IP Library Granted Patent US 7,329,676
Granted Patent B2
US 7,329,676 · App. 10/524,819 · Granted Feb 12, 2008

2-hydroxy-6-phenylphenanthridines as PDE-4 inhibitors

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Quick Facts
Patent No.
US 7,329,676
App. No.
10/524,819
Granted
Feb 12, 2008
Kind
B2
Abstract

The compounds of formula I in which R1, R2, R3, R31, R4, R5, R6 and R7 have the meanings as indicated in the description, are novel effective PDE4 inhibitors.

Claims (195)

1. A compound of the formula I,

in which

R1 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy,

R2 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy,

or in which

R1 and R2 together are a 1-2C-alkylenedioxy group,

R3 is hydrogen or 1-4C-alkyl,

R31 is hydrogen or 1-4C-alkyl,

R4 is hydrogen, 1-4C-alkyl, completely or predominantly fluorine-substituted 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl or 1-7C-alkylcarbonyl,

R5 is hydrogen or 1-4C-alkyl,

R6 is hydrogen, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, halogen, nitro, cyano, hydroxyl, 1-4C-alkylcarbonyloxy, amino, mono- or di-1-4C-alkylamino, phenyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonylamino, phenoxy or C(O)OR61, wherein

R61 is hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,

R7 is hydrogen, 1-4C-alkyl, hydroxyl, halogen, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or C(O)OR61,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

2. A compound of the formula I according to claim 1 , in which

R1 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or completely or predominantly fluorine-substituted 1-4C-alkoxy,

R2 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or completely or predominantly fluorine-substituted 1-4C-alkoxy,

or in which

R1 and R2 together are a 1-2C-alkylenedioxy group,

R3 is hydrogen or 1-4C-alkyl,

R31 is hydrogen or 1-4C-alkyl,

R4 is hydrogen, 1-4C-alkyl, completely or predominantly fluorine-substituted 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl or 1-7C-alkylcarbonyl,

R5 is hydrogen or 1-4C-alkyl,

R6 is hydrogen, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, halogen, nitro, cyano, hydroxyl, 1-4C-alkylcarbonyloxy, amino, mono- or di-1-4C-alkylamino, phenyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonylamino or C(O)OR61, wherein

R61 is hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,

R7 is hydrogen, 1-4C-alkyl, hydroxyl, halogen, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy or C(O)OR61,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

3. A compound of the formula I according to claim 1 , in which

R1 is 1-2C-alkoxy, 3-5C-cycloalkoxy, 3-5C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted 1-2C-alkoxy,

R2 is 1-2C-alkoxy, 3-5C-cycloalkoxy, 3-5C-cycloalkylmethoxy, or completely or predominantly fluorine-substituted 1-2C-alkoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is hydrogen, 1-4C-alkyl, 1-2C-alkoxy-2-4C-alkyl or 1-7C-alkylcarbonyl,

R5 is hydrogen,

R6 is 1-4C-alkyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkylmethoxy, halogen, nitro, cyano, hydroxyl, 1-4C-alkylcarbonyloxy, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, phenoxy or C(O)OR61, wherein

R61 is hydrogen or 1-7C-alkyl,

R7 is hydrogen, halogen, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy or 3-7C-cycloalkylmethoxy,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

4. A compound of the formula I according to claim 1 , in which

R1 is 1-2C-alkoxy, or completely or predominantly fluorine-substituted 1-2C-alkoxy,

R2 is 1-2C-alkoxy, or completely or predominantly fluorine-substituted 1-2C-alkoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is hydrogen, 1-4C-alkyl, 1-2C-alkoxyethyl or 1-7C-alkylcarbonyl,

R5 is hydrogen,

R6 is 1-4C-alkyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkylmethoxy, halogen, nitro, cyano, hydroxyl, 1-4C-alkylcarbonyloxy, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, phenoxy or C(O)OR61, wherein

R61 is hydrogen or 1-7C-alkyl,

R7 is hydrogen, halogen, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, or 3-7C-cycloalkylmethoxy,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

5. A compound of the formula I according to claim 1 , in which

R1 is ethoxy, and

R2 is methoxy or difluoromethoxy,

or

R1 is methoxy or difluoromethoxy, and

R2 is methoxy, difluoromethoxy or ethoxy,

or

R1 is difluoromethoxy, and

R2 is methoxy or ethoxy,

or

R1 is methoxy, and

R2 is ethoxy or difluoromethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is hydrogen, 1-4C-alkyl, 1-2C-alkoxyethyl or 1-7C-alkylcarbonyl,

R5 is hydrogen,

R6 is 1-4C-alkyl, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, 3-7C-cycloalkylmethoxy, halogen, nitro, cyano, hydroxyl, 1-4C-alkylcarbonyloxy, mono- or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, phenoxy or C(O)OR61, wherein

R61 is hydrogen or 1-7C-alkyl,

R7 is hydrogen, halogen, 1-4C-alkoxy, completely or predominantly fluorine-substituted 1-4C-alkoxy, or 3-7C-cycloalkylmethoxy,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

