Title of Invention	SUBSTITUTED BETA-CARBOLINES WITH IKB-KINASE INHIBITING ACTIVITY
Abstract	The subject matter of the present invention is directed to novel substituted beta- carbo lines, and specifically compounds of the formula I. which are suitable for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of IKB kinase is involved.

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The invention relates to novel substituted beta-carbolines, a process for their preparation and use thereof as pharmaceuticals. United States Patent 4,631,149 discloses beta-carbolines useful as antiviral, antibacterial and antitumor agents. United States Patent 5,604,236 discloses beta-carboline derivatives containing an acidic group, useful as thromboxane syntheses inhibitors. NFkB is a heterodimeric transcription factor which can activate a large number of genes which code, inter alia, for proinflammatory cytokines such as 1L-1, 11^2, TNFa or 11^6. NFkB is present in the cytosol of cells, building a comμLex with its naturally occurring inhibitor IkB. The stimulation of cells, for examμLe by cytokines, leads to the phosphorylation and subsequent proteolytic degradation of DcB. This proteolytic degradation leads to the activation of NFkB, which subsequently migrates into the nucleus of the cell and there activates a large number of proinflammatory genes. In disorders such as rheumatoid arthritis (in the case of inflammation), osteoarthritis, asthma, cardiac infarct, Alzheimer"s disease or atherosclerosis, NFkB is activated beyond the normal extent. Inhibition of NFkB is also of benefit in cancer therapy, since it is emμLoyed there for the reinforcement of the cytostatic therapy. It was possible to show that pharmaceuticals such as glucocorticoids, salicylates or gold salts, which are emμLoyed in rheumatic therapy, intervene in an inhibitory manner at various points in the NFkB-activating signal chain or interfere directly with the transcription of the genes. The first step in the signal cascade mentioned is the degradation of DcB. This phosphorylation is regulated by die specific IkB kinase. To date, no inhibitors are known which specifically inhibit IkB kinase. In the attempt to obtain active compounds for the treatment of rheumatoid arthritis (in the case of inflammation), osteoarthritis, asthma, cardiac infarct, Alzheimer"s disease, carcinomatous disorders (potentiation of cytotoxic therapies) or atherosclerosis, it has now been found that the benzimidazoles according to the invention are strong and very specific inhibitors of IkB kinase. The invention therefore relates to the compounds of me formula I and/ora stereoisomeric form ofthe compounds ofthe formula Iand/ora physiologically tolerable salt ofthe compounds ofthe formula I, where B6,B?,Ba and B9 are independently selected from the group consisting of carbon atom and nitrogen atom, where B6, B7, Bg and B9 together are no more than two nitrogen atoms at the same time; wherein in case a) the substituents R1, R2 and R independently of one another are 1.1. hydrogen atom, 1.2. halogen, 1.3. -CN, 1.4. -COOH, 1.5. -N02, 1.6. -NH2, 1.7. -0-(Ci-Cio)-alkyl, wherein alkylis unsubstituted or mono- to penta -substituted independently of one another by 1.7.1 phenyl, which is unsubstituted or mono- to penta-substituted by halogen or-0-(C,-C4)-alkyl, 1.7.2 halogen, 1.7.3 -NH3, 1.7.4 -OH, 1.7.5 -COOR16, wherein R16 is hydogen atom or -(CrCi0)-alkyl, 1.7.6 -N02, 1.7.7 -S(0)-R14 , wherein y is zero, 1 or2,R14is -(Ci-Cl0)-alkyl, phenyl, which is unsubstituted or mono-to penta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(R,3)2, wherein R13 is independently of one another hydrogen atom, phenyl, -(C,-C10)-alkyl, -C(0)-(CrC7)-alkyl, -C(0)-phenyl, -C(O)-NH-(CrC7)-alkyl, -C(0)-0-phenyl, -C(0)-NH-phenyl, -C(0)-0-(Ci- C7)-alkyl, -S(0)y-RM, wherein R14 and y are as defined above, and wherein alkyl or phenyl in each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, or R13 together with the nitrogen atom to whk:h it is bonded form a heterocycle having 5 to 7 ring atoms, 1.7.8 -O-phenyl, wherein phenyl is unsubstituted or mono- to penta-substituted independently of one another as denned under 1.7.1 to 1.7.11 above, 1.7.9 a radicafe selected from pyrrolidine, tetrahydropyrkline, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine, 1.7.10 -(C3-C7)-cycloalkylor 1.7.11 =0, 1.8. -N(RI3)2, wherein R13 is as defined in 1.7.7 above, 1.9. -NH-C(0)-R15, wherein R15 is 1.9.1 a radicale selected from pyrrolidine, tetrahydropyrkline, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2- isoxazoline, isothiazolidine, 2-isothiazoline, miophene or thiomorpholine, wherein said radical is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, -CF3, benzyl or by -(Ci-Cio)-alkyl, wherein alkyl is mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.9.2 -(Ci-Cio)-alkyl, wherein alkyl is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or by -0-(Ci-C,o)-alkyl, wherein alkyl is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.9.3 -(C3-C7)-cycloalkyl, 1.9.4 -N(RI3)2, wherein R13 is as defined in 1.7.7 above, or 1.9.5 phenyl, wherein phenyl is unsubstituted or mono-to penta -substituted independently of one another as defined under 1.7.1 to 1.7.11 above, by -O-(CrCi0)-alkyI, by -CN, by -CF3, by -(CrC10)-alkyl, wherein alkylis mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or two substituents of the phenyl radical form a dioxolan ring , 1.10. -S(0)y-R!4, wherein R14 and y are as defined in 1.7.7 above, 1.11. -C(0)-R12, wherein R12 is phenyl or -(C,-C7)-alkyI, wherein alkyl or phenyl are unsubstituted or mono* to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.12. -C(0)-0-R12, wherein R12 is as defined in 11. above, 1.13. -(Ci-Cio)-alkyl, wherein alkylis unsubstituted or mono- to penta -substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.14. -0-(Ci-C6)-akyl-0-(Ci-C6)-aIkyl, 1.15. -0-(Co-Cd)-alkyl-(C3-C7)-cycloalkyl, 1.16. -(C,-C4)-alkyl-N(Rn)2, wherein R13 is as defined in 1.7.7 above 1.17. -CF3or 1.18. -CF2-CF3, R4is 1. -(Ci-Cio)-alkyl, wherein alkylis mono-to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 2. -CF3 . 3. -CF2-CF3, 4. -CN, 5. -S(0)y-R14 , wherein R14 and y are as defined in 1.7.7 above, 6. -NH2, 7. -O-(C,-C10)-alkyl, wherein alkylis mono-to penta-substituted independently of one anotherby 7.1 phenyl, which is unsubstituted or mono- to penta- substituted by halogen or -0-(Ci-C4)-alkyl, 7.2 halogen, 7.3 -NH2, 7.4 -OH, 7.5 -COOR16, wherein R16 is hydogen atom or-(CrC10)-alkyl, 7.6 -N02, 7.7 -S(0)y-R14 , wherein y is zero, 1 or2,Ruis -(Ci-Cio)-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(R13)2, wherein R13 is independently of one another hydrogen atom, phenyl, -(C,-Ci0)-alkyl, -C(0)-(Ci-C7)-alkyl, -C(0)-phenyl, -C(O)-NH-(CrC7)-alkyl, -C{0)-0-phenyl, -C(0)-NH-phenyl, -C(0)-0-(Cr C7)-alkyl,-S(0)y-R"\ wherein R14 and y are as defined above, and wherein aikyl or phenyl in each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, or R13 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, 7.8 -O-phenyl, wherein phenyl is unsubstituted or mono- to penta -subs tituted independently of one another as defined under 1.7.1 to 1.7.11 above, 7.9 a radicale selected from pyrrolidine, tetrahydropyridine, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine,pyridine, pyridazine,pyrazine, oxolan, imidazoline, isoxazolidine, thiophene, 2-isoxazoline, isothiazolidine, 2-isothiazoline, or thiomorpholine, 7.10 -(C3-C7)-cycloalkylor 7.11 =0, 8. -N(RI7)2, wherein R17 is independently of one another hydrogen atom, phenyl,-(Ci-Cio)-Hlkyl,-C(0)-pheiiyl(-C(0)-NH-(Ci-C7)-aIkyl, -CfOMCrCioJ-alkyl, -C(0)-0-phenyl, -C(0)-NH-phenyl, -C(0)-0-{d-C7)- alkyl, -S(0)y-R14, wherein R14 and y are as defined above, and wherein alkyl or phenyl in each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, or R13 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, 9. -NH-C(0)-RIS, wherein R15 is 9.1 a radicale selected from pyrrolidine, tetrahydropyridine, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine.pyrazine.oxolan, imidazoline, isoxazolidine, 2- isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine, wherein said radical is unsubstituted or mono-to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above,-CF3- benzyl or by -(Ci-C]0)-alkyI, wherein alkyl is mono to tri- substituted independently of one anotheras defined under 1.7.1 to 1.7.11 above, 9.2 -(CrCl0)-alkyl, wherein alkyl is mono-to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or by -O-(CrCi0)-alkyl, wherein alkyl is unsubstituted or mono- to penta- substituted independently of one anotheras defined under 1.7.1 to 1.7.11 above, 9.3 -(C3-C7)-cycloalkyl, 9.4 -N(RI3)2, wherein R13 is as defined in 1.7.7 above provided that -N(Rl3)2is not-NH2,or 9.5 phenyl, wherein phenyl is unsubstituted or mono- to penta-substituted independently of one anotheras defined under 1.7.1 to 1.7.11 above, by -O-fd-doJ-alkyl, by -CN, by -CF3, by -(CrCl0)-alkyl, wherein alkyl is mono to tri- substituted independently of one anotheras defined under 1.7.1 to 1.7.11 above or two substituents of the phenyl radical form a dioxolan ring , 10. -C(0)-R12, wherein R12 is phenyl or-(CrC7)-alkyl, wherein alkyl or phenyl are mono-to penta- substituted independently of one anotheras denned under 1.7.1 to 1.7.11 above, 11. -C(0)-0-R12, wherein R12 is as defined in 10. above, 12. -O-(CrC6)-alkyl-0-{CrC6)-alkyl, 13. -0-(C0-C4)-alkyl-(crC7)-cycloalkyl or 14. -(Ci-C4)-alkyl-N(R13)2, wherein R13 is as defined in 1.7.7 above, R5 is 1. a hydrogen atom, 2. -(C,-Cio)-alkyl, wherein alkylis unsubstituted or mono-to penta -substituted independently of one another as defined under 1.7.1 to 1.7.4 above, 3. -C(0)-Ry, wherein R9 is -NH2, -(C]-C,0)-alkyl, wherein alkylis unsubstituted or mono- to penta- substituted independently of one another as defined under 7.1 to 7.4,or-N(Rn)2 .wherein R13 is as defined in 1.7.7 above, or 4. -S(0)2-R , wherein R9 is as defined in 3. above, or R4 and R5 together with the atom to which they are bonded form a heterocycle, or R3 and R5 together with the atom to which they are bonded form a heterocycle containing an additional oxygen atom in the ring and RS,R7 and R8 independently of one anotfierare hydrogen atom or methyl, or in case b) the substituents R",R2 and R4 independently of one another are as defined under 1.1 to 1.18 in case a) above, R3is 1. -CF3, 2. -CF2-CF3, 3. -CN, 4. -COOH, 5. -N02, 6. -NH2, 7. -0-(Ci-Cio)-alkyl, wherein alkylis mono- to penta substituted independently of one another by 7.1 phenyl, which is unsubstituted or mono-to penta- substituted by halogen or -0-(C|-O)-alkyl, 7.2 halogen, 7.3 -NH2, 7.4 -OH, 7.5 -COOR16, wherein R16 is hydogen atom or -(C,-C,o)-aik.yl, 7.6 -N02, 7.7 -S(0)y-R14 , wherein y is zero, 1 or2,R14 is -(C]-Ci0)-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as defined for subs time nts under 1.7.1 to 1.7.11, amino or-N(R13):, wherein R is independently of one another hydrogen atom, phenyl, -(Ci-C,0)-alkyl, -C{0)-(d-C7)-alkyl, -C(0)-phenyI, -C(O)-NH-(CrC7)-alkyI, -C(0)-0-phenyl, -C(0)-NH-phenyl, -C(0)-0-(C,-C7)-alkyl,-S(0)y-R14, wherein R14 and y are as defined above, and wherein alkylorphenyl in each case are unsubstituted or mono- to penta-substituted independently of one another as defined under 1.7.1 to 1.7.11 above, or R13 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, 7.8 -O-phenyl, wherein phenyl is unsubstituted or mono- to penta -substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 7.9 a radicale selected from pyrrolidine, tetrahydropyrkline, piperidine, piperazine, imidazoline, pyrazolidine, fiiran, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine, 7.10 -(C3-C7)-cycloalkylor 7.11 =0, 8. -N(RI3)2, wherein R13 is as defined in 1.7.7 above, 9. -NH-C(0)-R15, wherein R15 is 9.1 a radicale selected from pyrrolidine, tetrahydropyrkline, piperidine, piperazine, imidazoline, pyrazolidine, ftiran, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine, wherein said radical is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, -CF3, benzyl or by-(Ci-Cio)-alkyl, wherein alkylis mono to tri-substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 9.2 -(Ci-Cio)-alkyl, wherein alkylis unsubstituted or mono- to penta-substituted independendy of one another as defined under 1.7.1 to 1.7.11 above or by -O-(C,-Ci0)-alkyl, wherein alkyl is unsubstituted or mono-to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 9.3 -(C3-C7)-cycloalkyl, 9.4 -N(Ri3)2, wherein R13 is as defined in 1.7.7 above, or 9.5 phenyl, wherein phenyl is unsubstituted or mono- to penta-substituted independently of one another as defined under 1,7.1 to 1.7.11 above, by -O-(d-C10)-aIkyI, by -CN, by -CF3, by -(C.