O, - (d-C8) -alkyl, - (d-C4) -alcoxy, -NO2, - (C0-C4) - alkyl-C (O) -O-R18, -CN, - (C0-C4) - alkyl-N (R18) -R21, - (C0-C4) -alkyl-O-R18, - (C0-C4) -alkyl-het, wherein het is a residue selected from azetidine, azetidinone, piperidine, piperazine , pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1, 3,5-triazine, 1,2,3 -triazole, 1,4-triazole, tetrazine, tetrazole, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxazole, oxazole , isoxazole, isoxazolidine, 2-isoxazoine, morpholine, thiazole, siathiazole, thiadiazole or thiomorpholine, - (Co-C8) -aIqui-SO2- (d-C4) - alkyl, - (Co-C8) -alkyl- SO2- (C? -C3) -perfluoroalkyl, - (Co-C8) -alkyl-SO2- N (R18) -R21, -C (O) -NH- (d-C8) -alkyl, -C (O) -Nr (d-C8) -alkyl] 2, -NR18-C (O) -NH- (C? -C8) -alkyl, -C (O) -NH2, -S-R18, or -NR18-C ( O) -NH - [(d-C8) -alkyl] 2, wherein R18 and R21 are independently of each other hydrogen atom, - (C? -C3) -perfluoroalkyl or V is a heterocyclyl selected from the acridinyl group, azaindol (1H-pyrrolopyridine), azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxathiolyl, benzothiazolyl, benzotriazolyl, benzoteyrazolyl, benzisoxazolyl, benzisolyazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, cr Omanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 1,4-diazepane, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxoleyl, 6H-1,5,2-dithiazinyl, dihydrofide [ 2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl , isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4 -oxadiazolyIo, 1,2-oxa-tiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxythinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, teirahydroquinolinyl, 1, 4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1, 2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,4-thiadiazolyl, 1,2,5-diazodiazolyl, 1,3,4-diazodiazolyl, thiantrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolidyl, ynyl, yielyl, ethylenezolyl, isooxazolyl, ethiimidazolyl, thietanyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolium, 1, 2,5-triazolyl, 1,3,4-triazolyl and xanienyl, wherein said heterocyclic is unsubstituted or mono-, di- or trisusifuido independently of one another by R1, G is a direct bond, - (CH2) m-NR10-SO2-NR10- (CH2) n-, - (CH2) m-CH (OH) - (CH2) n-, - (CH2) m-, - (CH2) mO- (CH2) n-, - (CH2) mC (O) -NR10- (CH2) n-, - (CH2) -SO2- ( CH2) n-, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) -S- (CH2) n-, - (CH2) m-SO2- NR10- (CH2) n-, - (CH2) m-NR10-SO2- ( CH2) n-, - (CH2) m-NR10-, - (CH2) mO-C (O) -NR10- (CH2) n- or - (CH2) m-NR10-C (O) -O- (CH2 ) n-, n and m are independent One of the most identical or different ones is the zeroes, 1, 2, 3, 4, 5 or 6, M is 1) a hydrogen atom, 2) - (d-Cs) -a? chyl, in which the alkyl is unsubstituted or mono-, di- or di-iridescent independently of one another by R 14, 3) -C (O) -N (R 11) -R 12, 4) - (CH 2) m-NR 10, 5) a - ( C6-C? 4) -aryl, in which the aryl is unsuspended or mono-, di- or di-irosyriiuid independently of one another by R14, 6) a - (C4-Ci5) -heterocyclyl of 4 to 15 monocyclic or bicyclic , wherein the heterocyclic is not suspended or mono-, di- or di-irosubstituted independently of one another by R 14, or 7) - (C 3 -C 8) -cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or or iridescent independently of one another by R14, R3, R4 and R22 are independent of one another, are identical or different and are 1) hydrogen atom, 2) halogen, 3) - (dC) -alkyl, in which alkyl is not susíiúuido or mono-, di- or írisus independently substituted one by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, in which the phenyl is unsubstituted or mono-, di- or iris-separated independently of one another by R13, 6) - (C0-C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (dC) -alkyl, in which the alkyl is unsubstituted or mono-, di- or irosuitable independently of one ofro by R13, or c) phenyl, in which the phenyl is unsubstituted or mono-, di- or di-iridescent is one of another by R13, d) -CF3, oe) -CHF2, 7) -NO2, 8) -CN, 9) -SOs-R11, wherein s is 1 or 2, 10) -SOrN (R11) -R12, wherein l is 1 or 2 11) - (C0-C4) -alkylene-C ( O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 15) -NR10-SO2-R10, 16) -S-R10, 17) - (Co-C2) alkylene-C (O) -O- ( C2-C4) -alkylene-OC (O) - (C? -C4) -aIquio, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (Co-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O ) - (C? -C6) -alkyl, 20) -C (O) -OC (R15, R16) -OC (O) -R17, 21) - (Co-C4) -alkylene- (C6-Ci4) - Aryl, in which aryl is mono-, di- or di-irosulfuido independently of one another by R13, 22) - (Co-C4) -alkylene- (C4-C? 5) -heyerocyclyl, in which the heterocyclyl is not susíiuuido or mono-, di- or iris-separated independently of one another by R13, 23) - (Co-C4) -alkylene- (C3-C8) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisusituitute independently of one another by R13, 24) - (Co-d-alkylene-hei, in which het is unsubstituted or mono-, di- or one-fluoride independently of one another by R13, 25) - (C0-C4) -alkylene-O-CH2- (C? -C3) -perfluoroalkylene-CH2-O- (Co-C4) -alkyl, 26) -SOw-N (R11) -R13, wherein w is 1 or 2.27) - (C0-C4) -alkylene-C (O) -N (R11) -R13, 28) - (C0-C4) -alkylene-N (R11) -R13, or 29) a review of the following list , in which Me is methyl, or if two resins -OR19 are joined to adjacent atoms they can form june with the atoms to which they are attached to a ring of 1,3-dioxole or to a ring of 2,3-dihydro- [1,4] dioxin, which is not Substituted or substituted one, two, or four times by R13, R11 and R12 are independently one of different or different languages and are 1) hydrogen atom, 2) - (C? -C6) -alkyl, in which the alkyl is unsubstituted or mono-, di- or trisusylidene independently of one another by R13, 3) - (C0-C6) - (C3-C8) alkyl-cycloalkyl, 4) -SOrR10, wherein t is 1 or 2.5) - (Co-C6) -alkyl- (C6-C?) -aryl, wherein alkyl and aryl independently of one another are unsubstituted or mono-, di- or trisubstituted by R13, 6) - (C? -C3) -perfluoroalkyl, 7) -O-R17, or 8) - (Co-C6) -alkyl- ( C4-C? 5) -heterocyclyl, in which alkyl and heterocyclyl independently of one another are not susíifuidos or mono-, di- or trisusflidos by R13, or R11 and R12 together with the nitrogen atom to which they are attached can forming a monocyclic heterocyclic ring from the group azepine, azetidine, dioxazole, dioxazine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, midazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isoiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ceopiperazine, mor folina, [1,4] oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, fetrahydropyridine, teirazine, iodazole, iazole, iadiazole, iazolidine, fiazoline , Iomorpholine, 1,2,3-Iriazine, 1,2,4-Iriazine, 1, 3,5-triazine, 1, 2,3-Iriazole or 1,2,4-Iriazole, in which the heterocyclic ring is not substituted or mono-, di- or di-iridescent, independently of one another by R.sub.13, R.sub.4 and R.sub.22 in formula I or in the formula June with the carbon atoms to which they are attached may form a phenyl residue, R.sub.13 is halogen, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C3- C8) -cycloalkyl, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, -N (R10) -S (O) u-R10, wherein u is 1 or 2, - S-R10, -SOr-R10, wherein r is 1 or 2, -S (O) VN (R10) -R20, wherein v is 1 or 2, -C (O) -R10, - (C -C8) -alkyl, - (d-C8) -alkoxy, phenyl, phenyloxy-, -O-CF3, - (C0-C4) -alk uil-C (O) -OC (R15, R16) -OC (O) -R17, - (C? -C4) -alkoxy-phenyl, - (C0-C) -alkyl-C (O) -OC (R15) , R16) - OC (O) -O-R17, - (d-C3) -perfluoroalkyl, -O-R15, -NH-C (O) -NH-R10, -NH-C (O) -O-R10 or a resio of the following lisia R10 and R20 are independently one of the other hydrogen, - (C? -C6) -alkyl, - (Co-C) -alkyl-OH, - (Co-C4) -alkyl-O- (d-C4) -ariIo or - (C1-C3) -perfluoroalkyl, R15 and R16 are independently from each other hydrogen, - (d-Cßy-alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring is unsubstituted or substituted one to three times by R10, and R17 is - (C? -C6) -alkyl, - (d-C6) -alkyl-OH, - (d-C6) -aIqui-O- (C? -C6) -alkyl, - (C3-C8) -cycloalkyl, - (C? -C6) -alkyl-O- (C? -8) -alkyl- (C3-C8) -cycloalkyl, - (C? -C6) -alkyl- (C3-C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (CrC4) -alkyl or R10, in all its stereoisomeric forms and mixtures thereof any proportion, and their physiologically tolerable salts. 4) The present invention also relates to the compounds of formula I, wherein R ° is 1) a monocyclic or bicyclic 6 to 14-aryl group of the phenyl, naphthyl, biphenyl, anthryl or fluorenyl group, wherein aryl is mono-, di- or trisubstituted independently from each other by R8 , 2) a heterocyclyl of the benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridinyl, pyridoimidazolyl, pyridopyridinyl group , pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or ir-substituted independently of one another by R8, or 3) a heterocyclyl of the azabenzimidazolyl, benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoylazolyl, benzothiophenyl, benzisoxazolyl, chromanyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxazolinyl group , dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 2-furyl, 3-furyl; imidazolyl, indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl, pyrrolyl, 2-pyrroyl, 3-pyrrolid, quinolinyl, quinazolinyl, quinoxalinyl, teryrazolyl, liazolyl, 2-thienyl or 3-ynyl, which is further substituted by a heterocyclyl selected from the group of acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzoyiphenyl, benzoxathiolyl, benzothiazolyl, benzotriazolyl, benzoteyrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, 1,3- dioxolanyl, 1,3-dioxolenium, 6H-1,5,2-dithiazinyl, dihydrofuro [2,3-b] -tetrahydrofuran ilo, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazoly, indolinyl, indolizinyl, indolyl, 3H-indoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl , isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, cetopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl , 1,2-oxa-tiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxythinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pyridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, piridooxazolilo, pyridoimidazolyl, piridotiazolilo, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pirroI¡Io, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, íetrahidrofuranilo, teírahidroisoquinolinilo, Ieirahydroquinolinyl, 1,4,6,6-tetrahydro-pyridazinyl, teirahydropyridinyl, teirahydroiophenyl, terazyanediyl, fefrazolyl, 6H-1,2,5-diazinyl, 1,2,3-diazodiazol, 1,2,4-diazodiazolyl, 1, 2,5-diazodiazolyl, 1,4-diazodiazolyl, isoanaryl, 1,2-diazinyl, 1,3-fiazinyl, 1,4-thiazinyl, 1,3-diazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, and thienyl. Indolearylazolyl , isooxazolyl, fienoimidazolyl, fiefanil, fiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-Iriazinium, 1, 2,4-Iriazinyl, 1,2,3-rinizolyl, 1,2,4-frizolyl, 1,2,5-Iriazolyl, 1,4-triazolyl and xanophenyl, wherein said heterocyclyl is unsubstituted or mono-, di- or di-hydrosulfided independently of one of the other by R8, R8 is 1) fluorine, chlorine or bromine, 2) -NO2, 3) -OH, 4) -O-CF3 ) an aryl of 6 to 14 monocyclic or bicyclic elements, in which the aryl is mono-, di- or di-irosituituido independently of one of the other by halogen or -O- (C? -C8) -alkyl, 6) - (Ci- CsJ -alkyl, in which the alkyl is unsubstituted or mono-, di- or iris-independent independently of one of the other by halogen, -OH or a meioxy resin, 7) -O- (d-C8) -alkyl, in which alkyl is not susíifuido or mono-, di- or írisusfiíuido independent of each other by halogen, NH2, -OH or reslo meloxi, 8) -SO2-CH3 or 9) -SO2-CF3, with the proviso that R8 is at least one halogen or an -O- (d-C8) -alkyl radical, if R ° is an aryl or a heterocyclyl, are as defined above, Q is - (C0-C2) -alkylene-C (O) -NR10-, -NR10-C (O) -NR10-, -NR10-C (O) -, - (d- C6) ) -alkylene, - (C0-C3) -alkylene-C (O) -O- (Co-C2) -alkylene, R1 is a hydrogen atom, - (d-dj-alkyl, in which alkyl is unsubstituted or substituted one to three times by R13; - (C -? - C3) -acycline- C (O) -NH-R °, - (d-C3) -alkylene-C (O) -O-R15, - (d-C3) -perfluoro- alkylene; - (d-C3) -alkylene-S (O) - (C? -C4) -alkyl; - (d-C3) -alkylene-S (O) 2- (d-C3) -alkyl; - (dd -alkylene-SÍO ^ -NÍR ^ -R5; - (d-C3) - alkylene-O- (C? -C4) -alkyl; - (Co-C3) -alkylene- (C3-C8) -cycloalkyl or - (Co-C3) -alkylene-het, in which hei is a residue selected from the group azepine, azephidine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1, 4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxol, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isoiazole, isoiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, 1,2-oxathiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine , pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, pyridine, thiurahydropyridine, terazzoline, iorazol, iadiazine, thiadiazole, 1,2-thiazine, 1,3-iazine, 1,4 -fiazine, 1,3-fiazol, fiazol, iazolidin, fiazolin, íienil, íieía no, liomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-Iriazine, 1,3,5-friazine, 1,2,3-Iriazole or 1,2,4-Iriazole, in which it is not suspended or mono-, di- or iris-separated independently of one another by R14, R.sub.4 'and R.sub.5' are independently one of the dihedral or differential moieties and are a hydrogen atom or - (C? -C4) -alkyl, or R -NV forms a cyclic group of 4 to 8 elements selected from the azepine group , azephidine, 1,4-diazepam, dioxazole, diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, Imidazoline, imidazolidine, isoliazol, isoliazolidina, isoíiazolina, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ceíopiperazina, morpholine, 1, 4-oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine , pyrrole, pyrrolidine, pyrrolidinone, pyrroline, íefrahidropiridina, teírazina, íeírazol, thiazole, thiadiazole, thiazolidine, thiazoline, íiomorfolina, 1, 2,3-triazine, 1,2,4-triazine, 1, 3,5-triazine, 1 , 2,3-Iriazole or 1,2,4-Iriazole, in which said cyclic group is non-solidified or mono-, di- or frisus-free independently of one of R14, R14 is fluorine, chlorine, bromine, iodine, - OH, = O, - (d-Cs -alkyl, - (C? -C4) -aIkoxy, -NO2, -C (O) -OH, -CN, -NH2, -C (O) -O- (d -C4) -alkyl, - (C0-C4) -alkyl- SO2- (C4) -alkyl, - (Co-C8) -alkyl-SO2-N (R18) -R21, -C (O) - NH- (d- C8) -alkyl, -C (O) -N - [(d-C8) -alkyl] 2, -NR18-C (O) -NH- (C? -8) -alkyl, -C (O) -NH2, -S-R18 or -NR18-C (O) -NH - [(d-C8) -alkyl] 2, wherein R18 and R21 are n independently of the other hydrogen atom, - (d-C3) -perfIuoroalquilo or - (d-CSSJ-alkyl, V is a heterocyclyl moiety selected from the group azaindole (1H-pyrrolopyridine), azepine, azetidine, aziridine, 1, 4-diazepane, 1,2- diazepine, 1,3-diazepine, 1, 4-diazepine, diaziridine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isoíiazolidina, isoíiazolina, soxazol, isoxazoline, isoxazolidine, 2-isoxazoline, ceíopiperazina, morpholine, 1, 2-oxaíiepano, 1, 4-oxazepane, 1, 4-oxazepinyl, 1,2-oxazine, 1, 3-oxazine , 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, íeírahidropiridina, íeírazina, íefrazol, íiadiazina, ííadiazol , 1,2-iazine, 1,3-iazine, 1,4-iazine, 1,3-iazole, liazole, thiazolidine, thiazoline, thienyl, thietane, thiomorpholine, thio pyran, 1,2,3-Iriazine, 1,2,4-friazine, 1,3,5-Iriazine, 1,2,3-Iriazole or 1,2,4-Iriazole, which is as defined above and in the one that is not susi fi ed or mono-, di- or di-irosi-iuid independent of one of ofro by R14, G is a direct bond, - (CH2) m-NR10-S? 2-NR10- (CH2) n-, - (CH2 ) m-CH (OH) - (CH2) n-, - (CH2) m-, - (CH2) mO- (CH2) n-, - (CH2) mC (O) -NR10- (CH2) n-, - (CH2) -SO2- (CH2) n-, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10-C (O) - (CH2) n-, - (CH2) mC (O) - (CH2) n-, - (CH2) -S- (CH2) n-, - (CH2) m-SO2- NR10- (CH2) n-, - (CH2) ) m-NR10-SO2- (CH2) n-, - (CH2) m-NR10-, - (CH2) mO-C (O) -NR10- (CH2) n- or - (CH2) m-NR10-C (O) -O- (CH2) n-, n and m are independently one of other identical or different types and are zero, 1, 2, 3, 4, 5 or 6, M is 1) a hydrogen atom, 2) - (C? -C s) -a? Quilo, in which the alkyl is unsubstituted or mono-, di- or iris-separated independently of one another by R14, 3) -C (O) -N (R11) -R12, 4) - (CH2) m-NR10, 5) a phenyl or naphyl, in which the phenyl or naphthyl are unsubstituted or mono-, di- or iris-separated independently of one another by R14, 6) hemerocyclyl, in which the heterocyclyl is a residue of the group which may be derived from azepane, azepine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, Sofiazole, isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, cetopiperazine, morpholine, oxazole, [1,4] -oxazepane, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine, pyrrolidine, pyrrolidinone , hydra-1-hydropyran, 1, 4,5,6-feirahydro-pyridazinyl, eryrazine, terazosin, fiadiazole, thiazole, thiophene, thiomorpholine, 1,2,3-friazine, 1,2,4-Iriazine, 1,3,5-lirazine , 1, 2,3-iriazole or 1,2,4-iriazoI, wherein said heterocyclyl is unsubstituted or mono-, di- or trisusifuid independently of one another by R 14, or - (C 3 -C 8) -cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisusfifuid independently of one another by R14, R3, R4 and R22 are independent of one another, are identical or differ and are 1) hydrogen atom, 2) halogen, 3) - (C? -C) -alkyl, in which alkyl is unsubstituted or mono-, di- or trisusylidene independently one or more by R13, 4) - (C -? - C3) -perfluoroalkyl, 5) phenyl, in which the phenyl is unsubstituted or mono-, di- or trisusliuide independently of one another by R13, 6) - (C0-C4) -alkyllene- O-R19, wherein R19 is a) hydrogen atom, b) - (CrC4) -alkyl, in which the alkyl is unsuspended or mono-, di- or irosusiiuide independently of one another by R13, or c) phenyl , in which the phenyl is unsubstituted or mono-, di- or hydrosulifuted independently of one another by R13, d) -CF3, oe) -CHF2, 7) -CN, 8) - (Co-C4) -alene- (C4-Ci5) -heyerocycidyl, in which the heterocyclyl is not suspended or mono-, di- or di-irosyriiido independently of one another by R13, 9) -SOs-R10, where s is 1 or 2, 10) - SOt-N (R 11) -R 12, wherein t is 1 or 2, 11) - (Co-C 4) -acylene-C (O) -R 11, 1 2) - (C0-C4) -acylene-C (O) -O-R11, 13) - (C0-C4) -alene-C (O) -N (R11) -R12, 14) - (C0-C4) ) -alkylene-N (R11) -R12, 15) -NR 0-SO2-R1D, 16) - (Co-C) -alkylene-hei, in which hei is as defined above and is unsubstituted or mono- , di- or trisubstituted independently from each other by R13, 17) - (C0-C2) -alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (d-C4) -alkyl, 18) -C (O) -OC (R15) , R16) -O-CO-R17, 19) - (Co-C2) -alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (d-C6) -alkyl , 20) -C (O) -OC (R15, R16) -O-CO-O-R17, 21) - (Co-C4) -alkylene- (C6-C?) -aryl, wherein the aryl is as defined above and is not suspended or mono-, di- or di-substituted independently from each other by R 13, 22) - (Co-C 4) -alkylene- (C 3 -C 8) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, 23) - (C0-C3) -alkyllene-O-CH2-CF2-CH2-O- (Co-C3) -alkyl, 24) - (C0-C3) -alkyllene-O-CH2-CF2-CF2-CH2-O- (Co-C3) -alkyl, ) - (C0-C3) -alkylene-O-CH2- (C? -C3) -perfluoroalkylene-CH2-OH, 26) -SOw-N (R11) -R13, wherein w is 1 or 2.27) - (C0-C4) -alkylene-C (O) -N (R11) -R13, 28) - (C0-) C4) -alkylene-N (R11) -R13, or 29) a copy of the following list «• -? - iAA0 A in which Me is methyl, if two residues -OR19 are attached to adjacent atoms they can form, together with the aphids, those which are linked to a 1,3-dioxole ring or to a 2,3-dihydro- [1,4] dioxin ring, which is not subsumed or substituted one, two, three or sometimes times by R13, R11 and R12 are independently of one another identical or different and are 1) hydrogen atom, 2) - (C? -C6) -alkyl, in which the alkyl is unsubstituted or mono-, di- or unsubstituted independently of one another by R13, 3) - (Co-C6) - alkyl- (C6-C? 4) -aryl, in which aryl is as defined above and in which alkyl and aryl independently of one another are unsubstituted or mono-, di- or unsubstituted by R13, 4) -O-R17, or 5) - (Co-C6) -alkyl- (C4-C15) -heyerocyclyl, in which alkyl and heterocyclyl are as previously defined and independently one of the other non-solid or mono -, di- or i-substituted by R13, or R11 and R12 together with the nitrogen atom to which they are attached can form a monocyclic heterocyclic ring of the azepine group, azetidine, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine , 1,4-diazepine, midazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [1,4] oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, pherazine, tetrazole, thiazole, thiazole, liazolidine, iazoline, phycopholine, 1,2,3-iazine, 1, 2,4-friazine, 1, 3,5-Iriazine, 1,2,3-Iriazole or 1,2,4-IzozoI, which is not suspended or mono-, di- or iris-separated independently of one another by R13, R4 and R22 in formula I or in the formula June with the carbon atoms to which they are attached can form a phenyl residue, R13 is fluorine, chlorine, bromine, iodine, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, -N (R10) -S (O) 2-R 10, -S-R 10, -SO 2 -R 10, -S (O) 2-N (R 10) -R 20, -C (O) -R 10, - (d-C 8) -alkyl, - ( d-C8) -alcoxy, phenyl, phenyloxy-, -O-CF3, - (C? -C3) -perfluoroalkyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (C? -C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -O-C (R15, R16) -OC (O) -O-R17, -O-R15, -NH-C (O) -NH-R10, -NH-C (O) -O-R10 or a residue of the following lysis R 10 and R 20 are independently of one another hydrogen, - (d-Cι-alkyl, - (Co-C4) -alkyl-OH, - (Co-C4) -alkyl-O- (d-C4) -alkyl or - (d-C3) - perfluoroalkyl, R15 and R16 are independently of one another hydrogen, - (d-CβJ-alkyl, or together they form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, in which each ring is unsubstituted or substituted one to three times by R10, and R17 is - (C? -C6) -alkyl, - (d-CeJ-alkyl-OH, - (d-C6) -alkyl-O- (d-C6) -alkyl , - (C3-C8) -cycloa-alkyl, - (d-C6) -alkyl-O- (CrCs) -alkyl- (C3-C8) -cycloalkyl, - (d-C6) -alkyl- (C3-C8) - cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (C? -C4) -alkyl or R10, in all its stereoisomeric forms and mixtures thereof in any proportion, and its physiologically tolerable salts.

