Substituted beta carbolines

A compound of formula I

• 133
• or a stereoisomeric form of a compound of the formula I or a physiologically tolerable salt of a compound of the formula I, where B6, B7, B8 and B9 are ring atoms independently chosen from carbon atoms and nitrogen atoms, where B6, B7, B8 and B9 together comprise no more than two nitrogen atoms;
• wherein in case a)
• the substituents R1, R2 and R3 may be independently chosen from:
• 1.1. hydrogen atom,
• 1.2. halogen,
• 1.3. —CN,
• 1.4. —COOH,
• 1.5. —NO2,
• 1.6. —NH2,
• 1.7. —O—(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from:
• 1.7.1 phenyl, which is unsubstituted or mono- to penta-substituted by substituents independently chosen from halogen or —O—(C1-C4)-alkyl,
• 1.7.2 halogen,
• 1.7.3 —NH2,
• 1.7.4 —OH,
• 1.7.5 —COOR16, wherein R16 is hydrogen atom or —(C1-C10)-alkyl,
• 1.7.6 —NO2,
• 1.7.7 —S(O)y—R14, wherein y is zero, 1 or 2, R14 is —(C1-C10)-alkyl, phenyl, which phenyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those defined under 1.7.1 to 1.7.11, amino or —N(R13)2, wherein R13 is independently of one another chosen from hydrogen atom, phenyl, —(C1-C10)-alkyl, —C(O)—(C1-C7)-alkyl, —C(O)-phenyl, —C(O)—NH—(C1-C7)-alkyl, —C(O)—O-phenyl, —C(O)—NH-phenyl, —C(O)—O—(C1-C7)-alkyl, —S(O)y—R14, wherein R14 and y are as defined in 1.7.7, and wherein the R13 alkyl or phenyl groups in each case are unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11, or R13 together with the nitrogen atom to which it is bonded may be independently chosen to 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 defined under 1.7.1 to 1.7.11,
• 1.7.9 a radical selected from pyrrolidine, tetrahydropyridine, 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)-cycloalkyl or
• 1.7.11 ═O,
• 1.8. —N(R13)2, wherein R13 is as defined in 1.7.7 above,
• 1.9. —NH—C(O)—R15, wherein R15 is
• 1.9.1 a radical 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 by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, by —CF3, by benzyl or by —(C1-C10)-alkyl, wherein the —(C1-C10)-alkyl is mono to tri-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 1.9.2 —(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above or by —O—(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 1.9.3 —(C3-C7)-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 by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, by —O—(C1-C10)-alkyl, by —CN, by —CF3, by —(C1-C10)-alkyl, wherein alkyl is mono to tri-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, or by two substituents of said phenyl which form a dioxolan ring,
• 1.10. —S(O)y—R14, wherein R14 and y are as defined in 1.7.7 above,
• 1.11. —C(O)—R12, wherein R12 is phenyl or —(C1-C7)-alkyl, wherein alkyl or phenyl are unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 1.12. —C(O)—O—R12, wherein R12 is as defined in 1.11. above,
• 1.13. —(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 1.14. —O—(C1-C6)-alkyl-O—(C1-C6)-alkyl,
• 1.15. —O—(C0-C4)-alkyl-(C3-C7)-cycloalkyl,
• 1.16. —(C1-C4)-alkyl-N(R13)2, wherein R13 is as defined in 1.7.7 above
• 1.17. —CF3 or
• 1.18. —CF2—CF3,
• R4 is 1. —(C1-C10)-alkyl, wherein alkyl is mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 2. —CF3,
• 3. —CF2—CF3,
• 4. —CN,
• 5. —S(O)y—R14, wherein R14 and y are as defined in 1.7.7 above,
• 6. —NH2,
• 7. —O—(C1-C10)-alkyl, wherein alkyl is mono- to penta-substituted by substituents independently chosen from
• 7.1 phenyl, which is unsubstituted or mono- to penta-substituted by substituents independently chosen from halogen or —O—(C1-C4)-alkyl,
• 7.2 halogen,
• 7.3 —NH2,
• 7.4 —OH,
• 7.5 —COOR16, wherein R16 is hydrogen atom or —(C1-C10)-alkyl,
• 7.6 —NO2,
• 7.7 —S(O)y—R14, wherein y is zero, 1 or 2, R14 is —(C1-C10)-alkyl, phenyl, which phenyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11, amino or —N(R13)2, wherein R13 is independently of one another chosen from hydrogen atom, phenyl, —(C1-C10)-alkyl, —C(O)—(C1-C7)-alkyl, —C(O)-phenyl, —C(O)—NH—(C1-C7)-alkyl, —C(O)—O-phenyl, —C(O)—NH-phenyl, —C(O)—O—(C1-C7)-alkyl, —S(O)y—R14, wherein R14 and y are defined as in 7.7 above, and wherein the R13 alkyl or phenyl groups in each case are unsubstituted or mono- to penta-substituted by substituents independently chosen from those 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 by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 7.9 a radical 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)-cycloalkyl or
• 7.11 ═O,
• 8. —N(R17)2, wherein R17 is independently of one another chosen from hydrogen atom, phenyl, —(C1-C10)-alkyl, —C(O)-phenyl, —C(O)—NH—(C1-C7)-alkyl, —C(O)—(C1-C10)-alkyl, —C(O)—O-phenyl, —C(O)—NH-phenyl, —C(O)—O—(C1-C7)-alkyl, —S(O)y—R14, wherein R14 and y are as defined as in 7.7 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 R17 together with the nitrogen atom to which it is bonded form a heterocycle having 5 to 7 ring atoms,
