IP Library Granted Patent US 7,763,728
Granted Patent B2
US 7,763,728 · App. 11/920,501 · Granted Jul 27, 2010

Tetrahydropyridothiophenes

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Quick Facts
Patent No.
US 7,763,728
App. No.
11/920,501
Granted
Jul 27, 2010
Kind
B2
Abstract

Compounds of a certain formula (I) in which Ra and Rb have the meanings indicated in the description, are novel effective compounds with anti-proliferative and apoptosis inducing activity.

Claims (480)

1. A compound of formula I

wherein

Ra is —C(O)R1,

R1 is 1-4C-alkyl, 1-4C-alkyl substituted by Raa, or 2-4C-alkyl substituted by Rab and Rac on different carbon atoms,

Rb is -T-Q,

T is 1-6C-alkylene or 3-7C-cycloalkylene,

Q is substituted by Rba and Rbb and Rbc, and is phenyl,

Raa is selected from the group consisting of:

3-7C-cycloalkyl, halogen, trifluoromethyl, cyano, hydroxyl, Har, morpholino, —C(O)R2, —C(O)OR3, —C(O)N(R4)R5, —N(R6)C(O)R7, —OC(O)R8, completely or predominantly fluorine-substituted 1-4C-alkoxy, and —OR9,

wherein said Har is optionally substituted by one or two substituents independently selected from R10,

R2, R3, R4, R5, R6, R7 and R8 are the same or different and are independently selected from the group consisting of:

hydrogen and 1-4C-alkyl,

R9 is selected from the group consisting of:

1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl-1-4C-alkyl, pyridyl-1-4C-alkyl, and (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkyl,

Har is bonded via a ring carbon or a ring nitrogen atom, and is a 5-membered monocyclic unsaturated, aromatic heteroaryl ring comprising at least one heteroatom independently selected from the group consisting of nitrogen, oxygen and sulphur,

or

Har is bonded via a ring carbon atom, and is a 6-membered monocyclic unsaturated, aromatic heteroaryl ring comprising one or two nitrogen atoms,

or

Har is bonded via a ring carbon or a ring nitrogen atom, and is a 9- or 10-membered fused bicyclic unsaturated, aromatic heteroaryl ring comprising one to three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulphur,

each R10 is the same or different and is each independently selected from the group consisting of:

1-4C-alkyl, halogen and 1-4C-alkoxy,

Rab is hydroxyl,

Rac is hydroxyl,

or Rab and Rae bonded to adjacent carbon atoms form together an 1-2C-alkylenedioxy bridge which is optionally substituted by one or two substituents independently selected from the group consisting of fluorine and methyl,

or Rab and Rac bonded to carbon atoms two bonds distant from each other form together a methylenedioxy bridge which is optionally substituted by one or two substituents independently selected from the group consisting of fluorine and methyl,

Rba is selected from the group consisting of:

1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, phenyl-1-4C-alkoxy, cyano-1-4C-alkoxy, 3-6C-alkinyloxy, nitro, and completely and predominantly fluorine-substituted 1-4C-alkoxy,

Rbb is selected from the group consisting of:

hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, and 1-4C-alkoxy,

Rbc is selected from the group consisting of:

hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, and 1-4C-alkoxy,

or Rbb and Rbc bounded in ortho position to each other form together an 1-2C-alkylenedioxy bridge, or a completely or partially fluorine-substituted 1-2C-alkylenedioxy bridge,

or a salt thereof.

2. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib, Ic, Id and Id′

wherein

Ra is —C(O)R1,

R1 is 1-4C-alkyl, 1-4C-alkyl substituted by Rae, or 2-4C-alkyl substituted by Rab and Rac on different carbon atoms,

Q is substituted by Rba and Rbb and Rbc, and is phenyl,

Raa is selected from the group consisting of:

hydroxyl, Har, morpholino, —C(O)R2, —C(O)OR3, —C(O)N(R4)R5, —N(R6)C(O)R7, —OC(O)R8, and —OR9,

wherein said Her is optionally substituted by one or two substituents independently selected from R10,

R2, R3, R4, R5, R6, R7 and R8 are the same or different and are independently selected from the group consisting of:

hydrogen and 1-4C-alkyl,

R9 is selected from the group consisting of:

1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl-1-4C-alkyl, pyridyl-1-4C-alkyl, and (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkyl,

