Granted Patent B2

US 8,003,798 · App. 10/590,803 · Granted Aug 23, 2011

Assignee: NYCOMED GmbH

Abstract

Claims (437)

1. A compound of formula I

in which

R1 is methoxy or ethoxy,

R2 is methoxy, ethoxy, 2,2-difluoroethoxy or difluoromethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen or acetyl, and

R5 is hydrogen,

and

Har is Cyc1, in which

Cyc1 is benzo[1,3]dioxol-5-yl, dihydrobenzo[1,4]dioxin-5-yl, 2,2-difluoro-benzo[1,3]dioxol-5-yl, or 5-chloro-4-methyl-3,4-dihydrobenzo[1,4]oxazin-7-yl,

or

Har is Cyc2, in which

Cyc2 is quinolin-6-yl, benzofurazan-5-yl, benzothiazol-6-yl, 1-methyl-1H-benzotriazol-5-yl or 4-methoxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-5-yl, benzo[1,2,3] thiadiazol-5-yl or quinoxalin-5-yl,

or,

Har is optionally substituted by R6 and/or R7 and/or R8, and is a pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl radical, in which

R6 is chlorine, methyl, methoxy, ethoxy, methylthio, methoxycarbonyl, carboxyl, hydroxyl, oxo, or -A-N(R61)R62, in which

A is a bond or ethylene,

R61 is methyl,

R62 is methyl,

or R61 and R62 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het1, in which

either

Het1 is piperidin-1-yl, pyrrolidin-1-yl or morpholin-4-yl,

or

Het1 is pyrazol-1-yl or imidazol-1-yl,

R7 is methyl, methoxy, ethoxy, methylthio or dimethylamino,

R8 is chlorine or methoxy,

or

Har is isoxazolyl, 1-methylimidazolyl, or pyridyl-thiazolyl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

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

R1 is methoxy,

R2 is methoxy, ethoxy, 2,2-difluoroethoxy or difluoromethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen or acetyl, and

R5 is hydrogen,

and

Har is Cyc1, in which

Cyc1 is benzo[1,3]dioxol-5-yl, dihydrobenzo[1,4]dioxin-5-yl, 2,2-difluoro-benzo[1,3]dioxol-5-yl, or 5-chloro-4-methyl-3,4-dihydrobenzo[1,4]oxazin-7-yl,

or

Har is Cyc2, in which

Cyc2 is quinolin-6-yl, benzofurazan-5-yl, benzothiazol-6-yl, 1-methyl-1H-benzotriazol-5-yl or 4-methoxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-5-yl, benzo[1,2,3] thiadiazol-5-yl or quinoxalin-5-yl,

or

Har is pyridin-3-yl, pyridin-4-yl, 6-(morpholin-4-yl)-pyridin-3-yl, 6-(piperidin-1-yl)-pyridin-3-yl, 6-(pyrazol-1-yl)-pyridin-3-yl, 6-(imidazol-1-yl)-pyridin-3-yl, 6-methoxycarbonyl-pyridin-3-yl, 3-methoxycarbonyl-pyridin-2-yl, 2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, 2-methylsulfanyl-pyridin-3-yl, 6-hydroxy-pyridin-3-yl, 6-carboxy-pyridin-3-yl, pyrimidin-5-yl, 2-methoxy-pyrimidin-5-yl, 2-dimethylamino-pyrimidin-5-yl, 2-methylsulfanyl-pyrimidin-5-yl, pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-[2-(pyrrolidin-1-yl)-ethyl]-pyridin-3-yl, 2,6-dimethoxy-pyridin-3-yl, 2,6-dimethoxy-pyridin-4-yl, 4,6-dimethoxy-pyridin-3-yl, 5,6-dimethoxy-pyridin-3-yl, 4,6-diethoxy-pyridin-3-yl, 5-ethoxy-6-methoxy-pyridin-3-yl, 1-methyl-1H-pyridin-2-one-5-yl, 2,6-dimethoxy-pyrimidin-4-yl, 2,4-dimethoxy-pyrimidin-5-yl, 4,6-dimethoxy-pyrimidin-5-yl, 4-methyl-2-methylsulfanyl-pyrimidin-5-yl, 5-chloro-2-methylsulfanyl-pyrimidin-4-yl, 4-chloro-2-dimethylamino-pyrimidin-5-yl, 2-dimethylamino-4-methoxy-pyrimidin-5-yl, 1-methyl-1H-pyrimidin-2-one-5-yl, 3,6-dimethoxy-pyridazin-4-yl, 4-chloro-2,6-dimethoxy-pyridin-3-yl, 3-chloro-2,6-dimethoxy-pyridin-4-yl, 5-chloro-2,6-bisdimethylamino-pyrimidin-4-yl, or 2,4,6-trimethoxy-pyrimidin-5-yl,

or

Har is isoxazol-5-yl, 1-methylimidazol-2-yl, 1-methylimidazol-5-yl, or 2-(pyridin-3-yl)-thiazol-4-yl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