-CK,)-alkyl, wherein alkylis mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or two substituents of the phenyl radical form a dioxolan ring , 10. -S(0)y-R14 , wherein R14 and y are as defined in 1.7.7 above, 11. -C(0)-R12, wherein Ri2 is phenyl or -(Ci-C7)~alkyl, wherein alkyl or phenyl are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 12. -C(0)-0-R12, wherein R12 is as defined in 11. above, 13. -(C,-C|0)-alkyl, wherein alkylis unsubstituted or mono- to penta-substituted independently of one another as denned under 1.7.1 to 1.7.11 above, 14. -0-(C,-C6)-alkyl-0- 15. -O-(C0-C4)-alkyl-(C3-C7)-cycloalkylor 16. -(Ci-C4)-alkyl-N(R,3)2, wherein R13 is as denned in 1.7.7 above, R5 is as defined as R5 in case a) above, R6,R7 and R8 independently of one another are hydrogen atom or methyl. Preferred are compounds of formula I, wherein in case a) B6, B7, Bfi, and B9 are each a carbon atom, R1, R2and R3 independently of one another are hydrogen atom, halogen, cyano, nitro, amino, -0-{C,-C7)-alkyl, wherein alkyl is unsubstituted or substituted by phenyl, -CF2-CF3,-CF3,-N(R,S)2, wherein R,s is independently of one another hydrogen atom, -(C,-C7)-alkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyl, -C(0)-NH-phenyl, - C(0)-0-phenyl,-C(0)-0-(C,-C4>a]kyl or-C(0HC,-C7)-alkyI, wherein alkyl, pyridyl or phenyl are unsubstituted or mono-to tri-substituted independently of one another as denned under 1.7.1 to 1.7.11, or R,K together widi the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, S(0)y-RM, wherein y is zero, 1 or 2, and R14 is -(C,-Cm)-alkyl, phenyl, which is unsubstituted or mono-to penta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(R18)2, wherein R18 is as defined above, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C(0)-0-R12, wherein R12 is as defined above, R4 is cyano, amino,-0-(Ci-C7)-alkyl, wherein alkyl is substituted by phenyl; -CF2-CF3,-CF3,-N(R18)2, where in RiS is independently of one another hydrogen atom, -(Ci-C7)-alkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyl, -C(0)-NH-phenyl, -C(0)-0-phenyl, -CfOJ-OKCrC^-alkylor-CfOHd-CTValkyl, wherein alkyl, pyridyl or phenyl are unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or R18 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, S(0)y-R14, wherein y is zero, 1 or 2, and R14 is -(CrC,0)-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as denned for substituents under 1.7.1 to 1.7.11, amino or-N(R18)2, wherein R18 is as defined above, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C(0)-0-R12, wherein R12 is as defined above, R6,R7 and R8 independently of one another are hydrogen atom or methyl, and R5 is as defined in claim 1, or in case b) the substituents R",R2 and R4 independently of one another are hydrogen atom, halogen, cyano, nitro, amino, -0-(C]-C7)-aIkyl, wherein alkyl is unsubstituted ot substituted by phenyl, -CF2-CF3,-CF3,-N(R,S)2, 1 H wherein R is independently of one another hydrogen atom, -(CrC7)-a]kyl, phenyl, -C(0)-phenyl, -C(0)-pyrklyl, -C(0)-NH-phenyl, -C(0)-0-phenyl, -C(0)-0-(C,-C4)-alkyl or -C(0)-(Ci-C7)-alkyl, wherein alkyl, pyridyl or phenyl are unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or R18 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, S which is unsubstituted or mono- topenta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or wherein R18 is as defined above, wherein alkyl is unsubstituted or mono- to tri* substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C(0)-0-R12, wherein R12 is as defined above, R3 is cyano, nitro, amino, -0-{C]-C7)-alkyl, wherein alkyl is substituted by phenyl; -CF2-CF3,-CF3,-N(RI8)2, wherein Rn is independently of one another hydrogen atom, -(C,-C7)-alkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyI, -C(0)-NH-phenyl, -C(0)-0-phenyl,-C(0)-0-(Ci-C4)-alkyl or-C(0HCrC7)-alkyl, wherein alkyl, pyridyl or phenyl are unsubstituted or mono-to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or R together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, S(0)y-R14, wherein y is zero, 1 or 2, and R14 is -(C]-Cio)-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(R18)2, wherein R!8 is as defined above. wherein alkylis unsubstituted or mono-to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C(0)-0-R12, wherein R12 is as defined above, R ,R and R independently of one another are hydrogen atom or methyl, and R is as defined above. Even more preferred are compounds of formula (H) and/or a stereo isomeric form of the compound of the formula U and/or a physiologically tolerable salt of the compound of the formula D, wherein; R1 and R2 are independently of one another hydrogen atom, halogen, cyano. amino, -O- (Ci-C4)-alkyl, nitro, -CF3, -CF2-CF3, -S(0)y-R14, wherein y is 1 or 2, R14 is amino, - (C|-C7)-alkyl or phenyl, which is unsubstituted or mono-to tri- substituted as defined for substituents under 1.7.1 to 1.7.11 above, -N(Rl8)2, wherein RIB is independently of one another hydrogen atom -(CrCTj-alkyl-CtOHC.-CTj-alkyl, -C(0)-phenyl, -C(0)-pyridyl, -C(0)-NH-(d-C4)-alkyl, -C(0)-0-phenyl, -C(0)-0-(CrC4)-alkyl or -(Ci-Cio)-alkyl, wherein pyridyl, alkyl or phenyl are unsubstituted or mono-to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11,or R18 together with nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, R3 is cyano, amino, -0-(C,-C4)-alkyl, nitro, -CF3, -CF2-CF3, -S(0)y-R14, wherein y is I or 2, R14 is amino, -(Ci-C7)-alkyl or phenyl, which is unsubstituted or mono-to tri-substituted as defined for substituents under 1.7.1 to 1.7.11 above, -N(RI8)2, wherein R,s is independently of one another hydrogen atom, -(Ci-C7)-alkyl-C(0)-(CrC7)-alkyl, -C(0)-phenyl, -C(0)-pyridyI, -C(0)-0-phenyl, -C(0)-NH-(Ci-C4)-alkyl, -C(0)-0-(C,-C4)-alkyl or -(Cj-Cio)-alkyl, wherein pyridyl, alkyl or phenyl are unsubstituted or mono-to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11,or R18 together with nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, and R5 is hydrogen atom, -(CpCioJ-alkyl, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.4, -C(0)-R9 or -S(0)2-R9, wherein R9 is -(C,-C10)-alkyl, -O-(C,-Cl0)-alkyl, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one anotheras defined under 1.7.1 to 1.7.4, or phenyl, which is unsubstituted or mono-to tri- substituted as defined under 1.7.1 to 1.7.11,or-N(R%,whereinRlsis as defined above. Most preferred are compounds offormula (H),wherein R1 is bromo, -CF3 orchloro, R2 is hydrogen atom or 0-(Ci-C2)-alkyl, R3 is -N(R18)2, wherein R18 is independently of one another hydrogen atom, -N-C(0)-pyridyl, -C(0)-phenyI, - R5 is hydrogen atom, methyl or -S(0)2-CH3. N-(6-Chloro-9H-|3-carbolin-8-yr>nicotinamide,as well as the bismesylate salt, bistrifluoracetate saltand bis hydrochloride saltof N-(6-Chloro-9H-|3-carbolin-8-yl)-nicotinamide, N-(6-Chloro-9H-P-carbolin-8-yl)-3,4-difluoro-benzamide, as we lias the hydrochloride salt of N-(6-Chloro-9H-p-carbolin-8-yl)-3,4-difluoro-benzamide, N-(6-Chloro-7-methoxy-9H-P-carboliii-8-yi)-nicotinamide as we lias the bistrifluoracetate salt and bishydrochloride salt of N-(5-Chloro-7-methoxy-9H-p-carbolin-8-yl)-nicotinamide and 6-Chloro-N-(6-chloro-9H-p-carbolin-8-yl)-nicotinamide. The term "alkyl"by itself oras part on another substituent, unless odierwise stated means a straight or branched chain hydrocarbon radical having 1 to 10 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tertiary-butyl, pentyl, hexyl, heptyl, nonyl, octyl, decanyl or cycloalkyl having 3 to 7 carbon atoms such as cylopropyl, cyclobutyl, cyclone xyl orcycloheptyl. The term "alkoxy"by itself or as part on another substituent, unless otherwise stated means -O-alkylor-O-substituted alkyl. The term "heterocycle having 5 to 7 ring atoms" represents a radical of a monocyclic saturated system having 5 to 7 ring members, which contains 1, 2 or3 heteroatoms as ring members. ExamμLes of heteroatoms are N, O and S. ExamμLes of the term heterocycle having 5 to 7 ring atoms are pyrrolidine, tetrahydropyridine,piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxoIan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine. The term "aryl"by itself or as part on another substituent, unless otherwise stated refers to an organic radical derived from an aromatic molecule by removal of one atom; such as phenyl, pyridyl, thiazoly, morpholinyl and naphthyl. The term Substituted alkyl" means an alkyl radical substituted atone or more positions by one or more radicals of the group halogen, nitro, sulfo, amino, substituted amino, carboxyl, alkoxy, -O-aryl, -O-substituted aryl, and hydroxyl. The term Substituted aryl"means an aryl radcai substituted at one or more positions by one or more radicals of the group halogen, alkyl, substituted alkyl, nitro, sulfb, amino, alkoxy, aryl, substituted aryl, or hydroxyl groups, preferred is an aryl radical substituted at 1 to 3 positions by 1 to 3 groups. The term Substituted amino"refers to -N(R13)2 wherein R13 is independently of one another hydrogen atom, sulfo, alkyl, aryl, -C(0)-alkyl, C(0)-NH-aryl, -C(0)-0-aryl, -C(0)-0-alkyl, or C(0)-0-aryl, wherein each alkyl or aryl may be independently substituted. The term Sulfo"refers to -S(0)y-Ru .wherein R14 is an alkyl, aryl, substituted aryl. substituted alkyl, amino, or substituted amino and y is zero, one or two. The term "halogen" is understood as meaning fluorine, chlorine, bromine or iodine. The term "-(Ci-C4)-alkyl" is understood as meaning hydrocarbon radicals whose carbon chain is linear or branched and contains 1 to 4 carbon atoms. The invention further relates to a process for the preparation of the compounds ofthe formula I and/or a stereoisomeric form ofthe compounds ofthe formula land/or ofa physiologically tolerable salt ofthe compounds ofthe formula I, which comprises a) reacting a compound of formula HI where Y is halogen or -OH and R5 is as defined in formula I, to give a compound of the formula I, or c) resolving a compound of the formula I, which on account of its chemical structure occurs in enantiomeric forms, prepared by process a) orb) into the pure enantbmers by salt formation with enantiomerically pure acids or bases, chromatography on chiral stationary phases or derivatization by means ofchiral enantiomerically pure compounds such as amino acids, separation of the diastereomers thus obtained, and removal of the chiral auxiliary groups, or d) isolating the compound of die formula I prepared by process a), b) or c) either in free form or, in the case of the presence of acidic or basic groups, converting it into physiologically tolerable salts. The preparation of physiologically tolerable salts of compounds of the formula I capable of salt formation, including their stereoisomeric forms, is carried out in a manner known perse, With basic reagents such as hydroxides, carbonates, hydrogencarbonates, alkoxides and also ammonia or organic bases, for examμLe trimethyl- or triethylamine, ethanolamine or triethanolamine or alternatively basic amino acids, for examμLe lysine, ornithine orarginine, the carboxylic acids form stable alkali metal, alkaline earth metal or optionally substituted ammonium salts. If the compounds of the formula I contain basic groups, stable acid addition salts can also be prepared using strong acids. For this, both inorganic and organic acids such as