公开(公告)号：US06803381B1

公开(公告)日：2004-10-12

申请号：US10438361

申请日：2003-05-14

申请人： Konrad Bleicher ,  Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann ,  Thomas Johannes Woltering

发明人： Konrad Bleicher ,  Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann ,  Thomas Johannes Woltering

IPC分类号： A61K31352

CPC分类号： C07D295/088 ,  C07C233/91 ,  C07C271/64 ,  C07C333/10 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/30 ,  C07D213/61 ,  C07D263/48 ,  C07D271/07 ,  C07D271/113 ,  C07D311/84 ,  C07D333/16 ,  C07D335/14 ,  C07D413/12

摘要： The present invention relates to compounds of formula wherein R1 is hydrogen or lower alkyl; R2, R2′ are each independently hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; X is O, S or two hydrogen atoms not forming a bridge; A1/A2 is phenyl; B is a group of formula  wherein R3 is lower alkyl, lower alkenyl, lower alkinyl, benzyl, lower alkyl-cycloalkyl, lower alkyl-cyano, lower alkyl-pyridinyl, lower alkyl-lower alkoxy-phenyl, lower alkyl-phenyl, which is optionally substituted by lower alkoxy, or phenyl, which is optionally substituted by lower alkoxy, or lower alkyl-thienyl, cycloalkyl, lower alkyl-trifluoromethyl or lower alkyl-morpholinyl; Y is —O—, —S— or a bond; and Z is —O—; or a pharmaceutically acceptable salt thereof. These compounds are useful for the control or prevention of acute and/or chronic neurological disorders.

摘要翻译： 本发明涉及式I的化合物，R 1是氢或低级烷基; R 2，R 2各自独立地是氢，低级烷基，低级烷氧基，卤素或三氟甲基; X是O，S或两个氢 不形成桥的原子; A 1 / A 2是苯基; B是一个亚烷基的基团R 3是低级烷基，低级烯基，低级炔基，苄基，低级烷基 - 环烷基，低级烷基 - 氰基，低级 烷基 - 吡啶基，低级烷基 - 低级烷氧基 - 苯基，任选被低级烷氧基取代的低级烷基 - 苯基或任选被低级烷氧基取代的苯基或低级烷基 - 噻吩基，环烷基，低级烷基 - 三氟甲基或低级 烷基吗啉基; Y是-O - ， - S-或键; 和Z是-O-; 或其药学上可接受的盐。 这些化合物可用于控制或预防急性和/或慢性神经障碍。

公开(公告)号：US06596743B2

公开(公告)日：2003-07-22

申请号：US10008827

申请日：2001-12-10

申请人： Konrad Bleicher ,  Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann ,  Thomas Johannes Woltering

发明人： Konrad Bleicher ,  Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann ,  Thomas Johannes Woltering

IPC分类号： A61K31421

CPC分类号： C07D213/30 ,  C07C233/91 ,  C07C271/64 ,  C07C333/10 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/61 ,  C07D263/48 ,  C07D271/07 ,  C07D271/113 ,  C07D295/088 ,  C07D311/84 ,  C07D333/16 ,  C07D335/14 ,  C07D413/12

摘要： The present invention is a compound of formula: wherein R1, R2, R2′, X, A1/A2 and B are as defined in the specification. These compounds may be used in the control or prevention of acute and/or chronic neurological disorders such as restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest, hypoglycaemia, Alzheimer's disease, Huntington's chorea, ALS, dementia caused by AIDS, eye injuries, retinopathy, cognitive disorders, memory deficits, schizophrenia, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate deficiency functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, acute and chronic pain, dyskinesia and depression.

摘要翻译： 本发明是下式的化合物：其中R1，R2，R2'，X，A1 / A2和B如本说明书中所定义。这些化合物可用于控制或预防急性和/或慢性神经障碍，例如 作为由旁路手术或移植引起的限制性脑功能，脑供血不足，脊髓损伤，头部损伤，怀孕引起的缺氧，心脏骤停，低血糖，阿尔茨海默病，亨廷顿舞蹈症，ALS，艾滋病引起的痴呆，眼睛损伤 ，视网膜病变，认知障碍，记忆缺陷，精神分裂症，由药物引起的特发性帕金森综合症或帕金森综合征以及导致谷氨酸缺乏功能的病症，例如 肌肉痉挛，抽搐，偏头痛，尿失禁，尼古丁成瘾，精神病，鸦片成瘾，焦虑，呕吐，急性和慢性疼痛，运动障碍和抑郁症。

公开(公告)号：US06642247B2

公开(公告)日：2003-11-04

申请号：US09330724

申请日：1999-06-11

申请人： Geo Adam ,  Andrea Cesura ,  François Jenck ,  Sabine Kolczewski ,  Stephan Röver ,  Jürgen Wichmann