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

R1 is methoxy,

R2 is ethoxy, 2,2-difluoroethoxy or difluoromethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen, and

R5 is hydrogen,

and

Har is Cyc1, in which

Cyc1 is benzo[1,3]dioxol-5-yl, dihydrobenzo[1,4]dioxin-5-yl, 2,2-difluoro-benzo[1,3]dioxol-5-yl, or 5-chloro-4-methyl-3,4-dihydrobenzo[1,4]oxazin-7-yl,

or

Har is Cyc2, in which

Cyc2 is quinolin-6-yl, benzofurazan-5-yl, benzothiazol-6-yl, 1-methyl-1H-benzotriazol-5-yl or 4-methoxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-5-yl, benzo[1,2,3] thiadiazol-5-yl or quinoxalin-5-yl,

or

Har is pyridin-3-yl, pyridin-4-yl, 6-(morpholin-4-yl)-pyridin-3-yl, 6-(piperidin-1-yl)-pyridin-3-yl, 6-(pyrazol-1-yl)-pyridin-3-yl, 6-(imidazol-1-yl)-pyridin-3-yl, 6-methoxycarbonyl-pyridin-3-yl, 3-methoxycarbonyl-pyridin-2-yl, 2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, 2-methylsulfanyl-pyridin-3-yl, 6-hydroxy-pyridin-3-yl, 6-carboxy-pyridin-3-yl, pyrimidin-5-yl, 2-methoxy-pyrimidin-5-yl, 2-dimethylamino-pyrimidin-5-yl, 2-methylsulfanyl-pyrimidin-5-yl, pyrazin-2-yl, 5-methyl-pyrazin-2-yl, 6-[2-(pyrrolid in-1 -yl)-ethyl]-pyridin-3-yl , 2,6-dimethoxy-pyridin-3-yl , 2,6-dimethoxy-pyridin-4-yl, 4,6-dimethoxy-pyridin-3-yl, 5,6-dimethoxy-pyridin-3-yl, 4,6-diethoxy-pyridin-3-yl, 5-ethoxy-6-methoxy-pyridin-3-yl, 1-methyl-1H-pyridin-2-one-5-yl, 2,6-dimethoxy-pyrimidin-4-yl, 2,4-dimethoxy-pyrimidin-5-yl, 4,6-dimethoxy-pyrimidin-5-yl, 4-methyl-2-methylsulfanyl-pyrimidin-5-yl, 5-chloro-2-methylsulfanyl-pyrimidin-4-yl, 4-chloro-2-dimethylamino-pyrimidin-5-yl, 2-dimethylamino-4-methoxy-pyrimidin-5-yl, 1-methyl-1H-pyrimidin-2-one-5-yl, 3,6-dimethoxy-pyridazin-4-yl, 4-chloro-2,6-dimethoxy-pyridin-3-yl, 3-chloro-2,6-dimethoxy-pyridin-4-yl, 5-chloro-2,6-bisdimethylamino-pyrimidin-4-yl, or 2,4,6-trimethoxy-pyrimidin-5-yl,

or

Har is isoxazol-5-yl, 1-methylimidazol-2-yl, 1-methylimidazol-5-yl, or 2-(pyridin-3-yl)-thiazol-4-yl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

4. A compound of formula I

in which

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

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

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

and

Har is optionally substituted by R6 and/or R7, and is benzo[1,4]dioxanyl or benzo[1,3]dioxolyl, in which

R6 is fluorine,

R7 is fluorine,

or

Har is quinolinyl, benzofurazanyl or benzothiazolyl,

or

either

Har is optionally substituted by R6 and/or R7, and is pyridinyl, in which

R6 is 1-4C-alkoxy, -A-N(R61)R62, in which

A is a bond,

R61 and R62 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het1, in which

Het1 is morpholinyl, thiomorpholinyl, N—(R611)-piperazinyl or 4-N—(R611)-homopiperazinyl, in which

