3,4,4a,10b-Tetrahydro-1H-thiopyrano-[44,3-c] isoquinoline derivatives

1. A compound of formula 1

wherein

A is S, S(O) or S(O) 2 ,

either

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

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

or

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

R3 is a five membered heterocyclic ring, which is substituted by R4 and is selected from the group consisting of pyrazol-3-yl, pyrazol-4-yl, thiophen-2-yl, thiophen-3-yl, imidazol-2-yl, imidazol-4-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 1,3-oxazol-2-yl, 1,3-oxazol-4-yl, 1,3-oxazol-5-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,4-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,3,4-thiadiazol-2-yl, tetrazol-2-yl and tetrazol-5-yl, wherein

R4 is 1-4C-alkyl, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, propyloxymethyl, ethoxyethyl, methyl sulfanylmethyl, methyl sulfanylethyl, methylsulfanylpropyl, ethylsulfanylmethyl, propylsulfanylmethyl or ethylsulfanylethyl,

R5 is unsubstituted phenyl, phenyl substituted by R6 or phenyl substituted by R6 and R7, wherein

R6 is halogen, 1-4C-alkyl or 1-4C-alkoxy, and

R7 is halogen, 1-4C-alkyl or 1-4C-alkoxy,

or

R6 and R7 together form a 1-2C-alkylenedioxy group,

or a stereoisomer thereof.

2. A compound of formula 1 according to claim 1 wherein

A is S, S(O) or S(O) 2 ,

either

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

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

or

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

R3 is a five membered heterocyclic ring, which is substituted by R4 and is selected from the group consisting of pyrazol-3-yl, pyrazol-4-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 1,3-oxazol-2-yl, 1,3-oxazol-4-yl, 1,3-oxazol-5-yl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,4-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,3,4-thiadiazol-2-yl and tetrazol-5-yl, wherein

R4 is 1-4C-alkyl, methylsulfanylmethyl, ethylsulfanylmethyl, methylsulfanylethyl, methoxymethyl, ethoxymethyl or methoxyethyl, and

R5 is an unsubstituted phenyl,

or a stereoisomer thereof.

3. A compound of formula 1 according to claim 1 , wherein

A is S, S(O) or S(O) 2 ,

either

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

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

or

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

R3 is 1-methyl-1H-imidazol-2-yl, 1-ethyl-1H-imidazol-2-yl, 5-ethyl-thiophen-2-yl, 5-methyl-thiophen-2-yl, 3-methyl-thiophen-2-yl, 3-ethyl-thiophen-2-yl, 1-methyl-pyrazol-3-yl, 1-ethyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 2-ethyl-pyrazol-4-yl, 4-methyl-1,3-oxazol-2-yl, 4-ethyl-1,3-oxazol-2-yl, 5-methyl-1,3-oxazol-2-yl, 5-ethyl-1,3-oxazol-2-yl, 2-methyl-1,3-oxazol-4-yl, 2-methyl-1,3-oxazol-4-yl, 2-ethyl-1,3-oxazol-4-yl, 2-methyl-1,3-oxazol-5-yl, 2-ethyl-1,3-oxazol-5-yl, 4-methyl-1,3-oxazol-5-yl, 4-ethyl-1,3-oxazol-5-yl, 3-methyl-isoxazol-5-yl, 3-ethyl-isoxazol-5-yl, 5-methyl-isoxazol-3-yl, 5-ethyl-isoxazol-3-yl, 4-methyl-1,3-thiazol-2-yl, 4-ethyl-1,3-thiazol-2-yl, 5-methyl-1,3-thiazol-2-yl, 2-methyl-1,3-thiazol-4-yl, 2-ethyl-1,3-thiazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 2-ethyl-1,3-thiazol-5-yl, 3-methoxymethyl-1,2,4-oxadiazol-5-yl, 3-ethoxymethyl-1,2,4-oxadiazol-5-yl, 3-methoxypropyl-1,2,4-oxadiazol-5-yl, 3-propoxymethyl-1,2,4-oxadiazol-5-yl, 3-methylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-ethylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-methylsulfanylpropyl-1,2,4-oxadiazol-5-yl, 3-propylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 5-ethyl-1,3,4-oxadiazol-2-yl, 5-tert-butyl-1,3,4-oxadiazol-2-yl, 5-methoxymethyl-1,3,4-oxadiazol-2-yl, 5-ethoxymethyl-1,3,4-oxadiazol-2-yl, 5-methylsulfanylmethyl-1,3,4-oxadiazol-2-yl, 5-ethylsulfanylmethyl-1,3,4-oxadiazol-2-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 5-ethyl-1,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 3-ethyl-1,2,4-thiadiazol-5-yl, 2-methyl-1,2,3-triazol-4-yl, 2-ethyl-1,2,3-triazol-4-yl, 1-methyl-1,2,3-triazol-4-yl, 1-ethyl-1,2,3-triazol-4-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 1-ethyl-1H-1,2,4-triazol-3-yl, 1-methyl-1H-tetrazol-5-yl, 1-ethyl-1H-tetrazol-5-yl, 2-methyl-2H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 5-ethyl-2H-tetrazol-2-yl, 5-methyl-2H-tetrazol-2-yl, 1-methoxymethyl-1H-tetrazol-5-yl, 1-ethoxymethyl-1H-tetrazol-5-yl, 2-methoxymethyl-2H-tetrazol-5-yl, 2-ethoxymethyl-2H-tetrazol-5-yl, 1-methylsulfanylmethyl-1H-tetrazol-5-yl, 1-ethylsulfanylmethyl-1H-tetrazol-5-yl, 2-methylsulfanylmethyl-2H-tetrazol-5-yl or 2-ethylsulfanylmethyl-2H-tetrazol-5-yl,

