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1. 发明授权

US06511976B1 Halogen substituted tetracyclic tetrahydrofuran derivatives 失效
标题翻译：卤素取代四环四氢呋喃衍生物
公开(公告)号：US06511976B1
公开(公告)日：2003-01-28
申请号：US09529252
申请日：2000-04-06
申请人： José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Pilar Gil-Lopetegui , Adolfo Díaz-Martinez
发明人： José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Pilar Gil-Lopetegui , Adolfo Díaz-Martinez
IPC分类号： A61K31497
CPC分类号： C07D405/06 , C07D307/93 , C07D493/04
摘要： This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R1 and R2 each independently are hydrogen, C1-6alkyl, C1-6alkylcarbonyl, halomethylcarbonyl or C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R3 and R4 are both halogen; or R3 is halogen and R4 is hydrogen; or R3 is hydrogen and R4 is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.
摘要翻译：本发明涉及式（I）化合物，N-氧化物形式，其药学上可接受的加成盐和立体化学异构形式，其中n为0,1,2,3,4,5或6; X是CH 2或O; R 1和R 2各自独立地为氢，C 1-6烷基，C 1-6烷基羰基，卤代甲基羰基或被羟基，C 1-6烷氧基，羧基，C 1-6烷基羰基氧基，C 1-6烷氧基羰基或芳基取代的C 1-6烷基。或者R 1和R 2与它们所连接的氮原子一起可以形成吗啉基环或任选取代的杂环; R3和R4都是卤素; 或R3是卤素，R4是氢; 或R3是氢，R4是卤素; 并且芳基是苯基或被1,2或3个选自卤素，羟基，C 1-6烷基和卤代甲基的取代基取代的苯基。式（I）化合物可用作治疗剂。

2. 发明授权

US06699858B2 Halogen substituted tetracyclic tetrahydrofuran derivatives 失效
标题翻译：卤素取代四环四氢呋喃衍生物
公开(公告)号：US06699858B2
公开(公告)日：2004-03-02
申请号：US10292270
申请日：2002-11-12
申请人： José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Pilar Gil-Lopetegui
发明人： José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Pilar Gil-Lopetegui
IPC分类号： A61K31501
CPC分类号： C07D405/06 , C07D307/93 , C07D493/04
摘要： This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R1 and R2 each independently are hydrogen, C1-6alkyl, C1-6alkylcarbonyl, halomethylcarbonyl or C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R3 and R4 are both halogen; or R3 is halogen and R4 is hydrogen; or R3 is hydrogen and R4 is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.
摘要翻译：本发明涉及式（I）化合物，N-氧化物形式，其药学上可接受的加成盐和立体化学异构形式，其中n为0,1,2,3,4,5或6; X是CH 2或O; R 1和R 2各自独立地为氢，C 1-6烷基，C 1-6烷基羰基，卤代甲基羰基或被羟基，C 1-6烷氧基，羧基，C 1-6烷基羰基氧基，C 1-6烷氧基羰基或芳基取代的C 1-6烷基。或R 1和R 2与它们所连接的氮原子一起可以形成吗啉基环或任选取代的杂环; R 3和R 4都是卤素; 或R 3是卤素，R 4是氢; 或R 3为氢，R 4为卤素; 并且芳基是苯基或被1,2或3个选自卤素，羟基，C 1-6烷基和卤代甲基的取代基取代的苯基。式（I）化合物可用作治疗剂。