) The present invention also relates to the compounds of formula I, wherein RO is 1) a phenyl, wherein the phenyl is mono-, di- or trisubstituted independently from each other by R8, 2) a heterocyclyl of the benzimidazolyl group, 1,3-benzodioxoyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6- tetrahydro-pyridazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or di-substituted independently from each other by R8, or 3) a heterocyclyl of the pyridyl group, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl or 3-butyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, teryrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisusfluidide independently from another by R 8, and is further supported by a selected residue of the pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl group; thienyl, 2-thienyl or 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, diazodiazolyl, isothiazolyl, idriazolyl, teryrazolyl, pyridazinyl and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or trisubstituted independently one of the other by R8, R8 is 1) F, Cl, Br ol, 2) - (C? -C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisusituituted independently of one of halogen, -OH or a meioxy resin, or 3) -O- (C -? - C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or tri-substituted independently of one of the other by halogen or a methoxy moiety, with the proviso that R8 is at least one halogen or a -O- (C? -8) -alkyl moiety, if RO is an aryl or a heterocyclyl , which are as defined above, Q is -C (O) -, - (C? -C6) -aIcylene, - (C0-C2) -alkylene-C (O) -NR10- or - (C0-C3) -alkylene-C (O) -O- (Co-C) -alkylene, R1 is a hydrogen atom, - (C? -C2) -alkyl, - (d-C3) -alkylene-C (O) -NH - RO, - (C? -C3) -perfluoroalkylene, - (d-C3) -alkylene-C (O) -O-R15, - (d-C3) -alkylene-S (O) 2- (C? - C3) -alkyl or - (d-C3) -alkylene-S (O) 2-N (R4 ') -R5', wherein R4 'and R5' independently of one another are identical or different and are a hydrogen atom or - (d-C4) -alkyl, R1-NV can form a cyclic group of 4 to 7 elements selected from the group azetidine, azetidinone, piperidine, piperazine, pyrazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2 , 3-Iriazine, 1, 2,4-Iriazine, 1,3,5-Iriazine, 1, 2,3-Iriazole or 1,2,4-friazole, ina, ephedra, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxazepane, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, in which said cyclic group is unsubstituted or mono-, di- or di-irosylidene independently one of ofro by R14, R14 is fluorine, chlorine, -OH, = O, - (d-C8) -alkyl, -C (O) -OH, -CN, -NH2, -C (O) -O- (C? -C4) -alkyl, -C (O) -NH- (d-C8) - alkyl, -C (O) -N - [(d-C8) -alkyl] 2 or -N (R18) -R21, wherein R18 and R21 are independently of each other the hydrogen atom, - (C? - C3) -perfluoroaIqui! Oo - (C? -C4) -alkyl, V is a heterocyclyl moiety containing group compuesíos derived from azaindole (1H-pirroIopiridina), aziridine, azetidine, azetidinone, 1,4-diazepane, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3- Iriazole, 1,2,4-Iriazole, Fetrazole, Pyrimidine, Pyrazine, 1,2,3-Iriazine, 1,4-Triazine, 1,3-Triazine, Terazzine, Indolerazol, Azepine, Diazirine, 1, 2-diazepine, 1,3-diazepine, 1, 4-diazepine, pyridazine, diaziridine, piperidine, piperazine, pyrrolidinone, cefopiperazina, furan, pyran, dioxole, 1,4-oxazepane, oxazole, isoxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine, 1,3-dioxoIeno, 1, 3- dioxolane, 1, 2-oxazine, 1,3-oxazine, 1, 4-oxazine, oxaziridine, íiofeno, thiopyran, íietano, íiazol, isoíiazol, isothiazoline, isofiazolidina, 1,2- oxoíiolano, íiadiazol, thiopyran, 1, 2-thiazine, 1,3-íiazol, 1,3-íiazina, 1,4- íiazina, íiadiazina or íiomorfolina, wherein said heterocyclyl is mono- or sustiluido -, di- or trisusituituido independently of one of ofro by R14, G is a direct bond, CH2) m- or - (CH2) m-NR10-, m is the integer zero, 1, 2, 3, or 4, M is 1) a hydrogen atom 2) heíerociclilo, wherein Resio heíerociclilo is a group that can come from azepane, azepine, 1, 4-diazepane, 1, 2- diazepine, 1,3-diazepine, 1, 4-diazepine, imidazole, isofiazol, isoxazole, isoxazolidine, 2-¡soxazoIina, cetomorfolina, cefopiperazina, morpholine, oxazole, [1, 4] -oxazepano, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran , 1, 4,5,6-fefrahydropyridazinyl, tetrazine, tetrazol, thiazole, thiazole, thiomorpholine, thiophene, 1,2,3-Iriazine, 1,4-triazine, 1,3,5-friazine, 1,2 , 3-triazole or 1,2,4-triazole, wherein said heterocyclyl is unsubstituted or mono-, di- or frisusfituid independently of one another by R 14, 3) - (Ci-CβJ-alkyl, wherein alkyl is unsubstituted or mo no-, di- or irrespective of one another by R14, 4) (C3-C6) -cycloalkyl, or 5) -C (O) -N (R11) -R12, R3, R4 and R22 are independent of one another , are identical or different and are 1) hydrogen atom, 2) halogen, 3) - (d-dj-alkyl, in which alkyl is unsusiluted or mono-, di- or irrespective of one another by R 13, 4 ) - (C -? - C3) -perfluoroalkyl, 5) phenyl, in which the phenyl is unsubstituted or mono-, di- or unsubstituted independently from each other by R13, 6) - (C0-C4) -alkylene- O-R19, wherein R19 is a) hydrogen atom, b) - (CrC) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisusituituted independently from each other by R13, or c) phenyl , wherein the phenyl is unsubstituted or mono-, di- or iris-substituted independently one of ofro by R13, d) -CF3, oe) -CHF2, 7) -CN, 8) -NR10-SO2-R10, 9) -SOs-R10, where s is 1 or 2, 10) -SOt-N (R11) -R12, where t is 1 or 2, 11) - (C0-C 4) -alkyllene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) - N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 15) - (C0-C2) -alkylene-C (O) -O- (C2-C4) -alkylene -OC (O) - (C1-C4) -alkyl, 16) -C (O) -OC (R15, R16) -O-CO-R17, 17) - (C0-C2) -alkylene-C (O) -O- (C2-C4) -alkylene-OC (O ) -O- (d-C6) -alkyl, 18) -C (O) -OC (R15, R16) -O-CO-O-R17, 19) - (Co-C4) -alkylene- (C6-C) 4) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisusfifuid independently of one another by R13, or 20) - (Co-C3) -alkylene-O-CH2-CF2-CH2 -O- (C0-C3) -alkyl, 21) - (Co-C3) -alkylene-O-CH2-CF2-CF2-CH2-O- (C0-C3) -alkyl, 22) - (Co-C3) -aiquylene-O-CH2- (C? -C3) -perfluoroalkylene-CH2-OH, or 23) -SOw-N (R11) -R13, wherein w is 1 or 2, 24) - (C0-C4) -alkylene-C (O) -N (R11) -R13, 25) - (C0-) C4) -alkylene-N (R11) -R13, or 26) a remainder of the following list which is Me methyl, if two residues -OR19 are attached to adjacent atoms can form together with the atoms to which they are attached to a ring of 1,3-dioxol or a ring of 2,3-dihydro- [1,4 ] dioxin, which is not suspended or substituted one, two, three or four times by R.sub.13, R.sub.11 and R.sub.12 with the niologen atom to which they are attached may form a ring selected from the group azepine, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isoiazolidine, isofiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [1,4 ] oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiazole, thiazolidine, thiazoline , thiomorpholine, thiophene, 1, 2,3-triazine, 1, 2,4-triazine, 1, 3,5-Iriazine, 1,2,3-triazole or 1,2,4-Iriazole, which is unsubstituted or mono-, di- or trisusifuid independently of one another by R13, R4 and R22 in formula I or in the formula June n the carbon atoms to which they are attached can form a phenyl residue, R13 is fluorine, chlorine, -NO2, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C ( O) -N (R10) - R20, -N (R10) -R20, - (C0-C3) -alkylen-O-R10, -Si- (CH3) 3, -N (R10) -S (O ) 2- R 10, -S-R 10, -SO 2 -R 10, -S (O) 2-N (R 0) -R 20, -C (O) -R 10, - (d-C 8) -alkyl, - (d) -C8) -alkoxy, phenyl, phenyloxy-, -O-CF3, - (C? -C3) -perfluoroalkyl, -NH- C (O) -NH-R10, - (C0-C4) -alkyl-C (O ) -OC (R15, R16) -OC (O) -R17, - (dC4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC ( O) -O-R17, -O-R15, -NH-C (O) -O-R10 or a remainder of the following list R10 and R20 are independently one of the other hydrogen, - (d-CßJ-alkyl, - (Co-C4) -alkyl-OH, - (Co-C4) -alkyl-O- (C? -C4) -alkyl or - (d-C3) -perfluoroalkyl, R15 and R16 are independently from each other hydrogen, - (C? -C6) -alkyl, or together form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, wherein each ring is unsubstituted or substituted one to three times by R10, and R17 is - (d-C6) -alkyl, - (C? -C6) -alkyl-OH, - (C? -C6) -alkyl-O- (C? -C6) -alkyl, - (C3-C8) -cycloalkyl, - (C? -C6) -alkyl-O- (C8) -alkyl- (C3-C8) -cycloalkyl, - (C C6) -alkyl- (C3-C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (C? -C4) -alkyl or R10, in all their stereoisomeric forms and their mixtures in any proportion, and their physiologically tolerable salts. 6) The present invention also relates to the compounds of formula I, in which R ° is 1) phenyl, wherein the phenyl is mono-, di- or di-iridescent independently of one another by R 8, 2) a heteroaryl of the indolyl, isoindolyl, benzofuranyl, benzoyl phenyl group, 1,3- benzodioxolyl, indazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, chromanyl, isochromanyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, pyridinyl, purinyl and pteridinyl, wherein said heterocyclyl is unsubstituted or mono - independently, one of ofro per R8, or 3) a heterocyclyl of the pyridyl group, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-ienyl or 3-butyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, isoazolyl, isoiazolyl, isoiazolyl, isozolyl, teryrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisusylidene independently from another by R8, and further substituted by a residue selected from the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl or 3-fienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or iridescent independently of R8, R8 is 1) F, Cl, Br ol, 2) - (C? -C4) -alkyl, in which the alkyl is unsubstituted or mono-, di- or di-irosituituido independently of one another by halogen , -OH or a mephoxy resin, or 3) -O- (C? -C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisusituituted independently from each other by halogen or a methoxy moiety, with the proviso that R8 is at least one halogen or a residue -O- (C? -C8) -alkyl, if R ° is an aryl or a heterocyclyl, which are as defined above, Q is -C (O); -C (O) -methylene, - (dC) -alkylene or - (C0-C2) -alkylene-C (O) -NR10, R1 is a hydrogen atom or - (C? -C2) -acycium, or R1 -NV can form a cyclic group of 4 to 7 elements selected from the group piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1, 2,4-triazine, 1,3,5-triazine , 1, 2,3-triazole or 1,2,4-iazole, ε-frazine, io-erazol, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, oxazole, isoxazole, isoxazolidine, isoxazoline, morpholine, thiazole, isoiazole, thiadiazole or thiomorpholine, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of each other by R14, R14 is fluorine, chlorine, - (C? -C4) -alkyl or -NH2, V is a heterocyclyl moiety of the group containing the compounds that are derived from azaindolyl (1 H-pyrrolopyridyl), azetidine, azepine, aziridine, azirine, 1,2-diazepine, 1,3-diazepine, 1 , 4-diazepine, diazirine, 1,3-dioxolane, dioxazole, furan, imidazole, isoquinoline , isothiazole, isothiazolidine, isoiazoline, isoxazole, 2-isoxazoline, isoxazolidine, ceopiperazine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, 1,2-oxoyl, piperidine, pyrano, pyrazine , pyrazole, pyridazine, piperazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, quinazoline, quinoline, etrazine, fefrazole, thiadiazine, 1,2-thiazine, 1,3-iazine, 1,4-iazine, 1,3-liazole, thietane, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, in which said heterocyclyl is unsubstituted or mono-, di- or iso-substituted one independently by R 14, G is a direct bond, CH 2) m- or - (CH2) -NR10-, m is the integer zero, 1, 2, 3, or 4, M is 1) a hydrogen atom, 2) heyerocyclyl, in which heyerocyclyl is a residue of the group that may come from 1 , 4-diazepam, ketomorpholine, thiophene, pyridazone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine, 1,2,3-triazine, 1,4-triazine, 1,3 , 5-triazine, 1, 2,3-iriazole, 1,2,4-triazole, tetrahydroquinoline, isoezole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, isoazole, isoiazole, tetrahydropyran, 1,4,6,6-tetrahydropyridazinyl , fiadiazole or thiomorpholine, wherein said heterocyclyl is unsubstituted or mono-, di- or trisust independently from each other by R 14, 3) - (C? -C6) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisusifluid independently of one another by R14, 4) (C3-C6) -cycloalkyl, R3, R4 and R22 are independent of each other, are identical or different and are 1) hydrogen atom, 2) halogen, 3) - (C? -C4) -alkyl, in which alkyl is unsubstituted or mono-, di- or trichloride independently from each other by R 13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstituted or mono-, di- or tri-substituted independently of one another by R13, 6) - (C0-C) -alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (C? -C) -a! qui, in which the alkyl it is unsubstituted or mono-, di- or di-substituted independently of one another by R 13, or c) phenyl, in which the phenyl is unsubstituted or mono-, di- or unsubstituted independently of one another by R 13, d) -CF 3, oe) -CHF2, 7) -CN, 8) -NR10-SO2-R10, 9) -SOs-R11, wherein s is 1 or 2, 10) -SOrN (R11) -R12, wherein t is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - ( Co-C4) -alkylene-N (R 1) -R 12, 15) - (Co-C ^ -alkylene-CIOJ-O-^^ -alkylene-O-CIOOH-Id ^ -alkyl, 16) -C (O ) -OC (R15, R16) -O-CO-R17, 17) - (Co-C2) -alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (C ? -C6) -alkyl, 18) -C (O) -OC (R15, R16) -O-CO-O-R17, 19) - (Co-C3) -alkylene- (C3-C6) -cycloalkyl, in that the cycloalkyl is unsubstituted or mono-, di- or iris-substituted independently of one another by R 13, 20) - (Co-C 4) - (C 3 -C 6) -alkylene-cycloalkyl, in which the cycloalkyl is unsubstituted or mono-, di- or trisusituituido independently of each other by R13, or 21) - (C0-C3) -alkylen-O-CH2-CF2-CH2-O- (Co-C3) -alkyl, 22) - ( C0-C3) -alkylene-O-CH2-CF2-CF2-CH2-O- (Co-C3) -alkyl, 23) - (Co-C3) -alkylene-O-CH2- (C? -C3) -perfluoroalkylene -CH2-OH, or 24) -SOw-N (R11) -R13, wherein w is 1 or 2, 25) - (C0-C4) -aiqui-Une-C (O) -N (R1) -R13, 26) - (C0-) C4) -alkylene-N (R11) -R13, or 27) a remainder of the following list linden, R11 and R12 are independently one of different or different languages and are 1) hydrogen atom, 2) - (C? -C4) - alkyl, in which the alkyl is unsubstituted or mono-, di- or irrisuccinated independently of one another by R13, 3) - (Co-C6) - alkyl- (C3-C6) -cycloalkyl, 4) -O-R17, or 5) - (Co-C6) -alkyl- (C4-Ci5) -heterocyclyl, in which alkyl and heterocyclyl independently of one another are unsubstituted or mono-, di- or tri-substituted by R13 and wherein heterocyclyl is selected from the group azeididine, cyclopropyl, cyclobufyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, [1,4] oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydroliofen, iazolidine or iomorpholine, or R11 and R12 June with the nitrogen atom to which they are attached can form a monocyclic heterocyclic ring, which is selected from the group azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazoI, imidazolidine, morpholine, [1,4] oxazepane, [1,4] oxazepine, oxazolidine, piperidine, piperazine, pyrrolidine ,. tetrahydrothiophene, thiazolidine or thiomorpholine, R4 and R22 in the formula I or in the formula together with the carbon atoms to which they are attached can form a phenyl residue, R13 is fluorine, -CN, = O, -OH, -CF3 , -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C3-C6) -cycloalkyl, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, -SR10, SO2-R10, - (C ? -C3) -perfiuoroalkyl, or a remainder of the following list ? -? R? Y $ •. In which Me is methyl, R10 and R20 are independently of one another hydrogen, - (C? -C) -acyl or - (C? -C3) -perfluoroalkyl, R15 and R16 are independently of each other hydrogen, - (C? -C4) -aIqu or, together, they form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, wherein each ring is unsubstituted or substituted one to three times by R10, and R17 is - (C? -C6) -alkyl, - (C C6) -alkyl-OH, - (Ci-CßJ-alkyl-O-CiC-CßJ-alkyl, -C3-C8) -cycloalkyl, - (d-Cey-alkyl-O-CrCsJ-alkyls Cs-CsJ- cycloalkyl, - (C? -C6) -alkyl- (C3-C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (dC) -alkyl or R10, in all its stereoisomeric forms and their mixtures in any proportion, and their physiologically tolerable salts. 7) The present invention also relates to the compounds of formula I, wherein RO is 1) phenyl, wherein the phenyl is mono-, or disubstituted independently of one another by R8, 2) pyridyl, wherein the pyridyl is mono- or disubstituted independently of one another by R8, or 3) a heterocyclyl of the thienyl, thiadiazolyl, isoxazolyl and thiazolyl group, wherein said heterocyclyl is substituted by a residue selected from the group thienyl, 2-thienyl, 3-thienyl, wherein said residue is mono- or disubstituted independently from another one by R8, R8 is F, Cl, Br, -O-CH3 or -O-CF3, Q is -C (O); -C (O) -methylene, CH2-C (O) -NH, methylene or ethylene, R1 is a hydrogen atom, R1-NV can form a cyclic group of 4 to 8 elements of the azephidine, pyrrolidine, piperidine and piperazine group , R14 is fluorine, chlorine, methyl, ethyl or -NH2, V is a heterocyclyl of the group containing the compounds derived from azaindolyl (1H-pyrrolopyridyl), azetidine, 1,4-diazepam, isoxazole, isoquinoline, piperazine, piperidine , pyrazine, pyridazine, pyrimidine, pyrrolidine, quinazoline, quinoline or teirahydropyran, wherein said heterocyclyl is unsubstituted or mono- or diisocyanide independently of one another by R14, G is a direct bond, CH2) m- or - (CH2) m-NR10-, m is one of the integers zero, 1 or 2, M is a hydrogen atom, (C2-C) -alkyl, isopropyl, azepanyl, cyclopropyl, cyclobuyl, cyclopenyl, cyclohexyl, midazolyl, ceiomorpholinyl, morpholinyl , [1,4] oxacepanyl, piperidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidyl, pyrrolidinyl, 1,4, 5,6-tetrahydro-pyridazinyl or tetrahydropyranyl, in which the resins are unsubstituted or mono- or disubstituted independently of one another by R 14, R 3, R 4 and R 22 are independent of each other, are identical or different and are 1) atom of hydrogen, 2) fluorine, chlorine, bromine, iodine, 3) - (CrC4) -alkyl, in which alkyl is unsubstituted or mono-, di- or hydrisfifuided independently from each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, in which the phenyl is unsubstituted or mono-, di- or di-irosubstituted independently of one another by R13, 6) - (C0-C2) -alkylene-O-R19, in the that R19 is a) hydrogen atom, b) - (CrC4) -alkyl, in which the alkyl is unsubstituted or mono-, di- or tri-substituted independently of one of ofro by R13, or c) phenyl, wherein the phenyl is unsubstituted or mono-, di- or undissolved independently of one another by R13, d) -CF3, oe) -CHF2, 7) -NO2, 8) -NR10-SO2-R10, 9) -SOs-R11, in the one that s is 1 or 2, 10) -SOt-N (R11) -R12, wherein t is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0) -C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 15) - (C0-C2) -alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - (C1-C4) -alkyl, 16) -C (O) -OC (R15, R16) -O-CO-R17, 17) - (C0-C2) -alkylene-C (O) -O- (C2-C4) -alkylen-OC (O) -O- (C? -C6) -alkyl, 18) -C (O) -OC (R15, R16) -O-CO-O-R17, 19) - (Co-C3) -alkylene-phenyl , in which the phenol is not suspended or mono-, di- or irrisuclide independently of one another by R13, ) pyridinyl, in which the pyridinyl is unsubstituted or mono-, di- or irrisfused independently of one another by R13, or 21) isoalkyl, in which the aminoacyl is unsubstituted or mono-, di- or irrisuclide independent of one by R13, or 22) - (C0-C4) -alkylene- (C3-C6) -cycloalkyl, in which the cycloalkyl is not suspended or mono-, di- or di-iridested independently of one of the other by R13, 23) - (C0-C3) -alkyllene-O-CH2-CF2-CH2-O- (Co-C3) -alkyl, 24) - (C0-C3) -alkylene-O-CH2-CF2-CF2-CH2- O- (Co-C3) -alkyl, 25) - (Co-C3) -alkyllene-O-CH2- (d-C3) -perfluoroalkylene-CH2-OH, or 26) a remainder of the following list which Me is methyl, R11 and R12 are independently of one another identical or different and are 1) hydrogen atom, 2) - (d-C6) -alkyl, in which the alkyl is unsubstituted or mono-, di- or di-irosylurea independently of one another by R13, 3) - (C0-C6) -alkyl -phenyl, 4) -O-R17, or 5) ~ (Co-C6) -alkyl-heterocyclyl, in which alkyl and heterocyclyl independently of one another are unsubstituted or mono-, di- or trisubstituted by R13 and wherein heterocyclyl is selected from the group azetidine, imidazolidine, morpholine, [1,4] oxazepane, [1,4] oxazepine, piperazine, piperidine, pyrrolidine or thiomorpholine, R11 and R12 together with the nitrogen atom to which they are attached can form a monocyclic heterocyclic ring, which is selected from the group 0 azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazoI, imidazolidine, morpholine, [1,4] oxazepane, [1,4] oxazepine, oxazolidine , piperidine, piperazine, pyrrolidine, tetrahydrothiophene, iiazolidine or thiomorpholine, R13 is fluorine, chlorine, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10 ) -R20, -N (R10) -R20, - (C3-C6) -cycloalkyl, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, 5 -SR10, -SO2-R10 , - (d-C4) -alkyl, - (C? -C3) -perfluoroalkyl, or a remainder of the following list R10 and R20 are independently from each other hydrogen, - (C? -C4) -alkyl or - (d-C3) -perfiuoroalkyl, R15 and R16 are independently from each other hydrogen, - (dC) -alkyl, or together they form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, in which each ring is unsubstituted or substituted one to three times by R10, and R17 is - (d-C6) -acyl, - (d-C6) -alkyl -OH, - (C Cβ) -alkyl-0- (C? -Cβ) -alkyl, - (Cs-Csy-cycloalkyl, '- (C? -C6) -alkyl-O- (CrC8) -alkyl- ( C3-C8) -cycloalkyl, - (C? -C6) -alkyl- (C3-C8) -cyclohexyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or more times by - OH, -O- (C? -C4) -alkio or R10, in all their stereoisomeric forms and mixtures thereof in any proportion, and their physiologically tolerable salts.