6. A compound of the formula I according to claim 1 , in which

R1 is methoxy or difluoromethoxy,

R2 is methoxy, difluoromethoxy or ethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is hydrogen, methyl, ethyl, methoxyethyl or acetyl,

R5 is hydrogen,

R6 is methyl, methoxy, ethoxy, propoxy, butoxy, difluoromethoxy, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, cyclopropylmethoxy, fluorine, chlorine, bromine, nitro, cyano, hydroxyl, acetoxy, dimethylamino, acetamido, phenoxy or C(O)OR61, wherein

R61 is hydrogen or methyl,

R7 is hydrogen, fluorine, methoxy, ethoxy, propoxy, butoxy, difluoromethoxy or cyclopropylmethoxy,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

7. A compound of the formula I according to claim 1 , in which

R1 is methoxy, and

R2 is methoxy,

or

R1 is difluoromethoxy, and

R2 is methoxy,

or

R1 is methoxy, and

R2 is ethoxy or difluoromethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is hydrogen, methyl, ethyl, methoxyethyl or acetyl,

R5 is hydrogen,

R6 is methyl, methoxy, ethoxy, propoxy, butoxy, difluoromethoxy, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, cyclopropylmethoxy, fluorine, chlorine, bromine, nitro, cyano, hydroxyl, acetoxy, dimethylamino, acetamido, phenoxy or C(O)OR61, wherein

R61 is hydrogen or methyl,

R7 is hydrogen, fluorine, methoxy, difluoromethoxy or cyclopropylmethoxy,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

8. A compound of the formula I according to claim 1 , in which

R1 is methoxy,

R2 is methoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is hydrogen or acetyl,

R5 is hydrogen,

R6 is methoxy, cyclopropylmethoxy, nitro, dimethylamino or C(O)OR61, wherein

R61 is hydrogen or methyl,

R7 is hydrogen, methoxy or cyclopropylmethoxy,

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

9. A compound according to claim 1 , selected from the group consisting of

(±)-acetic acid (2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxy-phenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-methoxycarbonylphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-dimethylaminophenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(3,4-dimethoxphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b) hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-nitrophenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxyphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-yl ester,

(±)-(2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxyphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(4methoxycarbonylphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(4-dimethylaminophenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(3,4-dimethoxyphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(4-nitrophenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b) hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(4-carboxyphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxyphenyl)-8,9-dimethoxy-(1,2,3,4,4a,10b)-hexahydrophenanthridin-2-ol,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-butoxy-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-8,9-dimethoxy-6-(4-methoxy-phenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-cyano-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid 4-((2RS,4aRS,10bRS)-2-acetoxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)-phenyl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-acetylamino-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-chloro-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(2-chloro-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-8,9-dimethoxy-6-(4-methoxy-3-propoxy-phenyl)-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-8,9-dimethoxy-6-p-tolyl-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-4((2RS,4aRS,10bRS)-2-acetoxy-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-6-yl)-benzoic acid methyl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-9-ethoxy-6-(4-fluoro-phenyl)-8-methoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-cyano-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(3-cyclopropylmethoxy-4-ethoxy-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-[3-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-phenyl]-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-[3,4-bis(1,1-difluoro-methoxy)-phenyl]-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-[3,-(1,1-difluoro-methoxy)-phenyl]-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-9-ethoxy-8-methoxy-6-[4-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-9-ethoxy-8-methoxy-6-(4-trifluoromethoxy-phenyl)-1,2,3,4,4a, 10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-9-ethoxy-6-(3-fluoro-4-methoxy-phenyl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(3,4-difluoro-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-9-ethoxy-6-(3-fluoro-phenyl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-bromo-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-[4-(1,1-difluoro-methoxy)-phenyl]-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-8,9-dimethoxy-6-(4-phenoxy-phenyl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-fluoro-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-[3,4-bis-(1,1-difluoro-methoxy)-phenyl]-8-(1,1-difluoro-methoxy)-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6-(4-cyano-phenyl)-8-(1,1-difluoro-methoxy)-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-4-[(2RS,4aRS,10bRS)-2-acetoxy-8-(1,1-difluoro-methoxy)-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl]-benzoic acid methyl ester,

(±)-4-[(2RS,4aRS,10bRS)-2-acetoxy-9-(1,1-difluoromethoxy)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl]-benzoic acid methyl ester,

(±)-(2RS,4aRS,10bRS)-6-(4-butoxy-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(4-fluoro-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-N-[4-((2RS,4aRS,10bRS)-2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-phenyl]-acetamide,

(±)-(2RS,4aRS,10bRS)-6-(4-chloro-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(2chlorophenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydrophenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-8,9-dimethoxy-6-(4-methoxy-3-propoxy-phenyl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-[4-(1,1-difluoro-methoxy)-phenyl]-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-4-((2RS,4aRS,10bRS)-9-ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-benzoic acid methyl ester,

(±)-(2RS,4aRS,10bRS)-9-ethoxy-6-(4-fluoro-phenyl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-4-((2RS,4aRS,10bRS)-9-ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-benzonitrile,

