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    SPIROCOMPOUNDS USEFUL AS MODULATORS FOR DOPAMINE D3 RECEPTORS
    6.
    发明申请
    SPIROCOMPOUNDS USEFUL AS MODULATORS FOR DOPAMINE D3 RECEPTORS 失效

    公开(公告)号：US20100063078A1

    公开(公告)日：2010-03-11

    申请号：US12297253

    申请日：2007-04-24

    申请人： Barbara Bertani ,  Romano Di Fabio ,  Fabrizio Micheli ,  Alessandra Pasquarello ,  Luca Tarsi ,  Silvia Terreni

    发明人： Barbara Bertani ,  Romano Di Fabio ,  Fabrizio Micheli ,  Alessandra Pasquarello ,  Luca Tarsi ,  Silvia Terreni

    IPC分类号： A61K31/506 ,  C07D413/14 ,  C07D417/14 ,  C07D409/14 ,  A61K31/427 ,  A61K31/422 ,  A61P25/00

    CPC分类号： C07D403/06 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D491/10

    摘要： The present invention relates to novel compounds of formula (I) or salts thereof: wherein A is a substituent selected in the group consisting of P, P1, P2 and P3 wherein P is P1 is P2 is P3 is p is an integer ranging from 0 to 4; R4 is selected in the group consisting of halogen, hydroxy, cyano, C1-4 alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl, SF5 and a 5- or 6-membered monocyclic heteroaryl group; and when p is an integer ranging from 2 to 4, each R4 may be the same or different; R2 is hydrogen or C1-4alkyl; q is 3, 4 or 5; n is 0, 1 or 2; X is —CR1R3— or —O—; R1 is selected in the group consisting of hydrogen, C1-4 alkyl and fluorine; R3 is selected in the group consisting of hydrogen, C1-4alkyl and fluorine; R5 is selected in the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″; or R5 is a phenyl group, a 5-14 membered heterocyclic group; and any of such phenyl or heterocyclic group is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, haloC1-4alkyl, C1-4 alkoxy, C1-4alkanoyl and SF5; R6 is selected in the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″; or R6 is a phenyl group, a 5-14 membered heterocyclic group and any of such phenyl or heterocyclic group is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, haloC1-4alkyl, C1-4 alkoxy, C1-4alkanoyl and SF5; R7 is selected in the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, C1-4alkoxy, haloC1-4 alkoxy, C1-4 alkanoyl and NR′R″; or R7 is a phenyl group, a 5-14 membered heterocyclic group; and any of such phenyl or heterocyclic group is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, haloC1-4alkyl, C1-4 alkoxy, C1-4alkanoyl and SF5; R8 is selected in the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, C1-4alkoxy, haloC1-4 alkoxy, C1-4 alkanoyl and NR′R″; or R8 is a phenyl group, a 5-14 membered heterocyclic group; and any of such phenyl or heterocyclic group is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, haloC1-4alkyl, C1-4 alkoxy, C1-4alkanoyl and SF5; R9 is selected in the group consisting of hydrogen, a phenyl group, a heterocyclyl group, a 5- or 6-membered monocyclic heteroaryl group, and a 8- to 11-membered heteroaryl bicyclic, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C1-4 alkyl, haloC1-4alkyl, C1-4alkoxy and C1-4alkanoyl; R10 is C1-4alkyl; R11 is hydrogen or C1-4alkyl; R′ is H, C1-4 alkyl or C1-4 alkanoyl; R″ is defined as R′; R′ and R″ taken together with the interconnecting nitrogen atom may form a 5-, 6-membered saturated or unsaturated heterocyclic ring; wherein R5, R6, R7 and R8 are not simultaneously other than hydrogen; wherein only one R2 group ma be different from hydrogen and wherein when n is 0, X is a group —CR1R3—; 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, as antipsychotic agents, to treat obsessive compulsive spectrum disorders, premature ejaculation or to enhance cognition.

    Azabicyclo (3.1.0.) hexane derivatives useful as modulators of dopamine D3 receptors
    10.
    发明授权
    Azabicyclo (3.1.0.) hexane derivatives useful as modulators of dopamine D3 receptors 有权
    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

    公开(公告)号：US07855298B2

    公开(公告)日：2010-12-21

    申请号：US10598200

    申请日：2005-02-21

    申请人： Luca Arista ,  Giorgio Bonanomi ,  Anna Maria Capelli ,  Federica Damiani ,  Romano Di Fabio ,  Gabriella Gentile ,  Dieter Hamprecht ,  Fabrizio Micheli ,  Luca Tarsi ,  Giovanna Tedesco ,  Silvia Terreni

    发明人： Luca Arista ,  Giorgio Bonanomi ,  Anna Maria Capelli ,  Federica Damiani ,  Romano Di Fabio ,  Gabriella Gentile ,  Dieter Hamprecht ,  Fabrizio Micheli ,  Luca Tarsi ,  Giovanna Tedesco ,  Silvia Terreni

    IPC分类号： C07D215/38

    CPC分类号： C07D495/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/08

    摘要： 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.

    摘要翻译： 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。