Title of Invention

SUBSTITUTED BENZIMIDAZOLES AND THEIR PREPARATION

Abstract

Compounds of the formula Ia or Ib where R1is hydrogen or branched or straight-chain C1-C6-alkyl, where one carbon atom of the alkyl radical may furthermore carry OR5 (where R5 is hydrogen or C1-C4-alkyl) , or one carbon atom in the chain may also carry an =0 group or a group NR8R9, where RB and R9, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the carbon chains in R8 or R9 or the ring formed by NRBR9 may furthermore carry a radical R6 which, independently of R2, may have the same meaning as R2, R4 is hydrogen, branched or straight-chain C1-C6-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR8R9, NH-CO-R1O or OR8, where RB and R9, independently of one another, are each hydrogen or CI-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical (branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R41, COOR41 or phenyl), and R10 may be hydrogen, C1-C4-alkyl or phenyl and R41 may have the same meanings as R21, A is a saturated or monounsaturated heterocyclic, 4- to 8-membered ring which contains one or two nitrogen atoms, it being possible for an oxygen or sulfur atom additionally to be incorporated, which oxygen or sulfur atom is substituted by R2 and R3, where R2 is hydrogen, branched or straight-chain C1-C8-alkyl which may furthermore be substituted by R23, and a carbon atom of the chain may carry an =0 group, C3-C7-cycloalkyl-C1-C4-alkyl.