The present invention also relates to the compounds of formulas I and II, which are 1- [5- (5-chloro-thiophen-2-yl) (1- isopropyl-piperidin-4-yl) -amide. ) -isoxazol-3-ylmethyl] -1H-pyrrole-2-carboxylic acid, 1- (3-meioxy-benzyl) -1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide, (1- (5- (5-Chloropheno-2-yl) -isoxazol-3-ylmethyl] -4-yl-1-H-pyrrole-2- (1-isopropyl-piperidin-4-yl) -amide. carboxylic acid, 1- [5- (5-chloro-thiophen-2-yl) -isoxazole-3-ylmethyl] -3,5-d-methylic acid (1-ylpropyl-piperidin-4-yl) -amide. -1H-pyrrole-2-carboxylic acid, 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (perhydro-1,4-isopropyl-piperidin-4-yl) -amide. -oxazepine-4-carbonyl) -1H-pyrrole-2-carboxylic acid, 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -l (1-isopropyl-piperidin-4-yl) -amide] - (perhydro-1,4-oxazepine-4-carbonyl) -1H-pyrrole-2-carboxylic acid, 1- [5- (5-chloro-lofen-1-isopropyl-piperidin-4-yl) -amide] 2-yl) -isoxazole-3-ylmethyl] -5- (perhydro-1,4-oxaz) epine-4-carbonyl) -1 H-pyrrole-2-carboxylic acid, 3- [1 - [5- (5-chloro-thiophen-2-yl) -soxazol-3-ylmethyl] -5- (1 - isopropyl-piperidin-4-ylcabamoyl) -2,4-dimethyl-1H-pyrrol-3-yl] -propionic acid, benzyl ester of 1- [5- (5-chloro-iiophen-2-yl) -isoxazole- 3-ylmethyl] -5- (1- isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrro! -2-carboxylic acid, 1- [5- (5-chloro-phofen-2-yl) -isoxazole] -methyl ester -3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl!) - 1H-pyrrole-2-carboxylic acid, 1 - [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, benzyl ester of 1 - [(5-Chloro-pyridin-2-iicarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-iicarbamoyl) -1 H -pyrrole-2-carboxylic acid, benzyl ester of acid 1 - [5- (5-chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, (1-isopropyl) piperdin-4-yl) -amide of 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4-nitro-1H-pyrrole-2-carboxylic acid, 1-membered methyl ester of 1 - [( 5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, methyl ester of 1- [5- (5-Chloro- thiophen-2-yl) -isoxazol-3-methylmethyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrroyl-2-carboxylic acid, 1- [5- (5-chloro-thiophene- 2-yl) -isoxazol-3-ylmethyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1 H -pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide 1- [5- (5-chloro-f iofen-2-yl) -isoxazol-3-ylmethyl] -5- (3-meioxy-azeidin-1-carbonyl) -1 H -pyrrole-2-carboxylic acid, 2 - [(1-isopropyl-piperidin-4-yl) ) -amide] 5- [5- (5-Chloro-lyophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2,5 - [(2-meoxy-eyl) -amide] of the acid [5- (5-chloro-lyophen-2-yl)] -dicarboxyl, 2 - [(1-isopropyI-piperidin-4-yl) -amide] - [(2-meioxy-eyl) -methyl-amide] of 1- [5- (5-chloro-iiophen- 2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2, 5-dicarboxylic acid, 1- [5- (5-chloro-iiophen-2-1-isopropyl-piperidin-4-yl) -amide] -yl) -isoxazol-3-ylmethyl] -5-phenyl-1H-pyrrole-2-carboxylic acid or 1- [5- (5-chloro-thiophene)] - (1-ylpropyl-piperidin-4-yl) -amide] -2-yl) -isoxazol-3-ylmethyl] -3,5-dimethyI-4- (perhydro-1,4-oxazepine-4-sulfonyl) -1H-pyrrole-2-carboxylic acid.

In general, the meaning of any group, residue, hetero-atom, number, etc., that can happen more than once in the compounds of formulas I and is independent of the meaning of this group, remainder, hetero-atom, number, etc. in any other circumstance. All groups, residues, heteroatoms, numbers, efe, which can happen more than once in the compounds of formulas I and can be identical or different. As used in this specification, the term "alkyl" should be understood in the broadest sense to mean hydrocarbon radicals which may be linear, ie linear or branched chain. Examples of "- (d-C8) -alkyl" or "- (C? -8) -alkylene" are the alkyl resins containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms are methylated , methylene, effilo, ethylene, propyl, propylene, butyl, butylene, pentylene, penfilene, hexyl, hepfilo or octyl, the n-isomers of all these residues, isopropyl, isobufilo, 1-meiylbutyl, isopentyl, neopenyilo, 2,2- dimethylbuleyl, 2-methylpenphyl, 3-meitylpentyl, isohexyl, sec-buleyl, ibu, pentyl, sec-butyl, tert-butyl or tert-pentyl. The term "- (Co-Cβ) -alkyl" or "- (C0-C8) -alkylene" is a hydrocarbon resin containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. The term "-Co-alkyl" or "-C0-alkylene" is a covalent link. Examples of alkyl cyclic radicals of - (C3-Cs) -cycloalkyl are cycloalkyl radicals which contain 3, 4, 5, 6, 7 or 8 ring carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. , which may also be substituted and / or not subsumed. Uncured cyclic alkyl groups and unsaturated cycloalkyl groups such as, for example, cyclopenyl or cyclohexanyl may be attached by some carbon atom. The terms "an aryl of 6 to 14 monocyclic or bicyclic elements" or "- (C6-Ci4) -aryl" are intended to mean aromatic hydrocarbon radicals containing from 6 to 14 carbon atoms in the ring. Examples of radicals - (C6-Ci4) -aryl are phenyl, naphthyl, for example 1-naphthyl and 2-naphthyl, biphenylyl, for example 2-biphenylyl, 3-biphenylyl and 4-biphenylyl, anthryl or fluorenyl. Biphenylyl radicals, naphthyl radicals and, in particular, phenyl radicals are the preferred aryl radicals.

The terms "4 to 15 mono- or bicyclic heyanocyclyl" or - (C4-Ci5) -heterocyclyl "refers to heterocycles in which one or more of the 4 to 15 carbon atoms of the ring is suspended by hetero atoms. such as nitrogen, oxygen or sulfur Examples are acridinyl, azaindole (1 H-pyrrolopyridinyl), azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzotriazolyl, benzofetrazolyl, benzisoxazolyl, benzisofiazolyl, carbazolyl, 4aH-carbazoyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxoleyl, 6H-1, 5,2-dithiazinyl, dihydrofuro [ 2,3-b] -phehydrylfuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1 H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazo lyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), iso-aiazolyl, iso-aiazolidinyl, isofiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ceiopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazoliol, 1,2,4 -oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2-oxa-tiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinium , 1, 3-oxazinyl, 1, 4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, oxetanyl, oxocanyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalizinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, Pyrazolinyl, pyrazolyl, pyridazinyl, piridooxazolilo, pyridoimidazolyl, piridoiiazolilo, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl quinuclidinyl, teírahidrofuranilo, íeírahidroiso-quinolinyl, teírahidroquinolinilo, leírahidrofuranilo , hydrahydryranyl, tetrahydropyridinyl, hydroaliphiophenyl, fefrazinyl, tefrazolyl, 6H-1,2,5-diazinyl, 1,2,3-thiadiazolium, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4 -diazodiazolyl, thianryrenyl, 1,2-ishiazinyl, 1,3-ishiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolidyl, nicienyl, ethenynyl, isonylazoline, thienooxazolyl, isoimidazolyl, fietanyl, iomorpholinyl, fisphenolium, Iophenyl, Thiopyranyl, 1,2,3-Triazinyl, 1,4-Triazinyl, 1,3,5-Iriazinyl, 1,2,3-Triazolyl, 1,2,3-Iriazolyl, 1,2,4- Iriazolyl, 1, 2,5-triazolyl, 1,3,4-triazoyl and xanthenyl. Preferred are heterocyclyls, such as benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, chromanyl, cinnolinyl, 2-furyl, 3-furyl.; imidazolyl, indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, fialazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl, pyrrolyl; 2-pyrrolidone, 3-pyrrolyl, quinolinyl, quinazolinyl, quinoxalinyl, telrazolyl, yiazolyl, 2-ynyl and 3-ynyl. Also preferred: Q. *, (Y. «R r £ The expressions "het" or "a cyclic rest of 3 to 7 elements, which confands to 1, 2, 3 or 4 hetero-atoms" refers to the structures of the heterocycles that may come from the fale compounds such as azepine, azeidin, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isoliazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ceomyomorpholine, cetopiperazine, morpholine, 1,2-oxathiepane, 1,2-oxaiolamine, 1,4-oxazepane, 1,2- oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxeanane, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, hydrohydrofuran, tefrahydropyran, tetrahydropyridine, tetrazine, iorazol, iadiazine, thiadiazole, 1,2-thiazine, 1,3-iaz ina, 1,4-thiazine, 1,3-thiazoline, thiazolidine, thiazoline, thienyl, thietane, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1, 3,5- triazine, 1, 2,3-Iriazole or 1, 2,4-triazole. The expressions "R1-NV can form a cyclic group of 4 to 8 elements" or "R11 and R12 together with the nihorogen atom to which they are bound can form a heterocyclic monocyclic ring of 4 to 8 elements which besides the nitrogen atom can contain one or two identical ring heteroatoms or selected oxygen, sulfur and nitrogen "differences" refers to the structures of the heterocycles that may be derived from compounds such as azepane, azepine, azetidine, dioxazole, dioxazine, 1,4-diazepane, 1 , 2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, siathiazole, isoiazolidine, isopiazoline, isoxazole, isoxazoline, isoxazolidine, 2-oxazoline, cetopiperazine, morpholine, [1, 4] oxazepam, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, teirahydropyran, teirazine, tetrazol, thiazole, thiazole, thiazolidine, thiaz olin, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-Iriazine, 1,2,3-Iriazole or 1,4-triazole. The expression "R15 and R6 together with the carbon atom to which they are attached can form a carbocyclic ring of 3 to 6 elements" refers to the structures that can be derived from compounds such as cyclopropyl, cyclobutyl, cyclopenyl or cyclohexyl. The expression "R1 and R22 june with the atoms to which they are bound can form a cyclic group of 6 to 8 elements, which contains 1, 2, 3 or 4 selected hetero-atoms of oxygen, sulfur and nitrogen" refers to the structures of the heterocycles which may be derived from compounds such as azocan, azocan-2-one, cycloheptyl cyclohexyl, cyclooctane, cyclooctene, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [ 1,4] diazocan, [1, 2] diazocan-3-one, [1,3] diazocan-2-one, dioxazine, [1,4] dioxocan, dioxol, cetopiperazine, morpholine, 1,4-oxazepane, 1 , 2-oxa-iopane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4] oxazocane, [1,3] oxazo-2-one, oxocane, oxocan-2 -one, phenyl, piperazine, piperidine, pyran, pyrazine, pyridazine, pyrimidine or 5,6,7,8-teirahydro-1H-azocin-2-one or thiomorpholine. The fact that many of the heterocyclic designations listed above are the chemical designations of unsaturated or aromatic ring systems does not imply that the mono- or polycyclic group of 4 to 15 elements could come from the respective unsaturated ring system. The designations here only serve to describe the ring system with respect to the size of the ring and the number of hetero-atoms and their relative positions. As previously explained, the mono- or polycyclic group of 4 to 15 elements can be purified, partially unsaturated or aromatic and thus can come not only from the same chemical products listed above but also from their partially or completely hydrogenated analogs and also of its most insatiable analogues if applicable. As examples of fully or partially hydrogenated analogues of the heterocycles listed above, from which this group may proceed, the following may be mentioned: pyrroline, pyrrolidine, teirahydrofuran, teirahydrothiophene, dihydropyridine, tetrahydropyridine, piperidine, 1,3-dioxolane, 2-imidazoline, imidazolidine, 4,5-dihydro-1,3-oxazole, 1,3-oxazolidine, 4,5-dihydro-1 , 3- iazo I, 1,3-Iiazolidine, perhydro-1,4-dioxane, piperazine, perhydro-1,4-oxazine (= morpholine), perhydro-1,4-fiazine (= iomorpholine), perhydroazepine, indoline, isoindoline, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-eeryhydroisoquinoline, etc. The term "- (C? -C3) -perfluoroalkyl" is a partial or fluoroalkylated alkyl residue, which may be derived from residues such as -CF3, -CHF2, -CH2F, -CHF-CFs, -CHF-CHF2, -CHF -CH2F, -CH2-CF3, -CH2-CHF2, -CH2-CH2F, -CF2-CF3, -CF2-CHF2, -CF2-CH2F, -CH2-CHF-CF3, -CH2-CHF-CHF2, -CH2- CHF-CH2F, -CH2-CH2-CF3, -CH2-CH2-CHF2, -CH2-CH2-CH2F, -CH2-CF2-CF3, -CH2-CF2-CHF2, -CH2-CF2-CH2F, -CHF-CHF -CF3, -CHF-CHF-CHF2, -HF-CHF-CH2F, -CHF-CH2-CF3, -CHF-CH2-CHF2, -CHF-CH2-CH2F, -CHF-CF2-CF3, -CHF-CF2- CHF2, -CHF-CF2-CH2F, -CF2-CHF-CF3, -CF2-CHF-CHF2, -CF2-CHF-CH2F, -CF2-CH2-CF3, -CF2-CH2-CHF2, -CF2-CH2-CH2F , -CF2-CF2-CF3, -CF2-CF2-CHF2 or -CF2-CF2-CH2F. The term "- (C? -C3) -perfluoroalkylene" is a partial or fluoro alkylene radical, which may be derived from resins such as -CF2-, -CHF-, -CHF-CF2-, -CHF-CHF-, - CH2-CF2-, -CH2-CHF-, -CF2-CF2-, -CF2-CHF-, -CH2-CHF-CF2-, -CH2-CHF-CHF-, -CH2-CH2-CF2-, -CH2- CH2-CHF-, -CH2-CF2-CF2-, -CH2-CF2-CHF-, -CHF-CHF-CF2-, -CHF-CHF-CHF-, -CHF-CHF-CH2F, -CHF-CH2-CF2 -, -CHF-CH2-CHF-, -CHF-CH2-CHF-, -CHF-CF2-CF2-, -CHF-CF2-CHF-, -CF2-CHF-CF2-, -CF2-CHF-CHF-, -CF2-CH2-CF2-, -CF2-CH2-GHF-, -CF2-CF2-CF2- or -CF2-CF2-CHF-. Halogen is fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or iodine, particularly preferably chlorine or iodine.

The optically active carbon atoms present in the compounds of the formulas I or can independently of one another have the R configuration or the S configuration. The compounds of formula 1 can be present in the form of pure enantiomers or of pure diastereomers or in the form of mixtures of enantiomers and / or diastereomers, for example in the form of racemates. The present invention relates to pure enantiomers and to mixtures of enantiomers as well as to pure diastereomers and to mixtures of diastereomers. The invention comprises mixtures of two or more of two stereoisomers of the formulas I and the, and comprises all the proportions of the stereoisomers in the mixtures. In the case of the compounds of the formulas I and the can be present as E isomers or as Z isomers (or cis isomers or trans isomers) the invention relates to both the pure E isomers and the pure Z isomers and the E-mixtures. / Z in all proportions. The invention also comprises all tauomeric forms of the compounds of formulas I or la. The diastereomers, including the E / Z isomers, can be separated into individual isomers, for example, by chromatography. The racemates can be separated into two enantiomers by conventional methods, for example by chromatography on chiral phases or by resolution, for example by crystallization of the diastereomeric salts obtained with optically active acids or bases. Uniform stereochemical compounds of the formulas I can also be obtained or by using uniform stereochemical starting materials or by using skeletal-selective reactions. The physiologically tolerable salts of the compounds of the formulas I and II are the non-toxic salts which are physiologically acceptable, in particular the pharmaceutically usable salts. Said salts of the compounds of formula I containing acidic groups, for example a carboxyl group COOH, are for example the alkali metal salts or the alkaline earth metal salts such as the sodium salts, potassium salts, magnesium salts and salts of calcium and also salts with physiologically tolerable quaternary ammonium ions such as tetramethylammonium or erylacetylammonium, and acid addition salts with ammonia and physiologically tolerable organic amines, such as melamine, dimethylamine, trimethylamine, ethylamine, triethylamine, ethanolamine or tris. - (2-hydroxy-yl) amine. The basic groups contained in the compounds of the formulas I and the, for example the amino groups or the guanidino groups, form acid addition salts, for example with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid or phosphoric acid, or with organic carboxylic acids and sulfonic acids such as formic acid, acetic acid, oxalic acid, citric acid, lactic acid, malic acid, succinic acid, malonic acid, benzoic acid, maleic acid, fumaric acid, tartaric acid, methanesulfonic acid or p-toluenesulfonic acid. The compounds of formulas I and II, which simultaneously contain a basic group and an acid group, for example a guanidino group and a carboxyl group, can be present as bipolar ions (betaines), which are also included in the present invention. The salts of the compounds of the formulas I and the can be obtained by customary methods known to those skilled in the art, for example by combining a compound of the formulas I and the one with an inorganic or organic acid or base in a solvent or dispersant, or from other salts by cation exchange or anion exchange. The present invention also includes all the salts of the compounds of the formulas I and which, due to their physiologically low tolerance, are not suitable for use in pharmaceutical products but are suitable, for example, as intermediates for carrying out more chemical modifications of the compounds of the formulas I and the or as starting materials for the preparation of physiologically tolerable salts. The present invention also includes all the solvates of the compounds of the formulas I and, for example hydrates or adducts with alcohols. The invention also includes derivatives and modifications of the compounds of the formulas I and II, for example prodrugs, protected forms and other physiologically tolerable derivatives, as well as active metabolites of the compounds of the formulas I and II. The invention relates in particular to prodrugs and protected forms of the compounds of formulas 1 and 1, which can be converted into compounds of formulas I and 1 under physiological conditions. Suitable prodrugs for the compounds of the formulas I and II, ie the chemically modified derivatives of the compounds of the formulas I and the one with properties that are improved in a desired manner, for example with respect to the solubility, bioavailability or duration of acfuación, are known by the experts in maíeria. In the ordinary bibliography, more detailed information is found in relation to prodrugs, such as, for example, Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985; Fleisher et al., Advanced Drug Delivery Reviews 19 (1996) 115-130; or H. Bundgaard, Drugs of the Future 16 (1991) 443 which are all incorporated herein by reference. Suitable prodrugs for the compounds of formulas I and II are especially acyl prodrugs and carbamate prodrugs of acylating nitrogen containing groups such as amino groups and guanidino groups and also ester prodrugs and amine prodrugs of carboxylic acid groups which may be present in the compounds of formulas I and la. In the acyl prodrugs and in the prodrugs of carbamate one. or more, for example one or more, hydrogen atoms in nitrogen atoms in said groups are substituted with an acyl group or a carbamate group, preferably a - (C? -C6) -alkyloxycarbonyl group. Suitable acyl groups and the carbamate groups for the acyl prodrugs and the carbamate prodrugs are, for example, the groups Rp1-CO- and Rp2O-CO-, wherein Rp1 is hydrogen, (C? -C? 8) -alkyl, (C3-C8) -cycloalkyl, (C3-C8) -cycloalkyl- (C? -C4) -alkyl-, (C5-C? 4) -aryl, Het-, (C6-C14) - ar.l- (C? -C4) -alkyl-0 Het- (C? -C4) -alkyl- and wherein Rp2 has the meanings indicated for Rp1 with the exception of hydrogen. Especially preferred compounds of the formulas I and II are those in which two or more residues are defined as indicated above for the preferred compounds of the formulas I and II, or the residues having one or more of the specific indications of the residues given in their general definitions or in the definitions of the preferred compounds above. All possible combinations of the definitions given for the preferred definitions and the specific indications of the explicitly discussed terms are subject of the present invention. Likewise with respect to all the preferred compounds of the formulas I and all their stereoisomeric forms and their mixtures and any proportion and their physiologically acceptable salts are explicitly subject of the present invention, as well as their prodrugs. Likewise, also in all preferred compounds of formulas I and A, all residues that are present more than once in the molecule are independently of one another and can be identical or different. The compounds of formulas I and II can be prepared using methods and techniques, which are well known and appreciated by any expert in the field. Starting materials or building blocks for their use in the general synthetic processes which can be applied in the preparation of the compounds of the formulas I and are readily available to a person skilled in the art. In many cases they are available commercially or have been described in the literature. On the other hand, they can be prepared from readily available precursor compounds analogously to the processes described in the literature, by procedures or analogously to the methods described in this application. In general, the compounds of the formulas I and the can be prepared, for example in the course of a convergent synthesis, by joining two or more fragments that can be retrosynthetically processed from the formulas I and the. More specifically, the starting pyrrole derivatives suitably used are used as building blocks for the preparation of the compounds of formulas I and II. If they are not commercially available, said pyrrole derivatives can be prepared by the well-known, well-known procedures for the formation of the pyrrole ring system. By selecting the appropriate precursor molecules, these pyrrole syntheses allow the introduction of a variety of substitutes in various positions of the pyrrole system, which can be chemically modified in order to finally reach the molecule of the formulas I and the one presenting the configuration of the desired substitute. As one of the integral studies in which numerous references and bibliographic references can be found in the chemistry of pyrrole and in the synteptic procedures for the preparation, C.W. Bird in "Comprehensive Heterocyclic Chemistry" vol.4, C.W. Bird and G.W.H. Cheeseman, eds., Pergamon Press, Oxford, 1984; R.J. Sundberg in "Comprehensive Heterocyclic Chemistry" F 2, A. Kafriízky, Ch. Rees, E. Scriven, eds., Elsevier 1996, A. Gossauer in Houben-Weyl, "Methoden der Organischen Chemie" (Means of Organic Chemistry) , Thieme, Síuftgart, Germany 1994, vol. E6a "Hetarene f; D.M. Kefcha, Progress in Heterocyclic Chemistry 2002, 14, 114-138; D.M. Kelcha, Progress in Heterocyclic Chemistry 2001, 13, 111-129; D.M. Keicha, Progress in Heterocyclic Chemistry 2000, 12, 114-133; D.S. Black, Science of Synthesis 2002, 9, 441-552; D. van Leusen, A.M. van Leusen, Organic Reactions 2001, 57, 417-666; V.F. Ferreira et al., Org. Prep. Procedure Int. 2001, 33, 411-454. If the starting pyrrole derivatives are not commercially available and need to be synthesized, they can be carried out, for example, according to the well-known pyrrole syn- thesis, mentioned above. In the following procedures of particular interest for the invention method are briefly listed and referenced, however, they are standard procedures explained in a comprehensible manner in the literature, and are well known to those skilled in the art. Although not always presented explicitly, in certain cases the positional isomers will take place during the synthesis of the reactions mentioned below. Notwithstanding these mixtures of positional isomers, they can be separated by means of modern separation techniques, such as, for example, HPLC preparation.