hydrochloric, hydrobromic, sulfuric, phosphoric, methanesulfonic,benzenesulfonic,p-toluenesulfonic,4-bromobenzenesulfonic, cyclohexylamidosulfonic, trifluoromethylsulfonic, acetic, oxalic, tartaric, succinic or trifluoroacetic acid are suitable. The invention also relates to pharmaceuticals which comprise an efficacious amount of at least one compound of the formula I and/or of a physiologically tolerable salt of the compounds of the formula land/oran optbnallystereoisonieric form of the compounds of the formula I, together with a pharmaceutically suitable and physiologically tolerable excipient, additive and/or other active compounds and auxiliaries. On account of the pharmacological properties, the compounds according to the invention are suitable for the prophylaxis and therapy of all those disorders in whose course an increased activity of IkB kinase is involved. These include, for examμLe, asthma, rheumatoid arthritis (in the case of inflammation), osteoarthritis, Alzheimer"s disease, carcinomatous disorders (potentiation of cytotoxic therapies), cardiac infarct or atherosclerosis. The pharmaceuticals according to die invention are in general administered orally or parentally or by rectal, inhale or transdermal administration. and/ora stereoisomeric form of the compounds of the formula Iand/ora physiologically tolerable salt of the compounds of the formula I, for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of hrB kinase is involved, wherein B6, B7, Bs and B9 are independently selected from the group consisting of carbon atom and nitrogen atom and wherein B6,B7,B8 and B9 together are no more man two nitrogen atoms at the same time; where the substituents R1, R2, R3, R4 and R8 independently of one another are 1. hydrogen atom, 2. halogen, 3. -OH, 4. -CN, 5. sulfo, 6. -N02, 7. -NH2, 8. aikoxy, 9. substituted amino, 10. -NH-C(0)-R15, wherein R15 is a heterecycle having 5 to 7 ring atoms, alkyl, aryl, substituted aryl or substituted alkyl, 11. -COOH, 12. -O-R10. wherein Ri0 is alkyl, substituted alkyl or aryl, 13. -C(0)-R12, wherein R12 is alkyl, substituted alkyl or aryl, 14. -C(0)-0-R12, wherein R12 is as denned above, 15. aryl, 16. -O-aryl, 17. substituted aryl, 18. -O-substituted aryl, 19. alkyl, 20. substituted alkyl, 21. -CF3 or 22. -CF2-CF3, provided that at least one ofR1, R2,R3,R4 and R8 is not a hydrogen atom, R5 is 1. hydrogen atom, 2. alkyl, 3. alkyl radical, substituted at one or more positions by one or more of die radicals, halogen, amino orhydroxyl, 4. -C(0)-R9or 5. -S(0)2-R9, in which R9 is a) alkyl, b) alkyl radical, substituted atone or more positions by one or more of the radicals, halogen, amino or hydroxyl, c) aryl, d) aryl radical, substituted at one or more positions by one ormore of the radicals, halogen, amino, orhydroxyl, e) -NH2, f) alkoxyor g) substituted amino, and R6 and R7 independently of one anomerare 1. hydrogen atom, 2. halogen, 3. -OH, 4. methyl. 5. -O-(Ci-C]0)-alkyl, wherein alkylis unsubstituted or mono- to tri- substituted independently of one anotherby 5.1 aryl, 5.2 halogen, 5.3 -N02, 5.4 sulfo, 5.5 -COOH, 5.6 -NH2, 5.7 -0-(C,-C4)-alkylor 5.8 -OH, or 6. N(R13)2 , wherein R13 is independently of one another hydrogen atom, aryl, -C(0)-(Ci-C4)-alkyIor substituted aryl or alkyl, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one anotlieras defined under 5.1 to 5.8, or R13 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms. Preferred is the use of the compounds of formula I, wherein B6, B7, B8, and B9 are each a carbon atom, R1, R2, R3,R4 and RK independently of one another are 1. hydrogen atom, 2. halogen, 3. -CN, 4. -COOH, 5. -N02, 6. -NH2, 7. -0-(C]-Cio)-alkyl, wherein alkyl is unsubstituted or mono-to penta-substituted independently of one anotherby 7.1 phenyl, which is unsubstituted or mono- to penta- substituted by halogen or-0-(CrC4)-alkyl, 7.2 halogen, 7.3 -NH2, 7.4 -OH, 7.5 -COOR16, wherein R16 is hydogen atom or-(Ci-Cio)-alkyl, 7.6 -N02, 7.7 -S(0)y-Ru , wherein y is zero, 1 or 2, R14 is -(CrCl0)-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as defined for substituents under 7.1 to 7.11, amino or-N(R,3)2, wherein R13 is independendy of one another hydrogen atom, phenyl, -(C,-Cl0)-alkyl, -C(0)-(C,-C7)-alkyl, -C(0)-phenyl, -C(O)- NH-(C,-C7)-aIkyl, -C(0)-0-phenyl, -C(0)-NH-phenyl, -C{0)-0-(Cr C7)-alkyI,-S(0)y-R14,whe rein R14 and y are as defined above, and wherein alkyl or phenyl in each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 7.1 to 7.11 above, or R1 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, 7.8 -O-phenyl, wherein phenyl is unsubstituted or mono- to penta -substituted independently of one another as defined under 7.1 to 7.11 above, 7.9 a radicale selected from pyrrolidine, tetrahydropyridine, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoUne, thiophene or thiomorpholine, 7.10 -(C3-C7)-cycloa!kylor 7.11 =0, 8. -N(RI3)2, wherein R13 is as defined in 7.7 above, 9. -NH-C(0)-R15, wherein R15 is 9.1 a radicale selected from pyrrolidine, tetrahydropyridine, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine, wherein said radical is unsubstituted or mono- to penta- substituted independently of one another as defined under 7.1 to 7.11 above, -CF3, benzyl or by -(Ci-Cio)-alkyl, wherein alkyl is mono to tri- substituted independently of one another as defined under 7.1 to 7.11 above, 9.2 -(Ci-C]0)-alkyl, wherein alkyl is unsubstituted or mono- to penta -substituted independently of one another as defined under 7.1 to 7.11 above or by -O-(C]-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta- substituted independently of one another as defined under7.1 to 7.11 above, 9.3 -(C3-C7)-cycloalkyl, 9.4 -N(R,3)2, wherein RJ3 is as defined in 7.7 above, or 9.5 phenyl, wherein phenyl is unsubstituted or mono- to penta-substituted independently of one another as defined under 7.1 to 7.11 above, by -O-(C,-Ci0)-alkyl, by -CN, by -CF3, by -(CrC10)-alkyl, wherein alkyl is mono to tri- substituted independently of one another as defined under 7.1 to 7.11 above or two substituents of the phenyl radical form a dioxolan ring , 10. -S(0)y-R14 , wherein Ri4 and y are as defined in 7.7 above, 11. -C(0)-R12, wherein R12 is phenyl or-(Ci-C7)-alkyI, wherein alkyl or phenyl are unsubstituted or mono-to penta- substituted independently of one another as defined under 7.1 to 7.11 above, 12. -C(0)-0-R12, wherein R12 is as defined in 11. above, 13. -(Ci-Cio)-alkyl, wherein alkyl is unsubstituted or mono- to penta -substituted independently of one another as defined under 7.1 to 7.11 above, 14. -O-fd-QJ-alkyl-CMd-CO-alkyl, 15. -0-(Co-C4)-a]kyl-(C3-C7>-cycloalkyl, 16. ^Ci-C4}-aIkyi-N(Rl3):, wherein R13 is as defined in 7.7 above 17. -CF3or 18. -CF2-CF3, provided that at least one of R1, R2, R3, R4 and R8 is not a hydrogen atom, R5 is 1. hydrogen atom, 2. -(Ci-Cio)-alkyl, wherein alkyl is unsubstituted or mono-to penta -substiruted independently of one another as defined under 7.1 to 7.4 above, 3. -C(0)-R9, wherein R9 is -NH2,-(Cj-Cio)-alkyl, wherein alkylis unsubstituted or mono-to penta-substituted independently of one another as denned under 7.1 to 7.4,or-N(R,3)2 .wherein R13 is as defined in 7.7 above, or 4. -S(0)2-R9, wherein R9 is as defined in 3 above, orR4 and R5 together with the atom to which they are bonded form a heterocycle, orR3 and R15 together with the atom to which they are bonded form a heterocycle containing an additional oxygen atom in the ring and R and R independently of one another are hydrogen atom or methyl. More preferred is the use of compounds of formula I for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of l)fB kinase is involved, wherein B6, B7, B8, and B9 are each a carbon atom, R",R2, R3 and R4 independently of one another are hydrogen atom, halogen, cyano, nitro, amino, -0-{Ci-C7)-alkyl, phenyl, -O-phenyl, -CF2-CF3, -CF3,N(RI3)2, wherein R13 is independently of one another hydrogen atom, -(C,-C7)-alkyI, phenyl, -C(0)-phenyl, -C(0)-pyridyl, -C(0)-NH-phenyl, -C(0)-0-phenyl, -C(0)-0-(CrC4)-alkyl, -C(0)-(C,-C7)-alkylor-(C,-C,o)-alkyl, wherein alkyl, pyridyl or phenyl are unsubstituted or mono- to tri-substituted independently of one another as defined under 7.1 to 7.11, or R13 together with nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, S(0)y-RM, wherein y is zero, 1 or 2, and R14 is -(C,-C,0)-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as defined forsubstituents under 7.1 to 7.11, amino or-N(R13)2, wherein R13 is as defined above, wherein alkylis unsubstituted or mono-to tri- substituted independently of one another as defined under 7.1 to 7.11, or -C(0)-0-R12, wherein Ri2 is as defined above, R6,R7 and R8 independently of one another are hydrogen atom, methyl, amino,-N(R )i, wherein R13 is as defined above, provided that at least one of R1, R2, R3, R4 and RR is not a hydrogen atom, and R is as defined above. Even more preferred is the use of compounds of formula II and/ora stereoisomeric form ofdie compounds ofthe formula Hand/ora physiologically tolerable salt ofthe compounds ofthe formula n, for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of ^B kinase is involved, wherein; R",R2 and R3 are independently from one another hydrogen atom, halogen, cyano, amino, -0-(C,-C4)-alkyl, nitro,-CF3,-CF2-CF3,-S(0)y-R14, wherein y is I or 2, R14 is amino, -(C,-C7)-alkyl, phenyl, which is unsubstituted or mono- to tri-substituted as defined for substituents under 7.1 to 7.9, or-N(Rl3)2, wherein R13 is independently of one another-C(0)-pyridyl, hydrogen atom, -(CrCyJ-alkyl-CfOt-td-CTi-alkyl, -C(0)-phenyI, -(Ci-C10)-alkyl, -C(0)-NH-(C1-C4)-alkyI, -C(O)-0-phenyl or -C(0)-0-(CrC4)-alkyl, wherein pyridyl, alkyl or phenyl are unsubstituted or mono-to tri-substituted independently of one another as denned under7.1 to 7.11, or R13 together wirti nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms, provided that at least one ofR1, R2 and R3 is not a hydrogen atom, and Rs is hydrogen atom, -(Ci-Cl0)-alkyl, wherein alkyl is unsubstituted or mono-to tri- substituted independently of one another as defined under 7.1 to 7.4, -C(0)-R9 or-S(0)2-R9, wherein R9 is -(d-CioValkyL-O-CC-CoJ-alkyl, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one another as denned under 7.1 to 7.4, phenyl, which is unsubstituled or mono- to tri- substituted as defined undei 7.1 to7.11,or-N(Rn)2, wherein R13 is as defined above. Most preferred is the use of the compounds of formula II for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of I^B kinase is involved, wherein R1, R2 and R3 are independently from one another hydrogen atom, halogen, cyano, amino, -0-(d-C4)-alkyl, nitro, -CF3 or N(Rl3)2, wherein R13 is independently of one another hydrogen atom, -(CrC7)-alkyl, -C(0)-(Ci-C7)-a]kyl,-C(0)-pyridyl,-C(0)-phenyI or-C(0)-0-(C,-C4)-aIkyl, wherein alkyl or phenyl are unsubstituted or mono- to tri-substituted independently of one another by halogen or -0-(Ci-C4)-alkyl, and R5 is hydrogen atom, -C(0)-CH3, methyl, -S(0)2-CH3, -C(0)-morpholinyI, -CH2-CH2-OH or -CH2-C(0)-NH2, provided that no more than two of R",R2,R3 and R5 are a hydrogen atom. Most highly preferred is the use of the compounds of formula II for the production of pharmaceuticals for the prophylaxis and therapy of disorders in whose course an increased activity of IkB kinase is involved, wherein Rl is bromo, -CF3 orchloro, R2 is hydrogen atom or 0-(Ci-C2)-alkyl, R3 is hydrogen atom, bromo, chloro or-N(R1J)2, wherein Ri3 is independently of one another hydrogen atom, -C(0)-phenyl, -(CrC7)-alkyl,-C(OHCrC4)-alkyl or-C(0)-0-(C|-C4)-alkyl, where in alkyl or phenyl are unsubstituted or mono- to tri- substituted independently of one another by halogen or-0- (Ci-C2)-alkyl, and R5 is hydrogen atom, -C(0)-CH3, methyl or -S(0)2-CH3, provided that no more than two of R",R2,R3 and R5 are a hydrogen atom. Specific preferred is the use of the compounds of formula n for the production of pharmaceutic Is for the prophylaxis and therapy of disorders in whose course an increased activity of IkB kinase is involved, wherein R1 is chloro, R2 and R3 are each