3. 发明授权

US07423048B2 Compounds for treating fundic disaccomodation 有权
公开(公告)号：US07423048B2
公开(公告)日：2008-09-09
申请号：US11355402
申请日：2006-02-16
申请人： Kristol Van Emelen , Marcel Frans Leopold De Bruyn , Manuel Jesús Alcázar-Vaca , José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Maria Encamacion Matesanz-Ballesteros , José Manuel Bartolomé-Nebreda
发明人： Kristol Van Emelen , Marcel Frans Leopold De Bruyn , Manuel Jesús Alcázar-Vaca , José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Maria Encamacion Matesanz-Ballesteros , José Manuel Bartolomé-Nebreda
IPC分类号： C07D413/06 , C07D413/14 , C07D417/06 , C07D417/14 , C07D403/06 , C07D403/14 , A61K31/436 , A61P1/14
CPC分类号： C07D411/04 , C07D491/04
摘要： The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, wherein -a1═a2-a3═a4- is a bivalent radical wherein one or two of a1 to a4 are nitrogen and the remaining a1 to a4 are —CH═; -Z1-Z2- is a bivalent radical; -A- is a bivalent radical of formula —N(R6)-Alk2- or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R1, R2 and R3 are each independently selected from hydrogen, C1-6alkyl, hydroxy, halo and the like; Alk1 and Alk2 are optionally substituted C1-6alkanediyl; R5 is a radical of formula wherein n is 1 or 2; p1 is 0, and p2 is 1 or 2; or p1 is 1 or 2, and p2 is 0; X is oxygen, sulfur or ═NR9; Y2 is oxygen or sulfur; R7 is hydrogen, C1-6alkyl, C3-6cycloalkyl, phenyl or phenylmethyl; R8 is C1-6alkyl, C3-6cycloalkyl phenyl or phenylmethyl; R9 is cyano, C1-6alkyl, C3-6cycloalkyl, C1-6alkyloxycarbonyl or aminocarbonyl; R10 is hydrogen or C1-6alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation.

4. 发明授权

US07169786B2 Isoxazoline derivatives as anti-depressants 有权
标题翻译：异恶唑啉衍生物作为抗抑郁剂
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

5. 发明授权

US07081453B2 Compounds for treating impaired fundic relaxation 有权
公开(公告)号：US07081453B2
公开(公告)日：2006-07-25
申请号：US10311612
申请日：2001-06-13
申请人： Kristof Van Emelen , Marcel Frans Leopold De Bruyn , Manuel Jesús Alcázar-Vaca , José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Maria Encarnacion Matesanz-Ballesteros , José Manuel Bartolomé-Nebreda
发明人： Kristof Van Emelen , Marcel Frans Leopold De Bruyn , Manuel Jesús Alcázar-Vaca , José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea , Maria Encarnacion Matesanz-Ballesteros , José Manuel Bartolomé-Nebreda
IPC分类号： A61K31/397
CPC分类号： C07D411/04 , C07D491/04
摘要： The present invention concerns compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharma-ceutically acceptable acid addition salt thereof, wherein —a1═a2—a3═a4— is a bivalent radical wherein one or two of a1 to a4 are nitrogen and the remaining a1 to a4 are —CH═; —Z1—Z2— is a bivalent radical; —A— is a bivalent radical of formula —N(R6)—Alk2— or a 5, 6 or 7-membered saturated heterocycle containing one or two nitrogen atoms; R1, R2 and R3 are each independently selected from hydrogen, C1-6alkyl, hydroxy, halo and the like; Alk1 and Alk2 are optionally substituted C1-6alkanediyl; R5 is a radical of formula (d-1), (d-2), (d-3), (d-4), (d-5) wherein n is 1 or 2; p1 is 0, and p2 is 1 or 2; or p1 is 1 or 2, and p2 is 0; X is oxygen, sulfur or ═NR9; Y2 is oxygen or sulfur; R7 is hydrogen, C1-6alkyl, C3-6cycloalkyl, phenyl or phenylmethyl; R8 is C1-6alkyl, C3-6cycloalkyl phenyl or phenylmethyl; R9 is cyano, C1-6alkyl, C3-6cyclo-alkyl, C1-6alkyloxycarbonyl or aminocarbonyl; R10 is hydrogen or C1-6alkyl; and Q is a bivalent radical. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to disturbed fundic accomodation

6. 发明授权

US07501418B2 Fused heterocyclic isoxazoline derivatives and their use as anti-depressants 有权
标题翻译：稠合杂环异恶唑啉衍生物及其作为抗抑郁剂的用途
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。