R5 is unsubstituted phenyl, phenyl substituted by R6 or phenyl substituted by R6 and R7

wherein

R6 is fluorine, methyl or methoxy, and

R7 is fluorine, methyl or methoxy,

or a stereoisomer thereof.

4. A compound of formula 1 according to claim 1 wherein

A is S, S(O) or S(O) 2 ,

either

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

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

or

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

R3 is 1-methyl-pyrazol-3-yl, 1-ethyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 2-ethyl-pyrazol-4-yl, 4-methyl-1,3-oxazol-2-yl, 4-ethyl-1,3-oxazol-2-yl, 5-methyl-1,3-oxazol-2-yl, 5-ethyl-1,3-oxazol-2-yl, 2-methyl-1,3-oxazol-4-yl, 2-methyl-1,3-oxazol-4-yl, 2-ethyl-1,3-oxazol-4-yl, 2-methyl-1,3-oxazol-5-yl, 2-ethyl-1,3-oxazol-5-yl, 3-methyl-isoxazol-5-yl, 3-ethyl-isoxazol-5-yl, 5-methyl-isoxazol-3-yl, 5-ethyl-isoxazol-3-yl, 4-methyl-1,3-thiazol-2-yl, 4-ethyl-1,3-thiazol-2-yl, 5-methyl-1,3-thiazol-2-yl, 2-methyl-1,3-thiazol-4-yl, 2-ethyl-1,3-2-methyl-1,3-thiazol-5-yl, 2-ethyl-1,3-thiazol-5-yl, 3-methoxymethyl-1,2,4-oxadiazol-5-yl, 3-ethoxymethyl-1,2,4-oxadiazol-5-yl, 3-methylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-ethylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 5-ethyl-1,3,4-oxadiazol-2-yl, 5-methoxymethyl-1,3,4-oxadiazol-2-yl, 5-ethoxymethyl-1,3,4-oxadiazol-2-yl, 5-methylsulfanylmethyl-1,3,4-oxadiazol-2-yl, 5-ethylsulfanylmethyl-1,3,4-oxadiazol-2-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 5-ethyl-1,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 3-ethyl-1,2,4-thiadiazol-5-yl, 2-methyl-1,2,3-triazol-4-yl, 2-ethyl-1,2,3-triazol-4-yl, 1-methyl-1,2,3-triazol-4-yl, 1-ethyl-1,2,3-triazol-4-yl, 1-methyl-1H-tetrazol-5-yl, 1-ethyl-1H-tetrazol-5-yl, 2-methyl-2H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 1-methoxymethyl-1H-tetrazol-5-yl, 1-ethoxymethyl-1H-tetrazol-5-yl, 2-methoxymethyl-2H-tetrazol-5-yl, 2-ethoxymethyl-2H-tetrazol-5-yl, 1-methylsulfanylmethyl-1H-tetrazol-5-yl, 1-ethylsulfanylmethyl-1H-tetrazol-5-yl, 2-methylsulfanylmethyl-2H-tetrazol-5-yl or 2-ethylsulfanylmethyl-2H-tetrazol-5-yl, and

R5 is an unsubstituted phenyl,

or a stereoisomer thereof.