Full Text

Substituted benzimidazoles and their preparation and use The present invention relates to novel benzimidazoles, their preparation and their use as inhibitors of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30) for the preparation of drugs. Poly(ADP-ribose)polymerase (PARP) or, as it is also known, poly(ADP-ribose)synthase (PARS) is a regulatory enzyme which is found in cell nuclei (K. Ikai et al., J. Histochem. Cytochem. ii. (1983), 1261-1264). It is assumed that PARP plays a role in repairing DNA breaks (M.S. Satoh et al.. Nature 356 (1992), 356-358). Damage to or breaks in the DNA strands activate the enzyme PARP which, if it has been activated, catalyses the transfer of ADP-ribose from NAD (S. Shaw, Adv. Radiat.Biol. li (1984), 1-69). Nicotinamide is liberated from NAD. Nicotinamide is converted back into NAD with consumption of the energy carrier ATP by other enzymes. Overactivation of PARP would accordingly result in an unphysiologically high consumption of ATP, and this leads to cell damage and cell death in extreme cases. It is known that radicals such as the superoxide anion, NO and hydrogen peroxide can lead to DNA damage in cells and hence activate PARP. The formation of large amounts of radicals is observed in a number of pathophysiological conditions, and it is assumed that this accumulation of radicals leads or contributes to the observed cell or organ damage. These include, for example, ischemic conditions of organs, as in stroke, myocardial infarct (C. Thiemermann et al., Proc. Natl. Acad. Sci. USA 9± (1997), 679-683) or ischemia of the kidneys, as well as reperfusion damage as occurs, for example, following the lysis of myocardial infarct (see above: C. Thiemermann et al.). The inhibition of the enzyme PARP might accordingly be a means for preventing or reducing this damage at least in part. PARP inhibitors might therefore constitute a new therapeutic principle for treating a number of disorders. The enzyme PARP influences the repair of DNA dcimage and could thus also play a role in therapy of cancer diseases, since the higher action potential against tumor tissue was observed in combination with cytostatic substances (G. Chen et al. Cancer Chemo. Phairmacol. 22_ (1988), 303). Nonlimiting examples of tumors are leukemia, glioblastomas, lymphomas, melanomas, carcinoinas of the breast and cervical carcinomas. It was also found that PARP inhibitors can have an immunosuppressive effect (D, Weltin et al. Int. J. Iimunopharmacol. IZ (1995), 265-271). It was also discovered that PARP is involved in immunological diseases or disorders in which the immune system plays an important role, for example rheumatoid arthritis and septic shock, and that PARP inhibitors can have an advantageous effect on the course of the disorder (H. Kroger et al. Inflammation 2O, (1996), 203-215; W. Ehrlich et al. Rheumatol. Int. 15 (1995), 171-172; C. Szabo et al., Proc. Natl. Acad. Sci. USA 95. (1998), 3867-3872; S. Cuzzocrea et al. Eur. J. Pharmacol. 342 (1998), 67-76). For the purposes of this invention, PARP is also understood as meaning isoenzymes of the PARP enzyme described above. Furthermore, the PARP inhibitor 3-aminobenzamide exhibited protective effects in a model for circulatory shock (S. Cuzzocrea et al., Br. J. Pharmacol. 221 (1997), 1065-1074). PARP is also involved in diabetes mellitus (V. Burkhart et al.. Nature Medicine (1999), 5314-19). Benzimidazoles have been widely described. The synthesis of 2-phenylbenzimidaz-4-ylcunides which also carry a substituted alkyl chain on the amide radical and which are said to have a cytotoxic effect is mentioned in J. Med. Chem. 23L (1990), 814-819. WO 97/04771 mentions 4-benzimidazolamides which inhibit PARS. In particular, derivatives which carry a phenyl ring in the 2-position, where the phenyl ring may furthermore be substituted by simple substituents such as nitro, methoxy or CF3, are described there as being effective. Although some of these substances exhibit good inhibition of the enzyme PARP, the derivatives described there have the disadvantage that they have little or no solubility in aqueous solutions and hence cannot be applied as an aqueous solution. Benzimidazoles which carry a piperidine ring in the 2-position have also been described. Thus, in J. Het. Chem. 24 (1987), 31, derivatives have been prepared as antihistamine drugs. In J. Het. Chem. 12 (1995), 707 and J. Het. Chem. li (1989), 541, analogous compounds having the same use have been described. 2-Piperidinylbenzimidazoles are mentioned in EP 818454 as antihistamine drugs and in WO 9736554 as agents against hepatitis. Derivatives are likewise mentioned in CA 80, 146143, Fr. 2103639 and in Khim. Geterotsikl. Soedin 1 (1974), 104. However, the importance of substituents on the phenylaromatics in the benzimidazole fragment has not been investigated. Furthermore, those benzimidazoles which carry a 4- to 8-membered heterocycle, in particular a piperidine ring, in the 2-position have not been described to date as being PAR? inhibitors. The present application describes the surprising finding that the introduction of a carboxamide radical on the benzimidazole aromatic gives benzimidazoles which constitute novel and hi^ghly effective PARP inhibitors, provided that they are substituted in the 2-position by a saturated heterocycle. In a number of treatments, such as for stroke, the active compounds are applied intravenously as an infusion solution. For this purpose, it is necessary to have substances, in this case PARP inhibitors, which have sufficient water solubility at or about physiological pH (i.e. pH of 5-8), so that an infusion solution can be prepared. However, many of the PARP inhibitors described, in particular the more effective PARP inhibitors, have the disadvantage that they exhibit only little or no water solubility at the pH values and are therefore not suitable for intravenous application. Such active compounds can be applied only with excipients which are intended to impart water solubility (cf. WO 97/04771). These excipients, for example polyethylene glycol and dimethyl sulfoxide, frequently cause side effects or are even not tolerated. No highly effective PARP inhibitors having sufficient water solubility have been described to date. It was surprisingly found that benzimidazoles which carry a piperidine ring on the imidazole ring are highly effective inhibitors and, owing to the incorporation of the aliphatic eunine radical, permit salt formation with acids, resulting in substantially improved water solubility and hence permitting the preparation of an infusion solution. The present invention describes novel benzimidazole derivatives of the formula I which have advantages over the compounds described above and constitute potent PARP inhibitors and at the saline time have sufficient water solubility. When compounds of the formula I are referred to, they are understood as meaning the compounds of the formulae la and lb. The present invention relates to substituted benzimidazoles of the formula I: where R1 is hydrogen or branched or straight-chain C1-C6-alkyl, where one carbon atom of the alkyl radical may furthermore carry 0R5 (where R5 is hydrogen or C1-C4-alkyl), or one carbon atom in the chain may also carry an =0 group or a group NR8R9, where R8 and R9, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the carbon chains in R8 or R9 or the ring formed by NR8R9 may furthermore carry a radical R6 which, independently of R2, may have the same meaning as R2, R4 is hydrogen, branched or straight-chain C1-C6-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR8R9, NH-CO-R10 or OR8, where R^ and R^, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical (branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R41 COOR41 or phenyl), and R10 may be hydrogen, C1-C4-alkyl or phenyl and R41 may have the same meanings as R21, A is a saturated or monounsaturated heterocyclic, 4- to 8-membered ring which contains one or two nitrogen atoms, it being possible for an oxygen or sulfur atom additionally to be incorporated, which oxygen or sulfur atom is substituted by R2 and R3, where R2 is hydrogen, branched or straight-chain C1-C8-alkyl which may furthermore be substituted by R23, and a carbon atom of the chain may carry an =0 group, C3-C7-cycloalkyl-C1-C4-alkyl, -CO-(NH)O,I-R221/ C00R21 or phenyl, where R21 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C3-C7-cycloalkyl or phenyl, and each radical may furthermore carry (CH2)o-2-R23 and the respective phenyl ring in turn may furthermore be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain C1-C4-alkyl, nitro, CF3, cyano, -(CH2)O-2-NR24R25 NH-CO-RlO, OR10, COOR10, S02-C1-C4-alkyl, S02Ph, SO2NH, NHS02-Cl-C4-alkyl, NHS02Ph and CF3, where R24 and R25, independently of one another, are each hydrogen or Ci-C4-alkyl and NR24R25 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain C1-Cg-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R22, COOR22 (where R22 is hydrogen, branched or straight-chain Ci-Cg-alkyl, C3-C7-cycloalkyl-Ci-C4-alkyl, phenyl-C1-C4-alkyl, C3-C7-cycloalkyl or phenyl) or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and R23 is NR26R27 where R26 and R27 are each hydrogen, C1-C6-alkyl, Co-C4-alkylphenyl, where the phenyl ring may furthermore be substituted by up to 3 radicals Cl, F, Br, I, C1-C4-alkyl, CF3, CN, S02-C1-C4-alkyl, S02-phenyl, N02 NH2/ NHC0-C1-C4-alkyl, NHCO-phenyl, OH, 0-C1-C4-alkyl, 0-C1-C4-alkylphenyl, and NR26R27 may also be a cyclic amine having 3 to 8 members, where a further hetero atom such as 0, N and S may also additionally be present, and the ring may furthermore be