R611 is 1-2C-alkyl,

R7 is 1-4C-alkoxy,

or

Har is optionally substituted by R6, and is isoxazolyl, imidazolyl or thiazolyl, in which

R6 is 1-4C-alkyl or pyridyl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

5. A compound of formula I

in which

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

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

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

and

Har is Cyc1, in which

Cyc1 is dihydrobenzo[1,4]dioxinyl, benzo[1,3]dioxolyl or 2,2-difluoro-benzo[1,3]dioxolyl,

or

Har is Cyc2, in which

either

Cyc2 is quinolinyl, benzofurazanyl or benzothiazolyl,

or

Cyc2 is 1-(1-4C-alkyl)-1H-benzotriazolyl or 1-(1-4C-alkyl)-4-methoxy-3-methyl-1H-pyrazolo[3,4-b]pyridinyl,

or

either

Har is pyridinyl, pyrimidinyl, isoxazolyl, 1-(1-4C-alkyl)-1H-imidazolyl, methyl-pyrazinyl or pyridyl-thiazolyl,

or

Har is substituted by R6 and/or R7 and/or R8, and is pyrimidinyl, in which

R6 is 1-4C-alkoxy,

R7 is 1-4C-alkoxy,

R8 is 1-4C-alkoxy,

or

Har is substituted by R6, and is pyridinyl, in which

R6 is 1-4C-alkoxycarbonyl,

or

Har is substituted by R6, and is pyridinyl, in which

R6 is morpholin-4-yl, piperidin-1-yl, pyrazol-1-yl or imidazol-1-yl,

or

Har is substituted by R6 and/or R7, and is pyridinyl, in which

R6 is 1-4C-alkoxy,

R7 is 1-4C-alkoxy,

or

Har is substituted by R6 and R7 and R8, and is pyridinyl, in which

R6 is 1-4C-alkoxy,

R7 is 1-4C-alkoxy,

R8 is chlorine,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

6. A compound of formula I

in which

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

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

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen or 1-4C-alkylcarbonyl,

R5 is hydrogen,

Har is optionally substituted by R6 and/or R7 and/or R8, and is a pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl radical, in which

R6 is halogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylthio, 1-4C-alkoxycarbonyl, carboxyl, hydroxyl, oxo, or -A-N(R61)R62, in which

A is a bond or 1-4C-alkylene,

R61 is 1-4C-alkyl,

R62 is 1-4C-alkyl,

or R61 and R62 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het1, in which

either

Het1 is piperidin-1-yl, pyrrolidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin-1-yl or 4N-methyl-piperazin-1-yl,

or

Het1 is pyrrol-1-yl, pyrazol-1-yl, triazol-1-yl or imidazol-1-yl,

R7 is 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkylthio, hydroxyl, oxo, or di-1-4C-alkylamino,

R8 is halogen, 1-4C-alkyl or 1-4C-alkoxy,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

7. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

Har is substituted by R6, and is pyridinyl, in which

R6 is methoxy, ethoxy, methylthio, methoxycarbonyl, hydroxyl, carboxyl, or -A-N(R61)R62, in which

A is a bond, or ethylene,

R61 is methyl,

R62 is methyl,

or R61 and R62 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het1, in which

either

Het1 is piperidin-1-yl, pyrrolidin-1-yl or morpholin-4-yl,

or

Het1 is pyrazol-1-yl or imidazol-1-yl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

8. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

Har is 6-(morpholin-4-yl)-pyridin-3-yl, 6-(piperidin-1-yl)-pyridin-3-yl, 6-(pyrazol-1-yl)-pyridin-3-yl, 6-(imidazol-1-yl)-pyridin-3-yl, 6-methoxycarbonyl-pyridin-3-yl, 3-methoxycarbonyl-pyridin-2-yl,

2-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, 2-methylsulfanyl-pyridin-3-yl, 6-hydroxy-pyridin-3-yl, 6-carboxy-pyridin-3-yl, 2-methoxy-pyrimidin-5-yl, 2-dimethylamino-pyrimidin-5-yl, 2-methylsulfanyl-pyrimidin-5-yl, 5-methyl-pyrazin-2-yl, or 6-[2-(pyrrolidin-1-yl)-ethyl]-pyridin-3yl ,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

9. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

either

Har is substituted by R6 and R7, and is a pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl radical, in which

