公开(公告)号：US07875645B2

公开(公告)日：2011-01-25

申请号：US11655468

申请日：2007-01-19

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Marius Hoener ,  Sabine Kolczewski ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Marius Hoener ,  Sabine Kolczewski ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/415 ,  C07D233/56

CPC分类号： C07D233/06 ,  A61K31/4164 ,  A61K31/4178 ,  C07D233/20 ,  C07D233/22 ,  C07D233/56 ,  C07D233/64 ,  C07D401/10 ,  C07D403/06 ,  C07D405/06 ,  C07D409/06

摘要： The present invention relates a method for treating depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders which comprises administering to an individual a therapeutically effective amount of a compound of formula I wherein R, R1, R2, A and n are as defined in the specification and to their pharmaceutically active salts. The invention also relates to novel compounds of formula I, pharmaceutical compositions containing them, and methods for their preparation.

摘要翻译： 本发明涉及治疗抑郁症，焦虑障碍，双相情感障碍，注意缺陷多动障碍，应激相关障碍，精神病如精神分裂症，神经系统疾病如帕金森病，神经变性疾病如阿尔茨海默病，癫痫，偏头痛， 高血压，药物滥用和代谢障碍如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和同化障碍，体温平衡紊乱和失调，睡眠和昼夜节律紊乱以及心血管疾病，其包括给予 个体治疗有效量的式I化合物，其中R，R 1，R 2，A和n如说明书中所定义，并且其药物活性盐。 本发明还涉及式I的新型化合物，含有它们的药物组合物及其制备方法。

公开(公告)号：US07858652B2

公开(公告)日：2010-12-28

申请号：US11938801

申请日：2007-11-13

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/427 ,  A61K31/47 ,  C07D403/06 ,  C07D215/02

CPC分类号： C07D401/06 ,  C07D403/06 ,  C07D413/06

摘要： The present invention relates to a compound of formula I, wherein R1 is selected from the group consisting of hydrogen and lower alkyl; each R2 is independently selected from the group consisting of hydrogen and lower alkyl; each R3 is independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, phenyloxy, benzyloxy, halogen and lower alkyl substituted by halogen; R4 is selected from the group consisting of hydrogen and lower alkyl; X is selected from the group consisting of —CH2—, —CH— and —O—; Y is selected from the group consisting of —CH2—, —CH2CH2—, —CH— and a bond; with the proviso that, when X is —O—, Y is —CH2—; Z is selected from the group consisting of —CH2— and —CH—; m is 1 or 2; and n is 1 or 2. The invention relates also to a pharmaceutically-acceptable acid-addition salt of such a compound, methods for making the compound, and a composition comprising such a compound.It has been found that the compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1.

摘要翻译： 本发明涉及式I化合物，其中R 1选自氢和低级烷基; 每个R 2独立地选自氢和低级烷基; 每个R 3独立地选自氢，低级烷基，低级烷氧基，苯氧基，苄氧基，卤素和被卤素取代的低级烷基; R4选自氢和低级烷基; X选自-CH 2 - ， - CH-和-O-; Y选自-CH 2 - ， - CH 2 CH 2 - ， - CH-和键; 条件是当X是-O-时，Y是-CH 2 - ; Z选自-CH 2 - 和-CH-; m为1或2; 本发明还涉及这种化合物的药学上可接受的酸加成盐，制备该化合物的方法和包含这种化合物的组合物。 已经发现，式I化合物对微量胺相关受体（TAAR）具有良好的亲和力，特别是对于TAAR1。

公开(公告)号：US07812047B2

公开(公告)日：2010-10-12

申请号：US12146497

申请日：2008-06-26

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/4174 ,  C07D233/12 ,  C07D233/16

CPC分类号： C07D233/06 ,  C07D233/12 ,  C07D233/22 ,  C07D233/24

摘要： The present invention relates to compounds of formula wherein R1, R2, X, Y and Ar are as defined herein and to their pharmaceutically active salts, with the exclusion of the racemic compound 4-benzyl-4,5-dihydro-1H-imidazole or its tautomer (CAS 131548-83-9). Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1 and are useful for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

