公开(公告)号：US08722887B2

公开(公告)日：2014-05-13

申请号：US12706279

申请日：2010-02-16

申请人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A. W. Van Der Neut ,  Cornelis G. Kruse

发明人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A. W. Van Der Neut ,  Cornelis G. Kruse

IPC分类号： C07D231/06 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/10

CPC分类号： C07D513/04 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/1652 ,  A61K9/2054 ,  C07D231/06 ,  C07D231/12 ,  C07D231/54 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D491/10 ,  C07D491/107 ,  C07D519/00

摘要： This invention concerns compounds of the general formula (1): and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

摘要翻译： 本发明涉及作为5-HT 6受体的拮抗剂的通式（1）的化合物及其衍生物，其中符号具有说明书中给出的含义。 本发明还涉及制备这些化合物的方法，可用于其合成的新型中间体，以及这些化合物和组合物的用途，特别是它们在将它们给予患者以达到治疗至少在疾病或病症上的治疗效果 选自帕金森病，亨廷顿氏舞蹈病，精神分裂症，焦虑症，抑郁症，躁狂抑郁症，精神病，癫痫症，强迫症，情绪障碍，偏头痛，阿尔茨海默病，年龄相关认知衰退，轻度认知障碍，睡眠障碍，进食障碍，厌食症， 注意缺陷障碍，注意力缺陷障碍，可卡因滥用，乙醇，尼古丁或苯二氮卓类药物的疼痛，疼痛，与脊髓创伤或头部损伤相关的疾病，脑积水，功能性肠病，肠易激综合征 肠综合征，肥胖症和2型糖尿病。

公开(公告)号：US07728018B2

公开(公告)日：2010-06-01

申请号：US11859323

申请日：2007-09-21

申请人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A. W. Van Der Neut ,  Cornelis G. Kruse

发明人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A. W. Van Der Neut ,  Cornelis G. Kruse

IPC分类号： A61K31/4155 ,  C07D231/06 ,  C07D403/12 ,  C07D413/14 ,  C07D487/04

CPC分类号： C07D513/04 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/1652 ,  A61K9/2054 ,  C07D231/06 ,  C07D231/12 ,  C07D231/54 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D491/10 ,  C07D491/107 ,  C07D519/00

摘要： This invention concerns compounds of the general formula (1): and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

摘要翻译： 本发明涉及作为5-HT 6受体的拮抗剂的通式（1）的化合物及其衍生物，其中符号具有说明书中给出的含义。 本发明还涉及制备这些化合物的方法，可用于其合成的新型中间体，以及这些化合物和组合物的用途，特别是它们在将它们给予患者以达到治疗至少在疾病或病症上的治疗效果 选自帕金森病，亨廷顿氏舞蹈病，精神分裂症，焦虑症，抑郁症，躁狂抑郁症，精神病，癫痫症，强迫症，情绪障碍，偏头痛，阿尔茨海默病，年龄相关的认知衰退，轻度认知障碍，睡眠障碍，进食障碍，厌食症， 注意缺陷障碍，注意力缺陷障碍，可卡因滥用，乙醇，尼古丁或苯二氮卓类药物的疼痛，疼痛，与脊髓创伤或头部损伤相关的疾病，脑积水，功能性肠病，肠易激综合征 肠综合征，肥胖症和2型糖尿病。

公开(公告)号：US20080311179A1

公开(公告)日：2008-12-18

申请号：US11859323

申请日：2007-09-21

申请人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A.W. Van Der Neut ,  Cornelis G. Kruse

发明人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A.W. Van Der Neut ,  Cornelis G. Kruse

IPC分类号： A61K9/12 ,  C07D403/12 ,  C07D409/12 ,  C07D413/14 ,  A61K9/48 ,  A61P3/00 ,  A61P1/00 ,  A61P25/00 ,  A61K9/70 ,  A61K31/4155 ,  A61K31/4245