hydrogen atom, and Rs is -C(0)-CH3, or R1 is bromo, R2 and R3 are each hydrogen atom, and R5 is -C(0)-CH3, or R1 is chloro, R3 is -N-C(0)-CH2-0-CH3 and R2 and R5 are each hydrogen atom, or R" is chloro, R3 is -N-C(0)-para-fluoro-pheny] and R2 and R5 are each hydrogen atom, or R1 and R3 are each chloro, R2 is -C(0)-CH3 and R5 is hydrogen atom, or R" and R3 are each chloro, R5 is hydrogen atom and R2 is -C(0)-CH2-CH3. On account of the pharmacological properties, the compounds according to the invention are suitable for the prophylaxis and therapy of all those disorders in whose course an increased activity of IkB kinase is involved. Disorders in whose course an increased activity of JkB kinase is involved include, for examμLe the treatment of joint inflammation, including arthritis, rheumatoid arthritis and other arthritic conditions such as rheumatoid spondylitis, gouty arthritis, traumatic arthritis, rubella arthritis, psoriatic arthritis and osteoarthritis. Additionally, me compounds are useful in the treatment of acute synovitis, tuberculosis, atherosclerosis, muscle degeneration, cachexia, Re iter"s syndrome, endotoxaemia, sepsis, septic shock, endotoxic shock, gram negative sepsis, gout, toxic shock syndrome, chronic pulmonary inflammatory diseases including asthma and adult respiratory distress syndrome, silicosis, pulmonary sarcoidosis, bone resorption diseases, reperfusion injury, carcinoses, leukemia, sarcomas, lymph node tumors, skin carcinoses, lymphoma, apoptos is, graft versus host reaction, allograft rejection and leprosy. Furthermore, the compounds are useful in the treatment of: infections such as viral infections, for examμLe HIV, cytomegalovirus (CMV), influenza, adenovirus and the Herpes group of viruses, parasitic infections, for examμLe malaria such as cerebral malaria, and yeast and fungal infections, for examμLe fungal meningitis; fever and myalgias due to infection; AIDS; AIDS related comμLex (ARC); cachexia secondary to infection or malignancy; cachexia secondary to acquired immune deficiency syndrome (AIDS) or to cancer; keloid and scar tissue formation; pyre sis; diabetes; and inflammatory bowel diseases such as Crohn"s disease and ulcerative colitis. The compounds of the invention are also useful in the treatment of diseases of or injury to the brain in which over-expression of TNFa has been imμLicated such as multiμLe sclerosis, and head trauma. The compounds according to the invention are also useful in the treatment of psoriasis, Alzheimer"s disease, carcinomatous disorders (potentiation of cytotoxic therapies), cardiac infarct, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). The invention also relates to a process for the production of a pharmaceutical, which comprises bringing at least one compound of the formula I into a suitable administration form using a pharmaceutically suitable and physiologically tolerable excipient and, if appropriate, further suitable active compounds, additives or auxiliaries. Suitable solid or pharmaceutical preparation forms are, for examμLe, granules, powders, coated tablets, tablets, (micro)capsules, suppositories, syrups, juices, suspensions, emulsions, drops or injectable solutions, and preparations having protracted release of active compound, in whose preparation customary auxiliaries, such as excipients, disintegrants, binders, coating agents, swelling agents, glidants or lubricants, flavourings, sweeteners and solubilizers are used. Frequently used auxiliaries which maybe mentioned are magnesium carbonate, titanium dioxide, lactose, mannitoland other sugars, talc, lactoprotein, gelatin, starch, cellulose and its derivatives, animal and vegetable oils such as cod liver oil, sunflower, groundnut or sesame oil, polyethylene glycoland solvents such as, forexamμLe, sterite waterand mono- orpolyhydric aJcohoJs such as glycerol. The pharmaceutical preparations are preferably produced and administered in dose units, each unit containing as active constituent a certain dose of the compound of the formula I according to the invention. In the case of solid dose units such as tablets, capsules, coated tablets or suppositories, this dose can be up to approximately 1000 mg, preferably from approximately 50 mg to 300 mg and in the case of injection solutions in ampoule form up to approximately 300 mg, preferably from approximately 10 mg to 100 mg. For the treatment of an adult patient weighing approximately 70 kg, depending on die efficacy of me compound according to formula I, daily doses of approximately 20 mg to 1000 mg of active compound, preferably from approximately 100 mg to 500 mg,are indicated. Under certain circumstances, however, even higher or lower daily doses may be appropriate. The administration of the daily dose can be carried out both by single administration in the form of an individual dose unit or else of a number of smaller dose units and by multiμLe administration of subdivided doses at specific intervals. As a rule, final products are determined by mass-spectroscopic methods (FAB-, ES1- MS}. Temperatures are given in degrees Celsius, RTmeans room temperature (22 °C to 26 DC). Abbreviations used are either exμLained or correspond to the customary conventions. ExamμLe 1, 7-bromo-|3-carboline A solution of norharmane (600 mg,3.57 mmol) in tetrahydrofuran (THF;50 ml) was treated with bromine (0.40 ml, 7.80 mmol) at RT while stirring. After stirring for 18 h at RT, the reaction was concentrated under reduced pressure and the resulting residue was sonicated in 10% aqueous Na2C03 (100 ml). The product was μLtered and washed with water to give 905 mg of crude product. The crude product was crystallized from xylenes to provide in two crops 580 mg of 7-bromo-p-carboline. ExamμLe 2, l-acetyl-7-bromo- (3 -carboline A solution of ExamμLe 1 (25 mg,0.1 mmol) in dimetylformamide (DMF; 2 ml) was treated with 0.10 ml of 1M aqueous NaOH (0.10 mmol). After stirring at RT for 30 minutes, acetic anhydride (0.010 ml, 0.095 mmol) was added and reaction stirred 18 h atRT. The reaction was partitioned in EtOAc and 5% citric acid and the organic layer washed with water, dried (brine; MgS04), and concentrated to give 23 mg of crude product. The crude product was chroma tog rap he d (7:3 he xane-acetone) on silica gel to give 10 mg of l-acetyl-7-bromo-p-carboline. ExamμLe 3, 7-fiuoro-13 -carboline A mixture of 5-fluorotryptamine hydrochloride (200 mg, 0.93 mmol) in EtOAc (4 ml) and water (2 ml) was treated with glyoxalic acid hydrate (90 mg,0.98 mmol). The pH of the aqueous layerwas adjusted to 5 (with 5% NaHC03 then 1MHC1) and the mixture stirred vigorously at RT for 18 h. The mixture was then diluted with hexane (4 ml) and the product μLtered and washed with water and (1:1) hexane-ethylacetate. The crude product from above in 6NHC1(3 ml) was treated 3 times with concentrated HC1 (0.050 ml) every 15 min while refluxing. After refluxing for a total of 45 min, the reaction was concentrated to give a residue. The above residue was slurred in xylenes with triefhylamine (0.40 ml, 2.9 mmol) and 10% Pd/C (200 mg). The mixture was refluxed for 1 h and then μLtered hot through celite. The μLtrate was concentrated and the residue chroma tog raphed (5:95 methanol-chloroform) on silica gel to give 25 mg of 7-fluoro-p-carboline. ExamμLe 4, 7-isopropyl- p -carboline hydrochloride A mixture of4-isopropylphenylhydrazine hydrochloride (660 mg, 3.55 mmol) and 4-phthalimidobutanal diethyl acetal (1.15 g,3.95 mmol) in Ethanol (EtOH; 30 ml) was heated at 60 °C to 65 °C fori h with water (0.050 ml). The mixture was then treated with concentrated HCI(0.50 ml) and re fluxed for 14 h. After concentrating the reaction, the residue was partioned in methylene chloride and saturated aqueous NaHCOj. The aqueous solution was extracted with methylene chloride (3 times) and the combined organic solutions were dried (MgS04) and concentrated to give after chromatography (4:1 hexane-ethyl acetate) on silica gel 146 mg of product. The above product was treated with hydrazine hydrate (1 ml) in EtOH (4 ml) and water (1 ml) and stirred at RT overnight. After concentrating the reaction to an aqueous mixture, me product was extracted with methylene chloride (3 times). The combined organic solution was dried (MgS04) and concentrated. The residue was redissolved in methylene chloride and treated with lMHClin ether. The precipitate was collected and washed with ether and hexane and dried to provide 102 mg of 6-isopropyltryptamine hydrochloride salt. This tryptamine obtained above was transformed into 7-Isopropyl- (3 -carboline according to the procedure used in examμLe 3. The hydrochloride salt was obtained by treating a solution of 7-Isopropyl-|3-carboline in methylene chloride with 1M HClin ether and concentrating. The residue was triturated with (1:1) methylene chloride -hexane to give 15 mg of7-isopropyl-|3-carboline hydrochloride. ExamμLe 5, 7-cyano- p -carboline A dark solution of examμLe 1 (190 mg, 0.62 mmol) and CuCN(110 mg, 1.22 mmol) in N-methyl2-pyrrolidone (1.5 ml) was heated in a sealed reaction tube at200 °C for48 h. The mixture was μLtered and the μLtrate was diluted with water (50 ml). A brown solid that precipitated was μLtered, washed with water, saturated aqueous NaHC03, and then methanol. This material was dissolved in DMSO and diluted with aqueous HC1. This homogeneous dark solution was decolorized with charcoal, μLtered and concentrated to give a concentrated solution in DMSO. This DMSO solution was partitioned in (1:1) EtOAc-THF and saturated aqueous NaHC03. The organic solution was dried (MgS04) and concentrate to give 8 mg of 7-cyano- P -carboline. ExamμLe 6, 7-nitro-p-carboline hydrochloride Norharmane (100 mg,0.60 mmol) was treated with concentrated nitric acid (1.0 ml) and the resulting suspension was heated to 65 °C until the mixture became homogeneous (3 to 4 min). The solution was carefully poured into water(20 ml), and the precipitate μLtered and washed with water then methanol. The solid was suspended in saturated aqueous NaHCOj and stirred vigorously before μLtering and washing with water. The solid was taken up in hot methanol and this solution treated with 1M HO in ether (5 ml). The solution was concentrated and the residue triturated with ether to provide 58 mg of a 7:3 mixture of 7-nitro- P -carboline hydrochloride and 9-nitro- p -carboline hydrochloride. ExamμLe 7, 7-carboxy-13 - carboline trifluoroacetat Crude product from examμLe 5 (from 210 mg of examμLe 1,0.85 mmol) was treated with 6 MHClin a sealed reaction tube for 15 h at 110 °C. The reaction was evaporated to give a concentrated solution of product in N-methyl 2-pyrrolidone. A portion (half) was purified by preparative HμLC using a Cj8 -packed column and eluting with a gradient (5:95 to 50:50) of water-acetonitril (with 0.1% trifluoracetic acid). The pure fractions were combined and lyophilized to provide 11 mg of 7-carboxy- P -carboline trifluoroacetate. ExamμLe 8, 7,9-dibromo- p - carboline hydrochloride A solution of the product from examμLe 1 (140 mg, 0.58 mmol) in THF (2 ml) was treated with bromine (0.50 ml). After 10 min at RT, the reaction was diluted with chloroform and the product was μLtered. The μLtered product was taken up in methanol and treated with lMHClinetherand concentrated. The residue was triturated with ether to provide 160 mg of7,9-dibromo- P -carboline hydrochloride. ExamμLe 9, 7,9-dichloro- p - carboline To a suspension of norharmane (84 mg,0.50 mmol) in water (3 ml) at RT was added 1M aqueous HC1(1.1 ml, 1.1 mmol). To this homogenous solution was added N-chlorosuccinimide (747 mg,5.58 mmol) portionwise and the resulting solution was stirred at 60 °C to 70 °C for 3h. The reaction was partitioned in EtOAc and saturated aqueous NaHC03 and the organic layer was dried (brine; MgS04) and then concentrated. The residue was chromatographed (2:3 THF-hexane) on silica gel to give 24 mg of 7,9-dichloro- P -carboline after triturating with (1:1) methylene chloride-he xane, then with hexane. ExamμLe 10, l-acetyl-7-bromo- P - carboline To a suspension of NaH (95%, 14 mg, 0.60 mmol) in DMF (1.0 ml) at 5 °C to 10 °C was added the product from examμLe 1 (74 mg,0.30 mmol). The resulting mixture was stirred forl5minat5 °C to 10 QC before adding methanesulfonylchloride (0.030 ml, 0.38 mmol). The reaction was allowed to warm to RT and stirred for 2 h before partitioning into saturated aqueous NaHC03 and EtOAc. After stirring the mixture overnight, the organic layer was washed with water, dried (brine; MgS04), and concentrated. The residue was purified by chromatography (1:1 hexane-ethyl acetate) on silk:a gel to give 23 mg of l-acetyl-7-bromo- P -carboline. ExamμLe 11, 7-bromo-l-methyl- (3 - carboline To a suspension ofNaH (95%, 6 mg, 0.24 mmol) in DMF (2.0 ml) at 5 °C to 10 °C was added the product from examμLe 1 (50 mg, 0.20 mmol). The resulting mixture was stirred for 15 min at5 °C to 10 °C before adding methyl-iodide (0.030 ml,0.20 mmol) at 0 °C to 5 "C.The reaction stirred for 12 h at 0 °C to 5 °C before partitioning into waterand EtOAc. The organic layerwas washed with water, dried (brine ;MgS04), and concentrated. The residue was purified by chromatography (gradient, 1:3 hexane-ethyl acetate to ethyl acetate) on silica gel to give 10 mg of7-bromo-l-metyhl- P -carboline. ExamμLe 12, 7-chloro-p-carboline To a solution ofnorharmane (2.0 g, 11.9 mmol) in water (89 ml) and 1M aqueous HC1 (29.8 ml, 29.8 mmol) was added N-chlorosuccinimide (3.17 g, 23.8 mmol) portionwise. The resulting solution was stirred at RT for 6 h,and then at 0 °C to 5 °C for 12 h.The reaction was diluted with water (100 ml) and basified cautiously with solid K2C03 (4.3 g). After stirring atRTfor 1 h, the product was collected and washed with water. The crude product was re fluxed in chloroform for 1 h and μLtered after cooling to 15 °C to provide 2.05 g of 7-chloro- p -carboline. ExamμLe 13, l-acetyl-7-chloro- p - carboline To a solution of the product from examμLe 12 (104 mg,0.50 mmol) in DMF (2.0 ml) at 3 °C to 5 °C was added NaH (95%, 15 mg, 0.625 mmol). The resulting mixture was stirred for 15 min before adding acetic anhydride (0.083 ml, 0.875 mmol). The reaction was allowed to warm to RT and stirred for 3 h before pouring into with water (25 ml). The slurry was stirred for 12 h, and the product collected to give after chromatography (1:3 hexane-ethyl acetate) on silica gel 82 mg of l-acetyl-7-chloro- p -carboline. ExamμLe 14, 7-chloro-9-nitro- (3 - carboline A mixture of the product from examμLe 12 (500 mg, 2.48 mmol) in concen-trated nitric acid (20 ml) was stirred at RT for 22 h. The reaction mixture was carefully poured into cold (3 °C to 5 °C) water (50 ml), and after stirring for 2 h the precpitate was collected. The solid was suspended in saturated aqueous NaHCOj (50 ml) and stirred at RT for 12 h. The product was μLtered and washed with water to provide 550 mg of 7-chforo-9-nitro-3 -carboline ExamμLe 15, 9-amino-7-chioro- (3 - carboline To a suspension of the product from examμLe 14 (548 mg,2.22 mmol) in EtOH (14 ml) at 65 DC to 70 °C was added tin chloride dihydrate (2.5 g, 11.1 mmol). Thereafter, 6M aqueous HC1(14 ml) was added dropwise. The mixture was stirred at 70 °C to 80 °C for 3.5 h and then partitioned slowly into saturated aqueous NaHCOj (150 ml) and EtOAc (100 ml). The aqueous phase was extracted (2 times) and the combined organic solutions dried (brine; NaS04) and concentrated to give 484 mg of 9-amino-7-chloro-13 -carboline. ExamμLe 16, 9-amino-7-chloro- (3 - carboline trifuoroacetate To a solution of the product from examμLe 15 (35 mg, 0.16 mmol) in pyridine (0.80 ml) was added acetic anhydride (0.018 ml, 0.19 mmol). The resulting mixture was allowed to stand at RT for 12 h before pouring into water (15 ml). The crude product was μLtered and purified by preparative HμLC using a Cig -packed column and eluting with a gradient (5:95 to 60:40) of water-ace tonitril (with 0.1% trifluoracetic acid). The pure fractions were combined and lyophilized to provide 18 mg of 9-amino-7-chloro-13 -carboline trifluoroacetate. ExamμLe 17, 7-bromo-l-carbonyl-(4"-morpholine)- f5 - carboline A solution of the product from examμLe 1 (125 mg, 0.51 mmol) in DMF (2 ml) was treated with 0.55 ml of 1M aqueous NaOH (0.55 mmol). After stirring at RT for 30 minutes, 4-morpholinecarbonyl chloride (0.060 ml, 0.51 mmol) was added and reaction stirred 18 h at RT. The reaction was partitioned in EtOAc and 5% citric acid and the organic layer washed with water, dried (brine; MgSChXand concentrated. The residue was chromatographed (7:3 hexane-acetone) on silica gel to give 105 mg of7-bromo-l-carbonyl-(4"-morpholino)- P -carboline ExamμLe 18, l-(2"-ethylacetate)-7-chloro- p -carboline To a suspension ofNaH (95%, 28 mg, 1.15 mmol) in DMF (1.0 ml) at 5 °C to 10 °C was added the product from examμLe 12 (202 mg, 1.0 mmol) in DMF (3 ml). The resulting mixture was stirred for 30 min at 5 °C to 10 °C before adding ethyl bromoacetate (0.116 ml, 1.05 mmol). The reaction was allowed to be stirred for 1.5 h and then the reaction was diluted with saturated aqueous NaHC03 (30 ml). The product was extracted with EtOAc (30 ml; 2 times each 15ml), and the combined organic extracts were dried (brine; MgS04) then concentrated. The residue was purified by chromatography (1:3 hexane-ethyl acetate) on silica gel to give 270 mg of 1- (2"ethylacetate)-7-chloro-P-carboline. ExamμLe 19, l-(2"-ethanoyl)-7-chloro- p - carboline To a solution of the product from examμLe 18 (50 mg,0.17 mmol) in THE (1.7 ml) at 5 °C to 10 °C was added 1MLAH in THF (0.17 ml, 0.17 mmol). The resulting mixture was stirred for 2 hat 5 °C to 10 °C before adding EtOAc (0.10 ml). The mixture was subsequently diluted with EtOAc (5 ml) and slowly treated with saturated aqueous NaHC03 (5 ml). After diluting widi water (10 ml) and brine (10 ml) the mixture was extracted with EtOAc. The organic solution was dried (brine; MgS04) then concentrated to give 42 mg of l-(2"ethanol)-7-chloro- p -carboline. ExamμLe 20, l-(2"-acetyl)-7-chloro- P - carboline To a solution of the product from examμLe 18 (107 mg,0.37 mmol) in MeOH (3.7 mb at RT was added water (3.7 ml) followed by treatment with 1M aqueous NaOH (0.41 ml, 0.41 mmol). The resulting mixture was stirred for2 h and the volatile removed under reduced pressure. The mixture was subsequently diluted with water (5 ml) and the pH adjusted to 5 to 6. The precipitate was μLtered and washed with waterto give 96 mg of 1-(2"-acetyl)-7-chloro- p -carboline. ExamμLe 21, 8-methoxy- p - carboline Prepared from 6-methoxytryptamine using the procedure as in examμLe 3. ExamμLe 22, see table 1 for structure To a solution of the product from examμLe 20 (59 mg, 0.23 mmol) in DMF (2.8 ml) at RT was added p-nitrophenol (40 mg, 0.29 mmol) followed by l-ethyl-3-(3-dimethylaminopropyl)carbodiimide {48 mg, 0.25 mmol). The resulting mixture was stirred for 1.5 h atRTand then ammonium bicarbonate (55 mg, 0.69 mmol) was added. The reaction was stirred for 18 h atRTand then poured into water (20 ml). The aqueous mixture was basined to pH of about 10 with K2C03. The precipitate was μLtered and washed with waterto give 47 mg of the title compound. ExamμLe 23, 8-hydroxy-2-methyl- p - carboline A solution of harmine (616 mg, 2.9 mmol) in dichlo roe thane (20 ml) was treated with 2.0 ml of IMBBr3 (4 mmol) in dichloroethane. The reaction was stirred at 60 °C for 48 h and then cooled to 0 °C before quenching with MeOH (5 ml). The reaction was concentrated and the residue triturated wim methanol to give 413 mg of 8-hydroxy-2-methyl- p -carboline . ExamμLe 24, 6,8-dibromo-7-methoxy- P - carboline A solution of the product from examμLe 30 (90 mg, 0.45 mmol) in acetic acid (8 ml) was treated with bromine (0.025 ml, 0.48 mmol). The reaction was stirred at RT for 18 h and then concentrated. The residue was partitioned in EtOAc and aqueous NaHC03. The organic layer was dried (brine; MgS04) and concentrated. The residue was purified by chromatography (5:4 hexane-acetone) on silica gel to give 3 mg of 6,8- dibromo-7-methoxy- P -carboline. ExamμLe 25, see table 1 for structure A solution of the product from examμLe 23 (60 mg,0.30 mmol) in DMF (3 ml) was treated with K2CO3(100 mg)and t-butylbromoacetate (0,040 ml, 0.27 mmol). After stirring atRT for 18 h, the reaction was partitioned in EtOAc and water. The organic layer was dried (brine; MgS04) and men concentrated. The residue was chromatographed (1:1 hexane-EtOAc) on silica gel to give 20 mg of the title compound. ExamμLe 26, see table for structure A solution of die product from examμLe 23 (50 mg, 0.25 mmol) in DMF (3 ml) was treated withK2C03 (100 mg)and benzyl bromide (0,030 ml, 0.25 mmol). After stirring at RT for 18 h, the reaction was partitioned in EtOAc and water. The organic layer was dried (brine; MgS04) and then concentrated. The residue was chromatographed (1 :l hexane-EtOAc) on silica gel to give 12 mg of the title compound. ExamμLe 27, 7-ethoxy-2-methyl- 3 - carboline A solution of the product from examμLe 23 (60 mg, 0.30 mmol) in DMF (3 ml) was treated with K2C03 (100 mg) and ethyl iodide (0,029 ml, 0.36 mmol). After stirring at RT for 18 h, the reaction was partitioned in EtOAc and water. The organic layer was dried (brine; MgS04) and then concentrated. The residue was chromatographed (1:1 hexane- acetone) on silica gel to give 20 mg of7-ethoxy-2-methyl- [3-carboline. ExamμLe 28, 7-bromo-2-methyl-p - carboline Prepared from harmane using the same procedure as in examμLe 1. ExamμLe 29, see table 1 for structure A solution of the product from examμLe 23 (60 mg,0.30 mmol) in DMF (3 ml) was treated with K2C03 (100 mg) and acetic anhydride (0,034 ml, 0.36 mmol). After stirring atRTfor 18 h, the reaction was partitioned in EtOAc and water. The organic layer was dried (brine; MgS04) and men concentrated. The residue was chromatographed (1:1 hexane-acetone)on silica gelto give 18 mg of the title compound. ExamμLe 30, 7-methoxy- (3 - carboline Prepared from 5-methoxytryptamine using the procedure in examμLe 3. ExamμLe 31, 8-fluoro-(J-carboline Prepared from 6-fluorotryptamine using the same procedure as in examμLe 3. ExamμLe 32, 7-bromo-2-methyl-8-methoxy- p - carboline Prepared from harmine using the same procedure as in examμLe 1. ExamμLe 33, 7-hydroxy-P - carboline Prepared from the product of examμLe 30 using the procedure in examμLe 23. ExamμLe 34, 7-chloro-8-fluoro- P - carboline Prepared from the product of examμLe 31 using the procedure in examμLe 12. ExamμLe 35, 7-methoxy-l-methyl- p - carboline Prepared from the product of examμLe 30 using the procedure in examμLe 11. ExamμLe 36 9-chloro-8-metiioxy-p-carboline trifluoroacetate and ExamμLe 37 7,9-dichloro-8- methoxy-P-carboline trifluoroacetate A solution of the product from examμLe 21 (195 mg, 1.0mmol)in 1MHC1 (3 ml) was treated with N-chlorosuccinimkle (270 mg, 2 mmol) portionwise and the resulting solution was stirred at 60 °C to 70 °C for3h. The reaction was evaporated and the crude product purified by preparative HμLC using a C18- packed column and eluting with a gradient (5:95 to 50:50) of water-acetonitril (with 0.1 % trifluoroacetic acid). The pure fractions of each product were combined and lyophilized to provide 78 mg of 9-chloro~8-methoxy-(3-carboline trifluoroacetate and 51 mg of 7,9-dichloro-8- methoxy-p-carboline trifluoroacetate. ExamμLe 38 7,9-dichloro-8-hydroxy-P-carboline A mixture of the product of examμLe 37 (590 mg,2.21 mmol) in methylene chloride (25 ml) at 35 °C was treated with a solution ofBBr3 in methylene chloride (1M, 6 ml, 6 mmol). After refluxing for 3h, the reaction was quenched with methanol (5 ml) and then concentrated. The residue was slurred in 60% NaHC03 solution, the product μLtered and washed with water to give 500 mg of7,9-dichIoro-8-hydroxy-P-carboline. ExamμLe 39 7,9-dichloro-8-emoxy-|3-carboline A mixture of the product of examμLe 38 (35 mg,0.14 mmol), K2C03 (100 mg), and ethyl iodide (0.014 ml, 0.17 mmol) in acetone (5 ml) was stirred in a closed reaction tube at RT for 3 days. After concentrating the