摘要翻译： 本发明涉及下式的化合物，其中R 1，R 2，X，Y和Ar如本文所定义及其药学活性盐，排除外消旋化合物4-苄基-4,5-二氢-1H-咪唑或 其互变异构体（CAS 131548-83-9）。 式I化合物对微量胺相关受体（TAAR）具有良好的亲和力，尤其对于TAAR1，可用于治疗抑郁症，焦虑障碍，双相情感障碍，注意缺陷多动障碍（ADHD），应激相关疾病，精神病性 诸如精神分裂症，神经系统疾病如帕金森病，神经变性疾病如阿尔茨海默氏病，癫痫，偏头痛，高血压，药物滥用和代谢性疾病如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和同化障碍等疾病 ，体温平衡紊乱和失眠，睡眠障碍和昼夜节律，以及心血管疾病。

公开(公告)号：US20100041686A1

公开(公告)日：2010-02-18

申请号：US12504702

申请日：2009-07-17

申请人： Guido Galley ,  Annick Goergler ,  Katrin Groebke Zbinden ,  Roger Norcross

发明人： Guido Galley ,  Annick Goergler ,  Katrin Groebke Zbinden ,  Roger Norcross

IPC分类号： A61K31/506 ,  C07D263/28 ,  C07F7/10 ,  A61K31/421 ,  C07D403/12

CPC分类号： C07D263/28 ,  C07D413/12

摘要： The invention relates to compounds of formula I wherein R1, R2, X, Y, and n are defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The invention also provides pharmaceutical compositions and methods of manufacture of such compounds. The compounds are useful for the treatment of diseases related to the biological function of the trace amine associated receptors, which diseases are depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

公开(公告)号：US20090036452A1

公开(公告)日：2009-02-05

申请号：US12180571

申请日：2008-07-28

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/5377 ,  C07D403/04 ,  A61K31/496 ,  A61K31/444 ,  C07D401/12 ,  C07D413/12

CPC分类号： C07D213/80 ,  C07C233/66 ,  C07D213/82 ,  C07D235/08 ,  C07D401/12 ,  C07D405/12

摘要： The invention relates to a compound of formula wherein R1, R2, X, L, W, n, and o are defined herein and to pharmaceutically suitable acid addition salts thereof, with the exception of the following compounds 6-(4-methyl-piperazin-1-yl)-N-phenethyl-nicotinamide (CAS 199478-31-4), N-(3,4-dichloro-benzyl)-3-fluoro-benzamide (CAS 424815-98-5), N-(4-chloro-benzyl)-3-fluoro-benzamide (CAS 544661-83-8), N-(3-chloro-benzyl)-3-fluoro-benzamide (CAS 796051-07-5), and N-phenethyl-6-phenylamino-nicotinamide (CAS 571913-74-1). The compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1 and are useful for the treatment of CNS disorders.

摘要翻译： 本发明涉及下式的化合物，其中R 1，R 2，X，L，W，n和o在本文中定义及其药学上合适的酸加成盐，但以下化合物6-（4-甲基 - 哌嗪 （CAS 199478-31-4），N-（3,4-二氯 - 苄基）-3-氟 - 苯甲酰胺（CAS 424815-98-5），N-（4 - 氯 - 苄基）-3-氟 - 苯甲酰胺（CAS 544661-83-8），N-（3-氯 - 苄基）-3-氟 - 苯甲酰胺（CAS 796051-07-5）和N-苯乙基-6 - 苯基氨基 - 烟酰胺（CAS 571913-74-1）。 式I化合物对微量胺相关受体（TAAR）具有良好的亲和力，特别是TAAR1，可用于治疗CNS疾病。

公开(公告)号：US20090029962A1

公开(公告)日：2009-01-29

申请号：US12176456

申请日：2008-07-21

申请人： Guido Galley ,  Annick Goergler ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Annick Goergler ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/397 ,  C07D207/09 ,  C07D205/04 ,  A61K31/40

CPC分类号： C07D205/04 ,  C07D207/09

摘要： The present invention relates to compounds of formula I wherein R1, R2, R3, Ar, n and o are as defined herein and to their pharmaceutically acceptable active salts. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1 and are useful for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