Illusive examples for some general methods: 1) Preparation of the pyrroles from ß-dicarbonyl compounds, a-halocarbonyl compounds and amines (Hanízsch synisis): A. Hanfzsch, Ver. Dtsch. Chem. Ges. 1890, 23, 1474 2) Pyrroles from the compounds 1, 4-diketo and the amino compounds (synisis of Paal-Knorr): a) W.J. Thomson and C.A. Buhr, J. Org. Chem. 1983, 48, 2769 b) H. Síeí? Er and R. Lauterbach, Liebigs Ann. Chem. 1962, 655, 20 3) Pyrroles from compounds of α-aminocarbonyl and activated ceilones (Knorr synthesis): a) H. Ogoshi et al., Tetrahedron Lett. 1983, 24, 929 b) J.V. Cooney, E.J. Beal and R.N. Hazlett, Org. Prep. Procedure Int. 1983, 15, 292 c) J.M. Hamby and J.C. Hodges, Heterocycles 1993, 35, 843 4) 2-hydroxypyrroles can be obese by iniramolecular condensation with aldol of a-acylamino ketones: a) T. Kato, M. Sato and T. Yoshida, Chem. Pharm. Bull. 1971, 19, 292 b) R.L. Wineholt, E. Wyss and J.A. Moore, J. Org. Chem. 1966, 31, 48 ) Synthesis of 2-aminopyrroles: M.T. Coceo et al., Drug Ed. Sci. 1988, 43, 103 6) Pyrrole 2,5-unsupplemented: A.M. van Leuden et., Tetrahedron Lett. 1972, 5337 7) Reaction of 1, 3-dicarbonyl compounds and glycine esters to form pyrrole-2-esters: a) S. Maiaka ef al., Synthesis 1982, 157 b) G.H. Walizei and E. Breiimaier, Synthesis 1989, 337 c) H.K. Hombrecher and G. Horíer, Synthesis 1990, 389 In addition, in order to obtain the desired susiifuyeníes in the pyrrole ring system in formulas I and II, the functional groups introduced into the ring system during the pyrrole syn- thesis can be chemically modified. Especially the groups present in the pyrrole ring system can be modified by a variety of reactions and in this way the desired residues can be obtained. For example, a pyrrole carrying a hydrogen atom in the 2 or 3 position can also be obtained by saponification and decarboxylation of the pyrrole carrying an ester group in the respective position. The alkyl or hydroxymeryl groups as well as the formyl groups attached to the pyrrole core can be transformed into a variety of functional groups, for example, in the corresponding carboxylic acid or carboxylic ester by many oxidic reactions well known to those skilled in the art. In addition, a nyryl group attached to the pyrrole ring can be converted, for example, easily into the desired acid under acidic or basic conditions. In addition, the carboxylic acid groups and the acetic acid groups in the 2-position, the 3-position, the 4-position and the 5-position can be transformed into their homologues using reactions for the elongation of the carboxylic acid chain. The halogen atoms can be introduced, for example, into position 2, position 3, position 4 and position 5 according to procedures similar to the following described in the literature. For the fluorination of pyrroles, bis (teirafluoroboraide) of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2] octane ("selectfluor") can be used, see J. Wang and A.l. Scoui, J. Chem. Soc, Chem. Commun. 1995, 2399. However, other suitable fluorinating reactants may also be employed where appropriate, e.g. ex. Xenon difluoride (J. Wang and A. Scout, Tetrahedron 1994, 50, 6181). The chlorination, bromination and iodination of pyrroles can be carried out by means of the reaction with elemental halogens or by the use of NCS, NBS or NIS and many other reagents well known to those skilled in the art. In addition, suitable methods are, for example, those described by H.J. Anderson and S.-F. Lee, Can. J. Chem. 1965, 43, 409; H.M. Gilow, D.E. Burton, J. Org. Chem. 1981, 46, 2221; S. Petruso et al., J. Heterocycl. Chem. 1990, 27, 1209; M. D'Auria et al., J. Chem. Soc, Perkin Trans. 1 1997, 2369. Depending on the reaction conditions, the reactive, the functional and the suspending configuration, the halogen is introduced in position 2 and / or in position 3 and / or in position 4 and / or in position 5. Through selective exchange of halogen / metal or mefalation by selective exchange of hydrogen / metal and subsequent reaction with a wide range of electrophiles, several susfituyenf.es can be intro- duced into the heterocyclic nucleus (JA Ganske et al., J. Org Chem. 1989, 54, 4801; D. Monti and G. Sleiíer, Gazz. Chim. /fa/. 1990, 120, 587; A. Fürstner, R. Singer and P. ex. Knochel, Tetrahedron Lett. 1994, 35, 1047; A. Minato et al., Tetrahedron Lett. 1981, 22, 5319). Halogens or hydroxy groups (through their íriflates and nonaflates) or primary amines (through their diazonium salts) present in the pyrrole structure, can be transformed directly, or the ferrocopying of stannane or boric acid corresponding, in a variety of other functional groups such as for example -CN, -CF3, -C2F5, ethers, acids, amides, amines, alkyl or aryl groups mediated by transition metals, namely palladium or nickel catalysts or salts of copper and reagents, for example, referred to below (F. Diederich, P; Stang, "Metal-catalyzed Cross-coupling Reactions", Wiley-VCH, 1998; or M. Beller, C. Bolm, "Transition Metals for Organic Synthesis ", Wiley-VCH, 1998, J. Tsuji," Palladium Reagents and Catalysts ", Wiley, 1996, J. Hartwig, Angew, Chem. 1998, 110, 2154, B. Yang, S. Buchwaid, J. Organomet. Chem. 1999, 576, 125; T. Sakamofo, K. Ohsawa, J. Chem. Soc. Perkin Trans 1 1999, 2323; D. Nichols, S. Frescas , D. Marona-Lewika, X. Huang, B. Roth, G. Gudelsky, J. Nash, J. Med. Chem. 1994, 37, 4347; P. Lam, C.Cark, S. Saubem, J. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett. 1998, 39, 2941; D. Chan, K. Monaco, R. Wang, M. Winfers, Tetrahedron Lett. 1998, 39, 2933; V. Fariña, V. Krishnamurthy, W. Scoíí, "Th? Stille Reaction", Wiley, 1994; F. Qing et al., J. Chem. Soc. Perkin Trans. I 1997, 3053; S. Buchwaid et al., J. Am. Chem. Soc. 2001, 123, 7727; S. Buchwaid et al., Organic Lett. 2002, 4, 581; T. Fuchikami et al., Tetrahedron Lett. 1991, 32, 91; Q. Chen et al., Tetrahedron Lett. 1991, 32, 7689). For example, nitro groups can be reduced to amino groups by various ionic reducing agents such as sulfides, dithioniphates, complex hydrides or by catalytic hydrogenation. A reduction of a nitro group can also be carried out at a later stage of the synthesis of a compound of the formulas I and the one and a reduction of one group to an amino group can also be produced simulinely to a reaction carried out in another functional group, for example when a group is reacted as a cyano group with hydrogen sulfide or when a group is hydrogenated. In order to introduce the radicals R.sub.1a, R.sub.1b in formula 2, the amino groups can then be modified according to the standard procedures for alkylation, for example by reaction with alkyl halides (substitutes) or by reductive amination of carbonyl groups, according to the standard procedures of acylation, for example by reaction with acidic carboxylic acid derivatives such as acid chlorides, anhydrides, activated or other esters or by reaction with carboxylic acids in the presence of an activating agent or by standard procedures for sulfonylation, for example by reaction with the sulfonyl chlorides The ester groups present in the pyrrole nucleus can be hydrolyzed in the corresponding carboxylic acids (or, in the case of the substituted or unsubstituted benzyl esters, occasionally be converted to the corresponding carboxylic acids by methods of hydrogenation), which after activation can be reacted with amines or alcohols under standard conditions to give amides or alcohols, respectively. The ester groups present in the pyrrole nucleus can be transformed into other esters by transesterification. The carboxylic acids attached to a suitable pyrrole core can also be alkylated to give esters. The ether groups present in the pyrrole nucleus, for example the benzyloxy groups or other easily cleavable ether groups, can be cleaved to give hydroxy groups, which can then be reacted with several agents, for example etherification agents or acylating agents. that allow the substitution of the hydroxy group by other groups. The sulfur-containing groups can be reacted analogously. Last the synthesis procedure to modify groups R87 or R8 'in formulas 2 and 3 linked to the pyrrole ring system by application of the parallel synisis methodologyA variety of reactions can be extremely useful, including, for example, palladium with palladium, nickel or copper. Such reactions are described for example in F. Diederich, P. Stang, "Metal-catalyzed Cross-coupling Reactions", Wiley-VCH, 1998; or M. Beller, C. Bolm, "Transition Metals for Organic Synthesis", Wiley-VCH, 1998; J. Tsuji, "Alladium Reagents and Catalyst," Wiley, 1996, J. Hartwig, Angew, Chem. 1998, 110, 2154, B. Yang, S. Buchwaid, J. Organomet, Chem. 1999, 576, 125; Lam, C. Clark, S. Saubern, J. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett., 1998, 39, 2941; D. Chan, K. Monaco, R. Wang, M. Winíers, Tetrahedron Lett, 1998, 39, 2933, J. Wolfe, H. Tomori, J. Sadig, J. Yin, S. Buchwaid, J. Org. Chem. 2000, 65, 1158, V. Fariña, V. Krishnamurthy, W. Scoti, "The Stille Reaction", Wiley, 1994, S. Buchwaid et al., J. Am. Chem. Soc. 2001, 123, 7727, S. Buchwaid et al., Org. Lett., 2002, 4, 581. The reactions mentioned above for the transformation of the functional groups are also, in general, extensively described in organic chemistry textbooks such as M. Smith, J. March, "March's Advanced Organic Chemistry", Wiley-VCH , 2001 and in books such as Houben-Weyl, "Methoden der Organischen Chemie" (Means of Organic Chemistry, Georg Thieme Verlag, Sfuffgart , Germany, or "Organic Reactions", John Wiley & Sons, New York, or R.C. Larock, "Comprehensive Organic Transformations", Wiley-VCH, 2nd ed. 1999, B. Trosf, I. Fleming (eds.) "Comprehensive Organic Synthesis", Pergamon, 1991; A. Katriízky, C. Rees, E. Scriven, "Comprehensive Heterocyclic Chemistry II", Elsevier Science, 1996) in which the defalles of the reactions and the literature of the primary source can be found. Due to the fact that the functional groups present in the case are linked to a pyrrole ring, it may be necessary in certain cases to specifically adapt the reaction conditions or the specific reagents selected from a variety of reagents that can be used in principle in a conversion reaction, or if not take. specific measures to achieve a desired conversion, for example using protection group techniques. However, the discovery of suitable variances of the reaction and of the reaction conditions in such cases does not cause any problem for a maize expert. The structural elements present in the resins attached to the position 1 of the pyrrole ring in the compounds of the formulas I and the and in the group COR8 present in the position 2 and / or in the position 3, 4 and / or 5 of the ring of pyrrole can be introduced into a starting pyrrole derivative which can be obtained as outlined above by successive reaction steps using synthetic methodologies such as those outlined using procedures that are well known per se by a maize expert. Resins R8 which can be introduced in formula 2, for example, by condensing the corresponding carboxylic acid of formula 2 with a compound of formula HR8 ', ie with an amine of formula HN (R1) -VGM to give a compound of formula 3. The compound of formula 3 obtained in this way can already contain the desired end groups, ie the groups R8 'and R87 can be the groups -N (R1) -VGM and R -Q- defined in formulas I and the, or optionally in the compound of formula 3 thus obtained subsequently the residue or the residues R8 and the resin R87 are transformed into the residues -N (R) -VGM and R ° -Q-, respectively, to give the compound desired of the formulas I and the. 2 3 i - * - formulas I and the Thus, the residues R8 and the residues R1 and -VGM contained in these may have the indications of R1 and -VGM, respectively, given above or in addition in the resins R1 'and in the functional groups -VGM may also be present in the form of groups that can be transformed later into the final groups R and -VGM, that is to say they can present the functional groups in the form of precursor groups or derivatives, for example in the protected form. In the course of the preparation of the compounds of the formulas I and II, it may generally be advantageous or necessary to introduce functional groups which reduce or avoid unwanted reactions or side reactions in the respective synthesis step, in the form of precursor groups which they are then transformed into the desired functional groups, or into the functional groups of the block temporarily by a strategy of the protective group followed by the problem of synthesis. These strategies are well known to maize experts (see, for example, TW Greene and PGM Wuts, "Rotective Groups in Organic Synthesis", 3rd ed., Wiley, 1999, or P. Kocienski, "Protecting Groups", Thieme , 1994.) As examples of precursor groups, cyano groups and nickel groups can be mentioned.The cyano group can be converted to a carboxylic acid derivative at a later stage or by reduction to aminomethyl groups, or the nitro groups can be transformed by reduction. Similar to catalytic hydrogenation in amino groups Protective groups may also be the expression of a solid phase, and cleavage of the solid phase means the removal of the protecting group The use of these techniques is known to the experts in maigery ( K. Burgess (ed.), "Solid Phase Organic Synthesis", New York, Wiley, 2000) For example, a hydroxyphenolic group can be linked to a frityl-polysulfone resin, which serves as a pro-cyclic group and the molecule is cleaved from this resin by irradiation with TFA in a postero-anterior step of the syn- thesis. The rest R87 in the compounds of formulas 2 and 3 can designate the group -QR ° defined above which must ultimately be present in the desired target molecule of formulas I and A, or it can indicate a group that can subsequently be transformed into the group -QR °, for example a precursor group or a derivative of the group -QR ° in which the functional groups are present in the protected form, or R87 can designate a hydrogen atom or a protecting group for the hydrogen atom of the ring of pyrrole. Also, residues R1a and R1b in formulas 2 and 3 have the corresponding definitions of R4, and R3 in formulas I and the one defined above, however, for the syn- thesis of the contexts of formulas I and these residues, also , in principle they can be present in the step of condensation of a compound of formula 2 with a compound of formula HR8 giving a compound of formula 3 in the form of precursor groups or in protected form. The R86 residues in the compounds of formula 2 which can be identical or different, can be, for example, hydroxy or (d-C4) -alkoxy, ie the groups COR86 present in the compounds of formula 2 can be, for example , the free carboxylic acids or their esters as the alkyl esters as the COR8 groups can be in the compounds of the formulas I and la. The CR86 groups can be any other activated derivative of a carboxylic acid that allows the formation of the amide, the formation of the ester or the formation of the thioester with a compound of formula HR8 '. The CR86 group can be, for example, an acid chloride, an activated ester such as a substituted phenyl ester or an N-hydroxysuccinimide or a hydroxybenzotriazole ester, an azolide such as an imidazolide, an azide or a mixed anhydride, for example a mixed anhydride with a carbonic acid ester or with a sulfonic acid, which derivatives can all be prepared from the carboxylic acid by standard procedures and can be reacted with an amine, an alcohol or a mercaptan of formula HR8 'under standard conditions. The COOH carboxylic acid group representing COR86 in a compound of formula 2 may be obtained, for example, from a group esier iníroducido the pyrrole system during síníesis procedimieníos pyrrole by hydrolysis of esíándar. It can also be obtained, for example, by hydrolysis of a nitrile group introduced into the pyrrole system during a pyrrole synisis. The compounds of formulas I and in the COR8 'group is an ester group can be íambién prepared from the compuesíos of formula 2 in which COR86 is a carboxylic acid group medianíe reactions habiluales esíerificación such as by reacting the acid with an alcohol in acid catalysis or alkylation of a salt of the carboxylic acid with an electrophile such as an alkyl halide or by cross-esterification of the ester. The compounds of the formulas I and the one in which a group COR8 is an amide group can be prepared from amines and compounds of formula 2 in which COR86 is a carboxylic acid group or one of its esters by means of usual amination reactions. In particular, for the preparation of amides the compounds of formula 2 in which COR86 is a carboxylic acid group can be condensed under standard conditions with compounds of formula HR8 which are amines by reagents normal uíilizados coupling in síníesis of pépíidos. Such coupling reagents are, for example, carbodiimides as diciciohexilcarbodiimida (DCC), N- (3-dimetilam¡no offe!) - N'-ethylcarbodiimide (EDCI) or diisopropylcarbodiimide, carbonyldiazoles like carbonyldiimidazole (CDI) and similar reagents , propylphosphonic anhydride, O - ((cyano- (ethoxycarbonyl) -methylene) amino) -N, N, N ', N'-teírametiluranio (TOTU), dieíilfosforilo cyanide (DEPC), bromo-tripyrrolidinophosphonium hexafluorophosphate (PyBroP ) or bis- (2-oxo-3-oxazolidinyl) -phosphoryl chloride (BOP-CI) and many others. If the rest-QR ° present in a pyrrole of the formulas I and the or the rest R87 present in a pyrrole of formula 2, or a residue in which the functional groups in the rest -QR ° or R87 are present in protected form or in the form of a precursor group not already introduced during a preceding step, for example duraníe synthesis core pyrrole, esíos residues may be introduced, for example, at position 1 system pyrrol by conventional procedimieníos of the literature well known to those skilled in the art for N-alkylation, reductive amination, N-arylation, N-acylation or N-sulfonylation of the nitrogen atoms of the heterocycles. The starting pyrrole derivative to be used in said reaction has a nitrogen atom in position 1. The N-alkylation of the ring nitrogen atom can, for example, be carried out under standard conditions, preferably in the presence of a base such as K2CO3, CS2CO3, NaH, KOH or KOfBu, using an alkylation compound of formula LG-QR ° or of formula R87-LG, wherein. the atom in the group Q or in the group R87 linked to the group LG in this case is an aliphatic carbon atom of an alkyl group and LG is a leaving group, for example halogen as chlorine, bromine or iodine, or a sulfonyloxy group as tosyloxy, mesyloxy or trifluoromethylsulfonyloxy. LG may, for example, also be a hydroxy group which, in order to carry out the alkylation reaction, is activated in a well-known Mitsunobu reaction by a conventional acylating agent. For the preparation of compounds in which A is a direct bond and an aromatic group is directly attached at position 1 of the midazole system, conventional arylation procedures can be used. For example, aryl fluorides such as alkyl fluorobenzoates or 4-fluorophenyl methylsulfones can be used as arylating agents. These procedures are described, for example, by M. Yamada et al. J. Med. Chem. 1996, 39, 596; J. Ohmori et al. J. Med. Chem. 1996, 39, 3971. Alternatively, a wide variety of aryl iodides, aryl bromides or substituted aryl triflates can serve as arylation agents at the 1-position of the heterocyclic nitrogen in a salt-mediated reaction. of copper or palladium according to, for example, P. Cozzi et al. Drug 1987, 42, 205; P. Unangst, D. Connor, R. Siabler, R. Weikert, J. Heterocycl. Chem. 1987, 24, 811; G. Tokmakov, I. Grandberg, Tetrahedron 1995, 51, 2091; D. Oíd, M. Harris, S. Buchwaid, Org. Lett. 2000, 2, 1403, G. Mann, J. Hartwig, M. Driver, C. Femandez-Rivas, J. Am. Chem. Soc. 1998, 120, 827; J. Hartwig, M. Kawatsura, S. Hauk, K. Shaughnessy, LJ. Org. Chem. 1999, 64, 5575; S. Buchwaid et al., J. Am. Chem. Soc. 2001, 123, 7727. Furthermore, said arylations can be carried out by reacting a wide range of substituted arylboronic acids as demonstrated, for example, by W. Mederski, M. Lefort, M. Germann, D. Kux, Tetrahedron 1999, 55, 12757; J. Coliman et al., J. Org. Chem. 2001, 66, 7892. Preferred methods include, but are not limited to those described in the examples. The compounds of the present invention are inhibitors of serine protease, which inhibits the activity of Xa factors and / or Vlla factor of the blood coagulation enzyme. In particular, they are very active inhibitors of factor Xa. They are specific inhibitors of serine protease since they do not substantially inhibit the activity of other proteases whose inhibition is not desired. The activity of the compounds of the formulas I and the can be determined, for example, by the analyzes described below or by the analyzes known to experts in the maize. With respect to the inhibition of factor Xa, a preferred embodiment of the invention comprises compounds having a Ki < 1 mM for the inhibition of factor Xa determined in the assay described below, with or without corresponding inhibition of factor Vlla and which preferably do not substantially inhibit the activity of other proteases involved in coagulation and fibrinolysis whose inhibition is not desired (using the same concentration of inhibitor). The compounds of the invention inhibit the caffeitic activity of factor Xa either directly, independently of the pro-thrombinase complex or as a soluble subunit, or indirectly, by inhibiting the conjugation of factor Xa in the profrombinase complex. As inhibitors of factor Xa and / or factor Vlla the compounds of the formulas I and the and their physiologically tolerable salts and their prodrugs are generally suitable for the therapy and prophylaxis of diseases in which the activity of factor Xa and / or the Factor Vlla performs a function or presents the desired extent, or that may be favorably influenced by the inhibition of factor Xa and / or factor Vlla or by decreasing its activities, or for the prevention, relief or cure of which an inhibition of factor Xa and / or factor Vlla or a decrease in its activity is desired by the doctor. Since the inhibition of factor Xa and / or factor Vlla influences blood coagulation and fibrinolysis, the compounds of formulas I and II and their physiologically tolerable salts and their prodrugs are generally suitable for reducing blood coagulation or for the therapy and prophylaxis of diseases in which the activity of the blood coagulation system plays a role or has an undesired extent, or which can be favorably influenced by reducing blood coagulation, or for the prevention, relief or cure of which A decreased activity of the blood coagulation system is desired by the doctor. A specific subject of the present invention is therefore the reduction or inhibition of unwanted blood coagulation, in particular in an individual, by the administration of an effective amount of a compound I or of one of its salts or of a physiologically prodrug tolerable, as well as for its pharmaceutical preparations. The present invention also relates to the compounds of the formulas I and the and / or their physiologically tolerable salts and / or their prodrugs for use as pharmaceuticals (or medicaments), to the use of the compounds of the formulas I and and / or their physiologically tolerable salts and / or their prodrugs for the production of pharmaceuticals for the inhibition of factor Xa and / or factor Vlla or to influence blood coagulation, the inflammatory response or fibrinolysis or for therapy or prophylaxis of the diseases mentioned above or below, for example for the production of pharmaceutical products for the therapy and prophylaxis of cardiovascular diseases, Iromboembolic diseases or reslenosis. The invention also relates to the use of the compounds of the formulas I and II and / or their physiologically tolerable salts and / or their prodrugs for the inhibition of factor Xa and / or factor Vlla or to influence coagulation. blood or in fibrinolysis or for the therapy or prophylaxis of the diseases mentioned above or below, for example for the use in the therapy or prophylaxis of cardiovascular disorders, thromboembolic diseases or resenosis, and to treatment methods that aspire to such purposes, including the methods for such therapies and prophylaxis. The present invention also relates to pharmaceutical preparations (or pharmaceutical compositions) containing an effective amount of at least one compound of the formulas I and the and / or its physiologically tolerable salts and / or its prodrugs in addition to a pharmaceutically acceptable carrier usual, that is, one or more pharmaceutically acceptable carrier substances or excipients and / or auxiliary substances or additives. The invention also relates to the pathology of pathological states such as abnormal thrombus formation, acute myocardial infarction, unstable angina, thromboembolism, acute vessel closure associated with thebolic therapy or percutaneous transluminal coronary angioplasty (PTCA). , transient ischemic attacks, stroke, intermittent claudication or transplantation with coronary or peripheral artery bypass, luminal stenosis of the vessel, post-coronary resenhosis or venous angioplasty, maintenance of vascular access permeability in patients with long-term hemodialysis, the pathological formation of the thrombus that occurs in the veins of the lower extremities, the abdominal, knee or hip surgery, a risk of pulmonary thromboembolism or disseminated generalized invasive coagulopathy that occurs in vascular systems during the seventh shock co, certain viral infections or cancer. The compounds of the present invention can also be used to reduce an inflammatory response. Examples of specific strains for the treatment or prophylaxis of which the compounds of formulas I and I can be used are coronary heart disease, myocardial infarction, angina pectoris, vascular resphenosis, for example restenosis after angioplasty. as PTCA, adult acute dyspnoea syndrome, multiple organ failure and the transorbidity of disseminated infravascular coagulation. Examples of related complications associated with surgery are thrombosis such as thrombosis of the deep vein and the proximal vein, which may take place during the surgical intervention. The compounds of the formulas I and the and their physiologically tolerable salts and their prodrugs can be administered to animals, preferably to mammals and in particular to man as pharmaceuticals for therapy or prophylaxis. They can be administered alone or in mixtures with some other or in the form of pharmaceutical preparations, which allow intestinal or parenteral administration. Pharmaceutical products can be administered orally, for example in the form of pills, tablets, coated tablets, coated tablets, granules, hard or soft gelatin capsules, solutions, syrups, emulsions, suspensions or aerosol mixtures. The administration can also be carried out, however, via the body, for example in the form of suppositories, or parenterally, for example via inovravenous, intramuscular or subcutaneous route, in the form of injectable solutions or solutions in infusion, microcapsules, implants or bars or percutaneously or topically, for example in the form of ointments, solutions or tinctures, or in other forms, for example in the form of aerosols or nasal sprays. The pharmaceutical preparations according to the invention are prepared in a manner known per se and familiar to one skilled in the art, using inert inorganic and / or organic pharmaceutically acceptable carriers in addition to the compound or compounds of the formulas I and the and / or their (s) physiologically tolerable salt (s) and / or their prodrug (s). For the production of pills, tablets, coated tablets and hard gelatin capsules it is possible to use, for example, lactose, corn starch or one of its derivatives, talc, stearic acid or its salts, etc. Carriers of soft gelatin capsules and suppositories are, for example, fats, waxes, liquid semi-solid polyols, hardened natural oils, etc. Suitable carriers for the production of solutions, for example injectable solutions or of emulsions or syrups are, for example, water, saline, alcohols, glycerol, polyols, sucrose, invert sugar, glucose, vegetable oils, ele. Suitable carriers for the microcapsules, implants or bars are, for example, copolymers of glycolic acid and lactic acid. The pharmaceutical preparations normally contain about 0.5% to 90% by weight of the compounds of the formulas I and II and / or their physiologically tolerable salts and / or their prodrugs. The amount of active ingredient of the formulas I and the and / or their physiologically tolerable salts and / or their prodrugs in the pharmaceutical preparations is usually from about 0.5 mg to about 1000 mg, preferably from 1 mg to about 500 mg . In addition to the active ingredients of the formulas I and the and / or their physiologically acceptable salts and / or the prodrugs and / or the carrier substances, the pharmaceutical preparations may contain additives such as, for example, fillers, disintegrates, binders, lubricants, wetting agents, stabilizers, emulsifiers, preservatives, sweeteners, colorants, flavor enhancers, flavorings, thickeners, diluents, substances, solvents, solubilizers, agents to achieve a retarding effect, salts to alter the osmotic pressure, agents of coating or antioxidants. They may also contain two or more compounds of the formulas I and II, and / or their physiologically tolerable salts and / or their prodrugs. In case a pharmaceutical preparation contains two or more compounds of the formulas I and II, the selection of the individual compounds may claim a general pharmacological profile of the pharmaceutical preparation. For example, a very powerful compound with a shorter duration of action can be combined with a long acting compound of less power. The allowable flexibility with respect to the selection of the susfifuyeníes in the compounds of the formulas I and allows a great amount of control in all the biological and physicochemical properties of the compounds and in this way allows the selection of said desired compounds. Also, in addition to at least one compound of the formulas I and the and / or of a physiologically tolerable salt and / or its prodrug, the pharmaceutical preparations may also contain one or more other therapeutic or prophylactically active ingredients. When the compounds of the formulas I and the, the dose can vary within wide limits and, as usual and is known by the doctor, it must be adequate to the individual conditions in each particular case. This depends, for example, on the specific compound used, on the nature and severity of the disease to be treated, or on the mode and schedule of administration, or on whether it is acute or chronic disease or whether it is carried out the prophylaxis. An appropriate dose can be created using clinical methods well known in the medical art. In general, the daily dose to achieve the desired results in an adult weighing approximately 75 kg is 0.01 mg / kg to 100 mg / kg, preferably 0.1 mg / kg to 50 mg / kg, in particular 0 , 1 mg / kg to 10 mg / kg (in each case in mg per kg of body weight). The daily dose can be divided, in particular in the case of administration of relatively large quantities, in several partial administrations, for example 2, 3 or 4. As usual, depending on each behavior it may be necessary to deviate upwards or downwards from the indicated daily dose. A compound of the formulas I and the anticoagulant can be used advantageously externally to a patient. For example, an effective amount of a compound of the invention may be put into a fresh blood sample to prevent coagulation of the blood sample. In addition, a compound of the formulas I and the salt thereof can be used for diagnostic purposes, for example for in vitro diagnosis, and as an aid in biochemical investigations. For example, a compound of formulas I and II can be used in an assay to identify the presence of factor Xa and / or factor Vlla or to isolate factor Xa and / or factor Vlla in a substantially purified form. A compound of the invention can be labeled, for example, with a radioisotope and the labeled compound bound to factor Xa and / or factor Vlla is then detected using a routine method useful for detecting the particular marker. Therefore, a compound of the formulas I and / or one of its salts can be used as a probe to detect the position or amount of factor Xa activity and / or factor Vlla in vivo, in vitro or ex vivo.