reaction, die residue was partitioned in ethyl acetate and water. The organic layer was dried (MgS04) and concentrated to give crude product. The crude product was chromatographed (5% methanol in chloroform) on silica gel to give 8 mg of7,9-dichloro-8-ethoxy- P-carboline. ExamμLe 40 7-chloro-8-fluoro-p-carboline trifluoroacetate A solution of the product of examμLe 31 (78 mg,0.42 mmol) in 1MHC1(1 ml) was treated with N-chlorosuccinimide (115 mg,0.9 mmol) portionwise and the resulting mixture was stirred at 60 °C to 70 °C for 3h. The reaction was evaporated and the crude product purified by preparative HμLC using a Cis-packed column and eluting with a gradient (5:95 to 50:50) of water-acetonitril (with 0.1% trifluoroacetic acid). The pure fractions with product were combined and lyophilized to provide 33 mg of the title compound. ExamμLe 41 l-hydroxy-7-trifluoromethyl-P-carboline and ExamμLe 42 7-tri-fluoromethyl- P-carboline A solution of 3-hydroxy-2-piperdone (96 mg, 0.83 mmol) in methylene chloride (5 ml) was treated with Dess Martin reagent (352 mg,0.85 mmol) at RTand the resulting mixture was stirred for Ih. After μLtering the salts from the reaction, die ketone in solution was treated with 4-trifluoromethyl-phenyl-hydrazine (145 mg, 0.83 mmol). After 15 min, hexane (20 ml) was added and the hydrazone collected by μLtration. This crude hydrazone was heated at 95 °C in formic acid (70%, 10 ml) for Ih. The reaction was evaporated and the residue was chroma tog raphed (ethyl acetate) on silica gel to give 60 mg ofdfliydro l-hydroxy-7- trifluoromethyl-p-carboline. Aportion ofdfliydro l-hydroxy-7-trifluoromethyl-3-carboline (6 mg) in xylenes (1 ml) was treated with Pd/C (10%, 7 mg) and the mixture heated at 50 °C for one week. The reaction was concentrated after μLtering it through celite, and the residue was chromatographed (1:1 hexane-ethyl acetate) on silica gel to give 1 mg of l-hydroxy-7- trifluoromethyl-p-carboline. Aportion ofdihydro l-hydroxy-7-ttifluoromethyl-|3-carboline (25 mg) in THF (1 ml) was treated with a solution of lithium aluminum hydride in THF (1M, 0.5 ml). The reaction was stirred at 60 °C for6h before quenching with water (5 ml) and extracting with ethyl acetate (3 times 10 ml). The combined organic layers were dried (MgSO,i) and concentrated to provide tetrahydro 7-trifluoro-methyl-P-carboiine. This material was taken up in xylenes (5 ml) and treated with Pd/C (10%, 15 mg). The mixture was stirred at 150 °C for48h before μLtering through celite and concentrating. The residue was chromatographed (ethyl acetate) on silica gel to give 5 mg of7-tri- fluoromethyl-p-carboline. ExamμLe 43 7-chloro-9-(methylamino)-p-carboline trifluoroacetate A solution of the product of examμLe 15 (50 mg,0.23 mmol) in AcOH/methanol (1 %, 3 ml) was treated with sodium cyanoborohydride (30 mg,0.46 mmol) followed by formaldehyde (37%, 0.017 ml, 0.23 mmol). The reaction was stirred at RT for 36 h and then diluted with saturated NaHC03 (9 ml). After stirring for 15 min, the crude product was μLtered and washed with water. The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 13 mg of the title compound. ExamμLe 44 7-chIoro-9-(dimethylamino)-p-carboline trifluoroacetate A solution of the product of examμLe 15 (50 mg,0.23 mmol) in AcOH/methanol (1 %, 3 ml) was treated with sodium cyanoborohydride (30 mg, 0.46 mmol) followed by formaldehyde (37%, 0.060 ml, 0.69 mmol). The reaction was stirred at RT for 36 h and then diluted with saturated NaHCOs (9 ml). After stirring for 15 min, the crude product was μLtered and washed with water. The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 40 mg of the title compound. ExamμLe 45 7-chloro-9-(methytsulfonylamino)-p-carboline trifluoroacetate A solution of the product of examμLe 15 (30 mg, 0.14 mmol) in pyridine (0.5 ml) was treated with me thanesulfonyl chloride (0.024 ml, 0.30 mmol) in two portions over30h. The reaction was diluted with water (5 ml) and the crude product collected and washed with water {several times). The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 16 mg of the title compound. ExamμLe 46 7-chloro-9-(propyionylamino)-3-carboline trifluoroacetate A solution of the product of examμLe 15 (30 mg, 0.14 mmol) in pyridine (1.0 ml) was treated with propionyl chloride (0.015 ml, 0.17 mmol). After stirring atRTfor4h, the reaction was diluted with water (9 ml) and saturated NaHC03 (1 ml). The crude product was collected and washed with water (several times )■ The crude product was purified by preparative HμLC using a Cig-packed column and eluting with a gradient (5:95 to 50:50) of water-acetonitril(with 0.1% trifluoroacetic acid). The pure fractions with product were combined and lyophilized to provide 21 mg of the title compound. ExamμLe 47 7-chloro-9-(benzoylamino)-|3-carboline trifluoroacetate A solution of the product of examμLe 15 (30 mg, 0.14 mmol) in pyridine (1.0 ml) was treated with benzoyl chloride (0.020 ml, 0.17 mmol). After stirring at RTfor4h, the reaction was diluted with water(9 ml) and saturated NaHC03 (1 ml). The crude product was collected and washed with water (several times). The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 12 mg of 7-chloro-9-(benzoylamino)-3-carboline trifluoroacetate. ExamμLe 48 7-chloro-9-(Acetyl-methylamino)-|3-carboline trifluoroacetate A solution of the product of examμLe 43 (19 mg, 0.082 mmol) in pyridine (0.40 ml) was treated with acetic anhydride (0.037 ml, 0.36 mmol) in two portions over48h. The reaction was subsequently concentrated to dryness and die residue coevaporated with AcOH under reduced pressure. The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 9 mg of the title compound. ExamμLe 49 7-chloro-9-(4-fluorobenzovlaminol-B-carboline trifluoroacetate A solution of the product of examμLe 15 (30 mg,0.14 mmol) in pyridine (1.0 ml) was treated with 4-fluorobenzoyl chloride (0.018 ml, 0.17 mmol). After stirring atRTfor 18h, the reaction was diluted with water (10 ml). The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 13 mg of the title compound. ExamμLe 50 A cold (3 °C to 5 °C) solution of the product of examμLe 15 (30 mg, 0.14 mmol) and pyridine (0.014 ml, 0.17 mmol) in THF (0.7 ml) was treated with phenyl chloroformate (0.018 ml, 0.145 mmol). After stirring at RT for 2h, the reaction was partitioned in ethyl acetate and buffer (pH 7.2). The organic layer was dried (brine, Na2S04) and concentrated to give 43 mg ofphenylcarbamate. To a solution of phenyl carbamate (30 mg, 0.089 mmol) in DMSO (0.5 ml) was added 2- methoxyethylamine (0.010 ml, 0.10 mmol). After stirring atRTfor 30 min, the crude reaction mixture was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 21 mg ofthe title compound. ExamμLe 51 7-chloro-9-(methoxyacetylamino)-f3-carboline trifluoroacetate A solution ofthe product of examμLe 15 (35 mg, 0.16 mmol) in pyridine (1.0 ml) was treated with methoxyacetyl chloride (0.016 ml, 0.18 mmol). After stirring at RTfor2h, the reaction was diluted with water (10 ml). The crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 32 mg ofthe title compound. ExamμLe 52 7-chloro-9-(3-methoxybenzoxylamino)-p-carboline trifluoroacetate A solution ofthe product of examμLe 15 (30 mg, 0.14 mmol) in pyridine (1.0 ml) was treated with m-anisoyl chloride (0.027 ml, 0.19 mmol) in two portions over6h. The reaction was subsequently diluted with water (10 ml) and the crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 33 mg ofthe title compound. ExamμLe 53 7-chloro-9-(4-methoxybenzoxylamino)-p-carboline trifluoroacetate A solution ofthe product of examμLe 15 (30 mg, 0.14 mmol) in pyridine (1.0 ml) was treated with p-anisoylchloride (37 mg,0.22 mmol) in two portions over24h. The reaction was subsequently diluted with water (10 ml) and the crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 24 mg of the title compound. ExamμLe 54 7-chloro-9-(methylcarbamyIamino)-p-carboline trifluoroacetate A solution of the product of examμLe 15 (30 mg.0.14 mmol) in pyridine (1.0 ml) was treated with p-anisoyl chloride (0.017 ml, 0.21 mmol) in two portions over4h. The reaction was subsequently diluted with water (10 ml) and the crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 35 mg of the title compound. ExamμLe 55 7-chloro-9-(isovalerylamino)-(3-carboune trifluoroacetate A solution of the product of examμLe 15 (35 mg, 0.16 mmol) in pyridine (1.0 ml) was treated with isovalerylchloride (0.033 ml, 0.28 mmol) in two portions over 24h. The reaction was subsequently diluted with water (10 ml) and the crude product was purified as described in examμLe 46. The pure fractions with product were combined and lyophilized to provide 52 mg of the title compound. ExamμLe 60 N-(6-Chloro-9H-P-carboUn-8-yl)-nicotinamide To a solution of norharmane (2.0 g, 11.9 mmol) in water (89 ml) and 1M aqueous HC1 (29.8 ml, 29.8 mmol) was added N-chlorosuccinimide (3.17 g, 23.8 mmol) portkmwise. The resulting solution was stirred at RT for 6 h, and then at 0 °C to 5 °C for 12 h. The reaction was diluted with water (100 ml) and basified cautiously with solid K2C03 (4-3 g). After stirring at RT for 1 h, the product was collected and washed with water. The crude product was re fluxed in chloroform for 1 h and μLtered after cooling to 15 °C to provide 2.05 g of 7-chloro-p-carboline. A mixture 7-chloro-(3-carboline (500 mg, 2.48 mmol) in concentrated nitric acid (20 ml) was stirred at RTfor22 h. The reaction mixture was carefully poured into cold (3 °C to 5 °C) water (50 ml), and after stirring for 2 h the precipitate was collected. The solid was suspended in saturated aqueous NaHC03 (50 ml) and stirred at RT for 12 h. The product was μLtered and washed with water to provide 550 mg of 7-chloro-9-nitro- (3 - carboline. To a suspension of 7-chloro-9-nitro- p -carboline (548 mg,2.22 mmol) in EtOH (14 ml) at 65 °C to 70 °C was added tin chloride dihydrate (2.5 g, 11.1 mmol). Thereafter, 6M aqueous HC1(14 ml) was added dropwise. The mixture was stirred at 70 °C to 80 °C for 3.5 h and then partitioned slowly into saturated aqueous NaHCOj (150 ml) and EtOAc (100 ml). The aqueous phase was extracted (2 times) and the combined organic solutions dried (brine; NaS04) and concentrated to give 484 mg of 9-amino-7-chloro- p-carboline. To a cokf (3-5 °C) solution of 9-amino-7-chloro- (3 -carboline (2.75 g, 12.7 mmol) in pyridine (150 ml) was added nicotinyl chloride hydrochloride (2.82 g, 15.8 mmol). The reaction was allowed to warm to RTand stirred for20 h before diluting the reaction with water (100 ml) and lMNaOH (25 ml). After stirring for 1 h atRT.the mixture was poured into water (200 ml). The mixture was allowed to stand for 1 h and the product was μLtered to provide 3.80 g of the title compound after washing with water and drying under reduced pressure at RT. ExamμLe 68 N-(6-Chloro-7-methoxy-9H-p-carbolin-8-yl)-nicotinamide A mixture of 6-methoxytryptamine (9.10 g, 47.8 mmol) in EtOAc (40 ml) and pH 4.5 NaOAc buffer (40 ml) was treated with glyoxalic acid hydrate (5.30,57.6 mmol). The mixture was stirred vigorously for 2 days and then diluted with hexane (40 ml). The product was μLtered and washed with water and (1:1) hexane-ethyl acetate. The crude product was crystallized from methanol after μLtration of a hot methanol solution. The crude product (11.5 g) from above in 6N HC1(100 ml) was treated 3 times with concentrated HC1(5.0 ml) every 15 min while refluxing. After re fluxing for a total of 1 h, the reaction was concentrated to give a residue. This residue was slurried and sionicated with 10% Na2C03 (300 ml) and μLtered to give the free amine (7.20 g). The above amine was re fluxed in xylenes (200 ml) and pyridine (100 ml) with 10% Pd/C (3 g) for 5 h. The hot reaction was μLtered thru celite and the μLtrate was concentrated to give 6.38 g of 8-methoxy-P-carboline. To a mixture of 8-methoxy- P -carboline (1.0 g,5 mmol) in THF(100 ml) was added N-chlorosuccinimide (0.70 g, 5.2 mmol). The reaction was stirred at RT for 4 h before concentrating and washing the residue with 