5. A compound of formula 1 according to claim 1 , wherein

A is S, S(O) or S(O) 2 ,

R1 is methoxy or ethoxy,

R2 is methoxy,

R3 is 1-methyl-1H-imidazol-2-yl, 5-ethyl-thiophen-2-yl, 3-methyl-thiophen-2-yl, 1-ethyl-pyrazol-3-yl, 2-ethyl-pyrazol-4-yl, 4-ethyl-1,3-oxazol-2-yl, 5-ethyl-1,3-oxazol-2-yl, 2-ethyl-1,3-oxazol-4-yl, 2-ethyl-1,3-oxazol-5-yl, 4-methyl-1,3-oxazol-5-yl, 3-ethyl-isoxazol-5-yl, 5-methyl-isoxazol-3-yl, 4-methyl-1,3-thiazol-2-yl, 5-methyl-1,3-thiazol-2-yl, 2-methyl-1,3-thiazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 3-methoxymethyl-1,2,4-oxadiazol-5-yl, 3-methoxypropyl-1,2,4-oxadiazol-5-yl, 3-propoxymethyl-1,2,4-oxadiazol-5-yl, 3-methylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 5-ethyl-1,3,4-oxadiazol-2-yl, 5-tert-butyl-1,3,4-oxadiazol-2-yl, 5-methoxymethyl-1,3,4-oxadiazol-2-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-ethyl-1,2,4-thiadiazol-5-yl, 2-ethyl-1,2,3-triazol-4-yl, 1-ethyl-1,2,3-triazol-4-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 1-ethyl-1H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 5-ethyl-2H-tetrazol-2-yl, 1-methoxymethyl-1H-tetrazol-5-yl or 2-methoxymethyl-2H-tetrazol-5-yl, and

R5 is phenyl, 1,3-benzodioxol-5-yl, 2-fluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 2-methoxy-4-fluorophenyl, 2-methoxy-5-fluorophenyl or 2,5-dimethoxyphenyl,

or a stereoisomer thereof.

6. A compound of formula 1 according to claim 1 wherein

A is S, S(O) or S(O) 2 ,

R1 is methoxy or ethoxy,

R2 is methoxy,

R3 is 1-ethyl-pyrazol-3-yl, 2-ethyl-pyrazol-4-yl, 4-ethyl-1,3-oxazol-2-yl, 5-ethyl-1,3-oxazol-2-yl, 2-ethyl-1,3-oxazol-4-yl, 2-ethyl-1,3-oxazol-5-yl, 3-ethyl-isoxazol-5-yl, 5-methyl-isoxazol-3-yl, 4-methyl-1,3-thiazol-2-yl, 5-methyl-1,3-thiazol-2-yl, 2-methyl-1,3-thiazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 3-methoxymethyl-1,2,4-oxadiazol-5-yl, 3-methylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 5-ethyl-1,3,4-oxadiazol-2-yl, 5-methoxymethyl-1,3,4-oxadiazol-2-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-ethyl-1,2,4-thiadiazol-5-yl, 2-ethyl-1,2,3-triazol-4-yl, 1-ethyl-1,2,3-triazol-4-yl, 1-ethyl-1H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 1-methoxymethyl-1H-tetrazol-5-yl or 2-methoxymethyl-2H-tetrazol-5-yl, and

R5 is an unsubstituted phenyl,

or a stereoisomer thereof.

7. A compound of formula 1 according to claim 1 wherein

A is S, S(O) or S(O) 2 ,

R1 is ethoxy,

R2 is methoxy,

R3 is 5-ethyl-1,3-oxazol-2-yl, 3-ethyl-isoxazol-5-yl, 5-methyl-isoxazol-3-yl, 2-methyl-1,3-thiazol-5-yl, 3-methoxymethyl-1,2,4-oxadiazol-5-yl, 3-methylsulfanylmethyl-1,2,4-oxadiazol-5-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 1-ethyl-1H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 1-methoxymethyl-1H-tetrazol-5-yl or 2-methoxymethyl-2H-tetrazol-5-yl, and

R5 is an unsubstituted phenyl,

or a stereoisomer thereof.