In addition, the compounds of formulas I and II can be used as intermediate products of synthesis for the preparation of other compounds, in particular of other pharmaceutically active ingredients, which can be obtained from the compounds of formulas I and example mediation the iníroducción of susíituyeníes or the modification of the functional groups. The general synthesis sequences for the preparation of the compounds useful in the present invention outlined in the examples are given below. Where applicable, both an explanation and the current procedure of the various aspects of the present invention are described. The following examples are intended to be merely illusory of the present invention, and not limiting thereof in scope or spirit. Those skilled in the art will readily understand that known variations of the conditions and methods described in the examples can be used to synthesize the compounds of the present invention. It is understood that changes that do not substantially affect the activity of the various embodiments of this invention are included within the invention disclosed herein. Therefore, the following examples are intended to illustrate but not limit the present invention.

EXAMPLES When an acid such as trifluoroacetic acid or acidic acid was used in the final stage of the synthesis of a compound, for example, when uro-fluoroacetic acid was used to remove a tBu group or when a compound was purified by chromatography using an eluyen that said acid was conferred, in some cases, depending on the work-up procedure, for example, the details of a lyophilization process, the compound was partially or completely obtained in the form of a salt of the acid used, for example in the form of the salt of the acetic acid, of the trifluoroacetic acid salt or of the hydrochloric acid salt.

Abbreviations used: NEt3 triethylamine HPLC liquid chromatography at high Bu4NI tetra-n-pressure iodide Cs2C03 butylammonium LiOH lithium hydroxide DCM cesium carbonate MeOH methanol DIEA dichloromethane MTBE methyl-butyl methyl ether (2-methoxy-DME ethyldiisopropylamine 2-methyl-propane) DMF 1 , 2-dimethoxy-ethane NBS N-bromosuccinimide EDCI N, N-dimethylformamide NCS N-chlorosuccinimide N- (3-dimethylamino-propyl) - NIS N-iodosuccinimide HATU N'-ethyl-carbodiimide POCI3 phosphorus oxychloride Hexafluorophosphate of PyBroP hexafluorophosphate bromo- Idimethylamino-tripyrrolidinophosphonium HOAt ([1,2,3] triazolo [4,5- RT ambient temperature b] pyridin-3-yloxy) -methylene] - TFA trifluoroacetic acid dimethylammonium THF tetrahydrofuran 1-hydroxy-7- azabenzotriazole- ( [1,2,3] triazolo [4,5- b] pyridin-1-ol) Example 1: 1- [5- (5-Chloro-thiophene) (1-isopropyl-piperidin-4-yl) -amide] -2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2-carboxylic acid (i) 1- [5- (5-chloro-thiophen-2-yl) -isoxazoI-3-ylmethyl] ethyl ester ] -1H-pyrrole-2-carboxylic acid To a solution of 1H-pyrrole-2-carboxylic acid ethyl ester (70 mg) in MeCN was added 3-bromomethyl-5- (5-chloro-thiophen-2-yl) - isoxazole (139 mg), CS2CO3 (180 mg), Bu4NI (2 mg) and hexa-n-decyltri-p-butyl phosphonium bromide (10 mg). The mixture was stirred for 4 h at 60 ° C, whereby the cooled to RT and concentrated in vacuo. The residue was partitioned between water and ethyl acetate. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over anhydrous MgSO 4 and concentrated in vacuo to give the ethyl ester of 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2-ethyl ester. -carboxylic acid (169 mg) that was used directly in the next stage. MS (ESI +): m / e = 337 [M + H] +, chlorine standard. (ii) 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1 H -pyrrole-2-carboxylic acid To a solution of ethyl ester of 1 - [5- ( 5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2-carboxylic acid (135 mg) in MeOH / THF / H2O (3: 1: 1), 5 ml) was added LiOH monohydrate (100 mg). The mixture was heated to reflux for 2 h after which it was cooled to RT and concentrated. The mixture was acidified by the addition of 1N aqueous KHSO4 solution and extracted with acetyl elyl. The combined organic phases were dried (MgSO4) and concentrated in vacuo to give the acid 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2-carboxylic acid. (148 mg) crude that was used directly in the next step. MS (ESI-): m / e = 307 [MH] ", chlorine standard, (iii) (1-isopropyl-piperidin-4-yl) -amide of 1- [5- (5-cyclo-thiophene-) 2-iI) -isoxazol-3-ylmethyl] -1 H -pyrrole-2-carboxylic acid 1- [5- (5-chloro-phofen-2-yl) -isoxazoI-3-ylmethyl] -1 H-pyrrole -2-carboxylic acid (62 mg) in DCM (5 ml) was added HOAi (27 mg), EDCI hydrochloride (38 mg) and DIEA (106 μl) The mixture was stirred for 30 min at RT. Dihydrochloride 1-sodium-piperidin-4-ylamine (47 mg) and DME (1 ml) and stirring was continued for 16 h at RT.The mixture was concentrated in vacuo and the residue was purified by preparative HPLC. the fractions containing the product to give 66 mg of 1- [5- (5-cyclo-thiophen-2-yl) -isoxazol-3-ylmethyl] 1- (1-isopropyl-piperidin-4-yl) -amide] - 1H-pyrrole-2-carboxylic acid as its trifluoroacetate salt, MS (ESI +): m / e = 433 [M + H] +, chlorine standard.

Example 2: 1- (3-methoxy-benzyl) -1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide. Following the procedure of example 1, substitution of 3-bromomethyl-5- (5 -chloro-f-pheno-2-yl) -isoxazole by 1-bromomethyl-3-methoxy-benzene in step (i), the (1-isopropyl-piperidin-4-yl) -amide of the 1- ( 3-methoxy-benzyl) -1H-pyrrole-2-carboxylic acid after purification by HPLC of the crude reaction mixture as its trifluoroacetate salt. MS (ESI +): m / e = 356 [M + H] +.

Example 3: 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -4-nitro-1H (1-isopropyl-piperidin-4-yl) -amide pyrrole-2-carboxylic Following the procedure of example 1 substituting the ethyl ester of 1-H-pyrrole-2-carboxylic acid for the ethyl ester of 4-nitro-1-H-pyrrole-2-carboxylic acid in the step ( i), after purification by HPLC of the crude reaction mixture, the 1- [5- (5-chloro-thiophene) (1-isopropyl-piperidin-4-yl) -amide of the acid was isolated. 2-yl) -isoxazoI-3-ylmethyl] -4-n-tro-1 H-pyrrole-2-carboxylic acid, like its trifluoroacetaium salt. MS (ESI +): m / e = 478 [M + H] +, chlorine payroll.

Example 4: 1- [5- (5-Chloro-iiophen-2-yl) -soxazo-3-ylmethyl] -3,5-dimefil- (1-isopropyI-piperidin-4-yl) -amide. 1-Hydro-2-carboxylic acid Following the procedure of Example 1, substituting the ethyl ester of 1-H-pyrrole-2-carboxylic acid for 3,5-dimethyl-1-H-pyrrole-2-ethyl ester. -carboxylic acid in step (i), after purification by HPLC of the crude reaction mixture, the 1- [5- (5-chloro-1-isopropyl-piperidin-4-yl) -amide was isolated from the thiophen-2-yl) -isoxazol-3-ylmethyl] -3,5-dimethyl-1H-pyrrole-2-carbo-xylic acid, such as its trifluoroacetate salt. MS (ESI +): m / e = 461 [M + H] +, chlorine standard. 1 Example 5: 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (perhydro-1, 4- (1-isopropyl-piperidin-4-yl) -amide) oxazepine-4-carbonyl) -1H-pyrrole-2-carboxylic acid (i) 4-formyl-1H-pyrrole-2-carboxylic acid methylester and 5-formyl-1H- methyl ester pyrrole-2-carboxylic acid Both formyl-pyrrole derivatives were prepared by adopting a procedure described by C. Schmuck, Tetrahedron 2001, 57, 3063: POCI3 (3.37 g) was added drop wise to DMF (1.61 g) under Ar at 0 ° C. The mixture was allowed to warm to RT after which it was diluted with DCM (11 ml). A solution of 1H-pyrrole-2-carboxylic acid meitylic ester (2.51 g) in DCM (11 ml) was added dropwise. The mixture was heated to reflux for 30 min, whereupon it was cooled to 10 ° C and quenched with a solution of poiasium acetamide (10.8 g) in water (28 ml). The phases were separated and the aqueous layer was exfoliated with MTBE. The combined organic phases were washed with saturated aqueous K 2 C 3 solution and concentrated in vacuo. The residue was purified by flash column chromatography on silica (ethyl acetate / heptane 1: 5) to give the methyl ester 4-formyl-1 H-pyrrole-2-carboxylic acid (589 mg) and the methyl ester -formyl-1H-pyrrole-2-carboxylic acid (1.60 g) as solids. (ii) 2-methylic acid ester of 1 H-pyrroyl-2,4-dicarboxylic acid: To a solution of 4-formyl-1 H-pyrrole-2-carboxylic acid methyl ester (589 mg) in acetone / water (50 ml). ml, 1: 1) was added a solution of KMnO4 in acetone / water (70 ml, 1: 1) dropwise for one hour. The mixture was stirred for 3 h at RT, whereupon it was poured into a solution of NaHSÜ3 (10% or in 1N HCl, 100 ml). The resulting mixture was extracted with ethyl acetate. The combined organic phases were washed with water and extracted with 2N aqueous solution of K2CO3. The basic aqueous phase was acidified with 2N HCl and extracted with ethyl acetate. The combined organic phases were dried (MgSO 4) and concentrated in vacuo to give the 2-methyl ester of 1 H-pyrrole-2,4-dicarboxylic acid (530 mg) which was used directly in the following step. (iii) 4 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid ephryl ester: Al 2 H-pyrrole-2,4-dicarboxylic acid 2-meityl ester (291 mg ) in DCM (18 mL) was added [1,4] oxazepane hydrochloride (236 mg), PyBroP (802 mg) and DIEA (878 μl). The mixture was stirred for 3 h at RT after which it was washed with saturated aqueous solution of NaHCOs in 1N HCl. The organic phase was dried (MgSO 4) and concentrated in vacuo. The residue was purified by flash column chromatography on silica (ethyl acetate) to give the eyl ester of 4 - ([1,4] oxazepane-4-carbonyl) -1 H -pyrrole-2-carboxylic acid (533 mg ). This material was used directly in the next step although traces of phosphine oxide impurities resulting from the coupling reagent were still present. (iv) 4 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid: To a solution of the above ester (434 mg) in eneol (16 ml) was added 1N NaOH (1 ml). 82 ml). The mixture was stirred for two days at room temperature, concentrated, acidified with 2N HCl and extracted with ethyl acetate. The combined organic phases were dried over anhydrous MgSO 4 and concentrated in vacuo to give 4 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid (293 mg) which was used directly in the next stage. (v) 4 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide: To the above carboxylic acid (293 mg) DCM (10 ml) was added HOAt (167 mg), EDCI hydrochloride (236 mg) and DIEA (627 μl). The mixture was stirred for 30 min at RT. 1-Isopropyl-4-ylamine dihydrochloride (265 mg) was added and stirring was continued for 16 h at RT. The reaction mixture was washed with 2N NaOH and concentrated. The residue was purified by flash column chromatography on silica (ethyl acetate / MeOH / NEt.3 20: 2: 1) to provide 4 - ([1-isopropyl-piperidin-4-yl) -amide of 4 - ( , 4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid, MS (ESI +): m / e = 363 [M + H] +. (vi) 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (perhydro-1,4-oxazepine) (1-isopropyl-pyridin-4-yl) -amide. -4-carbonyl) -1H-pyrrole-2-carboxylic acid: NaH (20 mg, 60% in mineral oil) was added to the above pyrrole (72 mg) in anhydrous DMF (2.5 ml). The mixture was stirred for 30 min at RT. A solution of 2-bromo-N- (5-chloro-pyridin-2-yl) -acetamide (49 mg) in DMF (0.5 ml) was added dropwise and stirring was continued for 5 h at RT. The mixture was quenched by dropwise addition of acetic acid, which was concentrated. The residue was purified by preparative HPLC. The fractions containing the product were evaporated to give 11 mg of 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -1- (1-isopropyl-plperidin-4-yl) -amide. perhydro-1,4-oxazepine-4-carbonyl) -1H-pyrroyl-2-carboxylic acid as its trifluoroacetate salt, MS (ESI +): m / e = 531 [M + H] +, chlorine standard.

Example 6: 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -5- (perhydro-1,4-oxazepine- (1-ylpropyl-4-yl) -amide) 4-carbonyl) -1H-pyrrole-2-carboxylic acid (i) The 2-methyl ester of 1 H-pyrrole-2,5-dicarboxylic acid was prepared according to the procedure described in example 5, step (ii) using 5-hydroxycarboxylic acid. -formyl-1H-pyrrole-2-carboxylic acid (ii) 5- (1-Isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid ethyl ester: To the above carboxylic acid (845 mg) in DCM (50 ml) was added HOAi (680 mg), EDCI hydrochloride (960 mg) and DIEA (2.55 ml). The mixture was agitated for 30 min at RT. 1-Isopropyl-4-ylamine dihydrochloride (1.08 g) was added and the stirring was continued for 16 h at RT. The reaction mixture was washed with saturated aqueous solution of KHCO3 and water and concentrated in vacuo to give 1.05 g of the 5- (1-isopropyl-p-peridin-4-ylcarbamoyl) -1H-pyrrole-3-ethyl ester 2-carboxylic acid which was used directly in the following step, (iii) 5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylate sodium: The previous ester was dissolved in ethanol (33). ml) and 1 N NaOH (3.58 ml). The solution was stirred for 3 days at RT and concentrated in vacuo to give crude 5- (1-isopropyI-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylate (1.05 g) which was used without further purification. (iv) 5 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid (1-ylpropyl-piperidin-4-yl) -amide was prepared by a carbodiimide-mediated coupling according to example 5, step (v) using the above carboxylate and [1,4] oxazepane hydrochloride as reagents. (v) 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -5- (1-isopropyl-piperidin-4-yl) -amide (perhydro-1,4-oxazepine-4-carbonyl) ) -1 H-pyrrole-2-carboxylic acid: Following the procedure of example 5 substituting the 4 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide by (1-isopropyl-piperidin-4-yl) 5 - ([1,4] oxazepane-4-carbonyl) -1H-pyrrole-2-carboxylic acid amide in step (vi), after purification by HPLC was isolated from the crude reaction mixture (1-) isopropyl-piperidin-4-yl) -amide of 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -5- (perhydro-1,4-oxazepine-4-carbonyl) -1H- pyrrole-2-carboxylic acid as its trifluoroacetate salt. MS (ESI +): m / e = 531 [M + H] +, chlorine standard.

Example 7: 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -l- (1-isopropyl-piperidin-4-yl) -amide (perhydro-1, 4) -oxazepine-4-carbonyl) -1H-pyrrole-2-carboxylic Following the procedure of Example 6 substituting 2-bromo-N- (5-chloro-pyridin-2-yl) -aceamide for 3-bromomethyl-5- (5 -chloro-thiophen-2-yl) -isoxazole in the isolate (v), after purification by HPLC of the crude reaction mixture, the (1-isopropyl-piperidin-4-yl) -amide of the acid 1 was isolated. [5- (5- chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (perhydro-1,4-oxazepine-4-carbonyl) -1H-pyrroyl-2-carboxylic acid as its trifluoroacetyl salt. MS (ESI +): m / e = 560 [M + H] +, chlorine standard.

Example 8: 3- [1 - [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -2 acid , 4-DimetiI-1H-pyrrol-3-yl3-propionic acid (i) 4- (2-Methoxycarbonyl-ethyl) -3,5-dimethyl-1H-pyrrole-2-carboxylic acid: Benzyl ester of acid was dissolved 4- (2-methoxycarbonyl-yl) -3,5-dimethyl-1H-pyrrole-2-carboxylic acid (390 mg, 1.24 mmol) in anhydrous MeOH (20 ml). The solution was evacuated and rinsed with argon several times. 120 mg of palladium on charcoal (10%) was added and the mixture was again evacuated and rinsed with argon several times. Finally, the argon was changed to hydrogen (balloon filled with hydrogen) and the mixture was stirred for 3 hours at room temperature. The reaction mixture was filtered over Celite and the filter residue was washed with MeOH (150 ml). The filtrate was concentrated in vacuo to give 4- (2-methoxycarbonyl-ethyl) -3,5-dimethy1H-pyrrole-2-carboxylic acid as a colorless solid (263 mg). MS (ESI-): m / e = 225 [M-H] ". (Ii) 3- [5- (1-Isopropyl-piperidin-4-ylcarbamoyl) -2 methyl ester, 4-dimethyl-1 H-pyrrol-3-yl] -propionic 263 mg (1.17 mmol) of 4- (2-methoxycarbonyl-etiI) -3,5-dimethyl-1H-pyrrole-2-acid were dissolved. carboxylic acid in DMF (10 ml). 488.4 mg (1.28 mmoles) of HATU and DIEA (224 μl) and. The resulting mixture was stirred for 45 minutes at RT. A solution of 276.3 mg (1.28 mmol) of 1-isopropyl-piperidine-4-ylamine dihydrochloride and 448 μl of DIEA was added. The reaction mixture was stirred overnight, after which it was concentrated. The residue was diluted with DCM and washed with a saturated solution of NaHCO3 and brine. The organic layer was dried over MgSO 4 and concentrated. Preparation HPLC (gradient CH3CN / H2? + 0.05% formic acid) gave 3- [5- (1-isopropyl-piperidin-4-ylcarbamoyl) -2,4-dimethyl-1H-pyrrole methyl ester -3-yl] -propionic (166 mg) as a colorless amorphous material. MS (ESI +): m / e = 351 [M + H] 0 (iii) 3- [1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] - methyl ester - 5- (1-isopropyl-piperidin-4-ylcarbamoyl) -2,4-dimetiI-1H-pyrrol-3-yl] -propionic 55 mg (0.16 mmol) of 3- [5- methyl ester] were dissolved (1-isopropyl-piperidin-4-ylcarbamoll) -2,4-dimethyl-1H-pyrrol-3-yl] -propionic acid in DMF (5 ml). Subsequently, 103 mg (2 equiv.) Of CS2CO3 were added and 65.8 mg (1.5 equiv.) Of 3-bromomethyl-5- (5-chloro-thiophen-2-yl) -isoxazole and the resulting mixture were added. it was stirred for 4 h at 80 ° C. Due to the low conversion, 206 mg (4 equiv.) Of CS2CO3 was added, stirring was continued for 7 h at 80 ° C. The reaction mixture was acidified by the addition of acetic acid and concentrated. The residue was purified by preparative HPLC (gradient CH3CN / H2O + 0.05% formic acid) to give 3- [1- [5- (5-chloro-phenyl-2-yl) - methyl ester - isoxazoI-3-ylmethyl] -5- (1-isopropyl-plperidin-4-ylcarbamoyl) -2,4-dimethyl-1H-pyrrol-3-yl] -propionic acid (34 mg) as a colorless amorphous material. MS (ES40): m / e = 548 [M + H] +, chloro pattern. (iv) 3- [1 - [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -2,4-dimethyl acid -1H-pyrroI-3-yl] -propionic A 34 mg (0.06 mmol) of 3- [1- [5- (5-cyclo-iiophen-2-yl) -isoxazoI-3-ylmethyl) methyl ester ] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -2,4-dimethyl-1H-pyrrol-3-yl] -propionic acid in MeOH (4 mL) was added 1M aqueous solution of LiOH (0.3 mL) ) and the resulting mixture was stirred at 60 ° C for 5 h. The mixture was acidified by the addition of a 1M HCl solution (pH = 5) and concentrated under reduced pressure. The final purification by preparative HPLC (free CH3CN / H2O + 0.05% formic acid) gave the acid 3- [1- [5- (5-chloro-thiophen-2-yl) -isoxazole-3-ylmei l] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -2,4-dimethyI-1 H-pyrrol-3-yl] -propionic acid as a colorless amorphous material. The product was obtained as its hydroformate (11 mg). MS (ESI +): m / e = 534 [M + H] +, chlorine standard.

