Phthalazinone-piperidino-derivatives as PDE4 inhibitors

1. A compound of formula I

in which

R1 and R2 are both hydrogen or together form an additional bond,

R3 represents a benzene derivative of formula (a)

wherein

R4 is 1–4C-alkoxy,

R5 is 1–8C alkoxy,

R9 is (CH 2 ) m —C(O)—R15,

wherein

R15 is —N(R16)R17,

R16 and R17 are independent from each other and are hydrogen or 1–7C-alkyl, and

m is an integer from 1 to 4,

or a hydrate, salt or hydrate of a salt thereof.

2. A compound of formula I according to claim 1 or a hydrate, salt or hydrate of a salt thereof, in which the hydrogen atoms in the positions 4a and 8a are cis-configurated.

3. A compound of formula I according to claim 1 or a hydrate, salt or hydrate of a salt thereof, in which the absolute configuration is S in the position 4a and R in the position 8a.

4. A compound which is 2-{4[(4aS,8aR)-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a tetrahydro-1H-phthalazin-2-yl]-piperidin-1-yl}-acetamide or a hydrate, salt or hydrate of a salt thereof.

5. A compound which is 2-{4-[(4aS,8aR)-4-(3,4-dimethoxphenyl)-1-oxo-4a,5,8,8a-tetrahydro-1H-phthalazin-2-yl]-piperidin1-yl}-acetamide hydrochloride or a hydrate thereof.

6. A pharmaceutical composition comprising a compound of formula I according to claim 1 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, together with a suitable pharmaceutical auxiliary.

7. A pharmaceutical composition comprising a compound according to claim 2 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, together with a suitable pharmaceutical auxiliary.

8. A pharmaceutical composition comprising a compound according to claim 3 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, together with a suitable pharmaceutical auxiliary.

9. A pharmaceutical composition comprising a compound according to claim 4 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, together with a suitable pharmaceutical auxiliary.

10. A pharmaceutical composition comprising a compound according to claim 5 or a pharmaceutically acceptable hydrate thereof, together with a suitable pharmaceutical auxiliary.

11. A method of treating an airway disorder in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I according to claim 1 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, wherein the airway disorder is selected from the group consisting of bronchitis, allergic bronchitis, bronchial asthma, emphysema, COPD and allergic rhinitis.

12. A method of treating an airway disorder in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I according to claim 2 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, wherein the airway disorder is selected from the group consisting of bronchitis, allergic bronchitis, bronchial asthma, emphysema, COPD and allergic rhinitis.

13. A method of treating an airway disorder in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I according to claim 3 or a pharmaceutically acceptable hydrate, salt or hydrate of a salt thereof, wherein the airway disorder is selected from the group consisting of bronchitis, allergic bronchitis, bronchial asthma, emphysema, COPD and allergic rhinitis.

14. A method of treating an airway disorder in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 4 or a hydrate, salt or hydrate of a salt thereof, wherein the airway disorder is selected from the group consisting of bronchitis, allergic bronchitis, bronchial asthma, emphysema, COPD and allergic rhinitis.

15. A method of treating an airway disorder in a patient comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 5 or a hydrate thereof, wherein the airway disorder is selected from the group consisting of bronchitis, allergic bronchitis, bronchial asthma, emphysema, COPD and allergic rhinitis.