• 9. —NH—C(O)—R15, wherein R15 is
• 9.1 a radical 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 by substituents independently chosen from those 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 by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 9.2 —(C1-C10)-alkyl, wherein alkyl is mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above or by —O—(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 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 provided that —N(R13)2 is not —NH2, or
• 9.5 phenyl, wherein phenyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, by —O—(C1-C10)-alkyl, by —CN, by —CF3, by —(C1-C10)-alkyl, wherein alkyl is mono to tri-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, or by two substituents of the phenyl radical which form a dioxolan ring
• 10. —C(O)—R12, wherein R12 is phenyl or —(C1-C7)-alkyl, wherein phenyl or alkyl are mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 11. —C(O)—O—R12, wherein R12 is phenyl or —(C1-C7)-alkyl, wherein phenyl or alkyl are mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 12. —O—(C1-C6)-alkyl-O—(C1-C6)-alkyl,
• 13. —O—(C0-C4)-alkyl-(C3-C7)-cycloalkyl or
• 14. —(C1-C4)-alkyl-N(R13)2, wherein R13 is as defined in 1.7.7 above,
• R5 is 1. a hydrogen atom,
• 2. —(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.4 above,
• 3. —C(O)—R9, wherein R9 is —NH2, —(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 7.1 to 7.4, or —N(R13)2, wherein R13 is as defined in 1.7.7 above, or
• 4. —S(O)2—R9, 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
• R6, R7 and R8 independently of one another are chosen from hydrogen atom or methyl, or in case b)
• the substituents R1, R2 and R4 may be independently chosen as defined under 1.1 to 1.18 in case a) above,
• R3 is 1. —CF3,
• 2. —CF2—CF3,
• 3. —CN,
• 4. —COOH,
• 5. —NO2,
• 6. —NH2,
• 7. —O—(C1-C10)-alkyl, wherein alkyl is mono- to penta substituted by substituents independently chosen from
• 7.1 phenyl, which is unsubstituted or mono- to penta-substituted by substituents independently chosen from halogen or —O—(C1-C4)-alkyl,
• 7.2 halogen,
• 7.3 —NH2,
• 7.4 —OH,
• 7.5 —COOR16, wherein R16 is hydrogen atom or —(C1-C10)-alkyl,
• 7.6 —NO2,
• 7.7 —S(O)y—R14, wherein y is zero, 1 or 2, R14 is —(C1-C10)-alkyl, phenyl, which phenyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11, amino or —N(R13)2, wherein R13 is independently of one another chosen from hydrogen atom, phenyl, —(C1-C10)-alkyl, —C(O)—(C1-C7)-alkyl, —C(O)-phenyl, —C(O)—NH—(C1-C7)-alkyl, —C(O)—O-phenyl, —C(O)—NH-phenyl, —C(O)—O—(C1-C7)-alkyl, —S(O)y—R14, wherein R14 and y are defined as in 7.7 above, and wherein the R13 alkyl or phenyl groups in each case are unsubstituted or mono- to penta-substituted by substituents independently chosen from those 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- by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 7.9 a radical selected from pyrrolidine, tetrahydropyridine, piperidine, piperazine, imidazoline, pyrazolidine, furan, morpholine, pyridine, pyridazine, pyrazine, oxolan, imidazoline, isoxazolidine, 2-isoxazoline, isothiazolidine, 2-isothiazoline, thiophene or thiomorpholine,
• 7.10 —(C3-C7)-cycloalkyl or
• 7.11 ═O,
• 8. —N(R13)2, wherein R13 is as defined in 1.7.7 above,
• 9. —NH—C(O)—R15, wherein R15 is
• 9.1 a radical 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 by substituents independently chosen from those 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 by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 9.2 —(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above or by —O—(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 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 by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, by —O—(C1-C10)-alkyl, by —CN, by —CF3, by —(C1-C10)-alkyl, wherein alkyl is mono to tri-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above, or by two substituents of the phenyl radical which form a dioxolan ring,
• 10. —S(O)y—R14, wherein R14 and y are as defined in 1.7.7 above,
• 11. —C(O)—R12, wherein R12 is phenyl or —(C1-C7)-alkyl, wherein phenyl or alkyl are unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 12. —C(O)—O—R12, wherein R12 is phenyl or —(C1-C7)-alkyl, wherein phenyl or alkyl are unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 13. —(C1-C10)-alkyl, wherein alkyl is unsubstituted or mono- to penta-substituted by substituents independently chosen from those as defined under 1.7.1 to 1.7.11 above,
• 14. —O—(C1-C6)-alkyl-O—(C1-C6)-alkyl,
• 15. —O—(C0-C4)-alkyl-(C3-C7)-cycloalkyl or
• 16. —(C1-C4)-alkyl-N(R13)2, wherein R13 is as defined in 1.7.7 above,
• R5 is as defined as R5 in case a) above,
• R6, R7 and R8 independently of one another are chosen from hydrogen atom or methyl.