2-(Piperidin-4-yl)-4,5-dihydro-2h-pyridazin-3-one derivatives as pde4 inhibitors

Compounds of formula 1

• in which
• R1 is 1-4C-alkyl and
• R2 is 1-4C-alkyl,
• R3 represents a phenyl derivative of formulae (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,
• R9 is —C(O)R10, —S(O)2—R14, —(CH2)n—C(O)—R18 or —C(O)—(CH2)m—R21,
• R10 is 1-4C-alkyl, —N(R11)R12, phenyl or phenyl substituted by R13,
• R11 is hydrogen, 1-4-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• R12 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• or R11 and R12 together and with inclusion of the nitrogen atom to which they are bonded, form a 1-pyrrolidinyl-, 1-piperidinyl-, 1-piperazinyl, 1-(1-4C-alkyl)-piperazin-4-yl-, 1-hexahydroazepinyl-, 4-morpholinyl, 4-thiomorpholinyl-, thiomorpholin-1-oxide-4-yl- or thiomorpholin-1,1-dioxide-4-yl-ring,
• R13 is hydroxyl, halogen, nitro, cyano, hydroxycarbonyl, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, 1-4C-alkoxy which is completely or predominantly substituted by fluorine, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonylamino or 1-4C-alkylcarbonyloxy,
• R14 is 1-4C-alkyl, —N(R15)R16, phenyl or phenyl substituted by R17,
• R15 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• R16 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• or R15 and R16 together and with inclusion of the nitrogen atom to which they are bonded, form a 1-pyrrolidinyl-, 1-piperidinyl-, 1-piperazinyl, 1-(1-4C-alkyl)-piperazin-4yl-, 1-hexahydroazepinyl-, 4-morpholinyl, 4-thiomorpholinyl-, thiomorpholin-1-oxide-4-yl- or thiomorpholin-1,1-dioxide-4-yl-ring,
• R17 is hydroxyl, halogen, nitro, cyano, carboxyl, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, 1-4C-alkoxy which is completely or predominantly substituted by fluorine, 1-4C-alkoxycarbonyl, amino, mono- or di-1-4C-alkylamino, aminocarbonyl, mono- or di-1-4C-alkylaminocarbonyl, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonylamino or 1-4C-alkylcarbonyloxy,
• R18 is —N(R19)R20,
• R19 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• R20 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• or R19 and R20 together and with inclusion of the nitrogen atom to which they are bonded, form a 1-pyrrolidinyl-, 1-piperidinyl-, 1-piperazinyl, 1-(1-4C-alkyl)-piperazin-4-yl-, 1-hexahydroazepinyl-, 4-morpholinyl, 4-thiomorpholinyl-, thiomorpholin-1-oxide-4-yl- or thiomorpholin-1,1-dioxide-4-yl-ring,
• R21 is —N(R22)R23,
• R22 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• R23 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl,
• or R22 and R23 together and with inclusion of the nitrogen atom to which they are bonded, form a 1-pyrrolidinyl-, 1-piperidinyl-, 1-piperazinyl, 1-(1-4C-alkyl)-piperazin-4-yl-, 1-hexahydroazepinyl-, 4-morpholinyl, 4-thiomorpholinyl-, thiomorpholin-1-oxide-4-yl-, thiomorpholin-1,1-dioxide-4-yl-, pyrrolidin-2,5-dione-1-yl-, morpholin-3,5dione-4-yl-, piperidin-2,6-dione-1-yl, 4,4-dimethyl-piperidin-2,6-dione-1-yl or a 1-methyl-imidazolidine-2,4dione-3-yl-ring or a isoindol-1,3-dione-2-yl-ring-system,
• n is an integer from 1 to 4,
• m is an integer from 1 to 4,
• and the salts of these compounds.