7. 发明授权

US06403805B1 1,3-dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatves 有权
标题翻译： 1,3-二氢-1-（苯基烷基）-2H-咪唑-2-酮化合物
公开(公告)号：US06403805B1
公开(公告)日：2002-06-11
申请号：US09362007
申请日：1999-07-27
申请人： Eddy Jean Edgard Freyne , Gaston Stanislas Marcella Diels , José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea
发明人： Eddy Jean Edgard Freyne , Gaston Stanislas Marcella Diels , José Ignacio Andrés-Gil , Francisco Javier Fernández-Gadea
IPC分类号： C07D23332
CPC分类号： C07D401/06 , C07D233/36 , C07D233/38 , C07D233/70
摘要： The present invention describes compounds useful for treating warm-blooded animals suffering from disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase IV (PDE IV), and/or disease states related to a physiologically detrimental excess of cytokines, in particular allergic, atopic and inflammatory diseases, said compounds having the formula the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof.
摘要翻译：本发明描述了可用于治疗患有与磷酸二酯酶IV（PDE IV）的异常酶促或催化活性相关的疾病状态的温血动物的化合物和/或与生理上有害的细胞因子过量相关的疾病状态，特别是过敏性疾病，特应性和炎症性疾病，所述具有N-氧化物形式的化合物，其药学上可接受的酸或碱加成盐及其立体化学异构形式。

8. 发明授权

US08592422B2 Bicyclic triazole and pyrazole lactams as allosteric modulators of mGluR5 receptors 失效
标题翻译：双环三唑和吡唑内酰胺作为mGluR5受体的变构调节剂
公开(公告)号：US08592422B2
公开(公告)日：2013-11-26
申请号：US13329025
申请日：2011-12-16
申请人： P. Jeffrey Conn , Craig W. Lindsley , Shaun R. Stauffer , José Manuel Bartolomé-Nebreda , Susana Conde-Ceide , Gregor James MacDonald , Han Min Tong , Carrie K. Jones , Manuel Jesús Alcázar-Vaca , José Ignacio Andrés-Gil , Chrysa Malosh
发明人： P. Jeffrey Conn , Craig W. Lindsley , Shaun R. Stauffer , José Manuel Bartolomé-Nebreda , Susana Conde-Ceide , Gregor James MacDonald , Han Min Tong , Carrie K. Jones , Manuel Jesús Alcázar-Vaca , José Ignacio Andrés-Gil , Chrysa Malosh
IPC分类号： A61K31/4985 , A61P25/00 , C07D487/04
CPC分类号： C07D487/04 , A61K31/40 , A61K31/4985 , A61K31/501 , A61K31/506 , A61K31/695 , A61K45/06 , C07F7/1804
摘要： In one aspect, the invention relates to bicyclic triazole and pyrazole lactams, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
摘要翻译：一方面，本发明涉及双代三唑和吡唑内酰胺，其衍生物和相关化合物，其可用作代谢型谷氨酸受体亚型5（mGluR5）的正变构调节剂; 制备化合物的合成方法; 包含该化合物的药物组合物; 以及使用所述化合物和组合物治疗与谷氨酸官能障碍相关的神经和精神障碍的方法。该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