substituted by a radical R28 where R28 may be C1-C4-alkyl and C1-C4-alkylphenyl, R2 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl which is unsubstituted or substituted by C1-C6-alkyl or C3-C7-cycloalkyl which is unsubstituted or substituted by C1-C6-alkyl, where one carbon atom of the radical may furthermore carry a phenyl ring which in turn may also be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain C1-C4-alkyl, nitro, CF3, cyano, {CH2)O-2-NR322R33 NH-CO-R10, OR10, COOR10, S02-C1-C4-alkyl, S02Ph, CH3, SO2NH, NHS02-C1-C4-alkyl, NHS02Ph and CF3, where R32 and R33, independently of one another, are each hydrogen or C1-C4-alkyl and NR32R33 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R31, COOR31 or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and R31 may have the same meaning as R21, and their tautomeric forms, possible enantiomeric and diastereomeric forms, their prodrugs and possible physiologically tolerated salts. The compounds of the formula I where R1 is hydrogen are preferred. The compounds of the formula I where R2 is hydrogen are preferred. The compounds of the formula I where R4 is hydrogen are preferred. The compounds of the formula I where R3 is bonded to the nitrogen of A are preferred. The compounds of the formula I where R3 is hydrogen, C1-C6-alkyl, benzyl or phenethyl are preferred. The compounds of the formula I where R1, R2 and R4 are each hydrogen and A is piperidine which is bonded at the 4-position on the benzimidazole and R3 is hydrogen, C1-C6-alkyl, benzyl or phenethyl and is bonded in the 1-position on the piperidine ring are particularly preferred. The respective meanings of R5 to R10 are independent of one another in R1 to R4. The preferred meanings of NR8R9, NR24R25 and NR32R33 as cyclic amine, are piperidine, pyrrolidine, piperazine and homopiperazine. In the case of piperazine and homopiperazine, the ring may preferably furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R7 or phenyl. The preferred meaning of A is piperidine, pyrrolidine, piperazine, morpholine or homopiperazine. The compounds of the formula I where A is piperazine or piperidine are particularly preferred. The compounds of the formula I may be used in the form of racemates, enantiomerically pure compounds or diastereomers. If enantiomerically pure compounds are desired, these can be obtained, for exeunple, by carrying out a classical resolution of the racemate with the compounds of the formula I or their intermediates used in a suitable optically active base or acid. The saturated or monounsaturated cyclic structures A may be present as cis-isomers, trans-isomers or mixtures thereof. The present invention also relates to compounds which are mesomers or tautomers of compounds of the formula I. The present invention furthermore relates to the physiologically tolerated salts of the compound I, which can be obtained by reacting compounds I with a suitable acid or base. Suitable acids and bases are listed, for excunple, in Fortschritte der Arzneimittelforschung, 1966, Birkhauser Verlag, Vol. 10, pages 224-285. These include, for example, hydrochloric acid, citric acid, tartaric acid, lactic acid, phosphoric acid, methanesulfonic acid, acetic acid, formic acid, maleic acid, fumaric acid, etc., and sodium hydroxide, lithiiim hydroxide, potassixom hydroxide and Tris. Prodrugs are understood as meaning those compounds which are metabolized in vivo to give compounds of the formula I. Typical prodrugs are phosphates, carbeunates of cunino acids, esters and others. The preparation of the novel benzimidazoles I can be carried out by various routes which are shown in synthesis scheme 1. The benzimidazole I or VII is obtained by condensation of the aldehyde V with phenylenediamines VI, the procedure preferably being carried out in polar solvents, such as ethanol or dimethyIformamide, and with the addition of acids, such as acetic acid, at elevated temperatures, as a rule from 80 to 120°C. It is advantageous for the reaction to add weak oxidizing agents, such as copper(II) salts, which are added as aqueous solution. If, in the benzimidazole VII, R is NH2 novel compounds I are formed directly in the condensation. Otherwise, if R is 0-alkyl, these esters can be reacted with ammonia, if required at elevated temperatures and superatmospheric pressure, to give the amide I. Alternatively, the esters VII can be reacted with hydrazine in polar solvents, such as the alcohols butanol and ethanol or dimethylformamide, at elevated temperatures, preferably from 80 to 130OC, the result being hydrazide VII (R = NHNH2) which can then be reduced under reductive conditions, for example with Raney nickel in alcohols under reflux, to give the amide I. The radical R1 on the benzimidazole radical in I (R1 = H) is introduced under conventional alkylating conditions. Benzimidazoles I are alkylated with R1 — L, where L is a leaving group, using a base at from 25 to 150OC, but mainly at elevated temperatures such as from 60 to 130Oc, the novel product I where R1 hydrogen being obtained. The procedure is carried out in solvents, for example dimethylformamide, dimethylsulfoxide, alcohols, e.g. ethanol, ketones, e.g. methyl ethyl ketone or acetone, aliphatic ethers, e.g. tetrahydrofuran, and hydrocarbons, e.g. toluene, it also being possible to use mixtures. Suitable bases are, for example, alcoholates, e.g. sodium ethanolate and potassium tert-butanolate, carbonates, e.g. potassium carbonate, hydrides, e.g. sodium hydride, and hydroxides, e.g. sodium hydroxide and potassium hydroxide. Various crown ethers, such as 18-crown-6, may also be added in catalytic amounts. Phase transfer conditions may also be employed (for methods, cf. R.C. Larock, Comprehensive Organic Transformations, 1989, page 445 et seq.)« The leaving group L used may be a halide, e.g. bromide, chloride or iodide, or, for excimple, a tolysate or mesylate. Alternatively to the aldehydes V shown in Scheme 1 it is also possible to use benzoic acids, such as IX (cf. Scheme 2), or benzonitriles, such as XIII (cf. Scheme 3), instead of the benzaldehyde. The preparation of these derivatives is carried out analogously to the preparation of the substituted benzaldehydes V. Starting from IX, the condensation to give VII is carried out in two stages. First, the benzoic acid XI is reacted with the aniline VI with a peptide-like coupling to give the amide XII. The conditions used here are the conventional ones which are listed, for example, in Houben-Weyl, Methoden der Organischen Chemie, 4th Edition, E5, Chapter V, or C.R. Larock, Comprehensive Organic Transformations, VCH Publisher, 1989, page 972 et seq. Cyclization to the benzimidazole is then effected at elevated temperatures, for example from 60 to 180°C, with or without solvents, such as dimethylformamide, with the addition of acids, such as acetic acid, or directly in acetic acid itself. The reaction of the phenylenediamine VI with a benzonitrile XIII is likewise effected under conventional conditions. It is possible to employ solvents, such as dimethylformamide with the addition of acids at elevated temperatures, such as from 60 to 200OC. However, it is also possible to use the conventional methods for the preparation of amides from benzonitriles, as described in J. Amer. Chem. Soc. (1957), 427 and J, Org. Chem. (1987), 1017. The substituted benzimidazoles I contained in the present invention are inhibitors of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30). The inhibitory effect of the substituted benzimidazoles I was determined by an enzyme test already known in the literature, the Ki value being determined as a measure of activity. The benzimidazoles I were measured in this way for an inhibitory effect of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30). The substituted benzimidazoles of the formula I are inhibitors of poly(ADP-ribose)polymerase (PARP) or, as it is also referred to, poly(ADP-ribose)synthase (PARS) and can therefore be used for the treatment and prophylaxis of disorders which are associated with increased activity of these enzymes. The compounds of the formula I can be used for preparing drugs for the treatment of damage following ischemias and for prophylaxis where ischemias of various organs are expected. The present benzimidazoles of the formula I can then be used for the treatment and prophylaxis of neurodegenerative disorders which occur after ischemia, trauma (craniocerebral trauma), massive bleeding, subarachnoid hemorrhages and stroke, and of neurodegenerative disorders such as multi-infarct dementia, Alzheimer's disease and Huntington's disease and of epilepsies, in particular of generalized epileptic attacks, for example petit mal and tonoclonic attacks and partial epileptic attacks such as temporal lobe, and complex partial attacks, and furthermore for the treatment and prophylaxis of cardiac damage following myocardial ischemias and damage to the kidneys following renal ischemias, for example acute renal insufficiency, acute renal failure, damage which is caused by drug therapy such as, for example, during ciclosporin therapy or damage which occurs during or after a kidney transplantation. Furthermore, the compounds of the formula I can be used for the treatment of acute myocardial infarction and damage which occurs during and after its lysis under treatment with drugs (for example with TPA, reteplase or streptokinase or mechanically with a laser or Rotablator) and of microinfarcts such as, for example, during and after replacement of the heart valve, aneurysm resections and heart transplantations. The present benzimidazoles I can also be used for the