Novel Hydroxy-6-Heteroarylphenanthridines and Their Use as Pde4 Inhibitors

A compound of formula I,

• in which
• R1 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy,
• R2 is hydroxyl, 1-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, 2,2-difluoroethoxy, or completely or predominantly fluorine-substituted 1-4C-alkoxy,
• or in which
• R1 and R2 together are a 1-2C-alkylenedioxy group,
• R3 is hydrogen or 1-4C-alkyl,
• R31 is hydrogen or 1-4C-alkyl,
• either, in a first embodiment (embodiment a),
• R4 is —O—R41, in which
• R41 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or completely or predominantly fluorine-substituted 1-4C-alkyl, and
• R5 is hydrogen or 1-4C-alkyl,
• or, in a second embodiment (embodiment b),
• R4 is hydrogen or 1-4C-alkyl, and
• R5 is —O—R51, in which
• R51 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-7C-alkylcarbonyl, or completely or predominantly fluorine-substituted 1-4C-alkyl,
• Har is optionally substituted by R6 and/or R7 and/or R8, and is a 5- to 10-membered monocyclic or fused bicyclic unsaturated or partially saturated heteroaryl radical comprising 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R6 is halogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, 1-4C-alkylthio, sulfanyl, cyano, 1-4C-alkoxycarbonyl, carboxyl, hydroxyl, oxo, -A-N(R61)R62, pyridyl, or completely or partially fluorine-substituted 1-4C-alkyl, in which
• A is a bond or 1-4C-alkylene,
• R61 is hydrogen or 1-4C-alkyl,
• R62 is hydrogen or 1-4C-alkyl,
• or R61 and R62 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het1, in which
• Het1 is optionally substituted by R611, and is a 3- to 7-membered saturated or unsaturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R61 and R62 are bonded, and optionally one to three further heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R611 is 1-4C-alkyl,
• R7 is 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, 1-4C-alkylthio, sulfanyl, hydroxyl, oxo, amino or mono- or di-1-4C-alkylamino,
• R8 is halogen, 1-4C-alkyl or 1-4C-alkoxy, or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.