公开(公告)号：US07501418B2

公开(公告)日：2009-03-10

申请号：US10524123

申请日：2003-08-13

申请人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  José Manuel Bartolomé -Nebreda ,  Francisco Javier Fernández-Gadea ,  Margaretha Henrica Maria Bakker ,  Antonius Adrianus Hendrikus Megens

发明人： José Ignacio Andrés-Gil ,  Manuel Jesús Alcázar-Vaca ,  José Manuel Bartolomé -Nebreda ,  Francisco Javier Fernández-Gadea ,  Margaretha Henrica Maria Bakker ,  Antonius Adrianus Hendrikus Megens

IPC分类号： A01N43/54 ,  A01N43/40 ,  A61K31/445 ,  A61K31/497 ,  C07D211/32 ,  C07D211/68 ,  C07D211/80 ,  C07D213/02 ,  C07D261/20 ,  C07D239/00 ,  C07D237/26 ,  C07D237/36 ,  C07D413/00 ,  C07D417/00 ,  C07D419/00 ,  C07D471/00 ,  C07D487/00 ,  C07D491/00 ,  C07D495/00 ,  C07D497/00

CPC分类号： C07D498/14

摘要： The invention concerns fused heterocyclic isoxazoline derivatives of Formula (I), the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof and the N-oxide form thereof, more in particular, tetrahydropyranoisoxazole, hexahydroisoxazolopyridine, tetrahydrothiopyrano isoxazole and hexahydrobenzoisoxazole derivatives fused to a heterocyclic ring system via the 6-membered ring of the bicyclic moiety as well as processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine, in particular for treating depression, anxiety, movement disorders, psychosis, Parkinson's disease and body weight disorders including anorexia nervosa and bulimia, wherein the variables are defined as in Claim 1. The compounds have surprisingly been shown to have selective serotonine (5-HT) reuptake inhibitor activity as well as α2-adrenoceptor antagonist activity, compounds according to the invention are also suitable for treatment and/or prophylaxis in diseases where either one of the activities alone or the combination of said activities may be of therapeutic use.

摘要翻译： 本发明涉及式（I）的稠合杂环异恶唑啉衍生物，其药学上可接受的酸或碱加成盐，其立体化学异构体形式及其N-氧化物形式，更特别是四氢吡喃异恶唑，六氢异恶唑并吡啶，四氢噻喃异恶唑和六氢苯并异恶唑衍生物 通过双环部分的6元环以及其制备方法，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，焦虑症，运动障碍，精神病，帕金森病和 包括神经性厌食症和贪食症的体重紊乱，其中变量如权利要求1中所定义。化合物惊奇地显示具有选择性5-羟色胺（5-HT）再摄取抑制剂活性以及α2-肾上腺素受体拮抗剂活性，根据 发明也适用于f 或治疗和/或预防疾病，其中单独的一种活性或所述活性的组合可能具有治疗用途。