Example 9: 1- [5- (5-Chloro-thiophen-2-yl) -soxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1 H-pyrrole benzyl ester -2-carboxylic acid (i) 5-formyl-1H-pyrrole-2-carboxylic acid benzyl ester and 4-formyl-1H-pyrrole-2-carboxylic acid benzyl ester: A DMF (5.93 g) was added POCI3 (12.45 g) dropwise at 0 ° C. The mixture was warmed to RT, diluted with DCM (40 ml) and cooled again to 0 ° C. A solution of 1 H-pyrrole-2-carboxylic acid benzyl ester (15.00 g, prepared by adopting a procedure of J. Barry, G. Bram and A. Petií, Heterocycles 1985, 23, 875-880) in DCM ( 40 ml) was added dropwise at a rate at which the temperature of the reaction mixture did not increase above 0 ° C. The reaction was refluxed for 30 min after which it was cooled to 10 ° C. A solution of sodium acetate (28 g) in water (90 ml) was carefully added. After stirring for 15 min, the two resulting phases were separated and the aqueous phase was washed with DCM (3 * 75 ml). The combined organic phases were washed with saturated Na 2 CO 3 solution and brine, dried over MgSO 4 and concentrated. The residue was purified by flash column chromatography on silica (ethyl acetate / hepyan 1: 2) to give the benzyl ester of 5-formyl-1H-pyrroyl-2-carboxylic acid (8.0 g) and the ester 4-formyl-1H-pyrroyl-2-carboxylic acid benzyl ester (4.0 g). (ii) 1H-pyrrole-2,5-dicarboxylic acid monobenzyl ester: To a solution of 5-formyl-1H-pyrrole-2-carboxylic acid benzyl ester (8.0 g) in n-butanol (300 ml) and water (112 ml) was added sodium dihydrogen phosphate (6.28 g), sodium chlorite (9.47 g) and isobutene (58 g). The mixture was stirred for 20 h at RT after which it was concentrated. After purification of the residue by flash column chromatography on silica (DCM / MeOH 15: 1 to 1: 1), 10.0 g of 1H-pyrroyl-2,5-dicarboxylic acid monobenzyl ester were obviated. (iii) 5- (1-Isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid benzyl acid: A few drops of DMF were added to the above acid (1.72 g) in DCM (35). mi) followed by slow addition of oxalyl chloride (1.34 g). The mixture was refluxed for 3 h and then concentrated. To a solution of the acid chloride resulting in THF was added 1-isopropyl-piperidin-4-ylamine (1.00 g) and NE3 (3.89 ml) in THF (35 ml). The resulting mixture was stirred for 20 h at RT whereupon it was concentrated. The residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The phases were separated and the organic layer was washed with saturated aqueous NaHCO3 solution and brine, dried over MgSO4 and concentrated. Preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) gave the benzyl ester of 5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrroyl-2-carboxylic acid (287 mg). (iv) Benzyl acid 1- [5- (5-chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2 acid benzyl ester carboxylic acid: To a solution of the benzyl ester of 5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid (20 mg) in DMF (1 ml) was added Cs2CO3 (71 mg). The mixture was stirred for 30 min at RT. 3-Bromomethyl-5- (5-chloro-iiophen-2-yl) -isoxazole (15 mg) was added and the stirring was continued for 20 h at RT after which the mixture was filtered. The filtrate was subjected directly to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA). Benzyl ester of 1- [5- (5-chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1 H -pyrrole-2-benzyl ester was obtained -carboxylic (15 mg) pure as its urea-fluoride salt. MS (ESI +): m / e = 567 [M + H] +, chlorine standard.

Example 10: 1- [5- (5-Chloro-thiophen-2-yl) -isoxazo-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-1-methyl ester 2-carboxylic acid The product was obtained by transeslerification of the product of example 9, step (iv): The crude reaction mixture of example 9, step (iv) was triturated with MeOH for a few minutes after which it was filtered and concentrated . After the HPLC preparation (gradient CH3CN / H2O + TFA 0.05%) of the residue, the methyl ester of 1 - [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] was obtained] -5- (1-ylpropyl-piperidin-4-ylcarbamoyl) -1H-pyrroyl-2-carboxylic acid as its urea trifluoroacetate salt. MS (ESf): m / e = 491 [M + H] +, chlorine buffer.

Example 11: 1- [5- (5-Chloro-iiophen-2-yl) -isoxazo-3-ylmethyl] -5- (1-isopropyl-plperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid A a solution of 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic (example 10, 30 mg) in 5 ml of THF / water (3: 1) was added LiOH (9 mg). The mixture was stirred for 2 h at 45 ° C after which it was cooled to RT, acidified with TFA and concentrated. After the preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) of the residue, 1- [5- (5-chloro-1-ylphen-2-yl) -isoxazol-3-ylmethyl] -5- acid was obtained. (1-isopropyl-piperidin-4-ylcarbamoyl) -1 H-pyrrol-2-carboxylic acid. MS (ESI +): m / e = 477 [M + H] +, chlorine standard.

Example 12: 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid benzyl ester (i) Ester 1 H-Pyrrole-2,4-dicarboxylic acid benzyl ester: Following the procedure of Example 9, efapa (ii), the benzyl ester of 1H-pyrrole-2,4-dicarboxylic acid was obtained from the oxidation of the benzyl ester of the 4-formyl-1H-pyrrole-2-carboxylic acid. (ii) 4- (1-Isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid benzyl ester: This compound was obtained following the procedure of example 9, step (iii) by substituting the ester 1 H-pyrrole-2,5-dicarboxylic acid monobenzyl ester by the 2-benzyl ester of 1 H-pyrrole-2,4-dicarboxylic acid. (iii) 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid benzyl ester: To a solution of the benzyl ester of 1H-pyrrole-2,4-dicarboxylic acid (50 mg) in DMF (2 ml) was added Cs2CO3 (176 mg), followed by 2-bromo-N- (5-chloropyridine). 2-yl) -aceamide (34 mg). The mixture was stirred for 20 h at RT after which it was filtered. The filtrates were directly subjected to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA). The benzyl ester of 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid benzyl ester (28, 5 mg) as its urea fluoride salt. MS (ESI +): m / e = 538 [M + H] +, chlorine standard.

Example 13: Benzyl ester of 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -4- (1-yl-propyl-piperidin-4-ylcarbamoyl) -1 H -pyrrole- 2-carboxylic acid This compound was prepared following the procedure of example 12 substituting 2-bromo-N- (5-chloro-pyridin-2-yl) -aceamide for 3-bromomeyyl-5- (5-chloro-iiophen-2-yl). ) -isoxazoI. After the preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) it was obtained as its urea fluoride. MS (ESI +): m / e = 567 [M + H] +, chlorine payroll.

Example 14: 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -4-nitro-1 H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide (i) 4-Nifro-1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide: To 4-nitro-1H-pyrrole-2-carboxylic acid (200 mg) in DCM (10 ml) ) was added DIEA (436 μl), HATU (436 mg) and 1-isopropyl-piperidin-4-ylamine (182 mg). The mixture was stirred for 1 h at RT and concentrated. The residue was purified by HPLC to give (1-isopropyl-piperidin-4-yl) -amide of 4-nitro-1H-pyrroyl-2-carboxylic acid as its frifluoroacetic salt (50 mg). (ii) 1 - [(5-Chloro-plridin-2-ylcarbamoyl) -methyl] -4-yl-1H-pyrrole-2-carboxylic acid (1-isopropyI-piperidin-4-yl) -amide: A 4-Nitro-1 H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide trifiuoroacetyl salt solution (30 mg) in DMF (4 ml) was added Cs2CO3 (70 mg). The mixture was stirred for 30 min at RT after which 2-bromo-N- (5-chloro-pyridin-2-yl) -acelamide (27 mg) was added. The agitation was continued for 2 h at RT. The mixture was filtered and subjected directly to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) to give (1-isopropyl-piperidn-4-yl) -amide of 1 - [( 5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4-nitro-1 H-pyrrole-2-carboxylic acid (15 mg) as its trifluoroacetyl salt. MS (ESI +): m / e = 449 [M + H] +, chlorine payroll.

Example 15: 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid methyl ester Obtained the product by transesterification of the product of example 12: The crude reaction mixture of example 12 was disintegrated with MeOH for a few minutes after which it was filtered and concentrated. After the HPLC preparation (gradient CH3CN / H2O + TFA 0, 05%) of residue was obfuve the methyl ester of acid 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2 -carboxylic like its urea fluoride acetate. MS (ESI +): m / e = 462 [M + H] +, chlorine standard.

Example 16: 1- [5- (5-Chloro-phofen-2-yl) -isoxazol-3-ylmethyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-1-methyl ester -2-carboxylic acid The production was achieved by fransesitification of the product of Example 13: The reaction mixture in Example 13 was broken up with MeOH lasted a few minutes after which it was filtered and concentrated.

After preparative HPLC (CH3CN / H2O + 0.05% TFA gradient) of the residue, the 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmefyl] -methyl ester was obtained. 4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid as its trifluoroacetate salt. MS (ESI +): m / e = 491 [M + H] +, chlorine standard.

Example 17: 1 - [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrroyl-2-carboxylic acid LiOH monohydrate (50 mg) was added to a solution of 1- [5- (5-chloro-thiophen-2-yl) -isoxazoI-3-ylmefyl] -4- (1-isopropyl-piperidin-4) methyl ester. -carbamoyl) -1 H-pyrroyl-2-carboxylic acid (example 16, 60 mg) in 15 ml of THF / water (3: 1). The mixture was stirred for 2 h at 45 ° C whereupon it was cooled to RT, acidified with TFA and concentrated. After purification by HPLC (gradient CH3CN / H2O + TFA 0.05%) of the crude product, 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] - 4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid. MS (ESI +): m / e = 477 [M + H] +, chlorine buffer.

Example 18: 1- [5- (5-Chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -5- (3-meloxy-azeidine) (1-isopropyl-piperidin-4-yl) -amide. -1-carbonyl) -1 H-pyrrole-2-carboxylic acid To a solution of 1- [5- (5-cyclo-thiophen-2-yl) -isoxazol-3-ylmethyl] -4- (1-isopropyl- piperidin-4-ylcarbamoyl) -1 H-pyrrole-2-carboxylic acid (example 17.9 mg) in DCM (2 ml) was added HATU (7.2 mg), DIEA (13 μl) and 3-methoxy- azetidine. The mixture was stirred for 1 h at RT and then concentrated.

The residue was purified by preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) to give 1- (5- (5-cyclophofophen-1-isopropyl-piperidin-4-yl) -amide) 2-yl) -isoxazol-3-ylmethyl] -5- (3-meioxy-azeidin-1-carbonyl) -1H-pyrroI-2-carboxylic acid (4.3 mg) as its urea-trifluoroacetate salt. MS (ESI +): m / e = 546 [M + H] +, chlorine standard.

Example 19: 2 - [(1-isopropyl-piperidin-4-yl) -amide 5 - [(2-methoxy-efyl) -amide] of 1- [5- (5-cyclo-thiophene-2-yl)] -isoxazol-3-ylmethyl] -1H-pyrrole-2,5-dicarboxylic acid This compound was prepared following the procedure described in Example 18 by substituting 3-methoxy-azetidine for 2-methoxy-eylamine. After purification by HPLC (gradient CH3CN / H2O + TFA 0.05%) of the crude product was obtained 2 - [(1-isopropyl-piperidin-4-yl) -amide 5 - [(2-methoxy-ethyl) -amide] of 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1 H -pyrrole-2,5-dicarboxylic acid as its urea fluoride. MS (ESI +): m / e = 534 [M + H] +, chlorine buffer.

Example 20: 2 - [(1-isopropyl-piperidin-4-yl) -amide 5 - [(2-methoxy-ellyl) -methyl-amide] of 1- [5- (5-chloro-iiophenol- 2-yl) -isoxazol-3-ylmethyl] -1H-pyrrol-2,5-dicarboxylic acid This compound was prepared following the procedure described in Example 18 substituting 3-methoxy-azetidine for (2-meloxy-eyl) - methylamine After purification by HPLC (gradient CH3CN / H2O + TFA 0.05%) of the crude product was obtained 2 - [(1-isopropyl-piperidin-4-yl) -amide 5 - [(2-methoxy-ethyl) -methyl-amide] of 1- [5- (5-chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2,5-dicarboxylic acid as its urea fluoride. MS (ESI +): m / e = 548 [M + H] +, chlorine standard.

Example 21: 1- [5- (5-Chloro-thiophen-2-yl) -isoxazoI-3-ylmethyl] -5-phenyl-1 H-pyrrole (1-isopropyl-piperidin-4-yl) -amide. 2-Pheni-1 H -pyrrol-2-carboxylic acid (1) -I- (1-isopropyl-piperidin-4-yl) -amide: A 1-isopropyl-piperidin-4-ylamine (350 mg) in DCM (15 ml) was added DIEA (1.67 ml), followed by HATU (935 mg) and 5-phenyl-1H-pyrrole-2-carboxylic acid (461 mg). The mixture was stirred for 1 h at RT after which it was washed twice with saturated aqueous solution of NaHC 3, dried over MgSO 4 and concentrated to give (1-isopropyl-piperidin-4-yl) -amide of the crude 5-phenyl-H-pyrrole-2-carboxylic acid which was used directly in the next step. (ii) 1- [5- (5-chloro-thiophen-2-yl) -isoxazoI-3-ylmethyl] -5-phenol-1H- (1-isopropyl-piperidin-4-yl) -amide. pyrrol-2-carboxylic acid: To a solution of (1-isopropyl-piperidin-4-yl) -amide of 5-phenyl-1H-pyrrol-2-carboxylic acid (50 mg) in DMF (2 mg). ml) was added CS2CO3 (105 mg). The mixture was stirred for 30 min at RT. 3-Bromomethyl-5- (5-chloro-thiophen-2-yl) -isoxazole (45 mg) was added and the stirring was continued for 3 h at RT. The mixture was filtered and subjected directly to preparative HPLC (CH 3 CN / H 2 O + 0 TFA gradient)., 05%) to give 1- (5- (5-chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -5-phenyl-1H (1-isopropyl-piperidin-4-yl) -amide. -pyrrole-2-carboxylic acid (15 mg) as its urea-trifluoroacetate salt. MS (ESI +): m / e = 509 [M + H] +, chlorine payroll.

Example 22: 1- [5- (5-Chloro-1-phenyl-2-yl) -isoxazol-3-ylmethyl] -3,5-dimethylamino-4-yl-1-isopropy! -piperidin-4-yl) -amide. - (perhydro-1, 4-oxazepine-4-suIfoniI) -1 H-pyrroI-2-carboxylic acid (i) 3,5-Dimethyl-4 - ([1,4] oxazepane-4-suIfoniI) ethyl ester -1H-pyrrole-2-carboxylic acid: To [1,4] oxazepane hydrochloride (400 mg) in DCM (45 ml) was added DIEA (2.70 ml) followed by ethyl ester of 4-chlorosulfonyl-3,5- dimethyl-1H-pyrroyl-2-carboxylic acid (1.05 g). The mixture was stirred for 1 h at RT after which water was added and the two resulting phases were separated. The organic phase was washed twice with a saturated aqueous solution of NaHCO 3, dried over MgSO 4 and concentrated to give the 3,5-dimethylamino-4 - ([1,4] oxazepane-4-sulfonyl) -1H ethyl ester. -pyrrole-2 carboxylic acid (970 mg) which was used directly in the next step. (ii) 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -3,5-dimethyI-4 - ([1,4] oxazepane-4-sulfonyl) ethyl ester ) -1 H-pyrrole-2-carboxylic acid: To a solution of 3,5-dimethyl-4 - ([1,4] oxazepane-4-sulfonyl) -1 H-pyrrole-2-carboxylic acid ethyl ester (100 g) ) in DMF (5 ml) was added Cs2CO3 (197 mg). The mixture was stirred for 30 min at RT after which 3-bromomethyl-5- (5-chloro-lyophen-2-yl) -isoxazole (84 mg) was added. Stirring was continued for 20 h at RT after which the mixture was filtered and directly subjected to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) to give the erythyl ester of 1 - [5- (5 -chloro-lyofen-2-yl) -isoxazol-3-ylmellyl] -3,5-dimethyIyl-4 - ([1,4] oxazepane-4-sulfonyl) -1H-pyrrole-2-carboxylic acid (100 mg). (iii) 1- [5- (5-Chloro-thiophen-2-yl) -isoxazo-3-ylmethyl] -3,5-dimethyl-4 - ([1,4] oxazepano-4) acid sulfonyl) -1H-pyrrole-2-carboxylic acid: To a solution of [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -3,5-dlmeiyl-4- ( [1,4] oxazepane-4-sulfonyl) -1H-pyrrole-2-carboxylic acid (100 mg) in 20 ml of THF / water (3: 1) was added LiOH monohydrate (200 mg). The mixture was stirred for 2 h at 45 ° C and lasted 6 h at 60 ° C whereupon it was cooled to RT, concentrated, acidified with 2M HCl to pH = 2 and extracted with DCM (3 x 30 ml). The combined organic layers were dried (MgSO4) and concentrated to give the acid 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmefyl-3,5-dimei il-4 - ([ 1,4] oxazepane-4-sulfonyl) -1 H-pyrrole-2-carboxylic acid (80 mg) which was used directly in the next step, (iv) (1-isopropyl-piperidin-4-yl) -amide of the acid 1- [5- (5-chloro-iiophen-2-yl) -isoxazoI-3-ylmethyl] -3,5-dimetyl-4- (perhydro-1,4-oxazepine-4-suphonyl) -1H-pyrrole- 2-carboxylic acid: 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -3,5-dimethyl-4 - ([1,4] oxazepane-4-sulfonyl) -1H-pyrrole-2-carboxylic acid (80 mg) in DCM (5 ml) was added DIEA (110 μl), HATU (61 mg) and 1-isopropyl-piperidin-4-ylamine (23 mg). The mixture was stirred for 1 h at RT, which was concentrated. The residue was purified by preparative HPLC to give 1- (5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -l (1-isopropyl-piperidin-4-yl) -amide. , 5-dimethyl-4- (perhydro-1,4-oxazepine-4-sulfonyl) -1H-pyrrole-2-carboxylic acid as its trifluoroacetate salt (90 mg). MS (ESI +): m / e = 623 [M + H] +, chlorine standard.

Example 23: 4-bromo-1- [5- (5-chloro-iiophen-2-yl) -isoxazole-3-ylmethyl] -3,5-lido (4-bromo-1- [5- (5-chloro-iiophen-2-yl) -isoxazole-3-ylmethyl] -3,5-amino acid (1-isopropyl-piperidin-4-yl) -amide. -dimethyl-1H-2-carboxylic acid (i) 4-bromo-3,5-dimethy1H-pyrrole-2-carboxylic acid: 4-bromo-3,5-dimethyl-1H-pyrrole-2-ethyl ester -carboxylic acid (900 mg) was added 10 ml of a solution of boronibromide (1M) in DCM. The mixture was stirred at RT for 16 h (h), then heated to reflux for 5 h. To complete the reaction, pure boron tribromide (1.5 ml) was added dropwise and the mixture was refluxed for 3 h. After cooling to RT the mixture was poured into crushed ice and exfoliated with DCM. The combined organic phases were filtered through a plug of diatomaceous earth and concentrated under reduced pressure to give 4-bromo-3,5-dimethyl-1H-pyrrole-2-carboxylic acid (1.2 g) which was used directly in the next stage, (ii) 4-bromo-3,5-dimethyl-1H-pyrrole-2-carboxylic acid (1-ylpropyl-piperidin-4-yl) -amide: To 4-bromo-3,5-dimethyl acid -1 H-pyrrole-2-carboxylic acid (570 mg) in DCM (15 mL) was added DIEA (2.11 g), HATU (994 mg) and 1-isopropyl-piperidin-4-ylamine (372 mg). The mixture was stirred for 16 h at RT after which it was concentrated. The residue was purified by preparative HPLC to give the (1-isopropyl-piperidin-4-yl) -amide of 4-bromo-3,5-dimetyl-1H-pyrrole-2-carboxylic acid (65 mg) which it was used directly in the following period. (Ii) (1-isopropyl-piperidin-4-yl) -amide of 4-bromo-1- [5- (5-chloro-thiophen-2-yl) -isoxazole-3-methylmethyl] - 3,5-Dimethyl-1H-pyrrol-2-carboxylic acid: To a solution of 4-bromo-3,5-dimefi-1H-pyrrole (1-isopropyI-piperidin-4-yl) -amide -2- carboxylic acid (33 mg) in a mixture of DMF (2 mL) and DCM (2 mL) was added Cs2CO3 (62 mg). The mixture was stirred for 30 min at RT whereupon 3-bromomethyl-5- (5-cyclo-thiophen-2-yl) -isoxazole (84 mg) was added. The mixture was stirred for 1 h at RT. Cs 2 C 3 (62 mg) was added and stirring was continued for 48 h at RT after which the mixture was filtered and concentrated. The residue was subjected to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) to give 4-bromo-1- [5- (5-hydroxy-1-hydropropyl-piperidin-4-yl) -amide). -chloro-thiophen-2-yl) -isoxazoI-3-ylmethyl] -3,5-dime-lyl-1H-pyrrole-2-carboxylic acid as its trifluoroacetafo salt (9 mg). MS (ESI +): m / e = 539 [M + H] +, chlorine payroll.

Example 24: 4-Bromo-1 - [(5-cioro-pyridin-2-ylcarbamoyl) -methyl] -3,5-dimethy1-H-pyrrolene (1-isopropyl-piperidin-4-yl) -amide -2-carboxylic acid (i) 4-Bromo-1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -3,5-dimethyl-1H-pyrrole-2-carboxylic acid eyl ester: To one solution of the 4-bromo-3,5-dimethyl-1H-pyrroyl-2-carboxylic acid ethyl ester (492 mg) in DMF (5 ml) was added Cs2CO3 (912 mg). The mixture was stirred for 30 min at RT after which 2-bromo-N- (5-chloro-pyridin-2-yl) -acetamide (499 mg) was added. Stirring was continued for 2 h at RT after which the mixture was filtered and concentrated. The residue was subjected to preparative HPLC (gradient CHsCN / H2O + 0.05% TFA) to give the ethyl ester of 4-bromo-1 - [(5-chloro-pyridin-2-carbamoyl) -methyl] -3,5-dimethyI-1H-pyrrole-2-carboxylic acid (220 mg). (ii) 4-Bromo-1 - [(5-chloro-pyridin-2-ylcarbamoyl) -meiyl] -3,5-dimethy1-H-pyrrole-2-carboxylic acid: To 220 mg of the above ester was added drop drop boron bromide (1.5 ml). The mixture was refluxed for 8 h. Additional boron-bromide (1.5 ml) was added dropwise. Reflux was continued for 3 h after which the mixture was poured into crushed ice and cooled to RT. The phases were separated and the aqueous phase was extracted with DCM. The combined organic phases were washed with brine, dried (MgSO) and concentrated in vacuo to give the acid 4-bromo-1 - [(5-chloro-pyridin-2-ylcarbamoyl) -methyl] -3.5 -dimetiI-1 H-pyrrole-2-carboxylic acid (200 mg) which was used directly in the next step, (iii) (4-bromo-1) -amido-1-piperidin-4-yl) -amide - [5- (5-Chloro-thiophen-2-yl) -isoxazoyl-3-ylmethyl] -3,5-dimethyl-1H-pyrrole-2-carboxylic acid: To the above crude acid (200 mg) in DCM (2). ml) was added DIEA (33 mg), HATU (49 mg) and 1-isopropyl-piperidin-4-ylamine (18 mg). The mixture was stirred for 16 h at RT after which it was concentrated. The residue was subjected to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) to give 4-bromo-1 - [5- (4-bromo-1 - [5- (4-bromo-1-yl) -amido] 5-chloro-thiophen-2-yl) -isoxazoI-3-ylmethyl] -3,5-dimef-1-1H-pyrrole-2-carboxylic acid as its urea fluoride (19 mg). MS (ESI +): m / e = 510 [M + H] +, chlorine standard.