Har is bonded via a ring carbon or a ring nitrogen atom, and is a 5-membered monocyclic unsaturated, aromatic heteroaryl ring comprising at least one heteroatom independently selected from the group consisting of nitrogen, oxygen and sulphur, or

Har is bonded via a ring carbon atom, and is a 6-membered monocyclic unsaturated, aromatic heteroaryl ring comprising one or two nitrogen atoms,

each R10 is the same or different and is each independently selected from the group consisting of:

1-4C-alkyl, halogen and 1-4C-alkoxy,

Rab is hydroxyl,

Rac is hydroxyl,

or Rab and Rae bonded to adjacent carbon atoms form together a dimethylmethylenedioxy bridge,

Rba is selected from the group consisting of:

1-4C-alkoxy, 3-5C-cycloalkoxy, 3-5C-cycloalkyl-1-4C-alkoxy, cyano-2-4C-alkoxy, 3-5C-alkinyloxy, nitro, and completely and predominantly fluorine-substituted 1-4C-alkoxy,

Rbb is selected from the group consisting of:

hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, and 1-4C-alkoxy,

Rbc is selected from the group consisting of:

hydrogen, halogen, and 1-4C-alkoxy,

or Rbb and Rbc bounded in ortho position to each other form together a methylenedioxy, ethylenedioxy, difluoromethylenedioxy or tetrafluoroethylenedioxy bridge,

or a salt thereof.

3. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib, Ic, Id and Id′

wherein

Ra is —C(O)R1,

R1 is 1-4C-alkyl, or 1-4C-alkyl substituted by Raa, or 3-4C-alkyl substituted by Rab and Rac on different carbon atoms,

Q is substituted by Rba and Rbb and Rbc, and is phenyl,

Raa is selected from the group consisting of:

hydroxyl, Har, morpholino, —C(O)R2, —C(O)OR3, —C(O)N(R4)R5, —N(R6)C(O)R7, —OC(O)R8, and —OR9,

wherein said Har is optionally substituted by one or two substituents independently selected from R10,

R2, R3, R4, R5, R6, R7 and R8 are the same or different and are independently selected from the group consisting of:

hydrogen and 1-4C-alkyl,

R9 is selected from the group consisting of:

1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl-1-4C-alkyl, pyridyl-1-4C-alkyl, and (1-4C-alkoxy-2-4C-alkoxy)-2-4C-alkyl,

Har is bonded via a ring carbon or a ring nitrogen atom, and is imidazolyl, pyrazolyl or triazolyl,

or

Har is bonded via a ring carbon atom, and is pyridinyl, pyrazinyl or pyrimidinyl,

each R10 is the same or different and is each independently selected from the group consisting of:

1-4C-alkyl and 1-4C-alkoxy,

Rab is hydroxyl,

Rac is hydroxyl,

or Rab and Rac bonded to adjacent carbon atoms form together a dimethylmethylenedioxy bridge,

Rba is selected from the group consisting of:

1-4C-alkoxy, and completely and predominantly fluorine-substituted 1-4C-alkoxy,

Rbb is selected from the group consisting of:

hydrogen, 1-4C-alkyl, and 1-4C-alkoxy,

Rbc is selected from the group consisting of:

hydrogen, and halogen,

or Rbb and Rbc bounded in ortho position to each other form together a methylenedioxy, ethylenedioxy, difluoromethylenedioxy or tetrafluoroethylenedioxy bridge,

or a salt thereof.

4. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib and Ic

wherein

Ra is —C(O)R1,

R1 is 1-4C-alkyl,

or

R1 is 1-4C-alkyl which is substituted by Raa, in which

Raa is pyridyl, pyrimidinyl, R101- and/or R102-substituted pyridyl, or R101- and/or R102-substituted pyrimidinyl,

or

R1 is 1-4C-alkyl which is substituted by Raa, in which

Raa is 1N-(1-4C-alkyl)-imidazolyl, 1N-(1-4C-alkyl)-pyrazolyl, R101-substituted 1N-(1-4C-alkyl)-imidazolyl, or R101-substituted 1N-(1-4C-alkyl)-pyrazolyl,

or

R1 is 1-4C-alkyl which is substituted by Raa, in which

Raa is 1N—(H)-imidazolyl, 1N—(H)-pyrazolyl, R101-substituted 1N—(H)-imidazolyl, or R101-substituted 1N—(H)-pyrazolyl,

or

R1 is 3-4C-alkyl which is substituted by Rab and Rac on different carbon atoms, in which