treatment of a revascularization of critically narrowed coronary arteries, for example in PCTA and bypass operations, and critically narrowed peripheral arteries, for example arteries of the leg. Moreover, the benzimidazoles I may be useful in the chemotherapy of tumors and their metastasis and for the treatment of inflammations and rheumatic disorders, for example rheumatoid arthritis. In addition, the compounds of the formula I can be used to treat diabetes mellitus or to treat sepsis and multiorgan failure such as, for exeimple, during septic shock and adult respiratory distress syndrome (ARDS, shock lung). The novel drug formulations contain a therapeutically effective amount of the compounds I in addition to the conventional drug excipients. For local external application, for example in the form of powders, ointments or sprays, the active compounds may be present in the conventional concentrations. As a rule, the active compounds are present in an amount of from 0.001 to 1, preferably from 0.001 to 0.1, % by weight. In the case of internal use, the preparations are administered in single doses. From 0.1 to 100 mg per kg of body weight are administered in a single dose. The formulation can be administered daily in one or more doses, depending on the type and severity of the disorders. Depending on the desired method of application, the novel drug formulations contain the conventional carriers and diluents in addition to the active compound. For local external application, pharmaceutical excipients such as ethanol, isopropanol, oxethylated castor oil, oxethylated hydrogenated castor oil, polyacrylic acid, polyethylene glycol, polyethylene glycol stearate, ethoxylated fatty alcohols, liquid paraffin, vaseline and lanolin, may be used. For internal use, for example, lactose, propylene glycol, ethanol, starch, talc and polyvinylpyrrolidone are suitable. Antioxidants, such as tocopherol and butylated hydroxyanisole, and butylated hydroxytoluene, flavor-improving additives, stabilizers, emulsifiers and lubricants may furthermore be present. The substances contained in the formulation in addition to the active compound, and the substances used in the preparation of pharmaceutical formulations, are toxicologically safe and are compatible with the respective active compound. The preparation of the drug formulations is carried out in a conventional manner, for exanple by mixing the active compound with other conventional carriers and diluents. The drug formulations can be administered by various methods of application, for example perorally, parenterally, such as intravenously by infusion, subcutaneously, intraperitoneally and topically. Thus, the formulations such as tablets, emulsions, infusion and injection solutions, pastes, ointments, gels, creams, lotions, powders and sprays are possible. In addition to the substances stated in the examples, the following compounds are particularly preferred and can be synthesized according to said preparation methods: 1. 2-(N-(0-tert-butoxycarbonyl)piperidin-4-yl)benzimidazole-4-carboxamide 2. 2-(N-methylpiperidin-4-yl)benzimidazole-4-carboxamide 3 . 2- (N-isopropylpiperidin-4-yl)benzimidazole-4-carboxeunide 4. 2-(N-cyclohexylpiperidin-4-yl)benzimidazole-4-carbox£unide 5. 2-(N-(trans-4-propylcyclohex-l-yl)piperidin-4-yl)-benzimidazole-4-carboxamide 6 - 2-(N-benzylpiperidin-4-yl)benzimidazole-4-carboxcimide 7• 2-(N-(2-phenyl)eth-l-yl)piperidin-4-yl)benzimidazole-4-carboxamide 8. 2-(N-(2(4-fluorophenyl)eth-l-yl)piperidin-4-yl)benzimidazole'-4-c arboxamide 9. 2-(N-(2(4-chlorophenyl)eth-l-yl)piperidin-4-yl)benzimidazole-4 -c ar boxcunide 10. 2-(N-(2(4-bromophenyl)eth-l-yl)piperidin-4-yl)benzimida2ole-4-carboxamide 11. 2-(N-(2(4-iodophenyl)eth-l-yl)piperidin-4-yl)benzimidazole-4 -c ar boxcimide 12. 2-(N-(2(4-nitrophenyl)eth-l-yl)piperidin-4-yl)benzimidazole-4 -carboxeunide 13. 2-(N-(2(4-cyanophenyl)eth-l-yl)piperidin-4-yl)benzimidazole-4-c arboxamide 14. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-l-yl)piperidin-4-yl)-benzimidazole-4-carboxeunide 15. 2-(N-(2(4-methylphenyl)eth-l-yl)piperidin-4-yl)benzimidazole-4-carboxamide 16.. 2-(N-(2(4-hydroxyphenyl)eth-l-yl)piperidin-4-yl)-benzimidazole-4-carboxamide 17. 2-(N-(2(4-methoxypheny1)eth-1-y1)piperidin-4-y1)-benzimida2ole-4-carboxamide 18. 2-(N-(2(4-(N' ,N'-diinethylainino) phenyl) eth-l-yl) piper idin-4-yl)benziinida2ole-4-carboxainide 19. 2-(N-(2(4-(N'-acetylainino)phenyl)eth-l-yl)piperidin-4-yl)-benziniida2ole-4-carboxamide 20. 2-(N-(2(4-(N'-phenylsulfonylajnino)phenyl)eth-l-yl)piperidin-4-yl)benziinidazole-4-carboxainide 21. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-l-yl)piperidin-4-yl)-benzimidazole-4-carboxamide 22. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-l-yl)piperidin-4-yl)-benzimida2ole-4-carboxamide 23. 2-(N-acetylpiperidin-3-yl)benzimidazole-4-carboxamide 24. 2-{N-propylpiperidin-3-yl)benziinidazole-4-carboxamide 25. 2-(N-isopropylpiperidin-3-yl)benziroidazole-4-carboxainide 26. 2-(N-cyclohexylpiperidin-3-yl)benzimidazole-4-carboxamide 27. 2-(N-(trans-4-propylcyclohex-l-yl)piperidin-3-yl)-ben2imidazole-4-carboxamide 28. 2-(N-(2-phenyl)eth-l-yl)piperidin-3-yl)benziiiiidazole-4- carboxamide 29. 2-(N-(2(4-chlorophenyl)eth-l-yl)piperidin-3-yl)benzimidazole- 4-carboxamide 30. 2-pyrrolidin-3-ylbenziinidazole-4-carboxamide 31. 2-(N-acetylpyrrolidin-3-yl)benzimidazole-4-carbox2unide 32. 2-(N(0-tert-butoxycarbonyl)pyrrolidin-3-yl)benzimidazole-4-carboxamide 33. 2-(N-propylpyrrolidin-3-yl)benzimidazole-4-carboxainide 34. 2-(N-isopropylpyrrolidin-3-yl)benzimidazole-4-carboxamide 35. 2-(N-cyclohexylpyrrolidin-3-yl)benziinidazole-4-carboxainide 36. 2-(N-(trans-4-propylcyclohex-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxcunide 37. 2-(N-ben2ylpyrrolidin-3-yl)benzimidazole-4-carboxaiiiide 38. 2-(N-(2-phenyl)eth-l-yl)pyrrolidin-3-yl)benzimidazole-4-carboxamide 39. 2-(N-(2(4-chlorophenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxciinide 40. 2-(N-(2(4-nitrophenyl)eth-l-yl)pyrrolidin-3-yl)benzimidazole-4 -carboxcunide 41. 2-(N-(2(4-cyanophenyl)eth-l-yl)pyrrolidin-3-yl)benziinidazole-4 -carboxainide 42. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxcunide 43. 2-(N-(2(4-methylphenyl)eth-l-yl)pyrrolidin-3-yl)-benziinidazole-4-carboxamide 44. 2-(N-(2(4-hydroxyphenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxainide 45. 2-(N-(2 (4-methoxyphenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxaiiiide 46. 2-(N-(2(4-(N' ,N'-diinethylamino)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimidazole-4-carboxaniide 47. 2-(N-(2(4-(N'-acetylamino)phenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxainide 48. 2-(N-(2(4-(N'-phenylsulfonylamino)phenyl)eth-1-yl)pyrrolidin-3-yl)benzimida2ole-4-carboxamide 49. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxamide 50. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-l-yl)pyrrolidin-3-yl)-benzimidazole-4-carboxamide 51. 2-pyrrolidin-2-ylbenzimidazole-4-carboxamide 52. 2-(N-acetylpiperazin-4-yl)benzimidazole-4-carboxamide 53. 2-(N(0-tert-butoxycarbonyl)piperazin-4-yl)benzimidazole-4-carboxamide 54. 2-(N-methylpiperazin-4-yl)benzimidazole-4-carboxamide 55. 2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxamide 56. 2-(N-isopropylpiperazin-4-yl)benzimidazole-4-carboxamide 57. 2-(N-cyclohexylpiperazin-4-yl)benzimidazole-4-carboxeimide 58. 2-(N-(trans-4-propylcyclohex-l-yl)pipera2in-4-yl)-ben2imidazole-4-carboxamide 59. 2-(N-benzylpiperazin-4-yl)benzimida2ole-4-carboxamide 60. 2-(N-(2-phenyl)eth-l-yl)piperazin-4-yl)benzimidazole-4-carboxamide 61. 2-(N-(2(4-fluorophenyl)eth-l-yl)piperazin-4-yl)-benzimidazole-4-carboxamide 62. 2-(N-(2(4-chlorophenyl)eth-l-yl)piperazin-4-yl)benzimidazole-4-carboxamide 63. 2-(N-(2(4-bromophenyl)eth-l-yl)pipera2in-4-yl)benzimidazole-4 -c ar boxcimide 64. 2-(N-(2(4-iodophenyl)eth-l-yl)piperazin-4-yl)benzimidazole-4-c arboxamide 65. 2-(N-(2(4-nitrophenyl)eth-l-yl)piperazin-4-yl)benzimidazole-4-c arboxamide 66. 2-(N-(2(4-cyanophenyl)eth-l-yl)piperazin-4-yl)benzimidazole-4 -c ar boxcimide 67. 2-(N-(2(4-(trifluoromethyl)phenyl)eth-l-yl)piperazin-4-yl)-benzimidazole-4-carboxamide 68. 2-(N-(2(4-methylphenyl)eth-l-yl)piperazin-4-yl)benzimidazole-4-c arboxamide 69. 2-(N-(2(4-hydroxyphenyl)eth-l-yl)piperazin-4-yl)-benzimidazole-4-carboxamide 70. 2-(N-(2(4-methoxyphenyl)eth-l-yl)piperazin-4-yl)-benzimidazole-4-carboxamide 71.. 2-(N-(2(4-(N',N'-dimethylamino)phenyl)eth-l-yl)piperazin-4- yl)benzimidazole-4-carboxamide 72. 2-(N-(2(4-(N'-acetylamino)phenyl)eth-l~yl)piperazin-4-yl)~ benzimidazole-4-carboxamide 73. 2-{N-(2(4-{N'-phenylsulfonylamino)phenyl)eth-l-yl)piperazin-4-yl )benzijnidazole-4-carboxaxnide 74. 2-(N-(2(4~(phenylsulfonyl)phenyl)eth-l-yl)piperazin-4-yl)-benziinidazole-4-carboxainide 75. 2-(N-(2(4-(methoxycarbonyl)phenyl)eth-l-yl)piperazin-4-yl)-benziinidazole-4-carboxainide 76. 2-homopiperazin-4-ylbenzimidazole-4-carboxainide 77. 2-(N-acetylhomopiperazin-4-yl)benziinidazole-4-carboxainide 78. 2-(N(0-tert-butoxycarbonyl)homopiperazin-4-y 1)benzimidazole-4 -carboxaiaide 79. 2-(N-methylhomopiperazin-4-yl)benziinidazole-4-carboxamide 80. 2-(N-propylhomopiperazin-4-yl)benzimidazole-4-carboxainide 81. 2-(N-isopropylhoinopiperazin-4-yl)benzimidazole-4-carboxamide 82. 2-(N-cyclohexylhomopiperazin-4-yl)benziinidazole-4-carbox6unide 83. 2-(N-(trans-4*propylcyclohex-l-yl)hoinopiperazin-4-yl)-benzimidazole-4-carboxamide 84. 2-(N-benzylhomopiperazin-4-yl)benziinidazole-4-carboxainide 85. 2-(N-(2-phenyl)eth-l-yl)homopipera2in-4-yl)ben2imidazole-4-carboxamide 86. 2-(N-(2(4-fluorophenyl)eth-l-yl)hoinopiperazin-4-yl)-benzimidazole-4-carboxamide 87. 2-(N-(2(4-chlorophenyl)eth-l-yl)hoinopiperazin-4-yi)ben2-imidazole-4-carboxamide 88. 