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    • 5. 发明授权
    • Azabicyclo (3.1.0.) hexane derivatives useful as modulators of dopamine D3 receptors
    • 可用作多巴胺D3受体调节剂的氮杂双环(3.1.0。)己烷衍生物
    • US07855298B2
    • 2010-12-21
    • US10598200
    • 2005-02-21
    • Luca AristaGiorgio BonanomiAnna Maria CapelliFederica DamianiRomano Di FabioGabriella GentileDieter HamprechtFabrizio MicheliLuca TarsiGiovanna TedescoSilvia Terreni
    • Luca AristaGiorgio BonanomiAnna Maria CapelliFederica DamianiRomano Di FabioGabriella GentileDieter HamprechtFabrizio MicheliLuca TarsiGiovanna TedescoSilvia Terreni
    • C07D215/38
    • C07D495/04C07D401/14C07D403/04C07D403/12C07D403/14C07D405/14C07D413/14C07D417/14C07D471/08
    • The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: 1. wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl; or corresponds to a group R5; R2 is hydrogen or C1-4alkyl; R3 is C1-4alkyl; R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; R5 is a moiety selected from the group consisting of: isoxazolyl, —CH2—N -pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2 -pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; and when R1 is chlorine and p is 1, such R1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R1 corresponds to R5, p is 1; or a salt thereof which are useful as modulators of dopamine D3 receptors, e.g. to treat drug dependency or as antipsychotic agents.
    • 本发明涉及新的式(I)化合物或其药学上可接受的盐:1.其中G选自:苯基,吡啶基,苯并噻唑基,吲唑基; p为0〜5的整数。 R 1独立地选自:卤素,羟基,氰基,C 1-4烷基,卤代C 1-4烷基,C 1-4烷氧基,卤代C 1-4烷氧基,C 1-4烷酰基; 或对应于R5组; R2是氢或C1-4烷基; R3是C1-4烷基; R 4是氢或苯基,杂环基,5或6元杂芳族基团或8至11元双环基团,其中任何基团任选被1,2,3或4个取代基取代 选自:卤素,氰基,C 1-4烷基,卤代C 1-4烷基,C 1-4烷氧基,C 1-4烷酰基; R5是选自以下的部分:异恶唑基,-CH 2 -N-吡咯基,1,1-二氧化-2-异噻唑烷基,噻吩基,噻唑基,吡啶基,2-吡咯烷基,任选地被一个或多个 选自以下的两个取代基:卤素,氰基,C 1-4烷基,卤代C 1-4烷基,C 1-4烷氧基,C 1-4烷酰基; 当R1为氯且p为1时,该R1不存在于与分子的其余部分的连接键的邻位; 当R1对应于R5时,p为1; 或其盐,其可用作多巴胺D3受体的调节剂,例如, 治疗药物依赖或作为抗精神病药。
    • 6. 发明申请
    • Azabicyclo (3.1.0) Hexane Derivatives Useful As Modulators Of Dopamine D3 Receptors
    • 可用作多巴胺D3受体调节剂的氮杂双环(3.1.0)己烷衍生物
    • US20100160336A1
    • 2010-06-24
    • US12639282
    • 2009-12-16
    • Luca AristaGiorgio BonanomiAnna Maria CapelliFederica DamianiRomano Di FabioGabriella GentileDieter HamprechtFabrizio MicheliLuca TarsiGiovanna TedescoSilvia Terreni
    • Luca AristaGiorgio BonanomiAnna Maria CapelliFederica DamianiRomano Di FabioGabriella GentileDieter HamprechtFabrizio MicheliLuca TarsiGiovanna TedescoSilvia Terreni
    • A61K31/50C07D403/14
    • C07D495/04C07D401/14C07D403/04C07D403/12C07D403/14C07D405/14C07D413/14C07D417/14C07D471/08
    • The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl; or corresponds to a group R5; R2 is hydrogen or C1-4alkyl; R3 is C1-4alkyl; R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; R5 is a moiety selected from the group consisting of: isoxazolyl, —CH2—N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; and when R1 is chlorine and p is 1, such R1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R1 corresponds to R5, p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, e.g. to treat drug dependency or as antipsychotic agents.