R6 is methoxy or ethoxy, and

R7 is methoxy or ethoxy,

or

R6 is oxo, and

R7 is methyl,

or

R6 is methylthio, and

R7 is methyl,

or

R6 is chlorine, and

R7 is methylthio,

or

R6 is dimethylamino, and

R7 is methoxy or ethoxy,

or

R6 is dimethylamino, and

R7 is dimethylamino,

or

Har is substituted by R6 and R8, and is a pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl radical, in which

R6 is dimethylamino, and

R8 is chlorine,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

10. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

Har is substituted by R6 and R7, and is pyridinyl, in which

either

R6 is methoxy or ethoxy, and

R7 is methoxy or ethoxy,

or

R6 is oxo, and

R7 is methyl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

11. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

either

Har is substituted by R6 and R7, and is pyrimidinyl, in which

R6 is methoxy or ethoxy, and

R7 is methoxy or ethoxy,

or

R6 is oxo, and

R7 is methyl,

or

R6 is methylthio, and

R7 is methyl,

or

R6 is chlorine, and

R7 is methylthio,

or

R6 is dimethylamino, and

R7 is methoxy or ethoxy,

or

Har is substituted by R6 and R8, and is pyrimidinyl, in which

R6 is dimethylamino, and

R8 is chlorine,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

12. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

Har is substituted by R6 and R7, and is pyridazinyl, in which

R6 is methoxy or ethoxy, and

R7 is methoxy or ethoxy,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

13. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

Har is 2,6-dimethoxy-pyridin-3-yl, 2,6-dimethoxy-pyridin-4-yl, 4,6-dimethoxy-pyridin-3-yl, 5,6-dimethoxy-pyridin-3-yl, 4,6-diethoxy-pyridin-3-yl, 5-ethoxy-6-methoxy-pyridin-3-yl, 1-methyl-1H-pyridin-2-one-5-yl, 2,6-dimethoxy-pyrimidin-4-yl, 2,4-dimethoxy-pyrimidin-5-yl, 4,6-dimethoxy-pyrimidin-5-yl, 4-methyl-2-methylsulfanyl-pyrimidin-5-yl, 5-chloro-2-methylsulfanyl-pyrimidin-4-yl, 4-chloro-2-dimethylamino-pyrimidin-5-yl, 2-dimethylamino-4-methoxy-pyrimidin-5-yl, 1-methyl-1H-pyrimidin-2-one-5-yl, or 3,6-dimethoxy-pyridazin-4-yl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

14. A compound of formula I according to claim 6 in which

R1 is methoxy,

R2 is ethoxy, difluoromethoxy or 2,2-difluoroethoxy,

R3 is hydrogen,

R31 is hydrogen,

R4 is —O—R41, in which

R41 is hydrogen,

R5 is hydrogen,

Har is any one selected from the group consisting of

6-(imidazol-1-yl)-pyridin-3-yl, pyrimidin-5-yl, 2-methoxy-pyrimidin-5-yl, 2-dimethylamino-pyrimidin-5-yl, 2-methylsulfanyl-pyrimidin-5-yl, 2,6-dimethoxy-pyridin-3-yl, 2,6-dimethoxy-pyridin-4-yl, 4,6-dimethoxy-pyridin-3-yl, 5,6-dimethoxy-pyridin-3-yl, 4,6-diethoxy-pyridin-3-yl, 5-ethoxy-6-methoxy-pyridin-3-yl, 1-methyl-1H-pyridin-2-one-5-yl, 2,6-dimethoxy-pyrimidin-4-yl, 2,4-dimethoxy-pyrimidin-5-yl, 4,6-dimethoxy-pyrimidin-5-yl, 2-dimethylamino-4-methoxy-pyrimidin-5-yl, 1-methyl-1H-pyrimidin-2-one-5-yl, and 3,6-dimethoxy-pyridazin-4-yl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

15. A compound of formula I according to claim 6 comprising one or more of the following:

R1 is methoxy,

R2 is ethoxy, difluoromethoxy or 2,2-difluoroethoxy, and

R3 and R31 are both hydrogen,

R4 is —O—R41, in which

R41 is hydrogen, and

R5 is hydrogen,

Har is substituted by R6 and R7, and is pyridinyl, and

Har is optionally substituted by R6 and/or R7, and is pyrimidinyl or pyridazinyl,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

