Hydroxy-6-heteroarylphenanthridines and their use as PDE4 inhibitors
Compounds of the formula Ia***** in which the substituents have the definitions provided in the specification, are novel, effective PDE4 inhibitors, useful in the treatment of psoriasis.
1. A method of treating psoriasis in a patient, comprising administering to said patient a compound of formula Ia*****
wherein
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 pharmaceutically acceptable salt thereof.
2. The method of treating psoriasis in a patient according to claim 1 , comprising administering to said patient a compound of formula Ia*****,
wherein
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 pharmaceutically acceptable salt thereof.
3. The method of treating psoriasis in a patient according to claim 1 , comprising administering to said patient a compound of formula Ia*****,
wherein
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 pharmaceutically acceptable salt thereof.
4. The method of treating psoriasis in a patient according to claim 1 , comprising administering to said patient a compound of formula Ia*****, 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 pharmaceutically acceptable salt thereof.
5. The method of treating psoriasis in a patient according to claim 1 , comprising administering to said patient a compound of formula Ia*****, 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.