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

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(5-ethyl-1,3-oxazol-2-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(3-ethylisoxazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(5-ethyl-1,3,4-oxadiazol-2-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(4-ethyl-1,3-oxazol-2-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(5-methylisoxazol-3-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-(1-{4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoyl piperidin-4-yl)-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-{[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]methyl-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-1,3-oxazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-methyl-1,3-thiazol-4-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-(4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-({3-[(methylsulfanyl)methyl]-1,2,4-oxadiazol-5-yl}methyl)-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(5-methyl-1,3-thiazol-2-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(4-methyl-1,3-thiazol-2-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-(1-{4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]benzoyl}piperidin-4-yl)-1-{[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methyl}-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({ 4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-1,3-oxazol-4-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(1-ethyl-1H-pyrazol-4-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(1-ethyl-1H-pyrazol-3-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-2,2-dioxido-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-methyl-1,3-thiazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-1,2,3-triazol-4-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(3-ethyl-1,2,4-thiadiazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(1-ethyl-1H-1,2,3-triazol-4-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(2R,4aR,10bR)-9-ethoxy-8-methoxy-2-oxido-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(2S,4aR,10bR)-9-ethoxy-8-methoxy-2-oxido-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({3-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({3-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(3-ethyl-1,2,4-oxadiazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione;

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a, 10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-{[2-(methoxymethyl)-2H-tetrazol-5-yl]methyl}-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione and

3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-{[1-(methoxymethyl)-1H-tetrazol-5-yl]methyl}-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione.

9. A pharmaceutical composition comprising at least one of the compounds of formula 1 or a stereoisomer thereof according to claim 1 , together with at least one pharmaceutically acceptable auxiliary.

10. A composition comprising at least one compound of formula 1 or a stereoisomer thereof according to claim 1 , at least one therapeutic agent selected from the group consisting of corticosteroids, anticholinergics, β 2 -adrenoreceptor agonists, H1 receptor antagonists, leukotriene receptor antagonists, 5-lipoxygenase inhibitors, endothelin receptor antagonists, prostacyclins, calcium channel blockers, beta-blockers, type 4 phosphodiesterase inhibitors, type 5 phosphodiesterase inhibitors, immunosuppressants, vitamin D analogues, HMG-CoA reductase-inhibitors, lung surfactants, antibiotics, guanylyl-cyclase activators/stimulators, tetrahydrobiopterin tetrahydrobiopterin derivatives, anticoagulants, diuretics, pirfenidone and digitalis glycosides, and at least one pharmaceutically acceptable auxiliary.

11. A method of treating a disease, which is alleviated by inhibition of the type 4 and type 5 phosphodiesterase, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula 1 or a stereoisomer thereof according to claim 1 .

12. A method of treating an acute or chronic airway disease in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula 1 or a stereoisomer thereof according to claim 1 .

13. The method according to claim 12 , wherein the acute or chronic airway disease is selected from the group consisting of interstitial lung disease, pulmonary fibrosis, cystic fibrosis, bronchial asthma, chronic bronchitis, emphysema, chronic obstructive pulmonary disease (COPD) and COPD associated with pulmonary hypertension.

14. A compound of formula 1p or 1m

wherein

A is S, S(O) or S(O) 2 ,

R1 is ethoxy,

R2 is methoxy,

R3 is 2-ethyl-2H-tetrazol-5-yl, and

R5 is an unsubstituted phenyl,

or a stereoisomer thereof.

15. A compound of formula 1 according to claim 1 , which is 3-[1-({4-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione.

16. A compound of formula 1 according to claim 1 , which is 3-[1-({3-[(4aR,10bR)-9-ethoxy-8-methoxy-3,4,4a,10b-tetrahydro-1H-thiopyrano[4,3-c]isoquinolin-6-yl]phenyl}carbonyl)piperidin-4-yl]-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-phenylthieno[3,2-d]pyrimidine-2,4(1H,3H)-dione.

17. A pharmaceutical composition comprising a compound of formula 1p or 1m or a stereoisomer thereof according to claim 14 , together with at least one pharmaceutically acceptable auxiliary.

18. A pharmaceutical composition comprising the compound of formula 1 according to claim 15 , together with at least one pharmaceutically acceptable auxiliary.

19. A pharmaceutical composition comprising the compound of formula 1 according to claim 16 , together with at least one pharmaceutically acceptable auxiliary.