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    Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation
    2.
    发明公开
    Nitrogen-containing compounds and pharmaceutical compositions thereof for the treatment of atrial fibrillation 审中-公开
    化合物及其药物组合物为心房纤维性颤动的治疗含氮

    公开(公告)号：EP2746272A1

    公开(公告)日：2014-06-25

    申请号：EP14153418.0

    申请日：2010-08-20

    申请人： OTSUKA PHARMACEUTICAL CO., LTD.

    发明人： Oshima, Kunio ,  Matsumura, Shuuji ,  Yamabe, Hokuto ,  Isono, Naohiro ,  Takemura, Noriaki ,  Taira, Shinichi ,  Oshiyama, Takashi ,  Menjo, Yasuhiro ,  Nagase, Tsuyoshi ,  Ueda, Masataka ,  Koga, Yasuo ,  Nakayama, Sunao ,  Tsujimae, Kenji ,  Onogawa, Toshiyuki ,  Tai, Kuninori ,  Itotani, Motohiro

    IPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D471/04 ,  A61K31/551 ,  A61P9/06

    CPC分类号： C07D491/048 ,  C07D213/38 ,  C07D215/227 ,  C07D243/12 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04

    摘要： The present invention provides a novel amino compound that blocks the I Kur current or the Kv1.5 channel potently and more selectively than other K + channels. The present invention relates to an amino compound represented by General Formula (1):

    or a salt thereof,
    wherein R 1 and R 2 are each independently hydrogen or organic group;
    X A and X B are each independently a bond, alkylene, alkenylene, -CO-, -SO 2 -, or -CONH-, wherein each of the alkylene and alkenylene chains can optionally contain one or more substituents selected from the group consisting of -S-, -C(=S)-, -SO 2 -, -CO-, -O-, -NH-, -CONH- and -SO 2 NH-, and the hydrogen atom (H) bonded to the nitrogen atom (N) in X A and X B is optionnally substituted with a subsituent selected from the group consisting of lower alkyl, phenyl lower alkyl and phenyl;
    A 1 is lower alkylene optionally substituted with one or more substituents selected from the group consisting of hydroxyl and oxo;
    R 3 is (i) a heterocyclic group which is optionally substituted with one or more substituents, or
    (ii) an aryl group substituted with one or more substituents select from the group consisting of oxo, lower alkyl, carboxyl, halo-lower alkyl, lower alkanoyl lower alkyl, phenyl lower alkyl, cyclo lower alkyl, lower alkoxy, halo lower alkoxy, phenyl lower alkoxy, phenoxy, cyano, hydroxyl, halogen, nitro, lower alkylthio, lower alkanoyl,
    lower alkoxy carbonyl, lower alkenyl, phenyl, triazolyl, isoxazolyl, imidazolyl, pyrrolyl, benzo[d]oxazolyl,
    benzo[d]thiazolyl and the group represented by General Formula (2):

    wherein Y is a bond, lower alkylene, or -CO-; R 4 and R 5 are each independently hydrogen, lower alkyl, cyclo lower alkyl, phenyl, or lower alkanoyl; or R 4 and R 5 may be linked to form a ring together with the neighboring nitrogen, and the ring may optionally have one or more substituents.

    摘要翻译： 本发明提供了一种新颖的氨基化合物没有块的I库尔电流或对Kv1.5通道有力和比其他K +通道更有选择性。 本发明涉及在由通式（1）表示的氨基化合物：或其盐，worin R 1和R 2各自独立地为氢或有机基团; XA和XB分别unabhängig一个键，亚烷基，亚烯基，-CO - ， - SO 2 - ，或-CONH-，worin每个亚烷基和亚烯基链可任选地包含选自-S中选择的一个或多个取代基 - ， - C（= S） - ， - SO 2 - ， - CO - ， - O - ， - NH-，-CONH - 和-SO 2 NH-，和键合到氮原子上的氢原子（H）（ N）XA和XB是optionnally被取代基substituiertem已选自低级烷基，苯基低级烷基和苯基中选出; A 1是低级亚烷基任选被选自羟基和氧代的选择的一个或多个取代基substituiertem; R 3为（ⅰ），其任选被一个或多个取代substituiertem，或（ii）具有一个或多个取代基的芳基substituiertem杂环基选自氧代，低级烷基，羧基，卤代低级烷基选择， 低级烷酰基低级烷基，苯基低级烷基，环低级烷基，低级烷氧基，卤代低级烷氧基，苯基低级烷氧基，苯氧基，氰基，羟基，卤素，硝基，低级烷硫基，低级烷酰基，低级烷氧基羰基，低级烯基，苯基，三唑基 ，异恶唑基，咪唑基，吡咯基，苯并[d]恶唑基，苯并[d]噻唑基和由通式表示的基团（2）表示：其中Y是键，低级亚烷基，或-CO-; R 4和R 5各自独立地为氢，低级烷基，环低级烷基，苯基，或低级链烷酰基; 或R 4和R 5可连接到与相邻氮一起形成环，并且所述环可以具有一个或多个取代基OPTIONALLY。