Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as pde4 inhibtors

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,
• R6 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy,
• either,
• in a first aspect (aspect 1),
• R7 is —N(R8)R9, in which
• R8 is hydrogen, 1-4C-alkyl or 1-4C-alkoxy-2-4C-alkyl,
• R9 is hydrogen, 1-4C-alkyl, mono- or di-1-4C-alkoxy-2-4C-alkyl, hydroxy-2-4C-alkyl, mono- or di-1-4C-alkoxycarbonyl-1-4C-alkyl, Har1, pyridinyl-1-4C-alkyl, 3-7C-cycloalkyl, or 2-4C-alkyl substituted by —NR(93)R94, in which
• Har1 is optionally substituted by R91 and/or R92, and is a 5- to 10-membered monocyclic or fused bicyclic unsaturated heteroaryl radical comprising 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R91 is 1-4C-alkyl or 1-4C-alkoxy,
• R92 is 1-4C-alkyl or 1-4C-alkoxy,
• R93 is hydrogen or 1-4C-alkyl,
• R94 is hydrogen or 1-4C-alkyl,
• or R93 and R94 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 R931, and is a 3- to 7-membered saturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R93 and R94 are bonded, and optionally one further heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R931 is 1-4C-alkyl,
• or R8 and R9 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het2, in which
• Het2 is optionally substituted by R10, and is a 3- to 7-membered saturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R8 and R9 are bonded, and optionally one further heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R10 is 1-4C-alkyl, —C(O)R11, pyridyl, 2-4C-alkyl substituted by —NR(14)R15, or 1-4C-alkyl substituted by —C(O)N(R16)R17, in which
• R11 is 1-4C-alkyl substituted by —NR(12)R13, in which
• R12 is hydrogen or 1-4C-alkyl,
• R13 is hydrogen or 1-4C-alkyl,
• or R12 and R13 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het3, in which
• Het3 is optionally substituted by R121, and is a 3- to 7-membered saturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R12 and R13 are bonded, and optionally one further heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R121 is 1-4C-alkyl,
• R14 is hydrogen or 1-4C-alkyl,
• R15 is hydrogen or 1-4C-alkyl,
• or R14 and R15 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het4, in which
• Het4 is optionally substituted by R141, and is a 3- to 7-membered saturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R14 and R15 are bonded, and optionally one further heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R141 is 1-4C-alkyl,
• R16 is hydrogen, 1-4C-alkyl or pyridyl,
• R17 is hydrogen or 1-4C-alkyl,
• or R16 and R17 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het5, in which
• Het5 is optionally substituted by R161, and is a 3- to 7-membered saturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R16 and R17 are bonded, and optionally one further heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R141 is 1-4C-alkyl,
• or,
• in a second aspect (aspect 2),
• R7 is —NH—N(R18)R19, in which
• R18 is hydrogen,
• R19 is —C(O)R20, or R21-substituted phenyl, in which
• R20 is Har2, Het6, or Aryl-1-4C-alkyl, in which
• Har2 is optionally substituted by R201 and/or R202, and is a 5- to 10-membered monocyclic or fused bicyclic unsaturated heteroaryl radical comprising 1 to 4 heteroatoms independently selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R201 is 1-4C-alkyl or 1-4C-alkoxy,
• R202 is 1-4C-alkyl or 1-4C-alkoxy,
• Het6 is optionally substituted by R203 and/or R204, and is a monocyclic 3- to 7-membered saturated heterocyclic ring radical comprising one to three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, in which
• R203 is 1-4C-alkyl,
• R204 is 1-4C-alkyl,
• Aryl is R205- and/or R206-substituted phenyl,
• R205 is 1-4C-alkoxy,
• R206 is 1-4C-alkoxy,
• R21 is aminosulphonyl,
• or R18 and R19 together and with inclusion of the nitrogen atom, to which they are attached, form a heterocyclic ring Het7, in which
• Het7 is optionally substituted by R181, and is a 3- to 7-membered saturated monocyclic heterocyclic ring radical comprising the nitrogen atom, to which R18 and R19 are bonded, and optionally one further heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, in which
• R181 is 1-4C-alkyl,
• or a salt, enantiomer, N-oxide, salt of an N-oxide or enantiomer thereof.