CPC分类号： C07D513/04 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/1652 ,  A61K9/2054 ,  C07D231/06 ,  C07D231/12 ,  C07D231/54 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D491/10 ,  C07D491/107 ,  C07D519/00

摘要： This invention concerns compounds of the general formula (1). and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

摘要翻译： 本发明涉及通式（1）的化合物。 及其衍生物，其为5-HT 6受体的拮抗剂，其中符号具有说明书中给出的含义。 本发明还涉及制备这些化合物的方法，可用于其合成的新型中间体，以及这些化合物和组合物的用途，特别是它们在将它们给予患者以达到治疗至少在疾病或病症上的治疗效果 选自帕金森病，亨廷顿氏舞蹈病，精神分裂症，焦虑症，抑郁症，躁狂抑郁症，精神病，癫痫症，强迫症，情绪障碍，偏头痛，阿尔茨海默病，年龄相关认知衰退，轻度认知障碍，睡眠障碍，进食障碍，厌食症， 注意缺陷障碍，注意力缺陷障碍，可卡因滥用，乙醇，尼古丁或苯二氮卓类药物的疼痛，疼痛，与脊髓创伤或头部损伤相关的疾病，脑积水，功能性肠病，肠易激综合征 肠综合征，肥胖症和2型糖尿病。

公开(公告)号：US20100145042A1

公开(公告)日：2010-06-10

申请号：US12706279

申请日：2010-02-16

申请人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A.W. Van Der Neut ,  Cornelis G. Kruse

发明人： Arnold Van Loevezijn ,  Wouter I. Iwema Bakker ,  Hiskias G. Keizer ,  Jan Zorgdrager ,  Martina A.W. Van Der Neut ,  Cornelis G. Kruse

IPC分类号： C07D413/12 ,  C07D403/12 ,  C07D471/10 ,  C07D401/12 ,  C07D417/12 ,  C07D231/06

CPC分类号： C07D513/04 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/1652 ,  A61K9/2054 ,  C07D231/06 ,  C07D231/12 ,  C07D231/54 ,  C07D231/56 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D471/10 ,  C07D491/10 ,  C07D491/107 ,  C07D519/00

摘要： This invention concerns compounds of the general formula (1): and derivatives thereof, which are antagonists of 5-HT6 receptors, wherein the symbols have the meanings given in the description. The invention also concerns methods for the preparation of these compounds, to novel intermediates useful for their synthesis, and to uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in treating at least on disease or condition chosen from Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes.

摘要翻译： 本发明涉及作为5-HT 6受体的拮抗剂的通式（1）的化合物及其衍生物，其中符号具有说明书中给出的含义。 本发明还涉及制备这些化合物的方法，可用于其合成的新型中间体，以及这些化合物和组合物的用途，特别是它们在将它们给予患者以达到治疗至少在疾病或病症上的治疗效果 选自帕金森病，亨廷顿氏舞蹈病，精神分裂症，焦虑症，抑郁症，躁狂抑郁症，精神病，癫痫症，强迫症，情绪障碍，偏头痛，阿尔茨海默病，年龄相关认知衰退，轻度认知障碍，睡眠障碍，进食障碍，厌食症， 注意缺陷障碍，注意力缺陷障碍，可卡因滥用，乙醇，尼古丁或苯二氮卓类药物的疼痛，疼痛，与脊髓创伤或头部损伤相关的疾病，脑积水，功能性肠病，肠易激综合征 肠综合征，肥胖症和2型糖尿病。

公开(公告)号：US07271189B2

公开(公告)日：2007-09-18

申请号：US10965155

申请日：2004-10-15

申请人： Josephus H. M. Lange ,  Cornelis G. Kruse ,  Herman H. Van Stuivenberg ,  Hiskias G. Keizer

发明人： Josephus H. M. Lange ,  Cornelis G. Kruse ,  Herman H. Van Stuivenberg ,  Hiskias G. Keizer

IPC分类号： A61K31/4164 ,  C07D233/60

CPC分类号： C07D233/90

摘要： The invention relates to a group of 1H-imidazole derivatives which are modulators of cannabinoid receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders in which cannabinoid receptors are involved.The compounds have the general formula (I) wherein R, R1-R4 and X have the meanings given in the specification.