Example 25: 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -4-formyl-1-isopropyl-piperidin-4-yl) -amide, 5-Dimethyl-1H-pyrrole-2-carboxylic acid (i) 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -4-formyl-3 ethyl ester, 5-dimethyI-1H-pyrrol-2-carboxylic acid: To 4-formyl-3,5-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester (2.60 g) in DMF (26 ml) was added. added Cs2CO3 (6.51 g). The mixture was stirred for 30 min at RT, then 3-bromometyl-5- (5-chloro-iiophen-2-yl) -isoxazoI (3.71 g) was added. The agifation was continued for 2 h at RT. Water was added and the phases were separated. The aqueous phase was extracted with DCM. The combined organic phases were washed with brine, dried (MgSO) and concentrated under reduced pressure to give the ethyl ester of 1- [5- (5-cyoro-thiophen-2-yl) -isoxazole-3-ylmethyl] -4-formyl-3,5-dimethyl-1H-pyrrole-2-carboxy! Co (4.20 g), which was used directly in the next layer without further purification. (ii) 1- [5- (5-Chloro-thiophen-2-yl) -soxazol-3-ylmethyl] -4-formyl-3,5-dimethyl-1H-pyrrole-2-carboxylic acid: To a solution of the To the lower ester in a mixture of THF (7.5 ml) and water (2.5 ml) was added monohydroxy hydroxide (55 mg). The mixture was stirred for 2 h at 60 ° C. Additional lithium hydroxide monohydrate (60 mg) was added and the mixture was refluxed for 4 h. After cooling to RT, the mixture was concentrated, acidified to pH 3 with 2N HCl and extracted with ethyl acetate. The combined organic phases were washed with brine, dried (MgSO 4) and concentrated under reduced pressure to give the acid 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -4- crude formyl-3,5-dimethyl-1H-pyrrole-2-carboxylic acid (100 mg) which was used directly in the next step. (iii) 1- [5- (5-Chloro-thiophen-2-yl) -isoxazol-3-methylmethyl] -4-formyl-3-1-isopropyl-piperidin-4-yl) -amide., 5-dimethyl-1H-pyrrole-2-carboxylic acid: To the above acid (100 mg) in DCM (2 ml) was added DIEA (142 mg), HATU (104 mg) and 1-isopropyl-piperidin-4-ylamine ( 39 mg). The mixture was stirred for 2 h at RT after which it was concentrated. The residue was subjected to preparative HPLC (gradient CH3CN / H2O + 0.05% TFA) to give 1- (5- (5-chloro-iiophen) (1-isopropyl-piperidin-4-yl) -amide. -2-yl) -isoxazol-3-ylmethyl] -4-formyl-3,5-dimethyl-1 H-pyrrole-2-carboxylic acid as its urea fluoride (101 mg). MS (ESI +): m / e = 489 [M + H] +, chlorine payroll.

Pharmacological assay The ability of the compounds of the formulas I and that to inhibit factor Xa or factor Vlla or other enzymes such as thrombin, plasmin or trypsin can be evaluated by determining the concentration of the compound of the formulas I and that which inhibits 50% of enzymatic activity, that is, the index IC50, which was related to the inhibition constant K¡. Purified enzymes were used in chromogenic assays. The concentration of inhibitor that produces a 50% decrease in the rate of hydrolysis of the substrate was determined by linear regression after plotting the relative rates of hydrolysis (compared to the uninhibited reference) versus the log of the concentration of the compound of the formulas I and the. To calculate the inhibition constant K, the IC5o index for the competitiveness with the substrate was corrected using the formula K, = IC5o /. { 1 + (substrate concentration / Km)} where Km is the constant of Michaelis-Menten (Chen and Prusoff, Biochem Pharmacol 22 (1973), 3099-3108, IH Segal, Enzyme Kinetics, 1975, John Wiley &Sons, New York, 100-125; which are incorporated herein by reference. a) Analysis of factor Xa In the analysis for the determination of the inhibition of factor Xa activity, the TBS-PEG buffer (50 mM Tris-HCl, pH 7.8, 200 mM NaCl, 0 PEG-8000, 05% (w / v), NaN3 at 0.02% (w / v)). IC50 was determined by combining in appropriate wells of a Costar half-area microtiter plate 25 μl human factor Xa (Enzyme Research Laboratories, Inc., South Bend, Indiana) in TBS-PEG; 40 μl of 10% DMSO (v / v) in TBS-PEG (reference not inhibited) or various concentrations of the compound to be tested diluted in 10% DMSO (v / v) in TBS-PEG; and substrate S-2765 (N (a) -benzyloxycarbonyl-D-Arg-Gly-L-Arg-p-nitroanilide; Kabi Pharmacia, Inc.; Franklin, Ohio) in TBS-PEG. The analysis was carried out preincubando the compound of the formulas I and the enzyme plus during 10 min. The analysis was then started by adding substrate until a final volume of 100 μl was obtained. The initial rate of hydrolysis of the chromogenic substrate was measured by changing the absorbance at 405 nm using the kinetic plate reader of Bio-tek Insírumenfs (Ceres UV900HDÍ) at 25 ° C during the linear part of the time course (usually 1, 5 min after the addition of the substrate). The enzyme concentration was 0.5 nM and the substrate concentration was 140 μM. b) Vlla factor analysis The inhibitory activity activity was determined for the factor Vlla / tissue factor using essentially a chromogenic analysis as described above (JA Osírem et al., Biochemistry 37 (1998) 1053-1059 which is incorporated). to this report as a reference Kinetic analyzes were performed at 25 ° C on medium-area microtiter plates (Costar Corp., Cambridge, Massachusetts) using a cinefic plate pattern (Molecular Devices Specíramax 250) .A typical analysis consisted of 25 μl of human Vlla factor and TF (5 nM and 10 nM, respective final concentration) combined with 40 μl of inhibitor dilutions in 10% DMSO / TBS-PEG buffer (50 mM Tris, 15 mM NaCl, 5 mM CaCl2, PEG 8000 0.05%, pH 8.15) After about 15 minutes of preincubation period, the analysis was initiated by the addition of 35 μl of the chromogenic substrate S-2288 (D-Ile-Pro-Arg-p-nitroanilide, Pharmacia Hepar Inc., final concentration 5 00 μM) The results (constaníes of inhibition K¡ (FXa) for the Inhibition of factor Xa) are presented in Table 1. Table 1

Claims (9)

CLAIMS A compound of the formulas I and the, wherein R ° is 1) an aryl of 6 to 14 monocyclic or bicyclic elements, of the phenyl, naphthyl, biphenyl, anthryl or fluorenyl group, wherein the aryl is mono-, di- or tri-substituted independently of one another by R 8, ) a heterocyclyl of the benzimidazolyl, 1,3-benzodioxoyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiopyl, benzothiophenyl, cinolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl group , pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R8, or 3) a heterocyclyl of the group azabenzimidazolyl, benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, chromanyl, cinolinyl, 2-furyl, 3-furyl; imidazolyl, indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl, isofiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pyridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl, pyrrolyl; 2-pyrrolyl, 3-pyrroleyl, quinolinyl, quinazolinyl, quinoxalinyl, tetrazolyl, lyazolyl, 2-thienyl or 3-thienyl, which is further substituted with a heterocyclyl selected from the group of acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxathiolyl, benzothiazolyl, benzotriazolyl, benzotefrazolyl, benzisoxazolyl, benzisoyiazolyl, carbazolyl, 4aH-carbazoyl, carbolinyl, chromanyl, chromanyl, cinolinyl, decahydroquinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl , 1,3-dioxolenium, 6H-1,5,2-dihiazinyl, dihydrofuro [2,3-b] -tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H- indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isox azolinyl, isoxazolidinyl, 2-isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ceopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,3-oxadiazolyl, 1,4-oxadiazolyl, 1, 2,5-oxadiazolyl, 1, 3,4-Oxadiazolyl, 1,2-oxa-triestanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, fíalazinilo, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, piridooxazolilo, pyridoimidazolyl, piridoíiazolilo, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, teirahydrofuranyl, eidehydroisoquinolinyl, teirahydroquinolinyl, 1,4,5,6-tetrahydro-pyridazinyl, tefrahydropyridinyl, tetrahydroiiophenyl, t etrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,4-thiadiazoyl, 1,2,5-Friadiazolyl, 1,4-thiazodiazolyl, isoanaryl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienoyazolyl, fienooxazolyl, thienoimidazolyl, thienyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,3-triazoly, 1,4-triazolyl, 1, 2,5-triazolyl, 1, 3,4-f-riazolyl and xanthenyl, wherein heterocyclyl is unsubstituted or mono-, di- or trisusituituted independently of one another by R 8, R 8 is 1) fluorine, chlorine or bromine, 2) -NO 2, 3) -OH, 4) -O-CF3, 5) an aryl of 6 to 14 monocyclic or bicyclic elements, wherein the aryl is mono-, di- or trisusylidene independently of one another by halogen or -O- (d-C8) -alkyl, 6) - (C? -C8) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -OH or a methoxy, 7) -O- (C? -8) -alkyl moiety, wherein alkyl is unsubstituted or mono-, di- - or trisustifuid independently of one another by halogen, NH 2, -OH or a methoxy radical, 8) -SO 2 -CH 3 or with the proviso that R 8 is at least one halogen or a radical -O- (d-C 8) -alkyl , if R ° is an aryl or a heterocyclyl, which are as defined above, Q is - (C0-C2) -alkylene-C (O) -NR10-, -NR10-C (O) -NR10-, -NR 0-C (O) -, - (d-C6) -alkylene or - (C0-C3) -alkylene-C (O) -O- (Co-C2) -alkylene-, with the proviso that Q is not - (C? -C6) -alkylene, if R ° is a heterocyclyl as defined under 2), R1 is a hydrogen atom, - (dC) -alkyl, in which alkyl is unsubstituted or substituted one to three times by R13; - (d-C3) -alkylene-C (O) -NH-R °, - (C? -C3) -alkylene-C (O) -O-R15, - (d-C3) -perfluoroalkylene, - (C? -C3) -alkylene-S (O) - (C? -C4) -alkyl, - (d-C3) -alkylene-S (O) 2- (C? -C3) -alkyl, - (C ? -C3) -alkylene-S (O) 2-N (R ') -R5', - (d-C3) -alkylene-O- (d-C4) -alkyl; - (C0-C3) -alkylene- (C3-C8) -cycloalkyl or - (Co-C3) -alkylene-het, where het is a residue selected from the group azepine, azetidine, aziridine, azirine, 1,4 -diazepine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxol, 1,3-dioxoiene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine , isothiazole, isothiazolidine, isopiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoine, ceopiperazine, morpholine, 1,2-oxathiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, teirazine, tetrazol, thiadiazine, thiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, Tieian, thiomorpholine, thiopyran, 1,2,3-Iriazine, 1, 2,4-triazine, 1, 3,5-Iriazine, 1,2,3-triazole or 1,2,4-triazole, where he is not subsituted or mono-, di- or trisusiluido independently of each other by R14, R4 and R5 are, independently of one another, identical or different and are a hydrogen atom or - (C? -C4) -alkyl, or R1- NV form a cyclic group of 4 to 8 elements, selected from the group azepine, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, 1,4-oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tefrahydropyridine, iorazine, tetrazole, thiazole, thiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-Iriazine, 1, 2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein said cyclic group is unsubstituted or mono -, di- or trisubstituted independently from each other by R 14, R 14 is fluorine, chlorine, bromine, iodine, -OH, = O, - (C? -8) -alkyl, - (d-C4) -alkoxy, -NO2 , -C (O) -OH, -CN, -NH2, -C (O) -O- (d-C4) -alkyl, - (C0-C8) -alkyl- SO2- (d-C4) -alkyl, - (Co-C8) -alkyl-S? 2- (C? -C3) -perfluoroalkyl, - (C0-C8) -alkyl-SO2-N (R18) -R21, -C (O) -NH- (d-C8) -aikyl, -C (O) -N- [(C? -C8) - alkyl] 2, -NR18-C (O) -NH- (C? -C8) -alkyl, -C (O) -NH2, -S-R18 or -NR18-C (O) -NH - [(d- C8) -alkyl] 2, in which R18 and R21 are independently of each other the hydrogen atom, - (C? -C3) -perfiuoroalkyl or - (C? -C6) -alkyl, V is a heterocyclyl residue of the group azaindole (1 H-pyrrolopyridine), azepine, azetidine, aziridine, azirine, 1,4-diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxol, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-oxazoline, cetopiperazine, morpholine, 1,2-oxa-tiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tefrazine, tetrazole, thiadiazine, thiadiazole, 1,2-iazine, 1,3-liazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietane, thiomorpholine, thiopyran, 1,2,3-triazine, 1, 2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, which is defined as above and where het is unsubstituted or mono-, di- or trisubstituted independently of each other by R14, G is a direct bond, - (CH2) m-NR10-SO2-NR10- (CH2) n-, - (CH2) m-CH (OH ) - (CH2) n-, - (CH2) m-, - (CH2) mO- (CH2) n-, - (CH2) mC (O) -NR10- (CH2) n-, - (CH2) -SO2 - (CH2) n-, - (CH2) m-NR10-C (O) -NR10- (CH2) n-, - (CH2) m-NR10- C (O) - (CH2) n-, - (CH2) ) mC (O) - (CH2) n-, - (CH2) -S- (CH2) n-, - (CH2) m-SO2- NR10- (CH2) n-, - (CH2) m-NR10-SO2 - (CH2) n-, - (CH2) m-NR10-, - (CH2) mO- C (O) -NR10- (CH2) n- or - (CH2) m -NR10-C (O) -O- (CH2) n-, n and m are independently of each other identical or different and are the integers zero, 1, 2, 3, 4, 5 or 6, M is 1) an atom of hydrogen, 2) - (d-Cd) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, 3) -C (O) -N (R 11) -R 12, 4) - (CH2) prNR10, 5) phenyl or naphthyl, wherein phenyl or naphthyl are unsubstituted or mono-, di- or trisubstituted independently from each other by R14, 6) heterocyclyl, wherein heterocyclyl is a residue group derivable azepane, azepine, 1, 4-diazepane, 1, 2-diazepine, 1, 3-diazepine, 1,4-diazepine, imidazole, isothiazole, isoxazole , isoxazolidine, 2-¡soxazolina, cetomorfolina, ketopiperazine, morpholine, oxazole, [1, 4] -oxazepano, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran, 1, 4,5,6-tetrahydro-pyridazinium, tetrazine, tetrazole, thiadiazole, iazole, thiophene, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1, 2,3-ftiazole or 1,2,4-iriazole, wherein said heterocyclyl is unsubstituted or mono-, di- or trisusfied independently from each other by R 14, 7) - (C 3 -C 8) -cycloa-Icyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R14, or R3, R4 and R22 are, independent of each other, are identical or different and are 1) volume hydrogen, 2) halogen, 3) - (d-C) -alkyl, wherein alkyl is not sustiíuido or mono-, di- or independently frisuslituido one another by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C4) -alkylene-O- R19, wherein R19 is a) hydrogen atom, b) - (C? -C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, or c) phenyl , wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) -CF3, oe) -CHF2, 7) -CN, 8) - (Co-C4) -alkylene- ( C4-C? 5) -heterocyclyl, wherein the heterocyclyl is as defined above and is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 9) -SOs-R1, wherein s is 1 or 2, 10) -SOrN (R11) -R12, wherein t is 1 or 2, 11) - (C0-C4) -alkylene-C ( O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R11) -R12, 15) -NR10-SO2-R10, 16) - (C0-C) -alkylene-het, wherein the het is as defined above and is unsubstituted or mono-, di- or tri-unsubstituted independently of one another by R13, 17) - (Co-C2) alkylene-C (O) -O- (C2-C) -alkylene-OC (O) - (C? -C4) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (Co-C2) alkylen-C (O) -O- (C2-) C4) -alkylene-OC (O) - (C? -C6) -alkyl, 20) -C (O) -OC (R15, R16) -OC (O) -R17, 21) - (Co-C4) - alkylene- (C6-d) -aryl, wherein aryl is mono-, di- or trisubstituted independently from each other by R13, 22) - (C0-C) -alkylene- (C3-C8) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, 23) - (C0-C3) -alkylene-O-CH2-CF2-CH2-O- (Co-C3) -alkyl, 24) - (C0-C3) -alq uylene-O-CH2-CF2-CF2-CH2-O- (Co-C3) -alkyl, 25) - (C0-C3) -alkylene-O-CH2- (C1-C3) -perfluoroaxy-CH2-OH, or 26) -SOw-N (R1) -R13, wherein w is 1 or 2.27) - (C0-C4) -alkylene-C (O) -N (R11) -R13, 28) - (C0-) C4) -alkylene-N (R11) -R13, or 29) a residue of the following list and, in which Me is methyl, or if two resins -OR19 are attached to adjacent atoms they can form together with the atoms to which they are attached to a 1,3-dioxole ring or a 2,3-dihydro- [1,4] dioxin ring, which is not Substituted or substituted one, two, four or four times by R13, R11 and R12 are independently identical or different from each other and are 1) hydrogen atom, 2) - (C? -C6) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, 3) - (Co-C6) -alkyl- (C6-Cu) -aryl, wherein aryl is as defined above and alkyl and aryl independently one of the other are unsubstituted or mono-, di- or trisubstituted by R13, 4) -O-R17, or 5) - (Co-C6) -alkyl- (C4-Ci5) -heterocyclyl, wherein alkyl and heterocyclyl are as defined above and independently of one another are unsubstituted or mono-, di- or trisubstituted by R13, or R11 and R12 together with the nitrogen atom to which they are attached can form a ring selected from the group azepine, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [1,4] -oxazepane, 1, 4- oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, teirahydropyridine, telrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2, 3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, which is unsubstituted or mono-, di- or trisubstituted independently of another by R13, R4 and R22 in the formula I or in the formula la, together with the carbon atoms to which they are each attached, can form a phenyl residue, R13 is fluorine, chlorine, bromine, iodine, -NO2 , -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R0) -R20, -N (R10) -R20, - (C0-C3) ) -alkylene-O-R10, -Si- (CH3) 3, -N (R10) -S (O) 2 -R10, -S-R10, -SO2-R10, -S (O) 2-N (R10) ) - R 20, -C (O) -R10, - (C? -C8) -alkyl, - (d-C8) -alkoxy, phenyl, phenyloxy-, -O-CF3, - (C? -C3) -perfluoroalkyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (C? -C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C ( O) -O-C (R15, R16) -OC (O) -O-R17, -O-R15, -NH-C (O) -NH-R10, -NH-C (O) -O-R10 or a remainder of the following list where Me is methyl, R15 and R16 are independently of one another hydrogen, - (d-CβJ-alkyl, or together with the carbon atom to which they are attached can form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, in where each ring is unsubstituted or substituted one to three times by R10, and R17 is - (d-C6) -alkyl, - (d-C6) -alkyl-OH, - (d-CeJ-alkyl-Of € -rd -I rent, - (C3-C8) - cycloalkyl, - (C? -C6) -alkyl-O- (C? -8) -alkyl- (C3-C8) -cyclic alkyl, - (d-C? J-alkyl- (C3-C8) ) -cycloalkyl, wherein said ring is unsubstituted or substituted one, two or three times by -OH, -O- (C? -C4) -alkyl or R10, in all its stereoisomeric forms and mixtures thereof in any proportion, and its physiologically tolerable salts. 2. - A compound of formulas I and according to claim 1, wherein R ° is 1) a phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R8, 2) a heterocyclyl of the benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cynolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl group , quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R8, or 3) a heterocyclyl of the pyridyl group, 2- pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or tri-substituted independently of another by R8, and, in addition, is substituted with a moiety selected from the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or tri-substituted independently of another for Rd, R8 is 1) F, Cl, Br ol, 2) - (d-C4) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen, -OH or a methoxy, or 3) -O- (C? -C4) -alkyl moiety, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by halogen or a methoxy moiety, with the proviso that R8 is at least one halogen or an -O- (d-C8) -alkyl radical, if R ° is an aryl or a heterocyclyl which are as defined above, Q is-C (O) -; - (d-C6) -alkylene, - (C0-C2) -alkylene-C (O) -NR10- or - (C0-C3) -alkylene-C (O) -O- (Co-C2) -alkylene- , with the proviso that Q is not - (C? -C6) -alkylene if R ° is a heterocyclyl as defined under 2), R1 is a hydrogen atom, - (C? -C2) -alkyl, - (d-C3) -alkylene-C (O) -NH-R0, - (C1-C3) -perfluoroalkylene, - (d-C3) -alkylene-C (O) -O-R15, - (C1-C3) -alkylene-S (O) 2- (C? -C3) -alkyl or - (CirC3) -alkylene-S (O) 2-N (R4 ') -R5', wherein R4 'and R5' are, independently of one another, identical or different and are a hydrogen atom or - (C1 -C4) - alkyl, R1-NV can form a cyclic group of 4 to 7 elements, of the group azetidine, azetidinone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1, 2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1, 2,3-triazole, 1,4-triazole, tetrazine, tetrazole, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, 1,4-oxazepane, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, where said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of each other by R14, R14 is fluorine, chlorine, -OH, = O, - (C? -C) -alkyl, -C (O) -OH , -CN, -NH2, -C (O) -O- (C4) -alkyl, -C (O) -NH- (C8) -alkyl, -C (O) -N - [(C? C8) -alkyl] 2, -C (O) -NH2 or -NR18-R21, wherein R18 and R21 are independently from each other the hydrogen atom, - (C C3) -perfluoroalkyl or - (C? -C) -alkyl, V is a heterocyclyl moiety of the group containing compounds that are derived from azaindole (1 H-pyrro-pyridine), aziridine, azirine, azetidine, azetidinone, 1,4-diazepam, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3-triazole, 1,4-triazole, tetrazole, pyridine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1, 3,5-triazine, tetrazine, tetrazole, azepine, diazirine, 1,2-diazepine, 1, 3- diazepine, 1,4-diazepine, pyridazine, piperidine, piperazine, pyrrolidinone, cetopiperazine, furan, pyran, dioxol, 1,4-oxazepane, oxazole, isoxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine, 1,3- dioxolene, 1,3-dioxolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thietane, thiazole, isothiazole, isothiazoline, isothiazolidine, 1,2-oxathiolane, thiodiazole, thiopyran, 1,2-thiazine, 1,3-thiazole, 1,3-thiazine, 1,4-thiazine, diadiazine or thiomorpholine, thiopyran, wherein said heterocyclyl moiety is unsubstituted or mono-, di- or trisubstituted independently of each other by R 14, G is a direct bond, - (CH 2) mo - (CH 2) m-NR10, m is the integers zero, 1, 2, 3 or 4, M is 1) a hydrogen atom, 2) heterocyclyl, wherein heterocyclyl is a residue of the group that can be derived from azepane, azepine, 1, 4 -diazepam, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, isothiazole, isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, cetopiperazine, morpholine, oxazole, [1,4] -oxazepane, piperazine , piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran, 1,4,5,6-tetrahydropyridazinyl, tetrazine, tetrazole, thiadiazole, thiazole, thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,2,4-Iriazole, where said heyerocyclylyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, 3) - (d-C 8) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or tri-substituted independently one of another by R14, 4) - (C3-C6) -cycloalkyl, or 5) -C (O) -N (R11) -R12, R3, R4 and R22 are, independent of each other, are identical or different and are 1) hydrogen atom, 2) halogen, 3) - (C? -C) -alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, 4) - (C? - C3) -perfluoroalkyl, 5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C4) -alkylene-O-R19, wherein R19 is a) hydrogen atom, b) - (C? -C) -acyl, wherein the alkyl is unsubstituted or mono-, di- or ir-substituted indep one or the other of R13, oc) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13, d) -CF3, oe) -CHF2, 7) -CN, 8) -NR10-SO2-R10, 9) -SOs-R11, where s is 1 or 2, 10) -SOrN (R11) -R12, where t is 1 or 2.11) - (C0-C4) -alkylene -C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12 , 14) - (C0-C4) -alkylene-N (R11) -R12, 15) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) - ( C? -C4) -alkyl, 16) -C (O) -OC (R15, R16) -OC (O) -R17, 17) - (C0-C2) alkylene-C (O) -O- (C2-) C4) -alkylen-OC (O) -O- (d-C6) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (Co- C) -alkylene- (C3-C6) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, or 20) - (Co-C3) -alkylene-O-CH2 -CF2-CH2-O- (Co-C3) -acyl, 21) - (C0-C3) -alkylene-O-CH2-CF2-CF2-CH2-O- (Co-C3) -alkyl, 22) - ( Co-C3) -alkylene-O-CH2- (C? -C3) -perfluoroalkylene-CH2-O H, 23) -SOw-N (R 11) -R 13, wherein w is 1 or 2, 24) - (C 0 -C 4) -alkylene-C (O) -N (R 1) -R 13, 25) - ( C0-C4) -alkylene-N (R11) -R13, or 29) a remainder of the following list j, in which Me is methyl, or if two residues -OR19 are attached to adjacent atoms can form together with the atoms to which they are attached to a ring of 1, 3-dioxole or a 2,3-dihydro- [1,4] dioxin ring, which is unsubstituted or substituted one, two, three or four times by R13, R11 and R12 together with the nitrogen atom to which they are united may form a ring selected from the group azepine, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, Siathiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ceopiperazine, morpholine, [1,4] -oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine , pyrrole, pyrrolidine, pyrrolidinone, pyrroline, teirahydropyridine, fefrazine, iorazol, iazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine, 1,4-triazine, 1, 3,5-triazine, 1,2,3-triazole or 1,4-triazole, wherein said ring is unsubstituted or mono-, di- or trisubstituted independently of each other by R 13, R 4 and R 22 in the formula I or in the formula , together with the carbon atoms to which they are each attached, can form a phenyl moiety, R13 is fluorine, chlorine, -NO2, -CN, = O, -OH, -CF3, -C (O) -O- R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, -N (R10) - S (O) 2-R10, -S-R10, -SO 2 -R 10, -S (O) 2-N (R 10) -R 20, -C (O) -R 10, - (d-C 8) -acyl, - (C 8) -alkoxy, phenyl, phenyloxy-, O-CF3, - (C? -C3) -perfluoroalkyl, -NH-C (O) -NH-R10, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (C? -C4) -alkoxy-phenol, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) - O-R17, -O-R15, -NH-C (O) -O-R10 or a remainder of the following list R10 and R20 are independently of one another hydrogen, - (d-C6) -alkyl, or - (Co-C4) -alkyl-OH, - (Co-C4) -alkyl-O- (C? -C) - alkyl or - (C? -C3) -perfluoroaIlkyl, R15 and R16 are independently of one another hydrogen, - (d-C? -alkyl, or together form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, in which each ring is unsubstituted or substituted one to three times by R10, and R1 is - (C? -C6) -alkyl, - (d-C6) -alkyl-OH, - (C? -C6) -alkyl-O- (d -C6) -alkyl, - (C3-C8) -cycloalkyl, - (CrC6) -alkyl-O- (CrC8) -alkyl- (C3-C8) - cycloalkyl, - (C? -C6) -alkyl- (C3) -C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (dC) -alkyl or R10. 3. - A compound of the formulas I and according to claims 1 or 2, wherein R ° is 1) a phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R8, 2) a heterocyclyl of the indolyl, isoindolyl, benzofuranyl, benzothiophenyl, 1,3-benzodioxolyl group; ndazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, chromanyl, isochromanyl, cinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyridyl, purinyl and pteridinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or independently selected from each other by R 8, or 3) a heterocyclyl of the pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl group; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of another by R8, and, in addition, is substituted with a moiety selected from the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-ynyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tefrazolyl, pyridazinyl and pyrazinyl, wherein said residue is unsubstituted or mono-, di- or trisubstituted independently of another for R8, R8 is 1) F, Cl, Br, I, 2) - (C? -C) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently of one of ofro by halogen , -OH or a methoxy moiety, or 3) -O- (d-C4) -acyl, wherein the alkyl is unsubstituted or mono-, di- or trisustiluido independently of one another by halogen or a methoxy moiety, with the provided that R8 is at least one halogen or a radical -O- (C? -C8) -alkyl, if RO is an aryl or a heterocyclyl which is as defined above, Q is -C (O) -; -C (O) -O-methylene, - (dC) -alkyllene or - (C0-C2) -alkylene-C (O) -NR10-, with the proviso that Q is not - (C? -C ) -alkylene if R ° is a heterocyclyl as defined under 2), R1 is a hydrogen atom or - (C? -C2) -alkyl, or R1-NV can form a cyclic group of 4 to 7 elements, from the group piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-iazine, 1,3,5-triazine, 1,2,3-triazole1,2,4-Iriazole, tetrahydroquinoline, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, iso-diazol , thiadiazole or thiomorpholine, wherein said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of each other by R14, R14 is fluorine, chlorine, - (C? -C4) -alkyl or -NH2, V is a heterocyclyl residue of the group containing compounds that are derived from azaindole (1 H-pyrrolopyridyl), azetidine, azepine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diazirine, 1,3-dioxolane, dioxazole, furan, imidazole, isoquinoline, isothiazole, isothiazolidine, isothiazoline, isoxazole, 2-isoxazoline, isoxazolidine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, 1,2-oxathiolane, piperidine, pyran, pyrazine, pyrazole, pyridazine, piperazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, quinazoline, quinoline, fetrazine, leiorazol, thiadiazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thietane, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-friazine, 1,2,3-triazole or 1,2,4-triazole, wherein said heterocyclyl moiety is unsubstituted or mono -, di- or trisubstituted independently of each other by R14, G is a direct bond, - (CH2) mo - (CH2) m-NR10, m is the integers zero, 1, 2, 3 or 4, M is 1) a hydrogen atom, 2) heterocyclyl, wherein heterocyclyl is a residue of the group that can be derived from 1,4-diazepam, cetomorpholine, lyophen, pyridazone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, midazole, pyridazine, pyrazine, 1,2,3-Iriazine, 1,2,4-tr iazine, 1, 3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, cetopiperazine, oxazole, soxazoi, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, tetrahydropyran, 1,4,5,6-tetrahydropyridazinyl, thiadiazole or thiomorpholine, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, 3) - (C 6 -C 6) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 14, 4) - ( C3-C6) -cycloalkyl, R3, R4 and R22 are, independently of one another, identical or different and are 1) hydrogen atom, 2) halogen, 3) - (C? -C4) -alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisusituituted independently of one another by R13, 6) - (C0-C4) -alkylene-O- R19, wherein R19 is a hydrogen atom, - (d-dj-alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisusituituted independently from each other by R13, phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisusituituido independently of each other by R13, -CF3 or -CHF2, 7) -CN, 8) -NR10-SO2-R10, 9) -SOs-R11, where s is 1 or 2, 10) -SOrN (R11) -R12, where I is 1 or 2, 11) - (C0-C4) -alkylene-C (O) -R11, 12) - (C0-C4) -alkylene-C (O) -O-R11, 13) - (C0-C4) -alkylene-C (O) -N (R11) -R12, 14) - (C0-C4) -alkylene-N (R1) -R12, 15) - (Co-C2) alkylene-C (O) -O- (C2-C4) -alkylene -OC (O) - (C1-C4) -alkyl, 16) -C (O) -OC (R15, R16) -OC (O) -R17, 17) - (C0-C2) alkylene-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (d-C6) -alkyl, 18) -C (O) -OC (R15, R16) -OC (O) -R17, 19) - (Co-C3) -acylene- (C3-C6) -cycloalkyl, wherein the cycloalkyl is unsubfused or mono-, di- or trisubstituted independently from each other by R13, or 20) - (Co-C4) -alkylene - (C3-C6) -cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-, di- or tri-substituted independently of one another by R13, or 21) - (C0-C3) -alkylene-O-CH2-CF2-CH2 -O- (Co-C3) -alkyl, 22) - (Co-C3) -alkylene-O-CH2-CF2-CF2-CH2-O- (Co-C3) -alkyl, 23) - (Co-C3) -alkylene-O-CH2- (C? -C3) -perfiuoroa -quiyeno-CH2-OH, 24) -SOw-N (R11) -R13, wherein w is 1 or 2, 25) - (C0-C4) -alkylene-C (O) -N (R11) -R13, 26) - (C0-C4) ) -alkylene-N (R11) -R13, or 27) a remainder of the following lysis if two -OR19 moieties are attached to adjacent atoms they can form together with the atoms to which they are attached to a 1,3-dioxole ring or a 2,3-dihydro- [1,4] dioxin ring, which is not substituted or substituted one, two, three or four times by R13, R11 and R12 together with the nitrogen atom to which they are attached can form a ring selected from the group azepine, azetidine, 1,4-diazepam, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isoliazol, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, cetopiperazine, morpholine, [ 1,4] -oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, teirahydropyridine, iorazine, tetrazole, thiazole, thiadiazole , thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine, 1,2,4-friazine, 1,3,5-Iriazine, 1,2,3-triazole or 1,2,4-triazole, wherein said ring is unsubstituted or mono-, di- or tri-substituted independently of each other by R 13, R 4 and R 22 in the formula I or in the formula , together with the carbon atoms to which they are each attached, can form a phenyl moiety, R13 is fluorine, chlorine, -NO2, -CN, = O, -OH, -CF3, -C (O) -O- R10, -C (O) - N (R0) -R20, -N (R10) -R20, - (C0-C3) -alkylen-O-R10, -Si- (CH3) 3, -N ( R10) -S (O) 2 -R10, -S-R10, -SO2-R10, -S (O) 2-N (R10) -R20, -C (O) -R10, - (C | -8) -alkyl, - (d-C8) -alkoxy, phenyl, phenyloxy-, -O-CF3, - (C? -C3) -perfluoroalkyl, -NH-C (O) -NH-R10, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -R17, - (d-C4) -alkoxy-phenyl, - (C0-C4) -alkyl-C (O) -OC (R15, R16) -OC (O) -O-R17 , -O- R15, -NH-C (O) -O-R10 or a remainder of the following list R11 and R12 are independently one of different or different goods and are 1) hydrogen atom, 2) - (d-C4) -alkyl, in which the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 3) - (C0-C6) -alkyl - (C3-C6) -cycloalkyl, 4) -O-R17, or 5) - (Co-C6) -alkyl- (C4-Ci5) -heterocyclyl, wherein alkyl and heterocyclyl independently of each other are not Substituted or mono-, di- or frisuified by R13 and in which heyerocyclyl is selected from the group azeididine, cyclopropyl, cyclobuyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, [1,4] -oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine, or R11 and R12 together with the nitrogen atom to which they are attached can form a heterocyclic ring, which is selected from the group azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine , morpholine, [1,4] -oxazepane, 1,4-oxazepine, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine, R4 and R22 in the f Formula I or in the formula together with the carbon atoms to which they are attached can form a phenyl residue, R13 is fluorine, -CN, = O, -OH, -CF3, -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C3-C6) -cycloalkyl, - (C0-C3) -alkylen-O-R10, -Si- (CH3) 3, -SR10, SO2-R10, -i e-perfluoroalkyl , or a remainder of the following list R10 and R20 are independently of one another hydrogen, - (C -? - C4) -alkyl or - (C? -C3) -perfluoroalkyl, R15 and R1d are independently one of the other hydrogen, - (C -? - C4) -alkyl, or juni form a ring of the cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, wherein each ring is unsubstituted or substituted one to three times by R10, and R17 is - (d-C6) -alkyl, - (d-C6) -alkyl-OH, - (C? -C6) -alkyl-O- (C ? -C6) -alkyl, - (C3-C8) -cycloalkyl, - (Ci-CβJ-alkyl-O-CrCrCεí-alkyls Cs-CsJ-cycloalkyl, - (Ci-CβJ-C3-C8-alkyl) -cycloalkyl, wherein said ring of Cycloalkyl is unsubstituted or substituted one, two or three times by -OH, -O- (d-C4) -alkyl or R10. 4. - A compound of the formulas I and according to claims 1 to 3, wherein R ° is 1) phenyl, wherein the phenyl is mono-, or disustiluido independently of each other by R8, 2) pyridyl, in the that the pyridyl is mono- or disubstituted independently of one another by R8, or 3) a heterocyclyl of the thienyl, thiadiazolyl, isoxazolyl and thiazolyl group, wherein said heterocyclyl is substituted by a residue selected from the group thienyl, 2-thienyl and -thienyl, wherein said residue is unsubstituted or mono- or disubstituted independently of one another by R8, R8 is F, Cl, Br, -O-CH3 or -O-CF3, Q is -C (O); -C (O) -O-methylene, CH2-C (O) -NH, methylene or ethylene, with the proviso that Q is not methylene or ethylene if R ° is pyridyl, R1 is a hydrogen atom, R1-NV can form a cyclic group of 4 to 8 elements of the group azetidine, pyrrolidine, piperidine and piperazine, R14 is fluorine, chlorine, methyl, ethyl or -NH2, V is a residue of the group containing compounds that are derived from azaindolyl (1H- pyrrolopyridyl), azetidine, 1,4-diazepam, isoxazole, isoquinoline, piperazine, piperidine, pyrazine, pyridazine, pyrimidine, pyrrolidine, quinazoline, quinoline or tetrahydropyran, wherein said heterocyclyl moiety is unsubstituted or mono- or disubstituted independently of each other by R14, G is a direct bond, CH2) m- or - (CH2) m-NR10-, m is the integers zero, 1 or 2, M is a hydrogen atom, (C2-C4) -alkyl, isopropyl, azepanyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, cetomorpholinyl, morpholinyl, [1,4] -oxazepanyl, piperidinyl, piperidonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidyl, pyrrolidinyl, 1,4,5,6-tetrahydro-pyridazinyl or tetrahydropyranyl, in which the radicals are unsubstituted or mono- or disubstituted independently of one another by R 14, R 3, R 4 and R 22 are independent of one another, are identical or different, and They are I) hydrogen atom, 2) fluorine, chlorine, bromine, iodine, 3) - (C? -C) -alkyl, in which alkyl is unsubstituted or mono-, di- or trisubstituted independently of each other by R13, 4) - (C? -C3) -perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, 6) - (C0-C2) -alkylene- O-R19, wherein R19 is a hydrogen atom, - (C -? - C4) -alkyl, in which the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13, phenyl, that the phenyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R 13, -CF 3 or -CHF 2, 7) -NO 2, 8) -NR 10 -SO 2 -R 10, 9) -SOs-R 11, in where s is 1 or 2, 10) -SOt-N (R11) -R12, where t is 1 or 2, II) - (C0-C4) -alkylene-C (O) -R1, 12) - (C0 -C4) -alkylene-C (O) -OR 1 '1', 13) - (C0-C4) -alkylene-C (O) -N (R 1) -R 12, 14) - (C0-C4) - alkylene-N (R 1) -R 12, 15) - (Co-C 2) -alkyl [ene-C (O) -O- (C 2 -C 4) -alkylen-OC (O) - (C 1 -C 4) ) -alq uilo, 16) -C (O) -OC (R15, R16) -O-CO-R17, 17) - (Co-C2) -alkylen-C (O) -O- (C2-C4) -alkylene-OC (O) -O- (CrC6) -alkyl, 18) -C (O) -OC (R15, R16) -O-CO-O-R17, 19) - (Co-C3) -alkylene-phenyl, in the that the phenyl is unsubstituted or mono-, di- or tri-substituted independently from each other by R13, 20) pyridinyl, wherein the pyridinyl is unsubstituted or mono-, di- or trisusylidene independently of each other by R 13, or 21) thiazolyl, wherein the thiazolyl is unsubstituted or mono-, di- or trisusifluid independently one from another by R13, or 22) - (Co-C4) -alkylene- (C3-C6) -cycloalkyl, in which the cycloalkyl is unsubstituted or mono-, di- or frisusituituido independent of each other by R13, 23) - (C0-C3) -alkylene-O-CH2-CF2-CH2-O- (Co-C3) -alkyl, 24) - (C0-C3) -alkylene-O-CH2-CF2-CF2-CH2-O- (Co-C3) -alkyl, 25) - (Co-Cs-alkylene-O-CH ^ Id-Cs-perfluoroalkylene-CH OH, or 26) a remainder of the following list which Me is methyl, R11 and R12 are independently of one another identical or different and are