(±)-(2RS,4aRS,10bRS)-6-(3-cyclopropylmethoxy-4-ethoxy-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-[3-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-phenyl]-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-[3,4-bis-(1,1-difluoro-methoxy)-phenyl]-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-[3-(1,1-difluoromethoxy)-phenyl]-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-9-ethoxy-8-methoxy-6-[4-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-9-ethoxy-8-methoxy-6-(4-trifluoromethoxy-phenyl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-9-ethoxy-6-(3-fluoro-4-methoxy-phenyl)-8-methoxy-1,2,3,4,4a,10b-hexhydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(3,4-difluoro-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexhydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-9-ethoxy-6-(3-fluoro-phenyl)-8-methoxy-1,2,3,4,4a,10b-hexhydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-6-(4-bromo-phenyl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-8,9-dimethoxy-6-p-tolyl-1,2,3,4,4a,10b-hexhydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-8,9-dimethoxy-6-(4-phenoxy-phenyl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-(2RS,4aRS,10bRS)-8,9-dimethoxy-6-(4-methoxy-phenyl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-4-((2RS,4aRS,10bRS)-2-hydroxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-benzonitrile,

(±)-(2RS,4aRS,10bRS)-6-[3,4-bis-(1,1-difluoro-methoxy)-phenyl]-8-(1,1-difluoro-methoxy)-9methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(±)-4-[(2RS,4aRS,10bRS)-8-(1,1-difluoro-methoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl]-benzonitrile,

(±)-4-[(2RS,4aRS,10bRS)-8-(1,1-difluoro-methoxy)-2-hydroxy-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl]-benzoic acid methyl ester,

(±)-4-[(2RS,4aRS,10bRS)-9-(1,1-difluoro-methoxy)-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl]-benzoic acid methyl ester,

(±)-acetic acid (2RS,4aRS,10bRS)-6(4-hydroxy-phenyl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-yl ester,

(±)-4-((2RS,4aRS,10bRS)-2-acetoxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-benzoic acid hydrochloride,

(±)-4-((2RS,4aRS,10bRS)-2acetoxy-9-(1,1-difluoro-methoxy)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-benzoic acid,

(±)-(2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxy-phenyl)-2,8,9-trimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridine,

(±)-(2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxy-phenyl)-2-ethoxy-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridine,

(±)-(2RS,4aRS,10bRS)-6-(3,4-bis-cyclopropylmethoxy-phenyl)-8,9-dimethoxy-2-(2-methoxy-ethoxy)-1,2,3,4,4a,10b-hexahydro-phenanthridine, the salts of these compounds, the N-oxides of these compounds, and the salts of the N-oxides of these compounds.

10. A compound of the formula I according to claim 1 , in which the hydrogen atoms in positions 4a and 10b are in the cis position relative to one another, or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

11. A compound of the formula I according to claim 1 , which has with respect to the positions 4a and 10b, the configuration shown in formula I*:

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

12. A compound of the formula I according to claim 1 , which has with respect to the positions 2, 4a and 10b, the configuration shown either in formula I**, I*** or I****:

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

13. A compound of the formula I according to claim 1 , which has with respect to the position 2, 4a, and 10b, the configuration shown in formula I*****:

or a salt of this compound, an N-oxide of this compound, or a salt of an N-oxide of this compound.

14. A pharmaceutical composition comprising one or more compounds of the formula I as claimed in claim 1 , or a pharmaceutically acceptable salt of this compound, a pharmaceutically acceptable N-oxide of this compound, or a salt of said N-oxide, together with a pharmaceutical auxiliary and/or excipient.

15. A method for treating asthma, COPD, allergic rhinitis or Crohn's disease in a patient comprising administering to said patient a therapeutically effective amount of a compound of the formula I as claimed in claim 1 , or a pharmaceutically acceptable salt of this compound, a pharmaceutically acceptable N-oxide of this compound, or a salt of said N-oxide.

16. A method for treating asthma and/or COPD in a patient comprising administering to said patient a therapeutically effective amount of a compound of the formula I as claimed in claim 1 , or a pharmaceutically acceptable salt of this compound, a pharmaceutically acceptable N-oxide of this compound, or a salt of said N-oxide.

Assignments (6)
CHANGE OF NAME Recorded Jul 29, 2015
From: NYCOMED GERMANY HOLDING GMBH
To: TAKEDA GMBH
Reel/Frame 036205/0192 →
MERGER Recorded Jul 28, 2015
From: TAKEDA GMBH
To: NYCOMED ASSET MANAGEMENT GMBH
Reel/Frame 036193/0178 →
MERGER Recorded Jul 28, 2015
From: NYCOMED ASSET MANAGEMENT GMBH
To: NYCOMED GERMANY HOLDING GMBH
Reel/Frame 036201/0261 →
CHANGE OF NAME Recorded Mar 26, 2013
From: NYCOMED GMBH
To: TAKEDA GMBH
Reel/Frame 030091/0737 →
CHANGE OF NAME Recorded Sep 4, 2007
From: ALTANA PHARMA AG
To: NYCOMED GMBH
Reel/Frame 019783/0625 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2005
From: KAUTZ, ULRICH; SCHMIDT, BEATE
To: ALTANA PHARMA AG
Reel/Frame 016747/0768 →