发明人： Geo Adam ,  Andrea Cesura ,  François Jenck ,  Sabine Kolczewski ,  Stephan Röver ,  Jürgen Wichmann

IPC分类号： A61K31438

CPC分类号： C07D471/10 ,  C07D513/10

摘要： The present invention relates to compounds of the general formula wherein R1 is C6-10-cycloalkyl, optionally substituted by lower alkyl or —C(O)O-lower alkyl; decahydro-naphthalen-1-yl; decahydro-naphthalen-2-yl; indan-1-yl or indan-2-yl, optionally substituted by lower alkyl; decahydro-azulen-2-yl; bicyclo[6.2.0]dec-9-yl; acenaphthen-1-yl; 2,3-dihydro-1H-phenalen-1-yl; 2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl or octahydro-inden-2-yl; R2 is hydrogen; lower alkyl; ═O or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; is cyclohexyl or phenyl, optionally substituted by lower alkyl, halogen or alkoxy; X is —CH(OH)—; —C(O)—; —CHR3—; —CR3═; —O—; —S—; —CH(COOR4)— or C(COOR4)═; Y is —CH2—; —CH═; —CH(COOR4)—, —C(COOR4)═; or —C(CN)—; R3 is hydrogen or lower alkoxy; R4 is lower alkyl, cycloalkyl, phenyl, or benzyl and either a or b is optionally an additional bond, and to pharmaceutically acceptable acid addition salts thereof. The compounds are agonists of the orphanin FQ (QFQ) receptor and therefore useful in the treatment of diseases, related to this receptor.

摘要翻译： 本发明涉及通式化合物R 1的化合物是任选被低级烷基或-C（O）O-低级烷基取代的C 6-10 - 环烷基; 十氢萘-1-基; 十氢萘-2-基; 茚满-1-基或茚满-2-基，任选被低级烷基取代; 十氢 - 薁-2-基; 双环[6.2.0]癸-9-基; 苊-1-基; 2,3-二氢-1H-苯并芬-1-基; 2,3,3a，4,5,6-六氢-1H-吩酚-1-基或八氢 - 茚-2-基; R 2是氢; 低级烷基 任选被低级烷基，卤素或烷氧基取代的O或苯基;是任选被低级烷基，卤素或烷氧基取代的环己基或苯基; X是-CH（OH） - ; -C（O） - ; -CHR 3 - ; -CR 3 = -O-; -S-; -CH（COOR 4） - 或C（COOR 4）=; Y是-CH 2 - ; -CH =; -CH（COOR 4） - ， - C（COOR 4）=; 或-C（CN） - ; R 3是氢或低级烷氧基; R 4是低级烷基，环烷基，苯基或苄基，a或b任选是另外的键，以及其药学上可接受的酸加成盐 该化合物是孤儿素FQ（QFQ）受体的激动剂，因此可用于治疗与该受体有关的疾病。

公开(公告)号：US06462198B1

公开(公告)日：2002-10-08

申请号：US09545622

申请日：2000-04-10

申请人： Konrad Bleicher ,  Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann ,  Thomas Johannes Woltering

发明人： Konrad Bleicher ,  Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann ,  Thomas Johannes Woltering

IPC分类号： C07D41312

CPC分类号： C07D213/30 ,  C07C233/91 ,  C07C271/64 ,  C07C333/10 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/61 ,  C07D263/48 ,  C07D271/07 ,  C07D271/113 ,  C07D295/088 ,  C07D311/84 ,  C07D333/16 ,  C07D335/14 ,  C07D413/12

摘要： The present invention relates to compounds of formula wherein R1 signifies hydrogen or lower alkyl; R2, R2′ signify, independently from each other, hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; X signifies O, S or two hydrogen atoms not forming a bridge; A1/A2 signify, independently from each other, phenyl or a 6-membered heterocycle containing 1 or 2 nitrogen atoms; B is a group of formula  wherein R3 signifies lower alkyl, lower alkenyl, lower alkinyl, benzyl, lower alkyl-cycloalkyl, lower alkyl-cyano, lower alkyl-pyridinyl, lower alkyl-lower alkoxy-phenyl, lower alkyl-phenyl, which is optionally substituted by lower alkoxy, or phenyl, which is optionally substituted by lower alkoxy, or lower alkyl-thienyl, cycloalkyl, lower alkyl-trifluoromethyl or lower alkyl-morpholinyl, Y signifies —O—, —S— or a bond; Z signifies —O— or —S—; or B is a 5-membered heterocyclic group of formulas  wherein R4 and R5 signifies hydrogen, lower alkyl, lower alkoxy, cyclohexyl, lower alkyl-cyclohexyl or trifluoromethyl, with the proviso that at least one of R4 or R5 has to be hydrogen; as well as to their pharmaceutically acceptable salts. These compounds may be used in the control or prevention of acute and/or chronic neurological disorders such as restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest, hypoglycaemia, Alzheimer's disease, Huntington's chorea, ALS, dementia caused by AIDS, eye injuries, retinopathy, cognitive disorders, memory deficits, schizophrenia, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate deficiency functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, acute and chronic pain, dyskinesia and depression.