9. 发明授权

US08329704B2 Substituted pyrazinone derivatives for use in MCH-1 mediated diseases 有权
标题翻译：用于MCH-1介导的疾病的取代的吡嗪酮衍生物
公开(公告)号：US08329704B2
公开(公告)日：2012-12-11
申请号：US12091365
申请日：2006-12-18
申请人： José Ignacio Andrés-Gil , Manuel Jesús Alcázar-Vaca , Rosa María Álvarez-Escobar , Julen Oyarzabal Santamarina , Frank Matthias Dautzenberg , Jacqueline Macritchie , Donald Simpson , Sonia Martinez Gonzalez
发明人： José Ignacio Andrés-Gil , Manuel Jesús Alcázar-Vaca , Rosa María Álvarez-Escobar , Julen Oyarzabal Santamarina , Frank Matthias Dautzenberg , Jacqueline Macritchie , Donald Simpson , Sonia Martinez Gonzalez
IPC分类号： A61K31/4965 , C07D241/02
CPC分类号： C07D241/20 , C07D401/04 , C07D401/10 , C07D401/12 , C07D401/14 , C07D403/10 , C07D403/12 , C07D491/10
摘要： The present invention concerns aryl and heteroaryl substituted pyrazinone derivatives having antagonistic melanin-concentrating hormone (MCH) activity, in particular MCH-1 activity according to the general Formula (I) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, an N-oxide form thereof or a quaternary ammonium salt thereof, wherein the variables are defined in Claim 1. It further relates to their preparation, compositions comprising them and their use as a medicine. The compounds according to the invention are useful for the prevention and/or treatment of psychiatric disorders, including but not limited to anxiety, eating disorders, mood disorders, such as bipolar disorders and depression, psychoses, such as schizophrenia, and sleeping disorders; obesity; diabetes; sexual disorders and neurological disorders.
摘要翻译：本发明涉及具有拮抗性黑色素浓缩激素（MCH）活性的芳基和杂芳基取代的吡嗪酮衍生物，特别是根据通式（I）的MCH-1活性，其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式或其季铵盐，其中所述变量在权利要求1中定义。它还涉及它们的制备，包含它们的组合物及其作为药物的用途。根据本发明的化合物可用于预防和/或治疗精神病学障碍，包括但不限于焦虑，进食障碍，情绪障碍，例如双相性精神障碍和抑郁症，精神病如精神分裂症和睡眠障碍; 肥胖; 糖尿病; 性障碍和神经障碍。

10. 发明授权

US07414048B2 4,5-dihydro-isoxazole derivatives and their pharmaceutical use 失效
公开(公告)号：US07414048B2
公开(公告)日：2008-08-19
申请号：US10403543
申请日：2003-03-31
申请人： Eddy Jean Edgard Freyne , José Ignacio Andrés-Gil , Frederik Dirk Deroose , Davy Petrus Franciscus Maria Petit , Maria Encarnacion Matesanz-Ballesteros , Rosa Maria Alvarez Escobar
发明人： Eddy Jean Edgard Freyne , José Ignacio Andrés-Gil , Frederik Dirk Deroose , Davy Petrus Franciscus Maria Petit , Maria Encarnacion Matesanz-Ballesteros , Rosa Maria Alvarez Escobar
IPC分类号： C07D413/14 , A61K31/501 , A61K31/496
CPC分类号： C07D413/04 , C07D261/04 , C07D413/14
摘要： The present invention is concerned with the compounds of formula wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; -A1=A2-A3=A4- is a pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, —N—, —O—, —CR5R6—, amide, ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole, isoxazole or thiazole; L represents Ar or Het; R1 represents hydrogen, halo, hydroxy, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, cyano, guanidine, nitro, NR17R18, an optionally substituted C(1-6)alkyl or C(1-6)alkyloxy; R2 and R3 each independently represent hydrogen, halo, C(1-6)alkyloxy or an optionally substituted C(1-6)alkyl; R5 and R6 each independently represent hydrogen, hydroxy, halo, an optionally substituted C(1-6)alkyl, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, C(1-6)alkyloxy, cyano, (C═O)R25, (C—O)OR16, (SO2)R16, aminocarbonyloxy, aminoC(1-6)alkyl, NR17R18, N3, Ar or Het; or R5 and R6 together with the carbon atom to which they are attached, form an Ar or Het; Ar represents an optionally substituted C(6-14)aryl; Het represents an optionally substituted C(1-14)heterocycle; or a N-oxide, pharmaceutically acceptable addition salt, quaternary amine or stereochemically isomeric form thereof; the processes for their preparation and compositions comprising them. It further relates to their use as a medicine.

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