1:1:1 mixture of 10% Na3C03, hexane, and EtOAc (400 ml). The resulting residue was triturated with xylenes to provide 677 mg of 7-chloro-8-methoxy- P -carboline. A solution of 7-chloro-8-methoxy- P -carboline (677 mg, 2.9 mmol) in trifluoroacetic acid (10 ml) was treated with NaN03 (260 mg, 3.06 mmol). The reaction was stirred for 3 h at RTand then concentrated. The crude product was chromatographed on silica e luting with a 5 % to 10% methanol in chloroform gradient to provide 463 mg of 7-chloro-8-methoxy-9-nitro- p -carboline. A solution of 7-chloro-8-methoxy-9-nitro-p-carboline (460 mg, 1.66 mmol) in EtOH (25 ml) was treated with SnCt-2 H20 (450 mg, 2.00 mmol). The reaction was stirred for 5 h at 65 °C and then concentrated. The crude product was chromatographed on silica eluting with a 5 to 10% methanol in chloroform gradient to provide 410 mg of 7-chloro-8-methoxy-9-nitro-P-carboline. A solution of 7-chIoro-8-methoxy-9-nitro-p-carboline (21 mg, 0.085 mmol) in pyridine (1 ml) was treated with nicotinyl chloride hydrochloride (54 mg,0.30 mmol) and 4-dimethylaminopyridine (5 mg). After stirring at95 °C - 100 °C for7 h the reaction was concentrated, the residue slurried with 10% Na2C03, and then chromatographed on silica eluting with a 5 % to 10% methanol in chloroform gradient to provide 4.7 mg of the title compound. ExamμLe 82 N ExamμLe 83 6-Chloro-N-(6-chloro-9H-p-carbolin-8-yl)-nicotinarnide To a cold (3-5 °C) solution of 9-amino-7-chloro-p-carboline (1.40 g, 6.45 mmol, as prepared in examμLe 60 above) in pyridine (72 ml) was added 6-chloro-nicotinyl chloride (1.30 g,7.42 mmol). The reaction was allowed to warm to RTand stirred for 16 h before diluting the reaction with water (60 ml) and lMNaOH (8 ml). After stirring for 40 min at RT, the mixture was poured into water (200 ml). The mixture was allowed to stand for 30 min and the product was μLtered to provide 2.20 g of the title compound after washing with water and drying under reduced pressure at RT. The examμLes in Table 1 show the structures of the prepared compounds and were prepared according to the previous examμLes. Table 1: use of the ELK A method, the comμLex can be immobilized either onto a bio tin-binding μLate (such as Neutravidin coated μLate) and detected with a secondary antibody conjugated to HRP, or onto an antibody-binding μLate (such as Protein-A coated μLate) and detected with bio tin-binding protein conjugated to HRP (such as Streptavidin-HRP). The fevelofactivitycan be correlated with a standard curve using synthetic phosphopeptides corresponding to the substrate polypeptide. Experimental IKBO kinase comμLex was prepared by first diluting 10 mL of He La S3 cell-extracts S100 fraction with 40 mLof 50 mMHEPES pH 7.5. Then, 40% ammonium sulfate was added and incubated on ice for 30 minutes. Precipitated pellet was redissolved with 5 mLof SEC buffer (50 mMHEPES pH 7.5,1 mMDTT,0.5 mMEDTA, 10mM2-glycerophosphate), clarified by centrifugation at 20,000 x g for 15 min., and μLtration through a 0.22 μm μLter unit. SamμLe was loaded onto a 320-mLSuperose-6 FμLC column (Amersham Pharmacia Biotech AB, Uppsala, Sweden) equilibrated with SEC buffer operated at 2 mL/min flow rate at 4°C. Fractions spanning the 670-kDa molecular-weight marker were pooled for activation. Kinase-containing pool was then activated by incubating with 100 nM MEKK1A, 250 uM MgATP, 10mMMgCb,5 mMDTT, 10 mM2-gtycerophosphate, 2.5 ^MMicrocystin-LR, for 45 minutes at 37 °C. Activated enzyme was stored at-80°C until further use. Per well of a 96-we 11 μLate, compounds at various concentrations in 2 jiLDMSO were pre-incubated for 30 minutes at25°C with 43 μL of activated enzyme diluted [1:25] with assay buffer (50 mMHEPES pH7.5,5 mM DTT, 10 mMMgCfe, 10 mM 2-glycerophosphate, 2.5 /tM Microcystin-LR). Five microliters of peptide substrate (biotin-(CH2)6- DRHDSGLDSMKD-CONH2) at 200 μM stock solution was added to each well and incubated for 1 hour before quenching with 150 μLof 50 mMHEPES pH 7.5, 0.1 % BSA, 50 mMEDTA, μLus [1:200] antibody. Quenched kinase reaction samμLes and phospho-peptide-calibration standards (biotin-(CH2)6- DRHDS[P03]GLDSMKD-CONH2 , serially diluted in assay buffer) at 100 μLper well were transferred to a Protein-A μLate (Pierce Chemical Co., Rockford, 1L, USA) and incubated for 2 hours, with shaking. Following 3 washes with PBS, 100 μL of 0.5 jig/mLStreptavidin conjugated with HRP (horseradish peroxidase) diluted with 50 mMHEPES/0.1% BSA, was added for 30 minutes. After 5 washes with PBS, 100 μLTMB substrate (Kirkegaard &Perry Laboratories, Gaithersburg, MD, USA) was added and color development was stopped by adding 100 μL of 0.18 MH2S04. 0.6), and grafts in those given compound 60 survived for 20 days (20 +1). Current immunosuppressive therapies used in transμLantation have limited efficacy and/or considerable toxicity. Targeting of IkB-kinase with these agents significantly prolonged allograft survival without associated toxicity. WE CLAIM: 1. A compound of the formula I a physiologically tolerable salt of the compounds of the formula I, where B6, B7, Ba and B$ are independently selected from the group consisting of carbon atom and nitrogen atom, where B9, B7, BB and B« together are no more than two nitrogen atoms at the same time; wherein in case a) the substituents R1, R2 and R8 independently of one another are 1.1 hydrogen atom, 1.2. halogen, 1.3. -CN, 1.4. -COOH, 1.5. -N02, 1.6. -NH2l 1.7. -0-(Ci-Cio)-alkyl, wherein alkyl is unsubstituted or mono- to penta- substituted Independently of one another by 1.7.1 phenyl, which is unsubstituted or mono-to penta-substituted by halogen or-0-{Ci-C 1.7.2 halogen, 1.7.3 -NHa, 1.7.4 -OH, 1.7.5 -COOR16, wherein R16 Is hydogen atom or -(Ci-Cio)-alkyl, 1.7.6 -NOa, 1.7.7 -S(0)-R14, wherein y is zero, 1 or2, R14ls -(^-C1-)- alkyl, phenyl, which is unsubstituted or mono- to penta-substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(R13)2, wherein R13 is independently of one another hydrogen atom, phenyl, -(Ci-&o)-alkyl, -CfOMd-C1-J-aJkyl, -C(O)-phenyl, -C(0)-NH-(Ci-C7)-alkyl, -C{O)-0-phenyl, -C(O)-NH-phenyl, -C(0)-0-{Ci-C?)-alkyl, -S(OVR14, wherein RM and y are as defined above, and wherein alkyl or phenyl In each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, or R13 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms selected from pyrrolidine, tetrahydrcpyridine, piperidine, plperazine, imidazoline, pyrazolidine, morphollne, pyridine, pyrazine, pyridazine, imidazoline, isoxazolidine, 2-isoxazollne, isothlazolldine, 2-isothiazoline orthiomorphollne, 1.7.8 -Q-phenyl, wherein phenyl is unsubstituted or mono- to penta- substituted Independently of one another as defined under 1,7,1 to 1.7.11 above, 1.7.9 a radicale selected from pyrrolidine, tetrahydropyriOine, piperidine, plperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazollne, isothlazolldine, 2-isothiazoline, thiophene orthiomorpholine, 1.7.10 -(C1-CjJ-cycloalkyl or 1.7.11=0. 1.8. -N(Rl3)2, wherein R13 is as defined in 1.7.7 above, 1.9. -NH-C(0)-R15, wherein R1S Is 1.9.1 a radicale selected from pyrrolidine, tetrahydropyridine, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thtomorpnotirte, wherein said radical is unsubstituted or mono-to penta-substituted independently of one another as defined under 1.7.1 to 1.7.11 above, -CF3, benzyl or by-(C1-Cio)-alkyl, wherein alkyl is mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.9.2 -(C1-Cio)-alkyl, wherein alkyl is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or by-CMCI-CH,)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted independently of one another as defined under 1.7.1 to 1.7,11 above, 1.9.3 -(Cs-C1-)-cycloalkyl, 1.9.4 -N{R13)2| wherein R13 is as defined In 1.7.7 above, or 1.9.5 phenyl, wherein phenyl is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, by -O-fd-CiaJ-alKyl, by -CN, by -CF3, by -(Ci-C10)-alkyl, wherein alkyl is mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or two substltuents of the phenyl radical form a dioxolan ring, 1.10. -S(0)y-R14, wherein R14 and y are as defined in 1.7.7 above, 1.11. -C(0)-R12. wherein R12 is phenyl or -(Ci-C7)-alkyi, wherein aJkyl or phenyl are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.12. -C(0)-O-R12, wherein R12 is as defined in 11. above, 1.13. -(d-CioJ-alkyl, wherein alkyl is unsubstituted or mono* to penta-substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 1.14. -O-Cd-CgJ-aikyl-O-tCi-CeJ-alkyl, 1.15. -0-{Co-C4)-alkyl-(C3-C7)-cycioaIkyl, 1.16. -(C,-C4)-alkyl-N(R13)2, wherein R13 Is as defined in 1.7.7 above 1.17. -CF3or 1.18. -CF2-CF3, R4 is 1. -(Ci-CioJ-alkyl, wherein alky! is mono- to penta- substltuted Independently of one another as defined under 1.7.1 to 1,7.10 above, 2. -CF3, 3. -CF2-CF3, 4. -CN, 5. -S(0)y-R14. wherein R" and y are as defined In 1.7.7 above, 6. -0-(C1-C6)-alkyl-0-(Ci-C6)-alkyl, 7. -Q-(Ci-Cio)-a!kyl, wherein alkyl is mono-to pertta-substituted Independently of one another by 7.1 phenyl, which is unsubstltuted or mono- to penta-substituted by halogen or-0-(Ci-C4)-alkyl, 7.2 halogen, 7.3 -NH2, 7.4 -OH, 7.5 -COOR19, wherein R16 is hydogen atom or-(Ci-Cio}-alkyl, 7.6 -N02, 7.7 -S(0)y-R14, wherein y is zero, 1 or 2, R1" Is -(d-do)-alkyl, phenyl, which is unsubstituted or mono- to penta-substituted as defined for substltuents under 1.7.1 to 1.7,11, amino or-N(R13)2| wherein R13 is independently of one another hydrogen atom, phenyl, -(Ci-C10)-alkyl, -CCOMd-CyJ-alkyl.-CfO)- phenyl, -C(0)-NH-(C1-C7)-alkyl, -C(0)-0-phenyt, -C(0)- NH-phenyl, -CfOJ-O^Ci-CTj-alkyl, -S^VR1", wherein R14 and y are as defined above, and wherein alkyl or phenyl in each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7-1 to 1.7.11 above, or R13 together with the nitrogen atom to which it Is bonded form a heterocyde having 5 to 7 ring atoms as defined above, 7.8 -O-phenyl, wherein phenyl Is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 7.9 a radicale selected from pyrrolidine, tetrahydropyridlne, piperldine, plperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazlne, oxolan, imidazoline, isoxazolidine, thiophene, 2-isoxazoline, isothiazolldine, 2-lsothiazoline, orthiomorpholine, 7.10 -(Ca-C1-J-cycloalkyl or 8. -N(R17)s. wherein R17 Is Independently of one another hydrogen atom, phenyl, -(C-i-Cio)-alkyl, -C(0)-phenyl, - C(0)-NH-pheny(, -C1--NHKCi-C1-Valkyi, -C(0)-(Ci-C«)- alkyl, -C(0)-0-phenyl, -C{0)-0-fa-C7)-a\ky\, -S(OVR14, wherein Rw and y are as defined above, and wherein alky! or phenyl in each case are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, with the proviso that -N(R17)2 is not NH2, 9. -NH-C(0)-R13, wherein R18 Is 9.1 a radlcale selected from pyrrolidine, tetrahydropyridlne, piperldine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-laoxazollne, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine, wherein said radical is unsubstituted or mono- to penta-substitutsd Independently of one another as defined under 1.7.1 to 1.7.11 above, -CF3, benzyl or by -(C1-C10)-alkyl, wherein alkyl is mono to tri- substituted Independently of one another as defined under 1.7.1 to 1.7.11 above, 9.2 -{Ci-Cio)-a!kyl, wherein alkyl Is mono- to penta-substltuted independently of one another as defined under 1.7.1 to 1.7.11 above or by -0-(Cn-Cla)^lkyl, wherein alkyl is unsubstituted or mono- to penta-substituted independently of one another as defined under 1.7,1 to 1.7.11 above, 9.3 -(Cs-CyJ-cycloalkyl, 9.4 -N(R13)2, wherein R13 is as defined in 1.7.7 above provided that -N(R13)2 is not -NH2, or 9.5 phenyl, wherein phenyl is unsubstrtuted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, by -CMC1-CioValkyi, by -CN, by -CF3t by -(CT-C1D)-alkyl, wherein alkyl is mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above or two substituents of the phenyl radical form a dioxolan ring , 10. -C(0)-Rlz, wherein R12 is phenyl or -(d-C1--alKyl, wherein alkyl or phenyl are mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.10 above, 11. -C(0)-0-R12, wherein R12 ts as defined in 10. above, 12. -0-(Co-C4)-aikyl-(C3-C7)-cyclaaJkyl