公开(公告)号：US07169786B2

公开(公告)日：2007-01-30

申请号：US10468555

申请日：2002-02-13

申请人： José Ignacio Andrés-Gil ,  Francisco Javier Fernández-Gadea ,  Manuel Jesús Alcázar-Vaca ,  José Maria Cid-Nuñez ,  Joaquin Pastor-Fernandez ,  Antonius Adrianus Hendrikus Petrus Megens ,  Godelieve Irma Christine Maria Heylen ,  Xavier Jean Michel Langlois ,  Margaretha Henrica Maria Bakker ,  Thomas Horst Wolfgang Steckler

发明人： José Ignacio Andrés-Gil ,  Francisco Javier Fernández-Gadea ,  Manuel Jesús Alcázar-Vaca ,  José Maria Cid-Nuñez ,  Joaquin Pastor-Fernandez ,  Antonius Adrianus Hendrikus Petrus Megens ,  Godelieve Irma Christine Maria Heylen ,  Xavier Jean Michel Langlois ,  Margaretha Henrica Maria Bakker ,  Thomas Horst Wolfgang Steckler

IPC分类号： A61K31/496 ,  A61K31/454 ,  C07D498/04 ,  C07D498/14

CPC分类号： A61K31/495 ,  C07D261/20

摘要： The invention concerns substituted isoxazolines derivatives according to Formula (I): wherein X=CH?2#191, N—R7, S or O, R1, R2 and R3 are certain specific substituents, Pir is an optionally substituted piperidyl or piperazyl radical and R3 represents an optionally substituted aromatic homocyclic or heterocyclic ring system including a partially or completely hydrogenated hydrocarbon chain of maximum 6 atoms long with which the ring system is attached to the Pir radical and which may contain one or more heteroatoms selected from the group of O, N and S; a process for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for the treatment of depression and/of anxiety and disorders of body weight. The compounds according to the invention have surprisingly been shown to have a serotonine (5-HT) reuptake inhibitor activity in combination with additional α2-adrenoceptor antagonist activity and show a strong anti-depressant activity without being sedative. Compounds according to the invention arc also suitable for treating patients with anxiety disorders and disorders of body weight. The invention also relates to novel combination of substituted isoxazolines derivatives having anti-depressant activity and/or anxiolytic activity and/or body weight control activity with antidepressants, anxiolytics and/or antipsychotics to improve efficacy and/or onset of action

摘要翻译： 本发明涉及根据式（I）的取代的异恶唑啉衍生物：其中X = CH 2＃191，NR 7，S或O，R 1，R 2， 2和R 3是某些特定取代基，Pir是任选取代的哌啶基或哌嗪基，R 3表示任选取代的芳族碳环或杂环系统，其包括部分或完全氢化的烃链 最大6个原子长，其中环体系连接到Pir基团并且其可以含有一个或多个选自O，N和S的杂原子; 其制备方法，包含它们的药物组合物及其作为药物的用途，特别是用于治疗抑郁症和/或焦虑和体重紊乱。 根据本发明的化合物令人惊奇地显示具有与另外的α2-肾上腺素受体拮抗剂活性组合的5-羟色胺（5-HT）再摄取抑制剂活性，并且在没有镇静作用的情况下表现出强烈的抗抑郁活性。 根据本发明的化合物也适用于治疗患有焦虑症和体重紊乱的患者。 本发明还涉及具有抗抑郁活性和/或抗焦虑活性和/或体重控制活性的抗抑郁药，抗焦虑药和/或抗精神病药的取代的异恶唑啉衍生物的新组合，以改善作用和/或起效作用