16. A compound of formula I according to claim 6 comprising one or more of the following:

R1 is methoxy,

R2 is ethoxy, difluoromethoxy or 2,2-difluoroethoxy, and

R3 and R31 are both hydrogen,

R4 is —O—R41, in which

R41 is hydrogen, and

R5 is hydrogen, and

Har is either N-methyl-pyrid-2-onyl or N-methyl-pyrimid-2-onyl, or imidazol-1-yl-pyridinyl or pyrazol-1-yl-pyridinyl, or methylthio-pyrimidinyl, methoxy-pyrimidinyl, dimethylamino-pyrimidinyl or pyrimidinyl, or

Har is substituted by R6 and R7, and is pyridinyl, in which

R6 is methoxy or ethoxy, and

R7 is methoxy or ethoxy, or

Har is substituted by R6 and R7, and is pyrimidinyl or pyridazinyl, in which

R6 is methoxy, ethoxy or dimethylamino, and

R7 is methoxy or ethoxy,

or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.

17. A compound of formula I

which is selected from the group consisting of

(2RS,4aRS,10bRS)-6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(3-methyl-3H-imidazol-4-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(2-pyridin-3-yl-thiazol-4-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-6-isoxazol-5-yl-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-8,9-Dimethoxy-6-pyridin-4-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-8,9-Dimethoxy-6-pyridin-3-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-8,9-Dimethoxy-6-(6-morpholin-4-yl-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-Benzo[1,2,5]oxadiazol-5-yl-9-(1,1-difluoro-methoxy)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-Benzo[1,2,5]oxadiazol-5-yl-9-(2,2-difluoro-ethoxy)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-Benzo[1,2,5]oxadiazol-5-yl-8-(1 ,1-difluoro-methoxy)-9-methoxy-1,2,3,4,4a,1 Ob-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-Benzo[1,3]dioxol -5-yl-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

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

(2RS,4aRS,10bRS)-8,9-Dimethoxy-6-quinolin-6-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(2,2-Difluoro-benzo[1,3]dioxol -5-yl)-8,9-dimethoxy-1,2,3,4,4a,1 Ob-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-Benzo[1,2,5]oxadiazol-5-yl-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(1 -methyl-1H-imidazol-2-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

5-((2RS,4aRS,10bRS)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-pyridine-2-carboxylic acid methyl ester,

(2RS,4aRS,10bRS)-9-(2,2-Difluoro-ethoxy)-6-(2,6-dimethoxy-pyridin-3-yl)-8-methoxy-1,2,3,4,4a,1 Ob-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-(2,2-Difluoro-ethoxy)-8-methoxy-6-(2-methoxy-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-(2,2-Difluoro-ethoxy)-8-methoxy-6-(6-morpholin-4-yl-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-(2,2-Difluoro-ethoxy)-8-methoxy-6-pyridin-3-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4a RS,10bRS)-9-(2,2-Difluoro-ethoxy)-6-(2,6-dimethoxy-pyrimid in-4-yl)-8-methoxy-1,2,3,4,4a,1 Ob-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-8-(2,2-Difluoro-ethoxy)-6-(2,6-dimethoxy-pyridin-3-yl)-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(2,6-Dimethoxy-pyridin-3-yl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(2,6-Dimethoxy-pyridin-4-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(3-Chloro-2,6-dimethoxy-pyridin-4-yl)-9-(2,2-difluoro-ethoxy)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-pyrimidin-5-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(6-pyrazol-1-yl-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

6-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-nicotinic acid methyl ester,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(2-methoxy-pyrimidin-5-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(2,4,6-trimethoxy-pyrimidin-5--yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(2,4-Dimethoxy-pyrimidin-5--yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(5-methyl-pyrazin-2--yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(2,6-Dimethoxy-pyrimidin-4--yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-6-(6-imidazol-1-yl-pyridin-3-yl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-pyrazin-2-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(1-methyl-1H-benzotriazol-5-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(4-methoxy-1 ,3-dimethyl-1H-pyrazolo[3,4-b ]pyridin-5-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2S,4aS,10bS)-6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(3SR,4aRS,10bRS)-8,9-Dimethoxy-6-pyridin-3-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-3-ol,

(2R,4aR,10bR)-6-(4-Chloro-2,6-dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(2-methylsulfanyl-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(4-methyl-2-methylsulfanyl-pyrimidin-5-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(5-Chloro-2-methylsulfanyl-pyrimidin-4-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(2-methoxy-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(6-methoxy-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(4-Chloro-2-dimethylamino-pyrimidin-5-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(2-Dimethylamino-4-methoxy-pyrimidin-5-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,1 Ob-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(4,6-Diethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(4,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(2-Dimethylamino-pyrimidin-5-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(5,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-6-(5-ethoxy-6-methoxy-pyridin-3-yl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-9-Ethoxy-8-methoxy-6-(2-methylsulfanyl-pyrimidin-5-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1 -methyl-1H-pyrimidin-2-one,

