[EN] PYRIDAZINONE DERIVATIVES AND THEIR USE AS PDE4 INHIBITORS<br/>[FR] DERIVES DE PYRIDAZINONE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PDE4
申请人:ALTANA PHARMA AG
公开号:WO2005075437A1
公开(公告)日:2005-08-18
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(CH2)n-C(O)-R12, -(CH2), -C(O)-R26 or -N(R29)R30.
式(1)的化合物是有效的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1-4C-烷氧基,完全或主要被氟取代,R5是1-8C-烷氧基,3-7C-环烷氧基,3-7C-环烷基甲氧基或1-4C-烷氧基,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1-4C-烷氧基,完全或主要被氟取代,R7是1-4C-烷基,R8是氢或1-4C-烷基,或者R7和R8连同它们所连接的两个碳原子形成一个螺环状的5-、6-或7-成员烃环,可选择地由氧或硫原子中断,R9是羟基,卤素,硝基,氰基,1-4C-烷基,三氟甲基,1-4C-烷氧基,1-4C-烷氧基,完全或主要被氟取代,羟基羧酸,羟基羧酸-1-4C-烷基,1-4C-烷氧羰基,1-4C-烷基羰基,1-4C-烷基羰基氨基,1-4C-烷氧基羰基氧基,1-4C-烷基磺酰基,苄氧基,-C(O)R10,-S(O)2-R11,-O(CH2)n-C(O)-R12,-(CH2),-C(O)-R26或-N(R29)R30。