公开(公告)号：US06310208B1

公开(公告)日：2001-10-30

申请号：US09003446

申请日：1998-01-06

申请人： Michael Bös ,  Heinz Stadler ,  Jürgen Wichmann

发明人： Michael Bös ,  Heinz Stadler ,  Jürgen Wichmann

IPC分类号： C07D49156

CPC分类号： C07D221/10

摘要： Since the compounds in accordance with the invention can bind to serotonin receptors (5HT2), they are especially suitable for the treatment or prevention of central nervous disorders such as depressions, bipolar disorders, anxiety states, sleep and sexual disorders, psychoses, schizophrenia, migraine and other conditions associated with cephalic pain or pain of a different kind, personality disorders or obsessive-compulsive disorders, social phobias or panic attacks, mental organic disorders, mental disorders in childhood, aggressivity, age-related memory disorders and behavioral disorders, addiction, obesity, bulimia etc., nervous system damage caused by trauma, stroke, neurodegenerative diseases etc.; cardiovascular disorders such as hypertension, thrombosis, stroke etc.; and gastrointestinal disorders such as dysfunction of the gastrointestinal tract motility.

摘要翻译： 由于根据本发明的化合物可以结合5-羟色胺受体（5HT2），所以它们特别适用于治疗或预防中枢神经障碍如沮丧，双相情感障碍，焦虑状态，睡眠和性障碍，精神病，精神分裂症，偏头痛 以及与头痛或不同类型的疼痛，人格障碍或强迫症，社交恐惧症或惊恐发作，精神有机疾病，儿童精神障碍，侵略性，与年龄有关的记忆障碍和行为障碍，成瘾， 肥胖，贪食等，由创伤，中风，神经变性疾病等引起的神经系统损伤; 心血管疾病如高血压，血栓形成，中风等; 和胃肠道疾病如胃肠道运动功能障碍。

公开(公告)号：US06284785B1

公开(公告)日：2001-09-04

申请号：US09534380

申请日：2000-03-24

申请人： Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann

发明人： Vincent Mutel ,  Eric Vieira ,  Jürgen Wichmann

IPC分类号： A61K314025

CPC分类号： C07D401/04 ,  C07D207/48 ,  C07D405/04 ,  C07D417/04

摘要： 1-Arenesulfonyl-2-Aryl-pyrrolidine and pyridine derivatives having activity as ligands of metabotropic glutamate receptors of the formula are disclosed.

摘要翻译： 具有作为配方的代谢型谷氨酸受体的配体活性的1-甲磺酰基-2-芳基 - 吡咯烷和吡啶衍生物。

公开(公告)号：US06248901B1

公开(公告)日：2001-06-19

申请号：US09304909

申请日：1999-05-04

申请人： Geo Adam ,  Sabine Kolczewski ,  Vincent Mutel ,  Heinz Stadler ,  Jürgen Wichmann ,  Thomas Johannes Woltering

发明人： Geo Adam ,  Sabine Kolczewski ,  Vincent Mutel ,  Heinz Stadler ,  Jürgen Wichmann ,  Thomas Johannes Woltering

IPC分类号： C07D24908

CPC分类号： C07D257/04 ,  A61K31/41 ,  A61K31/4174 ,  A61K31/4196 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08

摘要： The compounds of the formula wherein R signifies halogen or lower alkyl; n signifies 0-3; R1 signifies lower alkyl; cycloalkyl; benzyl optionally substituted by hydroxy, halogen, lower alkoxy or lower alkyl; benzoyl optionally substituted by amino, lower alkylamino or di-lower alkylamino; acetyl or cycloalkyl-carbonyl; and signifies an aromatic 5-membered residue which is bonded via a N-atom and which contains further 1-3 N atoms in addition to the linking N atom, as well as their pharmaceutically acceptable salts as therapeutically active substances, especially for the control or prevention of acute and/or chronic neurological disorders.

摘要翻译： 化合物R表示卤素或低级烷基; n表示0-3; R1表示低级烷基; 环烷基 任选被羟基，卤素，低级烷氧基或低级烷基取代的苄基; 任选被氨基，低级烷基氨基或二 - 低级烷基氨基取代的苯甲酰基; 乙酰基或环烷基 - 羰基; 并且通过N-原子键合并且除了连接的N原子还含有1-3个N原子的芳族5元残基以及它们的药学上可接受的盐作为治疗活性物质，特别是用于控制或预防 的急性和/或慢性神经障碍。