Rab is hydroxyl,

Rac is hydroxyl,

or Rab and Rae bonded to adjacent carbon atoms form together a dimethylmethylenedioxy bridge,

or

R1 is 1-4C-alkyl which is substituted by Raa, in which

Raa is —C(O)OR3,

or

R1 is 1-4C-alkyl which is substituted by Raa, in which

Raa is hydroxyl, morpholino, —OC(O)R8, or —OR9,

or

R1 is 1-4C-alkyl which is substituted by Raa, in which

Rae is imidazol-1-yl, pyrazol-1-yl, mono- or di-(R101)-substituted imidazol-1-yl, or mono- or di-(R101)-substituted pyrazol-1-yl, and

Q is substituted by Rba and Rbb and Rbc, and is phenyl,

R3 is selected from the group consisting of:

hydrogen, and 1-4C-alkyl,

R8 is 1-4C-alkyl,

R9 is selected from the group consisting of:

1-4C-alkyl, phenyl-1-2C-alkyl, 1-2C-alkoxy-2-3C-alkyl, and (1-2C-alkoxy-2-3C-alkoxy)-2-3C-alkyl,

R101 is 1-4C-alkyl,

R102 is 1-4C-alkoxy, or 1-4C-alkyl,

Rba is selected from the group consisting of:

methoxy, ethoxy, trifluoromethoxy, and difluoromethoxy,

Rbb is selected from the group consisting of:

hydrogen, methyl, ethyl, methoxy, and ethoxy,

Rbc is hydrogen;

or a salt thereof.

5. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib and Ic

wherein

Ra is —C(O)R1,

R1 is methyl, ethyl or propyl,

or

R1 is (Raa)-methyl, 2-(Raa)-ethyl, or 3-(Raa)-propyl, in which

Raa is pyridyl, pyrimidinyl, methyl-substituted pyridyl, or methoxy-substituted pyridyl,

or

R1 is (Raa)-methyl, 2-(Raa)-ethyl, or 3-(Raa)-propyl, in which

Raa is 1N-methyl-imidazolyl,

or

R1 is 2,3-dihydroxy-propyl,

or

R1 is (Raa)-methyl, 2-(Raa)-ethyl, or 3-(Raa)-propyl, in which

Raa is carboxyl, methoxycarbonyl, hydroxyl, methylcarbonyloxy, methoxy, ethoxy, benzyloxy, or 2 methoxyethoxy,

or

R1 is (Raa)-methyl, 2-(Raa)-ethyl, or 3-(Raa)-propyl, in which

Raa is imidazol-1-yl, or mono- or di-methyl-substituted imidazol-1-yl;

Q is 2-(Rba)-phenyl, 3-(Rba)-phenyl, 2-(Rba)-3-(Rbb)-phenyl, 2-(Rba)-5-(Rbb)-phenyl, 2-(Rba)-6-(Rbb)-phenyl, 2-(Rbb)-3-(Rba)-phenyl or 2-(Rbb)-5-(Rba)-phenyl,

Rba is selected from the group consisting of:

methoxy and ethoxy,

Rbb is selected from the group consisting of:

methyl and methoxy;

or a salt thereof.

6. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib and Ic

wherein

Ra is —C(O)R1,

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is pyridyl,

or

R1 is (Raa)-methyl, in which

Raa is 1N-methyl-imidazolyl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is hydroxyl or methoxy,

or

R1 is (2-methoxyethoxy)-methyl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is imidazol-1-yl, or mono- or di-methyl-substituted imidazol-1-yl;

Q is 2-(Rba)-phenyl, 3-(Rba)-phenyl, 2-(Rba)-3-(Rbb)-phenyl, 2-(Rba)-5-(Rbb)-phenyl, 2-(Rba)-6-(Rbb)-phenyl, 2-(Rbb)-3-(Rba)-phenyl or 2-(Rbb)-5-(Rba)-phenyl,

Rba is selected from the group consisting of:

methoxy and ethoxy,

Rbb is methyl;

or a salt thereof.

7. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib and Ic

wherein

Ra is —C(O)R1,

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is pyridin-2-yl, pyridin-3-yl or pyridin-4-yl,

or

R1 is (Raa)-methyl, in which

Raa is 1-methyl-imidazol-2-yl or 1-methyl-imidazol-5-yl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is hydroxyl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is imidazol-1-yl, 2-methyl-imidazol-1-yl, 4-methyl-imidazol-1-yl or 2,4-dimethyl-imidazol-1-yl;

Q is 2-methoxyphenyl,

or

Q is 2-ethoxyphenyl,

or

Q is 3-methoxyphenyl,

or

Q is 3-ethoxyphenyl,

or

Q is 2-(Rba)-3-(Rbb)-phenyl, in which

Rba is methoxy or ethoxy,

Rbb is methyl,

or

Q is 2-(Rba)-5-(Rbb)-phenyl, in which

Rba is methoxy or ethoxy,

Rbb is methyl;

or a salt thereof.

8. A compound according to claim 1 , which is a compound of one of the formulae Ia, Ib and Ic

wherein

Ra is —C(O)R1,

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is pyridin-2-yl, pyridin-3-yl or pyridin-4-yl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is hydroxyl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is imidazol-1-yl;

Q is 2-methoxyphenyl,

or

Q is 2-ethoxyphenyl,

or

Q is 3-methoxyphenyl,

or

Q is 2-(Rba)-5-(Rbb)-phenyl, in which

Rba is methoxy,

Rbb is methyl;

or a salt thereof.

9. A compound according to claim 1 , which is a compound of one of the formulae Ia and Ic

wherein

Ra is —C(O)R1,

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is pyridyl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is methoxy,

or

R1 is (2-methoxyethoxy)-methyl,

or

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is imidazol-1-yl;

Q is 2-(Rba)-phenyl, 3-(Rba)-phenyl, 2-(Rba)-3-(Rbb)-phenyl, 2-(Rba)-5-(Rbb)-phenyl, 2-(Rba)-6-(Rbb)-phenyl, 2-(Rbb)-3-(Rba)-phenyl or 2-(Rbb)-5-(Rba)-phenyl,

Rba is selected from the group consisting of:

methoxy and ethoxy,

Rbb is methyl;

or a salt thereof.

10. A compound according to claim 1 , which is a compound of one of the formulae Ia and Ic

wherein

Ra is —C(O)R1,

R1 is (Raa)-methyl, or 2-(Raa)-ethyl, in which

Raa is pyridyl,

or

R1 is 2-(Raa)-ethyl, in which

Raa is imidazol-1-yl;

Q is 2-methoxyphenyl,

or

Q is 2-ethoxyphenyl,

or

Q is 3-methoxyphenyl,

or

Q is 3-ethoxyphenyl,

or

Q is 2-(Rba)-3-(Rbb)-phenyl, in which

Rba is methoxy or ethoxy,

Rbb is methyl,

or

Q is 2-(Rba)-5-(Rbb)-phenyl, in which

Rba is methoxy or ethoxy,

Rbb is methyl;

or a salt thereof.

11. A compound, which is selected from the group consisting of

N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

4-{3-Cyano-2-[3-(2-methoxy-phenyl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl}-4-oxo-butyric acid methyl ester,

N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

Acetic acid 2-{3-cyano-2-[3-(2-methoxy-phenyl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl}-2-oxo-ethyl ester,

N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

4-{3-Cyano-2-[3-(2-ethoxy-phenyl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl}-4-oxo-butyric acid methyl ester,

Acetic acid 2-{3-cyano-2-[3-(2-ethoxy-phenyl)-propanoylamino]-4,7-dihydro-5H-thieno[2,3-c]pyridin-6-yl}-2-oxo-ethyl ester,

N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(4-hydroxy-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(3-methoxy-phenyl)-propionamide,

N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2-methoxy-ethoxy)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methyl-pyridin-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyrimidin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methoxy-pyridin-3-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-[3-Cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2,5-dimethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methyl-pyridin-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methoxy-pyridin-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2,5-dimethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methoxy-6-methyl-pyridin-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2,5-dimethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methoxy-pyridin-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methoxy-6-methyl-pyridin-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2,5-dimethoxy-phenyl)-propionamide,