2-(N-(2(4-bromophenyl)eth-l-yl)homopiperazin-4-yl)benzim-idazole-4-carboxamide 89. 2-(N-(2(4-iodophenyl)eth-l-yl)homopipera2in-4-yl)benzim-idazole-4-carboxcunide 90. 2-(N-(2(4-nitrophenyl)eth-l-yl)homopiperazin-4-yl)benzimidazole-4 -carboxamide 91- 2-(N-(2(4-cyanophenyl)eth-l-yl)homopipera2in-4-yl)ben2im-idazole-4-carboxamide 92. 2-(N-(2(4-{trifluoromethyl)phenyl)eth-l-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide 93. 2-(N-(2(4-methylphenyl)eth-l-yl)homopiperazin-4-yl)-benzimidazole-4-carboxamide 94. 2-(N-(2(4-hydroxyphenyl)eth-l-yl)homopiperazin-4-yl)benzimidazole-4 -carboxcunide 95. 2-(N-(2(4-methoxyphenyl)eth-l-yl)homopiperazin-4-yl)benz-imidazole-4-carboxcLmide 96. 2-(N-(2(4-(N',N'-dimethylamino)phenyl)eth-l-yl)homopiperazin-4-yl)benzimidazole-4-carboxamide 97. 2-(N-(2{4-(N'-acetylamino)phenyl)eth-l-yl)homopiperazin-4-yl) -benzimidazole-4-carboxamide 98. 2-(N-(2(4-(N'-phenylsulfonylamino)phenyl)eth-l-yl)homo-piperazin-4-yl)benzimidazole-4-carboxamide 99. 2-(N-(2(4-(phenylsulfonyl)phenyl)eth-l-yl)homopipera2in-4-yl) benzimidazole-4-carboxcunide 100.2-(N-(2(4-(methoxyc arbony1)phenyl)eth-1-yl)homopiperaz in-4- yl)benziinidazole-4-carboxainide 101. l-methyl-2-(piperidin-4-yl)benzimidazole-4-carboxainide 10 2.2-(N(0-tert-butoxycarbonyl)piperidin-4-yl)-1-methylbenz imid- azole-4-carboxamide 103.l-methyl-2-(N-methyl-piperidin-4-yl)benziinidazole-4-carbox- amide 104.l-methyl-2-(N-isopropyl-piperidin-4-yl)ben2imida2ole-4- carboxamide 105.2-(N-benzylpiperidin-4-yl)-l-methylben2imidazole-4- carboxcunide 106.1-methyl-2-(N-(2-phenyl)eth-l-yl)piperidin-4-yl)- benziinidazole-4-carboxainide 107.2-(N-(2(4-chlorophenyl)eth-l-yl)piperidin-4-yl)-l-methyl- benzimidazole-4-carboxcunide 108.2-(N-acetylpiperidin-3-yl)-l-methylbenziinidazole-4-carbox- amide 109.l-methyl-2-(pyrrolidin-3-yl)benzimidazole-4-carboxamide 110.2-(N-acetylpyrrolidin-3-yl)-l-methylbenzimidazole-4-carbox- axnide 111.2-(N(0-tert-butoxycarbonyl)pyrrolidin-3-yl)-l-methyl- benziinidazole-4-carboxainide 112.l-inethyl-2-(N-methylpyrrolidin-3-yl)benzimidazole-4- carboxamide 113.l-methyl-2-(N-propylpyrrolidin-3-yl)benzimidazole-4- carboxamide 114.l-methyl-2-(N-isopropylpyrrolidin-3-yl)benzimidazole-4- carboxamide 115.2-(N-benzylpyrrolidin-3-yl)-l-methylbenzimida201e-4- carboxamide 116.1-methyl-2-(N-(2-phenyl)eth-l-yl)pyrrolidin-3-yl)- benzimidazole-4-carboxainide 117.2-(N-(2(4-chlorophenyl)eth-l-yl)pyrrolidin-3-yl)-l- inethylbenziinidazole-4-carboxamide 118. l-methyl-2-(pyrrolidin-2-yl)benziinidazole-4-carboxainide 119.2-(N-acetylpyrrolidin-2-yl)-l-methylbenziinidazole-4- carboxamide 120.l-methyl-2-piperazin-4-ylbenziinidazole-4-carboxamide 121.2-(N-acetylpiperazin-4-yl)-l-methylbenziniidazole-4- carboxcunide 122.2-(N(0-tert-butoxycarbonyl)piperazin-4-yl)-l-inethyl- benzimidazole-4-carboxamide 123.l-methyl-2-(N-methylpiperazin-4-yl)benzimidazole-4-carboxamide 124.l-methyl-2-(N-propylpiperazin-4-yl)benzimidazole-4- carboxaxnide 125. l-inethyl-2-(N-isopropylpiperazin-4-yl)benzimidazole-4- carboxamide 126.2-(N-benzylpiperazin-4-yl)-l-methylbenziinidazole-4- carboxamide 127.1-methyl-2-(N-"( 2-phenyl )eth-l-yl) piper azin-4-yl)- benziinidazole-4-carbox2unide 128.2-(N-(2(4-chlorophenyl)eth-l-yl)piperazin-4-yl)-l-methyl- benzimidazole-4-carboxamide 129.2-(homopiperazin-4-yl)-l-methylbenzimidazole-4-carboxainide 130.2-(N-acetylhomopiperazin-4-yl)-l-methylbenziniidazole-4- carboxcLznide 131.2-(N(0-tert-butoxycarbonyl)homopiperazin-4-yl)-l-methyl- benziinidazole-4-carboxeuiiide 132. l-inethyl-2-(N-methylhomopiperazin-4-yl)benziniidazole-4-carboxamide 133. l-methyl-2-(N-propylhomopiperazin-4-yl)benziinidazole-4-carboxamide 134. l-methyl-2-(N-isopropylhomopiperazin-4-yl)benzimidazole-4-carboxamide 135.2-(N-benzylhomopiperazin-4-yl)-l-methylbenzimidazole-4- carboxamide 136. l-methyl-2-(N-(2-phenyl)eth-l-yl)hoinopiperazin-4-yl)benziinida zole-4-carboxamide 137.2-(N-(2(4-chlorophenyl)eth-l-yl)homopiperazin-4-yl)-l-methyl- benziinidazole-4-carboxainide 138.l-ethyl-2-(piperidin-4-yl)benzimidazole-4-carboxamide 139.2-(piperidin-4-yl)-l-isopropylbenziinidazole-4-carboxamide 140. l-(2-(hydroxy)eth-l-yl)-2-(piperidin-4-yl)benziniidazole-4-carboxamide 141. l-(2-(methoxy)eth-l-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxcunide 142. l-(2-(ainino)eth-l-yl)-2-(piperidin-4-yl)benzimidazole-4-carboxamide 143. l-(2-(N,N-diinethylainino)eth-l-yl)-2-(piperidin-4-yl)benziinid-azole-4-carboxciinide 144. l-(2-(piperidin-l-yl)eth-l-yl)-2-(piperidin-4-yl)benzimid-azole-4-carboxainide 145.2-(piperidin-4-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)benzimid- azole-4-carboxciinide 146.1-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2-(piperidin-4-yl)- benzimidazole-4-carboxamide 147. l-ethyl-2-(piperidin-3-yl)benzimidazole-4-carboxamide 148.2-(piperidin-3-yl)-l-isopropylbenzimidazole-4-carboxeunide 149. l-(2-(hydroxy)eth-l-yl)-2-(piperidin-3-yl)benziniidazole-4- carboxamide 150.l-(2-(methoxy)eth-l-yl)-2-(piperidin-3-yl)benziinidazole-4-carboxamide 151.1-(2-(ainino)eth-l-yl)-2-(piperidin-3-yl)ben2iinidazole-4- carboxamide 152.1-(2-(N,N-dimethylainino)eth-l-yl)-2-(piperidin-3-yl)- benzimidazol-4-carboxainide 153.1-(2-(piperidin-.l-yl)eth-l-yl)-2-(piperidin-3-yl)benzixnid- azole-4-carboxamide 154.2-(piperidin-3-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)benziniid- azole-4-carboxainide 155.1-(2-(2-ethyl-piperidin-l-yl)eth-l-yl)-2-(piperidin-3-yl)- benziinidazole-4-carboxainide 156. l-ethyl-2-(pyrrolidin-3-yl)benziinidazole-4-carbox£unide 157.l-isopropyl-2-(pyrrolidin-3-yl)benzimidazole-4-carboxcunide 158.l-(2-(hydroxy)eth-l-yl)-2-(pyrrolidin-3-yl)benziinidazole-4- carboxamide 159.l-(2-(methoxy)eth-l-yl)-2-(pyrrolidin-3-yl)benzimidazole-4- carboxamide 160. l-(2-(ainino)eth-l-yl)-2-(pyrrolidin-3-yl)benziinidazole-4- carboxamide 161.l-(2-(N,N-dimethylamino)eth-l-yl)-2-(pyrrolidin-3-yl)-benzimidazole-4-carboxaInide 162.1-(2-(piperidin-l-yl)eth-l-yl)-2-(pyrrolidin-3-yl)benzimid- azole-4-carboxamide 163.2-(pyrrolidin-3-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)benzimid- azole-4-carboxamide 164.1-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2-(pyrrolidin-3-yl)- benzimidazole-4-carboxamide 165.l-ethyl-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide 166.l-isopropyl-2-(pyrrolidin-2-yl)benzimidazole-4-carboxamide 167.l-(2-(hydroxy)eth-l-yl)-2-(pyrrolidin-2-yl)benzimidazole-4- carboxamide 168.l-(2-(methoxy)eth-l-yl)-2-(pyrrolidin-2-yl)benzimida2ole-4- carboxamide 169.l-(2-(amino)eth-l-yl)-2-(pyrrolidin-2-yl)benzimidazole-4- carboxamide 170.1-(2-(N,N-dimethylamino)eth-l-yl)-2-(pyrrolidin-2-yl)- benzimidazole-4-carboxamide 171.l-(2-(piperidin-l-yl)eth-l-yl)-2-(pyrrolidin-2-yl)benzimid- azole-4-carboxamide 172.2-(pyrrolidin-2-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)benzimid- azole-4-carboxamide 173.1-(2-(2-ethyl-piperidin-l-yl)eth-l-yl)-2.(pyrrolidin-2-yl)- benzimidazole-4-carboxamide 174.l-ethyl-2-(piperazin-4-yl)benzimidazole-4-carboxamide 17 5,,. l-isopropyl-2-(piperazin-4-yl)benzimidazole-4-carboxamide 176.l-(2-(hydroxy)eth-l-yl)-2-(piperazin-4-yl)benziinidazole-4- carboxamide 177.l-(2-{inethoxy)eth-l-yl)-2-(piperazin-4-yl)benzimidazole-4- carboxamide 178. l-(2-(ainino)eth-l-yl)-2-(pipera2in-4-yl)benziniidazole-4- carboxamide 179.1-(2-(N,N-diinethylainino)eth-l-yl)--2-(piperazin-4-.yl)- benziiaidazole-4-carbox6unide 180.2-(piperazin-4-yl)-l-(2-(piperidin-l-yl)eth-l-yl)benzimid- azole-4-carboxamide 181.2-(piperazin-4-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)benzimid- azole-4-carboxcumide 182.1-(2-(2-ethyl-piperidin-l-yl)eth-l-yl)-2-(piperazin-4-yl)- benziinidazole-4-carbox£iinide 183. l-ethyl-2-(homopiperazin-4-yl)benziinidazole~4-carboxainide 184.l-isopropyl-2-(homopiperazin-4-yl)benziinidazole-4~carboxamide 185.l-(2-(hydroxy)eth-l-yl)-2-(homopiperazin-4-yl)ben2imidazole- 4-carboxamide 186.l-(2-(inethoxy)eth-l-yl)-2-(homopiperazin-4-yl)benzimidazole- 4 -carboxcunide 187. l-(2-(ainino)eth-l-yl)-2-(homopipera2in-4-yl)benzimidazole-4-carbox2unide 188. l-(2-(N,N-diinethylaniino)eth-l-yl)-2-(homopipera?in-4-yl)-benzimidazole-4-carboxainide 189.2-(homopiperazin-4-yl)-l-(2-(piperidin-l-yl)eth-l-yl)- benziinidazole-4-carboxainide 190.2-(hoinopiperazin-4-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)- benzimidazole-4-carboxamide 191.l-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2-(hoinopiperazin-4- yl) benziinidazole-4-carboxainide 192.l-ethyl-2-(N-propylpiperidin-4-yl)benziinidazole-4-carbox- amide 193.l-isopropyl-2-(N-propylpiperidin-4-yl)benziinidazole-4- carboxamide 194.l-(2-(hydroxy)eth-l-yl)-2-(N-propylpiperidin-4-yl)benziinid- a2ole-4-carboxamide 195. l-(2-(methoxy)eth-l-yl)--2-(N-propylpiperidin-4-yl)ben2ixnid- azole-4-carboxamide 196.l-(2-(amino)eth-l-yl)-2-(N-propylpiperidin-4-yl)benzimid- azole-4-carboxamide 197.l-(2-(N,N-dimethylamino)eth-l-yl)-2-(N-propylpiperidin-4-yl)- benzimidazole-4-carboxcimide 198.1-(2-(piperidin-l-yl)eth-l-yl)-2-(N-propylpiperidin-4-yl)- benzimidazole-4-carboxamide 199.2-(N-propylpiperidin-4-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)- benzimidazole-4-carboxamide 200.1-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2-(N-propylpiperidin-4-yl)benziinidazole-4-carboxainide 201.l-ethyl-2-(N-propylpiperidin-3-yl)benzimida2ole-4-carboxainide 202.l-isopropyl-2-(N-propylpiperidin-3-yl)benziinidazole-4- carboxamide 203.l-(2-(hydroxy)eth-l-yl)-2-(N-propylpiperidin-3-yl)benzimid- azole-4-carboxamide 204. l-(2-(methoxy)eth-l-yl)-2-(N-propylpiperidin-3'-yl)benziinid- azole-4-carboxainide 205.l-(2-(amino)eth-l-yl)-2-(N-propylpiperidin-3-yl)benzimid- azole-4-carboxainide 206.1-(2-(N,N-diinethylainino)eth-l-yl)-2-(N-propylpiperidin-3-- yl )benziinidazole-4-carboxcunide 207.1-(2-(piperidin-l-yl)eth-l-yl)-2-(N-propylpiperidin-3-yl)- benzimidazole*4-carboxainide 208.2-(N-propylpiperidin-3-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)- benzimidazole-4-carboxamide 209.l-(2-(2-ethylpiperidin-'l-yl)eth-l-yl)-2-(N"propylpiperidin- 3-yl)benziinidazole-4-carboxainide 210.l-ethyl-2-(N-propylpyrrolidin-3-yl)benziinidazole-4-carbox- amide 211 l-isopropyl-2-(N-propylpyrrolidin-3-yl)benziinidazole-4- carboxamide 212.l-(2-(hydroxy)eth-l-yl)-2-(N-propylpyrrolidin-3-yl)benzimid- azole-4-carbox£Linide 213.l-(2-{methoxy)eth-l-yl)-2-(N-propylpyrrolidin-3-yl)benzimid- azole-4-carboxainide 214. l-(2-(ainino)eth-l-yl)-2-(N-propylpyrrolidin-3-yl)benziinid- a2ole-4-carboxcimide 215.1-(2-(N,N-dimethylamino)eth-l-yl)-2-(N-propylpyrrolidin-3- yl)benzimidazole-4-carboxainide 216.1-(2-(piperidin-l-yl)eth-l-yl)-2-(N-propylpyrrolidin-3-yl)- benziinidazole-4-carboxamide 217.2-(N-propylpyrrolidin-3-yl)-l-(2-(pyrrolidin-l-yl)eth-l-yl)- benziniidazole-4-carbox2anide 218.1-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2"(N-propylpyrrolidin- 3-yl)benzimidazole-4-carboxamide 219.l-ethyl-2-(N-propylpyrrolidin-2-yl)benziinida2ole-4-carbox- amide 220.l-isopropyl-2-(N-propyl-pyrrolidin-2-yl)benzimidazole-4- carboxamide 221,l-(2-(hydroxy)eth-l-yl)-2-(N-propylpyrrolidin-2-yl)benzimid- azole-4-carboxainide 222.l-(2-(methoxy)eth-l-yl)-2-(N-propylpyrrolidin-2-yl)benzimid- azole-4-carboxainide 223. l-(2-(cunino)eth-l-yl)-2-(N-propylpyrrolidin-2-yl)benziinid- azole-4-carboxamide 224.1-(2-(N,N-diinethylainino)eth-l-yl)-2-(N-propylpyrrolidin-2- yl)benzimida2ole-4-carboxainide 225.1-(2-(piperidin-l-yl)eth-l-yl)-2-(N-propylpyrrolidin-2-yl)- benzimidazole-4-carboxamide 226*2-(pyrrolidin-2-yl)-l-(2-(N-propylpyrrolidin-l-yl)eth-l-yl)- benziinidazole-4-carboxainide 227.1-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2-(N-propylpyrrolidin- 2-yl)benziinidazole-4-carboxamide 228.l-ethyl-2-(N-propylpiperazin-4-yl)benzimidazole-4-carboxaniide 229.l-isopropyl-2-{N-propylpiperazin-4-yl)benzimidazole-4- carboxamide 230.l-(2-(hydroxy)eth-l-yl)-2-(N-propylpipera2in-4-yl)benzimid- a2ole-4-carboxamide 231. l-.(2-(methoxy)eth-l-yl)-2-(N-propylpipera2in-4-yl)ben2iinid- a2ole-4-carboxeanide 232.l-(2-(ainino)eth-l-yl)-2-{N-propylpiperazin-4-yl)ben2imid- azole-4-carboxainide 233.1-(2-(N,N-dimethylamino)eth-l-yl)-2-(N-propylpiperazin-4-yl)- ben2imidazole-4-carboxamide 234.1-(2-{piperidin-l-yl)eth-l-yl)-2-(N-propylpipera2in-4-yl)- ben2iinida2ole-4-carboxainide 235.2-(N-propyl-piperazin-4-yl)-l-(2-{pyrrolidin-l-yl)eth-l-yl)- ben2imida2ole-4-carbox£iinide 236.l-(2"(2-ethylpiperidin-l-yl)eth-l-yl)-2-(N-propyl-piperazin- 4-yl)benziinida2ole-4-carboxamide 237.l-ethyl-2-(N-propylhoinopiperazin-4-yl)ben2imidazole-4- carboxainide 238- l-isopropyl-2-(N-propylhomopiperazin-4-yl)ben2iinida2ole-4- carboxamide 239.l-(2-(hydroxy)eth-l-yl)-2-(N-propylhomopiperazin-4-yl)- ben2iinida20le-4-carboxamide 240.l-(2-(methoxy)eth-l-yl)-2-(N-propylhoinopipera2in-4-yl)- benzimida2ole-4-carboxainide 241.l-(2-(amino)eth-l-yl)-2-(N-propylhoinopiperazin-4-yl)- benzimidazole-4-carboxamide 242. l-(2-(N,N-diiaethylainino)eth-l-yl)-2-(N-propylhomopiperazin-4 -yl) benz iinidazole-4 -carboxamide 243. l"(2-(piperidin-l-yl)eth-l-yl)-2-(N-propylhoinopipera2in-4- yl)ben2imida2ole-4-carboxainide 244.2-(N-propylhoinopipera2in-4-yl)-l-(2-(pyrrolidin-l-yl)eth-l- yl)ben2imida20le-4-carboxainide 245.1-(2-(2-ethylpiperidin-l-yl)eth-l-yl)-2-(N-propylhomo- pipera2in-4-yl)ben2imida2ole-4-carboxainide 246.6-chloro-2-(piperidin-4-yl)ben2imidazole-4-carboxainide 247.6-chloro-2-{piperidin-3-yl)benz iinidazole-4-carboxamide 248.6-chloro-2-(pyrrolidin-3-yl)ben2imida2ole-4-carboxaniide 249.6-chloro-2-(piperazin-4-yl)benzimidazole-4-carboxcunide 250.6-chloro-2-(homopiperazin-4-yl)benziinidazole-4-carbox£uiiide 251.6-ethyl-2-( piper idin-4-yl)benziinidazole-4-carboxeunide 252.6-ethyl-2-(piperidin-3-yl)benzimidazole-4-carboxainide 253.6-ethyl-2-(pyrrolidin-3-yl)benziinidazole-4-carboxainide 254.6-ethyl-2-(piperazin-4-yl)benziinidazole-4-carboxainide 255.6"ethyl-2-(homopiperazin-4-yl)ben2iinidazole-4-carboxcunide 256.6-ainino-2-(piperidin-4-yl)benzimidazole-4-carboxainide 257.6"amino-2-(piperidin-3-yl)beuz imidazole-4-carboxamide 258.6-ainino-2-(pyrrolidin-3-yl)benzimidazole-4-carboxcunide 259.6-amino-2-(piperazin-4-yl)benzimidazole-4-carboxainide 260.6-amino-2-(homopiperazin-4-yl)benz imidazole-4-carboxeimide 261.2-(piperidin-4-yl)-6-(pyrrolidin-l-yl)benzimidazole-4- carboxamide 2 6 2.2-(piperidin-3-yl)-6-(pyrrolidin-1-yl)benzimidazole-4- carboxamide 263.2-(pyrrolidin-3-yl)-6-(pyrrolidin-l-yl)benzimidazole-4- carboxamide 264.2-(piperazin-4-yl)-6-(pyrrolidin-l-yl)benzimida2ole-4- carboxamide 265.2-(homopiperazin-4-yl)-6-(pyrrolidin-l-yl)ben2imidazole-4- carboxamide 266.2-(3-methylpiperidin-4-yl)benzimidazole-4-carboxcunide 267.2-(3-cyclohexylpiperidin-4-yl)benzimidazole-4-carboxeunide 268 • 2-(2-cyclohexylpiperidin-4-yl)benzimidazole-4-carboxcuriide 2 6 9.2-(3-phenylpiperidin-4-yl)benzimidazole-4-carboxamide 270.2-(4-phenylpiperidin-4-yl)benzimidazole-4-carboxamide 271.2-(2-(hydroxycarbonyl)piperidin-4-yl)benzimidazole-4- carboxamide 2 7 2.2-(2-(ethoxycarbonyl)piperidin-4-yl)benzimidazole-4- carboxamide 273.2-(2-(cyclohexyloxycarbonyl)piperidin-4-yl)benzimidazole-4- carboxamide 274.2-(2-(benoxycarbonyl)piperidin-4-yl)benzimidazole-4- carboxamide 275.2-(2-(phenoxycarbonyl)piperidin-4-yl)benzimidazole-4- carboxamide Example 1 2-(Piperidin-4-yl)benzimidazole-4-carboxamide • 2 HCl CONHg si >—V X 2 HCl a) N-(2-Amino-3-ethoxycarbonyl)-1-(tert-butoxycarbonyl)-piperidine-4-carboxanilide 5.5 g (24 mmol) of l-(tert-butoxycarbonyl)piperidine-4-ccu:boxylic acid and 4.3 g (24 mmol) of ethyl 2,3-diaminobenzoate were dissolved with 6.0 g (60 mmol) of triethylamine and 3.2 g (24 mmol) of l-hydroxybenzotriazole in 100 ml of anhydrous tetrahydrofuran. At 0OC, 4.6 g (24 mmol) of N' - (3 -dimethylaminopropyl) -N-ethylcarbodiimide were then added and the whole was stirred for 1 hour. Stirring was then continued for 24 hours at room temperature. The reaction mixture was evaporated down under reduced pressure and the residue obtained was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The ethyl acetate phase was also washed with 5% strength aqueous citric acid solution, dried and evaporated down under reduced pressure. 8.4 g of the product were obtained. b) Ethyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)ben2imidazole-4- carboxylate 8.1 g of the intermediate la in 100 ml of concentrated acetic acid were refluxed for 30 minutes. The whole was then evaporated down under reduced pressure and the residue was partitioned between ethyl acetate and water. The ethyl acetate phase was also washed with aqueous sodium bicarbonate solution and water then evaporated down under reduced pressure. 4.6 g of the product were obtained. c) 2-Piperidin-4-ylben2imidazole-4-carboxylate x 2 HCl 3.7 g (9.9 mmol) of the intermediate lb were added to 50 ml of a 4M solution of hydrogen chloride in dioxane and stirred for 1 hour at room temperature. Thereafter, the batch was diluted with a large amount of ether and the resulting precipitate was filtered off with suction. 3.2 g of the product were obtained. d) 2-Piperidin-4-ylbenzimidazole-4-carbohydrazide 2.7 g (7.8 mmol) of the intermediate Ic and 2.7 g (54 mmol) of hydrazine in 30 ml of n-butanol were refluxed for 15 hours. Thereafter, the whole was evaporated down under reduced pressure and the residue obtained was partitioned between ethyl acetate and aqueous sodium bicarbonate solution. The organic phase was separated off, dried and evaporated down under reduced pressure. 0.9 g of the product was obtained. e) 2-Piperidin-4-ylbenziinidazole-4-carboxamide x 2 HCl About 2.4 g of Raney nickel in 20 ml of water were added to 0.8 g (3.1 mmol) of the intermediate Id in 20 ml of dimethylformamide, and the whole was heated to lOO^c for 8 hours. The reaction mixture was then filtered. The residue was taken up in ethanol and a crude product was precipitated by adding ether. The precipitate was dissolved in isopropanol, and a solution of hydrogen chloride in isopropanol was added. The resulting precipitate was filtered off with suction. 0.52 g of the product was obtained. iR-NMR (De-DMSO). 6 = 1.8-2.3 (4H), 2.8-3.5 (5H), 7.2 (IH), 7.7 (IH), 7.8 (IH), 8.5 (broad) and 9.2 (broad) ppm. Example 2 2-Piperidin-4-ylbenzimidazole-4-carboxamide The example was prepared analogously to Example 1. iH-NMR (De-DMSO). 6 = 1.7 (IH), 1.9-2.2 (4H), 2.75 (IH), 3.8 (IH), 7.2 (IH), 7.6 (IH), 7.8 (IH) and 9.3 (broad) ppm. Example 3 2-(N-Acetylpiperidin-4-yl)benzimidazole-4-carboxcimide a) Methyl 2-(N-acetylpiperidin-4-yl)benzimidazole-4-carboxylate 3.3 g (19.9 mmol) of methyl 2,3-diaminobenzoate were dissolved in 100 ml of methanol, and a solution of 4.0 g (25.8 mmol) of N-acetylpiperidine-4-carbaldehyde in 100 ml of methanol was added dropwise at room temperature. The whole was stirred for about 10 minutes at room temperature. Thereafter, 5.2 g (25.8 mmol) of copper(II) acetate, which was dissolved in 100 ml of water, were added dropwise and the whole was refluxed for 30 minutes. After cooling, 25 ml of concentrated hydrochloric acid were added carefully and the whole was again refluxed. 7.15 g (29.8 mmol) of sodium sulfide nonahydrate, dissolved in 100 ml of water, were then added dropwise and the whole was boiled for a further 10 minutes. After cooling, the reaction solution was evaporated down under reduced pressure. The residue obtained was dispersed in water and filtered. The filtrate was rendered alkaline with aqueous sodium bicarbonate solution and was extracted several times with ethyl acetate. The combined organic phases were washed with water, dried and evaporated down under reduced pressure. 