or 13. -(Ci-C.0-alkyl-N(Rl3)2, wherein R13 is as defined in 1.7.7 above, R5 is 1. a hydrogen atom, 2. -(GrCio)-alkyl, wherein alky! Is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.4 above, 3. -C(0)-Rs, wherein Rs is -NH2, -(Ci-Cio)-alkyl, wherein alkyl is unsubstrtuted ormono- to psnta- substituted independently of one another as defined under 7.1 to 7.4, or -N(R1s)a, wherein R13 Is as defined in 1.7.7 above, or 4. -S(0)j-Rs, wherein R8 is as defined In 3. above, or RA and Rs together with the atom to which they are bonded form a heterocycle radicate selected from pyrrolidine, piperidine, tetrahydropyridine, piperazlne, imidazoline, pyrazoildlne, furan, morpholine, pyridine, pyridazine, pyrazine, imidazoline, isoxazoMne, thiophens, 2-isoxazoline, isothiazolidine, 2-lsothlazollne, or thiomorpholine, or R3 and Rfi together with the atom to which they are bonded form a heterocycle containing an additional oxygen atom in the ring selected from morphollne, iaoxazolidine or 2-isoxazoline, Rs, R7 and Ra independently of one another are hydrogen atom or methyl, or In case fc) the substituents R\ R2 and R4 independently of one another are as defined under 1.1 to 1.18 in case a) above, R3is 1. -CfV 2. -CF;rCF3, 3. -CN, 4. -COO 5. -N02, 6. -NHj, 7. -N(R1S)2, Wherein R1* Is as defined In 1.7.7 above, 8. -NH-C(0)-R"5, wherein R" is 9.1 a radicals selected from pyrrolidine, tetrahydrapyrtdlne, piperidine, piperazlne, imidazoline, pyrazolone, furan, morpholine, pyridine, pyridazine, pyrazine, cxotan, Imidazoline, isoxazolldlne, 2-isoxazoIine, isothiazolldine, 2-isotnia20line, thiophene or thlomorpholine, wherein said radical is unaubstitutsd or mono- to penta-substituted Independently of one another as defined under 1.7.1 to 1,7,11 above, -CF3l benzyl or by -(Ct-C«)-alkyl, wherein alkyl Is mono to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 9.2 -(C1-Cie)-alkyl, wherein alkyl Is unsubstltuted or mono-to penta- substituted independently of one another as defined under 1.7.1 to 1.7,11 above or by -O-(O-Cio)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted Independently of one another as defined under1.7.1 to 1.7.11 above, 9.3 -(C3-C7)-cycloalkyl, 9.4 -N(R13)2, wherein R13 is as defined In 1.7.7 above, or 9.5 phenyl, wherein phenyl is unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, by -0-{Ci-C.|o)-alkyl, by -CN, by -CF3, by -(Ci-CiD)-alky], wherein alkyl Is mono to trl- substituted independently of one another as defined under 1.7.1 to 1.7.11 above ortwo substituents of the phenyl radical form a dioxolan ring , 10. -S(0)y-R14, wherein RU and y are as defined in 1.7.7 above, 11. -C(0)-R12, wherein R" is phenyl or -(C1-J-alkyl, wherein alkyl or phenyl are unsubstituted or mono- to penta- substituted independently of one another as defined under 1.7.1 to 1.7.11 above, 12. -C(0)-0-R12, wherein R12 is as defined in 11. above, 13. - 14. -O-fd-CeJ-alkyl-O^d-CeJ-alkyl, or 15. -(C-OO-alkyl-NfR1^, wherein R13 Is as defined in 1.7.7 above, R5 is as defined as R8 in case a) above, R6. R7 and R8 independently of one another are hydrogen atom or methyl. 2, The compound of the formula I as claimed in claim 1, wherein in case a) BB, B7. Ba, and Bfl are each a carbon atom, R\ Rz and R3 Independently of one another are hydrogen atom, halogen, cyano, nltro, amino, -0-(Ci-C7)-alkyl, wherein alkyl is unsubstituted or substituted by phenyl, -CF2-CF3, -CF3, -N(R19)2, wherein R18 Is Independently of one another hydrogen atom, -{d-C1-J-alkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyl, -C(0)-NH-phenyl, -C(0)-0-phenyl, -C(0)-0-(Ci-C4)-aJkyl or -CfpMCi-C?)-alkyl, wherein alkyl, pyridyl or phenyl are unsubstituted or mono-to tri- substituted Independently of one another as defined under 1.7.1 to 1.7.11, or R1B together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms selected from pyrrolidine, tetrahydropyridlne, piperidine, piperazlne, imidazoline, pyrazolidine, morpholine, pyridine, pyrazlns, pyridazine, imidazoline, isoxazolidine, 2-isoxazollne, fsothiazolidine, 2-isothiazoline orthlomorpholine, wherein y Is zero, 1 or 2, and R14 Is -(d-doj-aikyl, phenyl, which Is unsubstituted or mono- to penta- substituted as defined for substltuents under 1.7.1 to 1.7.11, amino or-N(R18)2, wnerein R1B is as defined above, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C(0)-0-R12, wherein R12 is as defined above, R4 is cyano, -0-(Ci-C7)-alkyl, wherein alkyl is substituted by phenyl; -CFrCF3,-CF3,-N(R1s)3, wherein R18 is independently of one another hydrogen atom, -(Ci-C7)-aIkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyi, -C(0)-NH-phenyl, -C(0)-0-phenyl, -CfOJ-O-td-dJ-alkyl or -C(0)-(d-C7)-alkyl. wherein alkyl, pyridyl or phenyl are unsubstituted or mono-to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or R18together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms as defined above, with the proviso that -N(R18)2, is not NHz, SfOVR14, wherein y is zero, 1 or 2, and Ru Is -{Ci-Ci0)-alkyl, phenyl, which Is unsubstituted or mono- to penta- substituted as defined for substituents under 1.7.1 to 17.11, amino or-N(R18)2, wherein R18 is as defined above, wherein alkyl Is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C(O)-0-R12 wherein R12 Is as defined above, Re, R7 and RB independently of one another are hydrogen atom or methyl, and Rs is as; defined in claim 1, or in case b) the substituents R\ R2 and R* independently of one another are hydrogen atom, halogen, cyano, nitro, amino, -0-(C,-C7)-alky), wherein alkyl Is unsubstituted or substituted by phenyl, -CF2-CF3, -CF3, ~N(R15)2, wherein R18 is independently of one another hydrogen atom, -(d-CyJ-alkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyl, -C(0)-NH-phenyl, -C(O)-0-pheny|, -C(0)-0-(C-,-C4)-alkyl or-CfOHCi-C?)-alkyl, wherein alkyl, pyridyl or phenyl are unsubstituted ormono-to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or R18together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms as defined in case a) above, S wherein y is zero, 1 or2( and R14 is -(Ci-Cio)-alkyl, phenyl, which Is unsubstituted or mono- to penta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(R18)2, wherein R18 is as defined above, wherein alkyl Is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.11, or -C R3 is cyano, nitro, amino, -CF2-CF3l -CF3l -N(R18)2l wherein R18 is independently of one another hydrogen atom, -(CVC1--alkyl, phenyl, -C(0)-phenyl, -C(0)-pyridyJ, -C(0)-NH-phenyl, -C(O)-0-phenyl, -CfOJ-CMd-C1--alkyf or -C(0)-(C,-C7)-aikyi, wherein alkyl, pyridyl or phenyl are unsubstituted ormono-to tri-substituted Independently of one another as defined under 1.7.1 to 1.7.11, or R18together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms as defined In case a) above, -S(0)irR1"s, wherein y fs zero, 1 or 2, and RU Is -(Ci-CioJ-alkyl, phenyl, which is unsubstituted or mono- to penta- substituted as defined for substituents under 1.7.1 to 1.7.11, amino or-N(Rie)2, wherein R16 is as defined above, wherein alkyl is unsubstituted or mono- to tri- substituted independently of one another as defined under 1.7,1 to 1.7.11, or -C(O)-0-R12, wherein R12 is as defined above, Re, Rr and R8 independently of one another are hydrogen atom or methyl, and R6 is as defined in claim 1. 3. Thecompound of the formula II as claimed in claim 1 R1 and Ra are independently of one another hydrogen atom, halogen, cyano, amino, -0-(Ci-C)-alkyl, nitro, -CF3l -CF:-CF5, -S(0)y-R14, wherein y is 1 or 2, R14 is amino, -(C1-C7)-aJkyl or phenyl, which is unsubstituted or mono- to tri- substituted as defined for substituents under 1.7.1 to 1.7.11 in claim 1, -N(R1B)s, wherein R18 is independently of one another hydrogen atom, -(C1-J-alkyl-CfOHd-CzMlkyl. -C(0)-phenyI, -C(0)-pyridyI. -C(0)-NH-{Ci-O,)-alkyI. -C(0)~0-phenyl, -C{0)-O-(Ci-C4)-alkyl or -{Ci-Cio)-a]kyl, wherein pyridyl, alkyl or phenyl are unsubstltuted or mono- to tri-substituted Independently of one another as defined under 1.7.1 to 1.7.11, or R1fl together with nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms selected from pyrrolidine, tetrahydropyridine, piperidlne, piperazine, pyridine, imidazoline, pyrazolidlne, morpholine, pyrazine, pyridazlne, imidazoline, Isoxazolidine, 2-isoxazoiine, isothiazolidine, 2-isothiazoline orthiomorphcline, with the provlsio that R1 and Ra are not together hydrogen atom, R3 is cyano, amino, -0-(Ci-C4)-alkyl, nltro, -CF3, -CF2-CF3, -S(0)yR14, wherein y is 1 or 2, R14 is amino, -(d-C1-J-alkyi or phenyl, which is unsubstltuted or mono- to tri- substituted as defined for substituents under1.7.1 to 1.7.10 in claim 1, -NtR-18^, wherein Ria is Independently of one another hydrogen atom, -(Ct-C7)-alkyl-C(QMCi-C7>-all wherein alkyl is unsubstltuted or mono- to tri- substituted independently of one another as defined under 1.7.1 to 1.7.4, -C(0)-Re or -S(0)rR9, wherein R8 is -(Ci-Cl0)-alkyl, -CMC1-Cio)-alkyl, wherein alkyl is unsubstltuted or mono- to tri- substituted independent^ of one another as defined under 1.7.1 to 1.7.4, or phenyl, which is unsubstltuted or mono- to tri- substituted as defined under 1.7.1 to 1.7.11, or-N(R18)2, wherein R1B is as defined above. 4. Thecompound of the formula II as claimed In claim 3, wherein R1 fs bromo, -CF3 or chloro, R2 is hydrogen atom or 0-{C1-C2)-alkyl, R3 is -N(R18)2, wherein R18 is independently of one another hydrogen atom. -C(0)-pyr1dyl, -C(0)-phenyl, -(C-C/J-alkyl, -C(0>-(d-C1--alkyl or-C(0)0-(Ci-C4)-alkyl, wherein alkyl or phenyl are unsubstituted or mono- to trt- subetitutBd independently of one another by halogen or -0-(Ci-Cs)-alkyi, and Rs is hydrogen atom, methyl or-S(0)a-CH3. 5. The compound of the formula II as claimed in any one of claims 3 or 4, wherein R1 is chloro, R3 is -N-C(0)-CHrO-CH3 and R2 and R5 are each hydrogen atom, or R1 is chloro, R3 is -N-C(Q)-pyridyl, wherein pyridyl Is unsubstituted or substituted by chloro, R2 is hydrogen atom or -O-CHs and R5 is hydrogen atom, or R1 is chloro, R3 is -N-C(0)-phenyl, wherein phenyl is mono- or di-substituted by fluoro and RJ and R8 are each hydrogen atom. 6. A process for the preparation of the compounds of the formula I as claimed in any one of claims 1 to 5, which comprises b) a compound of the formula VII is reacted with a compound of the formula VIII Y-Rs (VII!) where Y is halogen or -OH and Rs is as defined In formula I, to give a compound of the formula I, or c) resolving a compound of the formula I, which on account of its chemical structure occurs Inenantlomeric forms, prepared by process a) or b) into the pure enantiomers by salt formation with enantiomerically pure acids or bases, chromatography on crtlrai stationary phases or derealization by means of chira! enantiomerically pure compounds such as amino adds, separation 9of trie dlastereomere Oius obtained, and removal of the chlrai auxiliary groups, or d) isolating the compound of the formula 1 prepared by process a), b) or c) either in free form or, In the case of the presence of acidic or basic groups, converting it into physiologically tolerable salts. A pharmaceutical comprising 20 mg to 1000 mg of at least one compound of formula I as claimed in any one of claims 1 to S and / or of a physiologically tolerable salt of the compound of the formula I, together with a known pharmaceutically suitable and physiologically tolerable excipents, additive and / or other known active compounds and auxiliaries.

Documents:

2002-1431.rtf

in-pct-2002-1431-che abstract duplicate.pdf

in-pct-2002-1431-che abstract.pdf

in-pct-2002-1431-che claims duplicate.pdf

in-pct-2002-1431-che claims.pdf

in-pct-2002-1431-che correspondence others.pdf

in-pct-2002-1431-che correspondence po.pdf

in-pct-2002-1431-che description (complete) duplicate.pdf

in-pct-2002-1431-che description (complete).pdf

in-pct-2002-1431-che form-1.pdf

in-pct-2002-1431-che form-13.pdf

in-pct-2002-1431-che form-18.pdf

in-pct-2002-1431-che form-26.pdf

in-pct-2002-1431-che form-3.pdf

in-pct-2002-1431-che form-5.pdf

in-pct-2002-1431-che pct.pdf

in-pct-2002-1431-che petition.pdf