    • 本发明涉及新的式(I)化合物或其药学上可接受的盐:其中G选自:苯基,吡啶基,苯并噻唑基,吲唑基; p为0〜5的整数。 R 1独立地选自:卤素,羟基,氰基,C 1-4烷基,卤代C 1-4烷基,C 1-4烷氧基,卤代C 1-4烷氧基,C 1-4烷酰基; 或对应于R5组; R2是氢或C1-4烷基; R3是C1-4烷基; R 4是氢或苯基,杂环基,5或6元杂芳族基团或8至11元双环基团,其中任何基团任选被1,2,3或4个取代基取代 选自:卤素,氰基,C 1-4烷基,卤代C 1-4烷基,C 1-4烷氧基,C 1-4烷酰基; R5是选自以下的部分:异恶唑基,-CH 2 -N-吡咯基,1,1-二氧化-2-异噻唑烷基,噻吩基,噻唑基,吡啶基,2-吡咯烷酮基,任选地被一个或多个 选自以下的两个取代基:卤素,氰基,C 1-4烷基,卤代C 1-4烷基,C 1-4烷氧基,C 1-4烷酰基; 当R1为氯且p为1时,该R1不存在于与分子的其余部分的连接键的邻位; 当R1对应于R5时,p为1; 它们的制备方法,这些方法中使用的中间体,含有它们的药物组合物及其在治疗中的用途,作为多巴胺D3受体的调节剂。 治疗药物依赖或作为抗精神病药。
    • 9. 发明申请
    • AZABICYCLIC COMPOUNDS AS INHIBITORS OF MONOAMINES REUPTAKE
    • US20100035914A1
    • 2010-02-11
    • US12440852
    • 2007-09-07
    • Barbara BertaniRomano Di FabioFabrizio MicheliGiovanna TedescoSilvia Terreni
    • Barbara BertaniRomano Di FabioFabrizio MicheliGiovanna TedescoSilvia Terreni
    • A61K31/435C07D221/02A61P25/24
    • C07D221/04
    • The present invention relates to novel compounds of formula (I)′, and pharmaceutically acceptable salts, prodrugs or solvates thereof: wherein R1 is hydrogen or C1-4 alkyl; R2 is a group A, K or W wherein A is K is an α or β naphthyl group, optionally substituted by 1 or 2 groups R18, each of them being the same or different; and W is and wherein G is a 5,6-membered monocyclic heteroaryl group, or a 8- to 11-membered heteroaryl bicyclic group; wherein G may be substituted by (R15)p, which can be the same or different; p is an integer from 0 to 5; R3 is selected from the group consisting of: hydrogen, fluorine, and C1-4 alkyl; or corresponds to a group X or X1; R4 is selected from the group consisting of: hydrogen, fluorine, and C1-4 alkyl; or corresponds to a group X or X1; R5 is hydrogen or C1-4 alkyl; R7 is hydrogen or C1-4 alkyl; or is a group X, X1, X2 or X3; wherein X is X1 is X2 is and X3 is R6 is hydrogen or C1-4 alkyl; or is a group X or X1; R9 is C1-4alkyl; R10 is selected from the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R8; R8 is a 5-6 membered heterocycle group, which may be substituted by one or two substituents selected from the group consisting of: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy and C1-4alkanoyl; R11 is selected from the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R8; R12 is selected from the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R8; R13 is selected from the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R8; R14 is selected from the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R8; R15 is selected from the group consisting of: halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R8; R16 is hydrogen, C1-4alkyl, C3-6cycloalkyl or C3-6cycloalkylC1-3alkyl; R17 is hydrogen or C1-4alkyl; R18 is selected from the group consisting of: halogen, cyano, and C1-4alkyl; R19 is haloC1-2alkyl; and n is 1 or 2; with the proviso that: if R2 is A, R3, R4, R5, R6, R7, R10, R11, R13, and R14 are hydrogen, and R12 is fluorine, R1 is C1-4 alkyl; if R2 is A, R3, R4, R5, R6, R7, R10, R11, R13, and R14 are hydrogen, and R1 is methyl, R12 is halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl or SF5; or corresponds to a group R8; and processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as serotonin (5-HT), dopamine (DA) and norepinephrine (NE), re-uptake inhibitors.