摘要翻译： 本发明涉及一组作为大麻素受体的调节剂的1H-咪唑衍生物，制备这些化合物的方法，可用于合成所述咪唑衍生物的新中间体，制备这些中间体的方法，药物 含有这些1H-咪唑衍生物中的一种或多种作为活性成分的组合物，以及这些药物组合物用于治疗涉及大麻素受体的精神病和神经障碍的用途。 化合物具有通式（I），其中R 1，R 1 -R 4和X具有说明书中给出的含义。

公开(公告)号：US07498348B2

公开(公告)日：2009-03-03

申请号：US11842657

申请日：2007-08-21

申请人： Josephus H. M. Lange ,  Cornelis G. Kruse ,  Herman H. Van Stuivenberg ,  Hiskias G. Keizer

发明人： Josephus H. M. Lange ,  Cornelis G. Kruse ,  Herman H. Van Stuivenberg ,  Hiskias G. Keizer

IPC分类号： A61K31/4523 ,  A61K31/4178 ,  A61K31/4166

CPC分类号： C07D233/90

摘要： The invention relates to a group of 1H-imidazole derivatives which are modulators of cannabinoid receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders in which cannabinoid receptors are involved.The compounds have the general formula (I) wherein R, R1-R4 and X have the meanings given in the specification.

摘要翻译： 本发明涉及一组作为大麻素受体的调节剂的1H-咪唑衍生物，制备这些化合物的方法，可用于合成所述咪唑衍生物的新中间体，制备这些中间体的方法，药物 含有这些1H-咪唑衍生物中的一种或多种作为活性成分的组合物，以及这些药物组合物用于治疗涉及大麻素受体的精神病和神经障碍的用途。 所述化合物具有通式（I），其中R，R 1 -R 4和X具有说明书中给出的含义。

公开(公告)号：US07678789B2

公开(公告)日：2010-03-16

申请号：US11349910

申请日：2006-02-09

申请人： Roelof W. Feenstra ,  Hiskias G. Keizer ,  Maria L. Pras-Raves ,  Bernard J Van Vliet ,  Gustaaf J. M. Van Scharrenburg

发明人： Roelof W. Feenstra ,  Hiskias G. Keizer ,  Maria L. Pras-Raves ,  Bernard J Van Vliet ,  Gustaaf J. M. Van Scharrenburg

IPC分类号： A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/4535 ,  A61K31/4436 ,  A61K31/41 ,  C07D417/04 ,  C07D413/04 ,  C07D285/01

CPC分类号： C07D285/01 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

摘要： The present invention relates to 5-imino-5H-[1,2,4]-dithiazol-3-yl-amine and [1,2,4]-dithiazolidine-3,5-diylidene-diamine derivatives as inducers of gluthathione-S-transferase (GST) and NADPH quinone oxidoreductase (NQO), to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said [1,2,4]-dithiazoli(di)ne derivatives. The invention also relates to the use of a compound disclosed herein for the treatment of adverse conditions associated with cytotoxicity in general and apoptosis in particular. The invention relates to compounds of the general formula (I): wherein wherein the symbols have the meanings given in the specification.

摘要翻译： 本发明涉及5-亚氨基-5H- [1,2,4] - 二噻唑-3-基 - 胺和[1,2,4] - 二噻唑烷-3,5-二亚胺基二胺衍生物作为谷胱甘肽 - S-转移酶（GST）和NADPH醌氧化还原酶（NQO），用于制备这些化合物的方法和用于合成所述[1,2,4] - 二噻唑（di）ne衍生物的新中间体。 本发明还涉及本文公开的化合物用于治疗与一般细胞毒性和特别是细胞凋亡相关的不利条件的用途。 本发明涉及通式（I）的化合物：其中符号具有说明书中给出的含义。