N-[6-(4-Chloro-butanoyl)-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-((RS)-3-imidazol-1-yl-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-((RS)-3-imidazol-1-yl-butanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-2-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-e]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-4-O-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-[3-Cyano-6-(3-pyridin-3-O-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-e]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-ethoxy-phenyl)-butyramide,

N-(6-Butyryl-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl)-3-(2-methoxy-phenyl)-propionamide,

(RS)—N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)butyramide,

N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(2-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)butyramide,

N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(4-methyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[2-(2,4-dimethyl-imidazol-1-yl)-ethanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(4-methyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-ethoxy-phenyl)-butyramide,

N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(3-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-ethoxy-phenyl)-propionamide,

N-{3-Cyano-6-[3-(2,4-dimethyl-imidazol-1-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(RS)—N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

(RS)—N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-butyramide,

N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(3-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-phenyl)-propionamide,

N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-ethoxy-phenyl)-propionamide,

N-[3-Cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

N-[3-Cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-3-(2-methoxy-5-methyl-phenyl)-propionamide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid {3-cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)cyclopropanecarboxylic acid [3-cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)cyclopropanecarboxylic acid [3-cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(2-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-3-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-pyridin-4-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-4-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-3-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-pyridin-2-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-imidazol-1-yl-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)cyclopropanecarboxylic acid [3-cyano-6-(3-imidazol-1-yl-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid {3-cyano-6-[3-(1-methyl-1H-imidazol-2-yl)-propanoyl]-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl}-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-hydroxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-hydroxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(3-methoxy-propanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide, and

(1RS,2RS)-2-(3-Methoxy-phenyl)-cyclopropanecarboxylic acid [3-cyano-6-(2-methoxy-ethanoyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin-2-yl]-amide,

and salts thereof.

12. An enantiomer of a compound according to claim 1 , or a salt thereof.

13. A pharmaceutical composition comprising one or more compounds according to claim 1 , together with a pharmaceutically acceptable excipient, diluent and/or carrier.

14. A combination comprising

a first active ingredient, which is at least one compound according to claim 1 , and

a second active ingredient, which is at least one anti-cancer agent selected from the group consisting of chemotherapeutic anti-cancer agents and target-specific anti-cancer agents,

for separate, sequential, simultaneous, concurrent or chronologically staggered use in therapy.

15. The combination according to claim 14 , in which said chemotherapeutic anti-cancer agents are selected from the group consisting of (i) alkylating/carbamylating agents; (ii) platinum derivatives; (iii) antimitotic agents/tubulin inhibitors; (iv) topoisomerase inhibitors; (v) pyrimidine antagonists; (vi) purin antagonists; and (vii) folic acid antagonists.

16. The combination according to claim 14 , in which said target-specific anti-cancer agents are selected from the group consisting of (i) kinase inhibitors; (ii) proteasome inhibitors; (iii) histone deacetylase inhibitors; (iv) heat shock protein 90 inhibitors; (v) vascular targeting agents, anti-angiogenic drugs and KDR tyrosine kinase inhibitors; (vi) monoclonal antibodies, mutants and conjugates of monoclonal antibodies and antibody fragments; (vii) oligonucleotide based therapeutics; (viii) Toll-like receptor/TLR 9 agonists, TLR 7 agonists and TLR 7/8 agonists; (ix) protease inhibitors; (x) hormonal therapeutics; (xi) aromatase inhibitors; (xii) bleomycin; (xiii) retinoids; (xiv) DNA methyltransferase inhibitors; (xv) alanosine; (xvi) cytokines; (xvii) interferons; (xviii) death receptor agonists; (xix) DR4/5 agonistic antibodies; (xx) FasL; and (xxi) TNF-R agonists.

17. A pharmaceutical composition comprising one or more compounds according to claim 11 , together with a pharmaceutically acceptable excipient, diluent and/or carrier.

Assignments (3)
CHANGE OF NAME Recorded Feb 26, 2009
From: ALTANA PHARMA AG
To: NYCOMED GMBH
Reel/Frame 022315/0364 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 20, 2008
From: NYCOMED GMBH
To: 4SC AG
Reel/Frame 021414/0417 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 14, 2007
From: PEKARI, KLAUS; SCHMIDT, MATHIAS; BAR, THOMAS; BECKERS, THOMAS; GIMMNICH, PETRA
To: NYCOMED GMBH
Reel/Frame 020315/0161 →