Piperazino-derivatives and their use as PDE4 inhibitor

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) or (b)
• wherein
• R4 is 1–4C-alkoxy or 1–4C-alkoxy which is completely or predominantly substituted by fluorine,
• R5 is 1–8C-alkoxy, 3–7C-cycloalkoxy, 3–7C-cycloalkylmethoxy, or 1–4C-alkoxy which is completely or predominantly substituted by fluorine,
• R6 is 1–4C-alkoxy, 3–5C-cycloalkoxy, 3–5C-cycloalkylmethoxy, or 1–4C-alkoxy which is completely or predominantly substituted by fluorine,
• R7 is 1–4C-alkyl and
• R8 is hydrogen or 1–4C-alkyl,
• or wherein
• R7 and R8 together and with inclusion of the two carbon atoms, to which they are bonded, form a spiro-linked 5-, 6- or 7-membered hydrocarbon ring, optionally interrupted by an oxygen or sulphur atom,
• A is a bond or methylene (—CH2—),
• R9 is —C(O)R10, —(CH2)m—C(O)R11, —(CH2)nR12, Aryl, Hetaryl, phenylprop-1-en-3-yl or 1-methyl-piperidin-4-yl,
• R10 hydrogen, 1–4C-alkyl, —OR13, furanyl, indolyl, phenyl, pyridyl, phenyl substituted by R16 and/or R17 or pyridyl substituted by R18 and/or R19,
• R11 is —N(R14)R15,
• R12 is —N(R14)R15, tetrahydrofuranyl or pyridinyl,
• R13 is 1–4C-alkyl,
• R14 is hydrogen, 1–4C-alkyl, 3–7C-cycloalkyl or 3–7C-cycloalkylmethyl,
• R15 is hydrogen, 1–4C-alkyl, 3–7C-cycloalkyl or 3–7C-cycloalkylmethyl,
• or R14 and R15 together and with inclusion of the nitrogen atom to which they are bonded, form a 4-morpholinyl-, 1-pyrrolidinyl-, 1-piperidinyl- or 1-hexahydroazepinyl-ring,
• Aryl is phenyl, pyridyl, pyrimidinyl, phenyl substituted by R16 and/or R17, pyridyl substituted by R18 and/or R19,
• R16 is halogen, nitro, 1–4C-alkyl, trifluoromethyl or 1–4C-alkoxy,
• R17 is halogen or 1–4C-alkyl,
• R18 is halogen, nitro, 1–4C-alkyl, trifluoromethyl or 1–4C-alkoxy,
• R19 is halogen or 1–4C-alkyl,
• Hetaryl is indol-4-yl, 2-methyl-quinolin-4-yl, 5-chloro-6-oxo-1-phenyl-1,6-dihydro-pyridazin-4-yl, 3-phenyl-1,2,4-thiadiazol-5-yl or 3-o-tolyl-1,2,4-thiadiazol-5-yl,
• n is an integer from 1 to 4,
• m is an integer from 1 to 4,
• s is an integer from 1 to 2,
• X is —C(O)— or —S(O)2—,
• or a hydrate, salt, or hydrate of a salt thereof.