4.5 g of the product were obtained. b) 2-(N-Acetylpiperidin-4-yl)ben2imidazole-4-carbohydrazide 4.3 g (14.9 mmol) of the intermediate 3a were refluxed with 3.7 g (74.3 mmol) of hydrazine hydrate in 100 ml of ethanol for 2.5 hours. The whole was then evaporated down under reduced pressure, the crude product obtained being used directly in the following reaction step. c) 2-(N-Acetylpiperidin-4-yl)benzimidazole-4-carboxamide 5 g Raney nickel were added to a mixture of 100 ml of dimethylformamide and 50 ml of water. The residue from reaction step 3b, dissolved with water, was then carefully added dropwise at room temperature so that the gas evolution observed could be controlled. The whole was then heated to lOOOC for 2 hours. After cooling, filtration was carried out and the filtrate was evaporated down under reduced pressure. The residue obtained was taken up in a little methylene chloride and the product was precipitated by carefully adding ether. 3.2 g of the product were obtained. iH-NMR (De-DMSO). 6 = 1.8-2.3 (4H), 2.8-3.5 (5H), 7.2 (IH), 7.7 (IH), 7.8 (IH), 8.5 (broad) and 9.2 (broad) ppm. Example 4 2-{N-Propylpiperidin-4-yl)benz imidazole-4-carboxamide 0.25 g (1 mmol) of the product from Exanple 2, 59 mg (1 mmol) of n-propanal and 125 \il (2 mmol) of acetic acid were dissolved in 25 ml of ethanol. Thereafter, 64 mg (1 mmol) of sodium cyanoborohydride were added at room temperature and the whole was stirred for 16 hours. The reaction solution was evaporated down under reduced pressure and the.residue was partitioned between methylene chloride and aqueous sodium bicarbonate solution. The organic phase was washed with water, separated off, dried and evaporated down under reduced pressure. The residue obtained was purified chromatographically using the mobile phase 4/1 ethyl acetate/methanol, 0.07 g of the product being obtained. iH-NMR (De-DMSO). 8 = 0.9 (3H), 1.5 (2H), 1.9 (2H), 2.3 (2H), 2.9 (2H), 3.3 (IH), 7.25 (IH), 7.6 (IH), 7.8 (IH), 9,3 (IH) and 12.8 (IH) ppm. Example 5 2-Piperidin-3-ylbenzimida2ole-4-carbQxamide x 2 HCl 1.3 g (3.8 mmol) of the product from Excunple 6 were dissolved in 20 ml of isopropanol, and 50 ml of isopropanolic hydrochloride solution were added. The whole was stirred for 1 hour at room temperature. The resulting precipitate was filtered off with suction, 1.1 g of the product being obtained. iH-NMR (De-DMSO). 6 = 1.95-2.3 (3H), 2.45 (IH), 3.2 (IH), 3.5 (IH), 3.9 (IH), 7.6 (IH) and 7.95 (2H) ppm. Example 6 2-(N-(0-tert-Butoxycarbonyl)piperidin-3-yl)benzimidazole-4- carboxamide a) Ethyl 2-cunino-3-(N-(0-tert-butoxycarbonyl)piperidin-3-yl)amido-benzoate 4 g (17.4 mmol) of N-(0-tert-butoxycarbonyl)piperidine-3-carboxylic acid and 4.8 ml (34.9 mmol) of triethyleunine were dissolved in 100 ml of anhydrous tetrahydrofuran. 1.7 ml (17.4 mmol) of ethyl chloroformate, dissolved in 10 ml of anhydrous tetrahydrofuran, were then added dropwise at -lOOC. The whole was stirred for 1 hour at OOC. Thereafter, 2.9 g (17.4 mmol) of methyl 2,3-diaminobenzoate were added, once again at -10°C, and the whole was stirred for 12 hours at room temperature. The reaction solution was evaporated down under reduced pressure and the residue obtained was partitioned between ethyl acetate and water. The organic phase was also washed with aqueous sodium bicarbonate solution and water, dried and evaporated down under reduced pressure. 5.5 g of the product were obtained. b) Methyl 2-(N-(0-tert-butoxycarbonyl)piperidin-3-yl)ben2imidazole-4-carboxylate 5.4 g (14.3 mmol) of the product from 6a in 100 ml of acetic acid were refluxed for 75 minutes. After cooling, the whole was evaporated down under reduced pressure and the resulting residue was purified chromatographically using the mobile phase 1/1 ethyl acetate/heptane. 2.7 g of the product were obtained. c) 2-{N-(0-tert-Butoxycarbonyl)piperidin-3-yl)benzimidazole-4- carbohydrazide 2.3 g (6.4 mmol) of the product from 6b were refluxed with 1.6 g (32 mmol) of hydrazine hydrate in 20 ml of ethanol for 2.5 hours. After coolingr the whole was evaporated down under reduced pressure. The residue was treated with water, the resulting precipitate being filtered off with suction and dried. 1.6 g of the product were obtained. d) 2-(N-0-tert-Butoxycarbonyl)piperidin-3-yl)benzimidazole-4- carboxcunide 1.6 g of the product from 6c were reacted analogously to the method from 3c. 1.3 g of the product were obtained. ^H-NMR (De-DMSO). 6 = 1.4 (IH), 1.5 (IH), 2.9 (IH), 3.1 (IH), 3.9 (IH), 4.2 (IH), 7.3 (IH), 7.7 (IH), 7.8 (IH), 9.1 (broad) and 13 (broad) ppm. The substances mentioned in the following examples were prepared in analogy to Examples 1 to 6: Example 7 2-(N-Benzylpiperidin-3-yl)-benzimidazole-4-carboxamide iH-NMR (Dg-DMSO); 6 = 1.6-1.8(3H), 2.1(2H), 2.3(1H), 2.8(1H), 3.1(1H), 3.2(1H), 3.5(2H), 7.2-7.4(6H), 7.6(2H), 7.8(2H) and 9.2 (broad) ppm. Example 8 2-(N-Methylpiperidin-3-yl)-benzimidazole-4-carboxamide x 2 HCl IH-NMR (D2O): 6 = 2.1(2H), 2.3(1H), 2.5(1H), 3.1(3H), 3.2(1H), 3.5(1H), 3.7(1H), 4.0(2H), 7.7(1H) and 8.0(2H) ppm. Excimple 9 2-Piperazin-4-yl-benzimida2ole-4-carboxamide iH-NMR (De-DMSO): 8 = 2.5(4H), 3.3(4H), 7.2(1H), 7.6-7.7(2H), 7.8(1H) and 9.3(1H) ppm. Example 10 2"(N-Propylpiperidin-3-yl)-ben2imida2ole-4-carboxamide x 2 HCl IH-NMR (De-DMSO): 8 = 0.9(3H), 1.5(2H), 1.9(2H), 2.0(4H), 2.3(2H), 2.9(3H), 7.2(1H), 7.6(2H), 7.8(1H) and 9.3 (broad) ppm. Example 11 2- (N- (3-Phenylprop-l-yl) -piperidin-3-yl) -ben2iniidazole-4- carboxcimide x 2HC1 iH-NMR (Dfi-DMSO): 6 = 2.0-2.5(6H), 2.8(2H), 3.1(1H), 3.2-3.4(3H), 3.7(1H), 3.8-4.0(2H), 7.3-7.5(5H), 7.7(1H) and 8.0{2H) ppm. Example 12 2-(N-Ben2oylpiperidin-3-yl)-benzimidazole-4-carbox6imide iH-NMR (CF3COOD): 6= 1.9(1H), 2.6(1H), 3.8(1H), 3.9-4.2(4H), 4.3(1H), 4.8(1H) and 7.5-8.2(8H) ppm. Excunple 13 2-{N-Ben2ylpiperidin-4-yl)-ben2imidazole-4-carboxcunide x 2 HCl iH-NMR (D2O): 6 = 2,3(2H), 2.6(2H), 3.3(2H), 3.8(3H), 4.5(2H) and 7.5-8.0(8H) ppm. Example 14 2-(1-(l-Methylpiperidin-4-yl)piperidin-4-yl)-ben2imidazole-4- carboxcimide x 3 HCl iH-NMR (De-DMSO): 6 = 1.4(2H), 1.6-2.0(6H), 2.0-2.4(7H), 2.7-3.0(6H), 7.2(1H), 7.7(2H), 7.8(1H) and 9.4 (broad) ppm. Example 15 2-(N-n-Pentylpiperidin-4-yl)-benzimida2ole-4-carboxamide ^H-NMR (De-DMSO): 6= 0.9(3H), 1.2-1.5(6H), 1.7-2.1(6H), 2.3(2H), 2.8-3.0(4H), 7.3(1H), 7.6-7.8(3H), 9.4(1H) and 12.8 (broad) ppm. Excimple 16 2-(N-Isobut-l-yl-piperidin-4-yl)-benzimidazole-4-carboxamide iH-NMR (De-DMSO): 8 = 0.9(6H), 1.8-2.1(lOH), 2.9(2H), 7.2(lH)r 7.6(2H), 7.8(1H), 9.2(1H) and 12.5 (broad) ppm. Example 17 2-(N-n-Butylpiperidin-4-yl)-benzimidazole-4-carboxamide x HCl iH-NMR (De-DMSO): 8 = 0.9(3H), 1.3(2H), 1.7(2H), 2.2-2.4(4H), 3.0-.3.2(4H), 3.4-3.6(3H), 7.5(1H), 7.8-8.0(2H), 8.0(1H), 8.7 (broad) and 10.9 (broad) ppm. Example 18 2-(N-(3-Methyl-but-l-yl)piperidin-4-yl)-benzimidazole-4- carboxamide x HCl iH-NMR (De-DMSO): 6 = 0.9(6H), 1.7(3H), 2.2-2.4(4H), 3.1(4H), 3.3(1H), 3.7(2H), 7.5(1H), 7.8-8.0(3H), 8.7 (broad) and 10.5 (broad) ppm. Example 19 2-(l,4-Diinethylpiperazin-2-yl)-benziinidazole-4-carboxamide x 2 HCl IH-NMR (De-DMSO): 6 = 2.5 (3H), 2.9 (3H), 3.3-3.8 (5H), 3.9 (IH), 5.0 (IH), 7.4 (IH), 7.7 (IH), 7.8 (IH), 7.9 (IH) and 8.6 (broad) ppm. Example 20 2-Piperazin-2-yl-ben2imidazole-4-carboxamide x 2 HCl 1.83 g (3.67 mmol) of the product from Example 23 were introduced into 250 ml of methanol with 1 g of 10% palladium on carbon and hydrogenated with about 165 ml of hydrogen. The catalyst was filtered off with suction, and the filtrate was concentrated. The residue was dissolved in 20 ml of isopropanol, and 50 ml of isopropanolic hydrochloric acid solution were added. The resulting precipitate was filtered off with suction to obtain 1.1 g of the product. ^H-NMR (De-DMSO): 6 = 3.2-3.7(5H), 4.0(1H), 5.2(1H), 7.4(1H), 7.8(1H), 7.9(1H) and 10.2 (broad) ppm. Example 21 2-(N-Isopropylpiperidin-4-yl)-benzimidazole-4-carboxamide x HCl IH-NMR (De-DMSO): 6 = 1.25(6H), 2.3(4H), 3.1(1H), 3.4-3.6(4H), 3.7(1H), 7.5(1H), 7.7-8.0(3H), 8.7(1H) and 10.7 (broad) ppm. Example 22 2-(4-(2-Ethyl-prop-l-yl)piperidin-4-yl)-benzimidazole-4- carboxcimide Example 23 2-(l,4-Dibenzylpiperazin-2-yl)-benzimidazole-4-carboxcimide x 2 HCl IH-NMR (De-DMSO): 6 = 2.95-3.7 (7H), 3.8-4.9 (4H), 7.1-7.55 (8H), 7.65 (2H), 7.85 (2H), 7.94 (IH), 8.7 (broad) and 12.2 (broad) ppm. Example 24 2-(N-Benzylpiperidin-4-yl)-l-(l-benzylpiperidin-4-ylcarbonyl)- benzimidazole-4-carboxamide IH-NMR (De-DMSO): 6 = 1.7(2H), 1.8-2.0(6H), 2.1(4H), 2.5-2.7(2H), 2.8-3.0(4H), 3.5(4H), 7.2-7.5(IIH), 7.7(1H), 8.6(1H), 9.5(1H) and 12.3 (broad) ppm. Example A: Inhibition of the enzyme poly(ADP-ribose)polymerase or PARP (EC 2.4.2.30) A 96-well microtiter plate (Falcon) was coated with histones (type II-AS; SIGMA H7755). In addition, histones were dissolved in carbonate buffer (0.05 M NaHC03; pH 9.4) to a concentration of 50 ug/inl. The individual wells of the microtiter plate were incubated overnight, each with 100 \il of the histone solution. Thereafter, the histone solution was removed and the individual wells were incubated with 200 u1 of a 1% strength BSA (bovine serum albumin) solution in carbonate buffer for 2 hours at room temperature. Washing was then carried out three times with wash buffer (0.05% TweenlO in PBS). For the enzyme reaction, 50 u1 of the enzyme reaction solution per well (5 ^1 of reaction buffer (IM Tris-HCl pH 8.0, 100 mM MgCl2, 10 mM DTT), 0.5 \il of PARP (c = 0.22 \iq/\xl), 4 Rl activated DNA (SIGMA D-4522, 1 mg/ml in water), 40.5 p.1 of H2O) were preincubated