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    • 3. 发明申请
    • PYRIDAZINONE DERIVATIVES AND THEIR USE AS PDE4 INHIBITORS
    • 吡咯烷酮衍生物及其作为PDE4抑制剂的用途
    • WO2005075437A1
    • 2005-08-18
    • PCT/EP2005/050412
    • 2005-02-01
    • ALTANA PHARMA AGMENGE, Wiro M. P. B.STERK, Geert Jan
    • MENGE, Wiro M. P. B.STERK, Geert JanHATZELMANN, ArminBARSIG, JohannesMARX, DegenhardKLEY, Hans-PeterCHRISTIAANS, Johannes A. M.
    • C07D237/04
    • C07D237/04C07D401/12C07D403/12
    • Compounds of formula (1) are effective PDE4 inhibitors in which R1 is 1-4C-alkyl and R2 is 1-4C-alkyl, R3 represents a phenyl dervative 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 and R9 is hydroxyl, halogen, nitro, cyano, 1-4C-alkyl, trifluoromethyl, 1-4C-alkoxy, 1-4C-alkoxy which is completely or predominantly substituted by fluorine, hydroxycarbonyl, hydroxycarbonyl-1-4C-alkyl, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonylamino, 1-4C-alkylcarbonyloxy, 1-4C-alkylsulfonyl, benzyloxy, -C(O)R10, -S(O) 2 -R11, -O(CH 2 ) n -C(O)-R12, -(CH 2 ), -C(O)-R26 or -N(R29)R30.
    • 式(1)化合物是有效的PDE4抑制剂,其中R1是1-4C-烷基,R2是1-4C-烷基,R3代表式(a)或(b)的苯基衍生物,其中R4是1-4C-烷氧基 或完全或主要被氟取代的1-4C-烷氧基,R5是1-8个碳原子的烷氧基,3-7C-环烷氧基,3-7C-环烷基甲氧基或1-4C-烷氧基,其完全或主要被氟取代, R6是1-4C-烷氧基,3-5C-环烷氧基,3-5C-环烷基甲氧基或完全或主要被氟取代的1-4C-烷氧基,R7是1-4C-烷基,R8是氢或1-4C - 烷基,或其中R 7和R 8一起并且与它们所键合的两个碳原子一起形成螺键连接的5-,6-或7-元烃环,任选被氧或硫原子中断, R9是羟基,卤素,硝基,氰基,1-4C-烷基,三氟甲基,1-4C-烷氧基,完全或主要被氟取代的1-4C-烷氧基,羟基羰基,羟基羰基-1,4- C-alk 1-4C-烷氧基羰基,1-4C-烷基羰基氨基,1-4C-烷基羰基氧基,1-4C-烷基磺酰基,苄氧基,-C(O)R10,-S(O)2-R11, -O(CH 2)n C(O)-R 12, - (CH 2),-C(O)-R 26或-N(R 29)R 30。