(2R,4aR,10bR)-9-Ethoxy-6-(6-hydroxy-pyridin-3-yl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(3,6-Dimethoxy-pyridazin-4-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(4,6-Dimethoxy-pyrimidin-5-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-pyridin-4-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-pyridin-3-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(6-morpholin-4-yl-pyridin-3-yl)- 1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

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

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

(2RS,4aRS,10bRS)-6-Benzo[1,2,5]oxadiazol-5-yl-8-(1,1-difluoro-methoxy)-9-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(2,6-Dimethoxy-pyrimidin-4-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(5-Chloro-2,6-bis-dimethylamino-pyrimidin-4-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-pyrimidin-5-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-pyrazin-2-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(5-Chloro-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(6-pyrazol-1-yl-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-6-(6-imidazol-1-yl-pyridin-3-yl)-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-Benzo[1,2,3]thiadiazol-5-yl-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-[6-(2-pyrrolidin-1-yl-ethyl)-pyridin-3-yl]-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(2-methoxy-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-(1-methyl-1H-benzotriazol-5-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-9-Ethoxy-8-methoxy-6-quinoxalin-5-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-6-(3-Chloro-2,6-dimethoxy-pyridin-4-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-8-(1,1-Difluoro-methoxy)-9-methoxy-6-pyridin-3-yl-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2RS,4aRS,10bRS)-8-(1,1-Difluoro-methoxy)-9-methoxy-6-(6-morpholin-4-yl-pyridin-3-yl)-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-pyridine-2-carboxylic acid,

(2S,4aS,10bS)-6-(2,6-Dimethoxy-pyridin-3-yl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(2R,4aR,10bR)-6-(2,6-Dimethoxy-pyridin-3-yl)-8,9-dimethoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-2-ol,

(3SR,4aRS,10bRS)-6-(2,6-Dimethoxy-pyridin-3-yl)-9-ethoxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-3-ol,

and the salt, enantiomer, N-oxide, salt of the N-oxide and enantiomer thereof.

18. A compound of 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, N-oxide or salt of an N-oxide thereof.

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

or a salt, N-oxide or salt of an N-oxide thereof.

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

or a salt, N-oxide or salt of an N-oxide thereof.

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

or a salt, N-oxide or salt of an N-oxide thereof.

22. A compound of formula I according to claim 5 , which has with respect to the positions 4a and 10b the configuration shown in formula I*:

or a salt, N-oxide or salt of an N-oxide thereof.

23. A compound of formula I according to claim 5 , which has with respect to the positions 2, 4a and 10b the configuration shown in formula Ia*****:

or a salt, N-oxide or salt of an N-oxide thereof.

24. A compound of formula I according to claim 6 , which has with respect to the positions 4a and 10b the configuration shown in formula I*:

or a salt, N-oxide or salt of an N-oxide thereof.

25. A compound of formula I according to claim 6 , which has with respect to the positions 2, 4a and 10b the configuration shown in formula Ia*****:

or a salt, N-oxide or salt of an N-oxide thereof.

26. A pharmaceutical composition comprising one or more compounds of formula I as claimed in claim 1 , or a pharmaceutically acceptable salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof, together with a pharmaceutically acceptable excipient and/or vehicle.

27. A pharmaceutical composition comprising one or more compounds of formula I as claimed in claim 4 , or a pharmaceutically acceptable salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof, together with a pharmaceutically acceptable excipient and/or vehicle.

28. A pharmaceutical composition comprising one or more compounds of formula I as claimed in claim 5 , or a pharmaceutically acceptable salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof, together with a pharmaceutically acceptable excipient and/or vehicle.

29. A pharmaceutical composition comprising one or more compounds of formula I as claimed in claim 6 , or a pharmaceutically acceptable salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof, together with a pharmaceutically acceptable excipient and/or vehicle.

30. A pharmaceutical composition comprising one or more compounds of formula I as claimed in claim 17 , or a pharmaceutically acceptable salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof, together with a pharmaceutically acceptable excipient and/or vehicle.

Assignments (16)

Priority Claims (2)

Continuity (1)