with 10 \il of an inhibitor solution for 10 minutes. The enzyme reaction was started by adding 40 ul of a substrate solution (4 ul of reaction buffer (see above), 8 ul of NAD solution (100 ^un in H2O), 28 ul of H2O). The reaction time was 20 minutes at room temperature. The reaction was stopped by washing three times with wash buffer (see above). This was followed by incubation for one hour at room temperature with a specific anti-poly~ADP-ribose antibody. The antibodies used were monoclonal anti-poly-(ADP-ribose) antibodies "lOH" (Biomol SA-276). The antibodies were used in a 1:5000 dilution in antibody buffer (1% BSA and PBS; 0.05% Tween20). Washing three times with wash buffer was followed by incubation for an hour at room temperature with the secondary antibody. Here, an anti-mouse-IgG coupled with peroxidase (Boehringer Mannheim) was used for the monoclonal antibody and an anti-rabbit-IgG coupled with peroxidase (SIGMA A-6154) was used for the rabbit antibody, each in a 1:10,000 dilution in an antibody buffer. After washing three times with wash buffer, the color reaction was carried out using a 100 fil/well of color reagent (SIGMA, TMB ready-mix, T8540) for about 15 minutes at room temperature. The color reaction was stopped by a 100 ul of 2M H2SO4. Measurement was then carried out immediately (450 against 620 nm; ELISA "Easy Reader" EAR340AT plate reader, SLT-Lab instruments, Austria). The Ki can be determined in a conventional manner from the inhibition curves at various substrate concentrations. Example B: Determination of the water solubility A compound to be measured was dissolved directly in a specified volume of water and the resulting solution was brought to a pH of from 5 to 6 with a sodium acetate solution so that the concentration of the active compound to be tested was reached. If the test substance was not present as a water-soluble salt, it was dissolved in a very small amount of dimethyl sulfoxide and then diluted with water (final concentration of dimethyl sulfoxide s 1%), after which the pH was adjusted here too. Here, Example 1 according to the invention gave a solubility of > 0.5%. We claim:- 1. The compound of the formula la or lb I where Ri is hydrogen or branched ox straight-chain Ci^-Cfi-alkyl, where one carbon atom of the alkyl radical may furthermore carry OR^ (where R^ is hydrogen or Ci-C4-alkyl), or one carbon atom in the chain may also carry an =0 group or a group NR^R^/ where R^ and R^, independently of one another, are each hydrogen or Ci-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the carbon chains in R^ or R^ or the ring formed by NR®R9 may furthermore carry a radical R^ which, independently of R^, may have the same meaning as R^, R^ is hydrogen, branched or straight-chain Gi-Cg-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR^R^, NH-CO-R^° or ORS, where R^ and R^, independently of one another, are each hydrogen or Ci-C4-alkyl and NR^R^ together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical (branched or straight-chain Ci-Ce-alkyl, C3-C7-cycloalkyl-Ci-C4-alkyl, CO-R^i- COOR^i or phenyl), and R^^ may be hydrogen, Ci-C4-alkyl or phenyl and R^^ may have the same meanings as R21, A is a saturated or monounsaturated heterocyclic, 4- to 8-membered ring which contains one or two nitrogen atoms, it being possible for an oxygen or sulfur atom additionally to be incorporated, which oxygen or sulfur atom is substituted by R2 and R^, where R2 is hydrogen, branched or straight-chain Ci-Ce-alkyl which may furthermore be substituted by R^^, and a carbon atom of the chain may carry an =0 group. C3-C7-cycloalkyl-Ci-C4-alkyl, -CO-(NH)o,i-R^"^/ COOR^-^ or phenyl, where R^i is hydrogen, branched or straight-chain Ci-Cg-alkyl, C3-C7-cycloalkyl-Ci-C4-alkyl, phenyl-Ci-C4-alkyl, C3-C7-cycloalkyl or phenyl, and each radical may furthermore carry (CH2)o-2-R^'^/ and the respective phenyl ring in turn may furthermore be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain Ci-C4-alkyl, nitro, CF3, cyano, -(CH2)O-2-NR24R25, NH-CO-R10^ OR^O, COOR^O, S02-Ci-C4-alkyl, S02Ph, SO2NH, NHS02-Cl-C4-alkyl, NHS02Ph and CF3, where R24 and R25, independently of one another, are each hydrogen or Ci-C4-alkyl and NR24R25 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain Ci-Ce-alkyl, C3-C7-cycloalkyl-Ci-C4-alkyl, CO-R22, COOR22 (where R22 is hydrogen, branched or straight-chain Ci-Cg-alkyl, C3-C7-cycloalkyl-Ci-C4-alkyl, phenyl-Ci-C4-alkyl, C3-C7-cycloalkyl or phenyl) or phenyl, and Rio is hydrogen, Ci-C4-alkyl or phenyl, and R23 is NR26R27 where R26 and R27 are each hydrogen, Ci-Ce-alkyl, Co-C4-alkylphenyl, where the phenyl ring may furthermore be substituted by up to 3 radicals Cl, F, Br, I, Ci-C4-alkyl, CF3, CN, S02-Ci-C4-alkyl, S02-phenyl, N02f NH2, NHC0-Ci-C4-alkyl, NHCO-phenyl, OH, 0-Ci-C4-alkyl, 0-Ci-C4-alkylphenyl, and NR26R27 may also be a cyclic amine having 3 to 8 members, where a further hetero atom such as 0, N and S may also additionally be present, and the ring may furthermore be substituted by a radical R28 where R28 may be Ci-C4-alkyl and Ci-C4-alkylphenyl, R3 is hydrogen, branched or straight-chain Ci-Ca-alkyl, C3-C7-cycloalkyl-Ci-C4-alkyl which is unsubstituted or substituted by Ci-Cg-alkyl or C3-C7-cycloalkyl which is unsubstituted or substituted by Ci-Ce-alkyl, where one carbon atom of the radical may furthermore carry a phenyl ring which in turn may also be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain Ci-C4-alkyl, nitro, CF3, cyano, (CH2)O-2-NR32R33^ NH-CO-R^O, OR^O^ COOR^O, S02-Ci-C4-alkyl, S02Ph, CH3, SO2NH, NHS02-Ci-C4-alkyl, NHS02Ph and CF3, where R32 and R^^, independently of one another, are each hydrogen or Ci-C4-alkyl and NR32R33 together may be a cyclic cimine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain Ci-Cg-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R31, COOR31 or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and R31 may have the same meaning as R21, and its tautomeric forms, possible enantiomeric and diastereomeric forms, its prodrugs and possible physiologically tolerated salts. 2.. A compound as claimed in claim 1, wherein R1, R2 and R4 are each hydrogen and A is piperidine, pyrrolidine, piperazine, morpholine or homopiperazine and R3 is bonded to the nitrogen of A. 3. A compound as claimed in either of claims 1 and 2, wherein A may be piperdine which has bonded to the 4-position on the benzimidazole and R3 may be hydrogen, C1-C4-alkyl, benzyl or phenylethyl and is in the 1-position on the piperidine ring. 4,. A drug containing a compound as claimed in any of claims 1 to 3 in addition to conventional carriers and excipients. 5« The use of a compound of the formula I as claimed in any of claims 1 to 3 for the preparation of drugs for treating disorders in which pathologically increased PARP activities occur. 6. The use of a compound of the formula I as claimed in any of claims 1 to 3 for the preparation of drugs for treating neurodegenerative disorders and neuronal damage. 7« The use as claimed in claim 6 for treating those neurodegenerative disorders and neuronal damage which are caused by ischemia, trauma or massive bleeding. 8. The use as claimed in claim 6 for treating stroke and craniocerebral trauma. 9. The use as claimed in claim 6 for treating Alzheimer's disease, Parkinson's disease and Huntington's disease. iO., The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for the treatment or prophylaxis of damage through ischemias. 11,. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating epilepsies, in particular generalized epileptic attacks, for example petit mal and tonoclonic attacks and partial epileptic attacks, such as temporal lobe, and complex partial attacks. 12. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating renal damage following renal ischemias, d£unage which is caused by drug therapy, and for treatment during and after kidney transplantations. 13. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating cardiac damage following myocardial ischemias and damage which is caused by reperfusion of narrowed or closed vessels. 14. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating microinfarcts. 15. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treatment associated with revascularization of critically narrowed coronary arteries. 16. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating acute myocardial infarction and deimage during or after its lysis by means of drugs or mechanically. 17. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating tumors and their metastasis. 18. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating sepsis and multiorgan failure. 9 .2 D ., The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating immunological disorders, such as inflammations and rheumatic diseases. The use of a compound of the formula I as claimed in any of claims 1 to 3 for preparing drugs for treating diabetes mellitus. 21 The compound of the formula la or lb substantially as hereinbefore described. 22. A drug substantially as hereinbefore described.

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in-pct-2001-0730-che-abstract.pdf

in-pct-2001-0730-che-claims filed.pdf

in-pct-2001-0730-che-claims grand.pdf

in-pct-2001-0730-che-correspondnece-others.pdf

in-pct-2001-0730-che-correspondnece-po.pdf

in-pct-2001-0730-che-description(complete) filed.pdf

in-pct-2001-0730-che-description(complete) grand.pdf

in-pct-2001-0730-che-form 1.pdf

in-pct-2001-0730-che-form 19.pdf

in-pct-2001-0730-che-form 26.pdf

in-pct-2001-0730-che-form 3.pdf

in-pct-2001-0730-che-form 5.pdf

in-pct-2001-0730-che-other documents.pdf

in-pct-2001-0730-che-pct.pdf