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    • 8. 发明申请
    • AMINO NICOTINIC AND ISONICOTINIC ACID DERIVATIVES AS DHODH INHIBITORS
    • 氨基酸和异柠檬酸衍生物作为DHODH抑制剂
    • WO2008077639A1
    • 2008-07-03
    • PCT/EP2007/011401
    • 2007-12-21
    • LABORATORIOS ALMIRALL, S.A.CASTRO PALOMINO LARIA, Julio CesarERRA SOLA, MontserratLOZOYA TORIBIO, Maria EstrellaNAVARRO ROMERO, Eloisa
    • CASTRO PALOMINO LARIA, Julio CesarERRA SOLA, MontserratLOZOYA TORIBIO, Maria EstrellaNAVARRO ROMERO, Eloisa
    • C07D213/79C07D213/80A61K31/465A61P35/00
    • C07D213/79C07D213/80
    • A compound of formula (I) wherein : - one of the groups G 1 represents a nitrogen atom or a group CR c and the other represents a group CR c ; - G 2 represents a nitrogen atom or a group CR d ; - R 1 represents a group selected from hydrogen atoms, halogen atoms, C 1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C 3-8 cycloalkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - R 2 represents a group selected from hydrogen atoms, halogen atoms, hydroxyl groups, C 1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, C 1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C 3-8 cycloalkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - R a , R b and R c independently represent groups selected from hydrogen atoms, halogen atoms, C 1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C 1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - R d represents a group selected from hydrogen atoms, halogen atoms, hydroxyl groups, C 1-4 alkyl groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C 1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, and C 3-8 cycloalkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; - one of the groups G 3 and G 4 is a nitrogen atom and the other is a CH group; - M is a hydrogen atom or an pharmaceutically acceptable cation with the proviso that, when at least one of the groups R a and R b represent a hydrogen atom and G 2 is a group CR d , then Rd represents a groups selected from C 1-4 alkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups, C 3-8 cycloalkoxy groups which may be optionally substituted by 1, 2 or 3 substituents selected from halogen atoms and hydroxy groups; and the pharmaceutically acceptable salts and N-oxides thereof.
    • 式(I)的化合物,其中:基团G 1中的一个表示氮原子或基团CR c,另一个表示基团CR ; G 2表示氮原子或基团CR 11; R 1表示选自氢原子,卤素原子,C 1-4烷基的基团,其可任选被1,2或3个选自卤素原子的取代基取代 和羟基,以及可以被1,2或3个选自卤素原子和羟基的取代基任选取代的C 3-8环烷基; R 2表示选自氢原子,卤素原子,羟基,C 1-4烷基的基团,其可任选被1,2或3个选自以下的取代基取代 可以任选被1,2或3个选自卤素原子和羟基的取代基取代的C 1-4烷氧基和C 3-8烷基, 可以任选地被1,2或3个选自卤素原子和羟基的取代基取代的环烷基; R a,R b和R c独立地表示选自氢原子,卤素原子,C 1-4烷基的基团, 可以任选被1,2或3个选自卤素原子和羟基的取代基取代的亚烷基,和可以被1,2或3个取代基任意取代的C 1-4烷氧基 选自卤素原子和羟基; -R d表示选自氢原子,卤素原子,羟基,C 1-4烷基的基团,其可任选被1,2或3个选自下列的取代基取代: 可以任选地被1,2或3个选自卤素原子和羟基的取代基取代的C 1-4烷氧基和C 3-8烷氧基, 其可任选被1,2或3个选自卤素原子和羟基的取代基取代; G 3和G 4之一是氮原子,另一个是CH基团; - M是氢原子或药学上可接受的阳离子,条件是当基团R a和R b中的至少一个表示氢原子时,G 2 是基团CR d,则Rd表示选自C 1-4烷氧基的基团,其可任选被1,2或3个取代基 选自卤素原子和羟基的取代基,可以任选被1,2或3个选自卤素原子和羟基的取代基取代的C 3-8环烷氧基; 及其药学上可接受的盐和N-氧化物。