1) hydrogen atom,

2) - (CrC6) -alkyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted independently from each other by R13,

3) - (C0-C6) -alkyl-phenyl ,

4) -O-R17, or

5) - (C0-C

6) -alkyl-heterocyclyl, in which alkyl and heterocyclyl independently of one of the other unsubstituted or mono-, di- or iris-substituted by R13 and in which heterocyclyl is selected from the group azetidine, imidazolidine, morpholine, [1,4] -oxazepane or piperidine, or R11 and R12 together with the nitrogen atom to which they are attached can form a ring that is selected from the group azetidine, imidazolidine, morpholine, [ 1, 4] - oxazepane, 1,4-oxazepine, piperazine, piperidine, pyrrolidine or thiomorpholine, R13 is fluorine, chlorine, -CN, = O, -OH, -CF3I -C (O) -O-R10, -C (O) -N (R10) -R20, -N (R10) -R20, - (C3-C6) -cycloalkyl, - (C0-C3) -alkylene-O-R10, -Si- (CH3) 3, -SR10, -SO2-R10, - (d- C4) -alkyl, - (C -C3) -perfluoroalkyl, or a remainder of the following list R10 and R20 are independently of one another hydrogen, - (C -? - C4) -alkyl or - (C1-C3) -perfluoroalkyl, R15 and R16 are independently from each other hydrogen, - (C? -C4) -alkyl, or together form a ring of the cyclopropyl, cyclobuyl, cyclopentyl or cydohexyl group, wherein each ring is unsubstituted or substituted one to three times by R10, and R17 is - (C6C6) alkyl, - (dC6) ) -alkyl-OH, - (d-C6) -alkyl-O- (C? -C6) -alkyl, -cydoalkyl, - (C? -C6) -alkyl-O- (C? -8) -alkyl- (C3-C8) -cycloalkyl, - (d-C6) -alkyl- (C3-C8) -cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by -OH, -O- (C? -C4) -alkyl or R10. 5. - A compound of the formulas I and according to claim 1, wherein the compound of the formulas I and the is 1- (5- (5-chloro) - (1-isopropyl-piperidin-4-yl) -amide of the acid -thiophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2-carboxylic acid1- (3-methoxy-benzyl) -1H-pyrrol-2-carboxylic acid (1-isopropyl-piperidin-4-yl) -amide, (1-isopropyl-piperidin-4-yl) -amide 1- [5- (5-chloro-iiophen-2-yl) -isoxazol-3-ylmethyl] -4-nitro-1H-pyrrole-2-carboxylic acid, (1-isopropyl-piperidin-4-yl) -amide 1- [5- (5-Chloro-thiophen-2-yl) -isoxazo-3-ylmethyl] -3,5-dimethyl-1H-pyrrole-2-carboxylic acid, (1-isopropyl-piperidin-4) -yl) -amide of 1 - [(5-chloro-pyridin-2-ylcarbamoyl) -mellyl] -4- (perhldro-1,4-oxazepine-4-carbonyl) -1 H-pyrrole-2-carboxylic acid amide 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -5- (1-isopropyl-piperidin-4-yl) -amide (perhydro-1,4-oxazepine-4-carbonyl) -1H-pyrroyl-2-carboxylic acid, 1- [5- (5-chloro-phofen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-yl) -amide. (perhydro-1,4-oxazepine-4-carbonyl) -1H-pyrrole-2-carboxylic acid, 3- [1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] - 5- (1-isopropyl-piperidin-4-ylcabamoyl) -2,4-dimethyl-1H-pyrrol-3-yl] -propionic acid, benzyl ester of the acid 1- [5- (5 -chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-ylpropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, methyl ester of 1- [5- ( 5-Chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1 H -pyrro-2-carboxylic acid, 1 - [5- (5- chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -5- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, benzyl ester of 1 - [(5-chloro- pyridin-2-carbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrol-2-carboxylic acid, benzyl ester of 1- [5- (5-chloro-thiophene- 2-yl) -isoxazol-3-ylmethyl] -4- (1-isopropyl-p-peridin-4-l-carbamoyl) -1 H-pyrrol-2-carboxylic acid, (1-isopropyl-piperidin-4-yl) - 1 - [(5-Chloro-pyridin-2-ylcarbamoyl) -methyl] -4-nitro-1 H -pyrrole-2-carboxylic acid amide, 1 - [(5-chloro-pyridin-2-methyl) methyl ester -carbamoyl) -methyl] -4- (1-isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, methyl ester of 1- [5- (5-chloro-thiophen-2-yl) - isoxazol-3-ylmethyl] -4- (1- isopropyl-piperidin-4-ylcarbamoyl) -1 H-pyrrole-2-carboxylic acid, 1 - [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmeiyl] -4- (1 - isopropyl-piperidin-4-ylcarbamoyl) -1H-pyrrole-2-carboxylic acid, 1- [5- (5-chloro-thiophen-2-yl) -isoxazole], (1-isopropyl-piperidin-4-yl) -amide. -3-ylmethyl] -5- (3-meioxy-azetidine-1-carbonyl) -1H-pyrrole-2-carboxylic acid, 2 - [(1-isopropyl-piperidin-4-yl) -amide] 5 - [(2 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1 H -pyrrole-2,5-dicarboxylic acid, 2 - [(1-methoxy-eyl) -amide] -isoprop.il-piperidin 4-yl) -amida] 5 - [(2-meloxy-ethyl) -methyl-amide] of the acid 1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -1H-pyrrole-2,5-dicarboxylic acid, 1- [5- (5-chloro-thiophen-2-yl) - (1-isopropyl-piperidin-4-yl) -amide) - isoxazol-3-ylmethyl] -5-phenyl-1H-pyrrole-2-carboxylic acid, 1- [5- (5-chloro-thiophen-2-yl) (1- isopropyl-piperidin-4-yl) -amide) -isoxazol-3-ylmethyl] -3,5-dimethyl-4- (perhydro-1,4-oxazepine-4-sulfonyl) -1H-pyrrole-2-carboxylic acid, 4-Bromo-1- [5- (5-chloro-thiophen-2-yl) -isoxazol-3-ylmethyl] -3,5-dimethyl-1-isopropyl-piperidin-4-yl) -amide. H-pyrrole-2-carboxylic acid, 4-bromo-1 - [(5-chloro-pyridin-2-ylcarbamol) -methyl] -3,5-dimethyl (1-isopropyl-piperidin-4-yl) -amide -1 H-pyrrole-2-carboxylic acid or 1- [5- (5-chloro-thiophen-2-yl) -isoxazoI-3-ylmethyl] (1-isopropyl-piperidin-4-yl) -amide] - 4-formyl-3,5-dimethyl-1H-pyrrole-2-carboxylic acid. 6. - A process for the preparation of a compound of the formulas I and the one according to claims 1 to 5, comprising the condensation of a compound of the formula 2 with a compound of the formula HR8 to give a compound of formula 3 and optionally to transform the compound of formula 3 into a compound of formulas I and 2 - - - »- formulas I and the one in which the radical R8 has the contribution of -N (R1) -VGM indicated in claims 1 to 5, but in which the functional groups R8 can also be present in form of groups that are subsequently transformed into the final functional groups present in -N (R1) -VGM and in which the rest R87 indicates the group -QR ° or can indicate a group that subsequently changes in the group -QR °, and wherein the group -C (O) -R86 can be a carboxylic acid group or one of its derivatives, and wherein the R1a and R1b groups in formulas 2 and 3 possess the corresponding definitions of R3 and R4 in the formulas I and that defined in claims 1 to 5 or the functional groups in them may also be present in protected form or in the form of precursor groups.

7. - A pharmaceutical preparation, comprising at least one compound of the formulas I or the one, according to one or more of claims 1 to 5 in all its stereoisomeric forms and mixtures thereof in any proportion and / or its physiologically tolerable salts and a pharmaceutically carrier acceptable.

8. The use of a compound of the formulas I or the one according to one or more of claims 1 to 5 in all its stereoisomeric forms and mixtures thereof in any proportion and / or its physiologically tolerable salts for the production of pharmaceutical products for inhibition of factor Xa and / or factor Vlla or to influence blood coagulation or fibrinolysis.

9. The use according to claim 8, for abnormal thrombus formation, acute myocardial infarction, cardiovascular disorders, inesiable angina, thromboembolism, acute vessel closure associated with thrombolytic therapy or percutaneous transluminal coronary angioplasty (PTCA) , transient ischemic attacks, stroke, intermittent claudication or implantation with coronary or peripheral artery bypass, luminal stenosis of the vessel, post-coronary restenosis or venous angioplasty, maintenance of vascular access permeability in patients with long-term hemodialysis, the pathological formation of the thrombus that occurs in the veins of the lower extremities after abdominal, knee or hip surgery, a risk of pulmonary thromboembolism or disseminated generalized intravascular coagulopathy that occurs in vascular systems during septic shock, deter mined viral infections or cancer, or the reduction of an inflammatory response, fibrinolysis or treatment of coronary heart disease, myocardial infarction, angina pectoris, vascular restenosis, eg restenosis after PTCA-type angioplasty, dyspnoea syndrome acute adult, multiorgan failure and disorder of disseminated intravascular coagulation, thrombosis of the deep vein and proximal vein, which may occur after surgery.