申请人:BEECHAM GROUP PLC
公开号:EP0095262A1
公开(公告)日:1983-11-30
Compounds of formula (I), or a pharmaceutically acceptable salt thereof, or a solvent adduct or N-oxide thereof, or a solvate of any of the foregoing:
wherein: n is 0 or 1;
one of X and Y is CO and the other is NR9, R9 being hydrogen or as defined with R,;
R, is C1-6 alkoxy, C1-6 alkylthio or, together with R9 when Y is NR9, C1-2 alkylene, and one of R2, R3 and R4 is hydrogen and the other two together are C1-2 alkylenedioxy; or the other two are the same or different and are selected from hydrogen, halogen, trifluoromethyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, carboxylic C1-7 acyl, carboxylic C1-7 acylamino, C1-6 alkylsulphonyl, C1-6 alkylsulphinyl, hydroxy, nitro. C1-6 alkylsulphonylamino or N-C1-6, alkylsulphonyl-N- C1-6 alkaylamino, or amino, aminocarbonyl, aminosulphonyl, aminosulphonylamino or N-(aminosufphonyl)-N-C1-8 alkylamino, optionally N-substituted by one or two C1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl C1-4alkyl, phenyl or phen C1-4alkyl groups, any of which phenyl moieties may be substituted by one or more halogen, trifluoromethyl, C1-6 alkoxy or nitro groups, or optionally N-dissubstituted by C4-5 polymethylene, or R, and R2 together are C1-2 alkylenedioxy, C1-2 oxyalkylenethio, C2-3 alkyleneoxy or N-(C1-2 oxyalkylene)-N-C1-6 alkylamino; and R3 and R4 together are C1-2alkylenedioxy or R3 or R4 are same or different and are selected from the previously defined class of substituents;
R5 is C1-7 alkyl, -(CH2)sR10, s being 0 to 2 and R,o being C3-8 cycloalkyl, -(CH2)2R11, t being 1 or 2 and R11 being thienyl or phenyl optionally substituted by one or two substituents selected from C1-4 alkoxy, trifluoromethyl. halogen, nitro, carboxy, esterfied carboxy and C1-4 alkyl optionally substituted by hydroxy, C1-4 alkoxy, carboxy, esterified carboxy or in vivo hydrolysable acyloxy; and
one of R6 and R7 when n=0 is C1-4 alkoxy, C1-4 alkoxycarbonyl, hydroxy or C1-4alkyl optionally substituted by hydroxy, C1-4 alkoxy or C1-4acyloxy, and the other is hydrogen or C1-4 alkyl or one of R8, R7 and Re when n=1 is C1-4alkyl and the other two are the same on different and are hydrogen or C1-4alkyl, process for their preparation and compositions containing them.
式(I)化合物,或其药学上可接受的盐,或其溶剂加成物或 N-氧化物,或上述任一物质的溶液:
其中: n 为 0 或 1;
X 和 Y 中的一个是 CO,另一个是 NR9,R9 是氢或如 R, 所定义;
R,是 C1-6 烷氧基、C1-6烷硫基或当 Y 是 NR9 时与 R9 一起是 C1-2 亚烷基,且 R2、R3 和 R4 中的一个是氢,另外两个一起是 C1-2 亚烷基二氧基;或另外两个相同或不同且选自氢、卤素、三氟甲基、C1-6 烷基、C1-6 烷氧基、C1-6 烷硫基、羧基 C1-7 丙烯酸基、羧基 C1-7 丙烯酸氨基、C1-6 烷基磺酰基、C1-6 烷基亚磺酰基、羟基、硝基。C1-6烷基磺酰基氨基或N-C1-6、烷基磺酰基-N-C1-6烷基氨基,或氨基、氨基羰基、氨基磺酰基、氨基磺酰基氨基或N-(氨基磺酰基)-N-C1-8烷基氨基,可选择被一个或两个C1-6烷基、C3-8环烷基、C3-8环烷基C1-4烷基、苯基或苯基C1-4烷基基团N-取代、其中任一苯基可被一个或多个卤素、三氟甲基、C1-6 烷氧基或硝基取代,或任选被 C4-5 聚亚甲基 N-取代,或 R 和 R2 合在一起为 C1-2 烯二氧基、C1-2 氧代烯硫基、C2-3 亚烷氧基或 N-(C1-2 氧代亚烷基)-N-C1-6 烷基氨基;R3 和 R4 同为 C1-2 烯二氧基,或 R3 或 R4 相同或不同,且选自前面定义的取代基类别;
R5 是 C1-7 烷基,-(CH2)sR10,s 是 0 至 2,R,o 是 C3-8 环烷基,-(CH2)2R11,t 是 1 或 2,R11 是噻吩基或苯基,可任选被一个或两个取代基取代,这些取代基选自 C1-4 烷氧基、三氟甲基、卤素、硝基、羧基、酯化羧基和可任选被羟基、C1-4 烷氧基、羧基、酯化羧基或体内可水解酰氧基取代的 C1-4 烷基;和
当 n=0 时,R6 和 R7 中的一个是 C1-4 烷氧基、C1-4 烷氧羰基、羟基或任选被羟基、C1-4 烷氧基或 C1-4 乙酰氧基取代的 C1-4 烷基,另一个是氢或 C1-4 烷基;或当 n=1 时,R8、R7 和 Re 中的一个是 C1-4 烷基,另两个相同或不同,并且是氢或 C1-4 烷基。