Hydroxy-6-heteroarylphenanthridines and their use as PDE4 inhibitors
View Patent ↗Compounds of the formula Ia***** in which the substituents have the definitions provided in the specification, are novel, effective PDE4 inhibitors.
1. A compound of formula Ia*****
in which
R1 is methoxy,
R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,
R3 is hydrogen,
R31 is hydrogen,
R41 is hydrogen,
R5 is hydrogen,
Har is substituted by R6 and R7, and is pyridinyl, in which
R6 is oxo, and
R7 is methyl,
or a salt of this compound.
2. A compound of formula Ia***** according to claim 1 in which
R1 is methoxy,
R2 is methoxy, ethoxy, difluoromethoxy or 2,2-difluoroethoxy,
R3 is hydrogen,
R31 is hydrogen,
R41 is hydrogen,
R5 is hydrogen,
Har is 1-methyl-1H-pyridin-2-one-5-yl,
or a salt of this compound.
3. A compound of formula Ia***** according to claim 1 in which
R1 is methoxy,
R2 is ethoxy, difluoromethoxy or 2,2-difluoroethoxy,
R3 is hydrogen,
R31 is hydrogen,
R41 is hydrogen,
R5 is hydrogen,
Har is 1-methyl-1H-pyridin-2-one-5-yl,
or a salt of this compound.
4. A compound of formula Ia***** according to claim 1 which is selected from the group consisting of
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 and a salt of this compound.
5. A compound of formula Ia***** according to claim 1 which is 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.
6. A pharmaceutical composition comprising a compound of formula Ia***** according to claim 1 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient and/or vehicle.
7. A pharmaceutical composition comprising a compound of formula Ia***** according to claim 2 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient and/or vehicle.
8. A pharmaceutical composition comprising a compound of formula Ia***** according to claim 3 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient and/or vehicle.
9. A pharmaceutical composition comprising a compound of formula Ia***** according to claim 4 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient and/or vehicle.
10. A pharmaceutical composition comprising a compound of formula Ia***** according to claim 5 together with a pharmaceutically acceptable excipient and/or vehicle.
11. A method of treating diabetes mellitus in a patient, comprising administering to said patient a compound of formula Ia***** according to claim 1 , or a pharmaceutically acceptable salt thereof.
12. A method of treating diabetes mellitus in a patient, comprising administering to said patient a compound of formula Ia***** according to claim 2 , or a pharmaceutically acceptable salt thereof.
13. A method of treating diabetes mellitus in a patient, comprising administering to said patient a compound of formula Ia***** according to claim 3 , or a pharmaceutically acceptable salt thereof.
14. A method of treating diabetes mellitus in a patient, comprising administering to said patient a compound of formula Ia***** according to claim 4 , or a pharmaceutically acceptable salt thereof.
15. A method of treating diabetes mellitus in a patient, comprising administering to said patient a compound of formula Ia***** according to claim 5 .