摘要翻译： 本发明涉及其中R 1，R 2，R 3，Ar，n和o如本文所定义的式I化合物及其药学上可接受的活性盐。 式I化合物对微量胺相关受体（TAAR）具有良好的亲和力，尤其对于TAAR1，可用于治疗抑郁症，焦虑障碍，双相情感障碍，注意缺陷多动障碍（ADHD），应激相关疾病，精神病性 诸如精神分裂症，神经系统疾病如帕金森病，神经变性疾病如阿尔茨海默氏病，癫痫，偏头痛，高血压，药物滥用和代谢性疾病如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和同化障碍等疾病 ，体温平衡紊乱和失眠，睡眠障碍和昼夜节律，以及心血管疾病。

公开(公告)号：US20090018180A1

公开(公告)日：2009-01-15

申请号：US12145541

申请日：2008-06-25

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： C07D233/04 ,  C07D233/20 ,  C07D233/30 ,  A61K31/4164 ,  A61K31/4166 ,  A61K31/4168 ,  C07D233/32 ,  C07D233/44

CPC分类号： C07D233/24 ,  C07D233/20 ,  C07D233/22 ,  C07D233/42 ,  C07D233/52 ,  C07D405/12

摘要： The present invention relates to compounds of formula I wherein X—Y, R1, and n are as defined herein and to their pharmaceutically active salts. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1 and are useful for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

摘要翻译： 本发明涉及式I化合物，其中X-Y，R 1和n如本文所定义，及其药学活性盐。 式I化合物对微量胺相关受体（TAAR）具有良好的亲和力，尤其对于TAAR1，可用于治疗抑郁症，焦虑障碍，双相情感障碍，注意缺陷多动障碍（ADHD），应激相关疾病，精神病性 诸如精神分裂症，神经系统疾病如帕金森病，神经变性疾病如阿尔茨海默氏病，癫痫，偏头痛，高血压，药物滥用和代谢性疾病如进食障碍，糖尿病，糖尿病并发症，肥胖症，血脂异常，能量消耗和同化障碍等疾病 ，体温平衡紊乱和失眠，睡眠障碍和昼夜节律，以及心血管疾病。

公开(公告)号：US07417144B2

公开(公告)日：2008-08-26

申请号：US11482441

申请日：2006-07-07

申请人： Markus Boehringer ,  Katrin Groebke Zbinden ,  Wolfgang Haap ,  Hans Hilpert ,  Narendra Panday ,  Fabienne Ricklin

发明人： Markus Boehringer ,  Katrin Groebke Zbinden ,  Wolfgang Haap ,  Hans Hilpert ,  Narendra Panday ,  Fabienne Ricklin

IPC分类号： A61K31/5375

CPC分类号： C07D487/04 ,  C07D471/04

摘要： The invention is concerned with novel heteroaryl fused cyclic amines of formula (I) wherein A, X1 to X3, Y1 to Y3, Z, R1, R2, m and n are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit coagulation factor Xa and can be used as medicaments.

摘要翻译： 本发明涉及式（I）的新的杂芳基稠合环胺，其中A，X 1至X 3，Y 1至Y 1， Z，R 1，R 2，m和n如说明书和权利要求书中所定义，以及生理上可接受的盐 其中。 这些化合物抑制凝血因子Xa，可用作药物。

公开(公告)号：US20080146634A1

公开(公告)日：2008-06-19

申请号：US11950446

申请日：2007-12-05

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/4168 ,  A61K31/4164 ,  C07D233/64 ,  C07D233/88

CPC分类号： C07D233/88 ,  C07D233/64

摘要： The present invention relates to compounds of formula I, wherein X is —CH2— or —NH—; Y is —CH(lower alkoxy)-, —CH(lower alkyl)-, —O—, —S—, —S(O)—, —S(O)2— or —CH2—; and Ar is phenyl or naphthyl, which rings are optionally substituted by one or two substituents selected from the group consisting of halogen, lower alkoxy, lower alkyl and lower alkyl substituted by halogen; or a pharmaceutically-acceptable acid-addition salt thereof; with the proviso that, when X is —NH—, Y is —CH(lower alkyl)- or —CH2—; and the further proviso that the compound is not 2-phenethyl-1H-imidazole hydrochloride, 2-(3,4-dichloro-phenoxymethyl)-1H-imidazole hydrochloride, 2-(2-chloro-phenoxymethyl)-1H-imidazole hydrochloride, 2-(2,3-dichloro-phenoxymethyl)-1H-imidazole, benzyl-(1H-imidazol-2-yl)-amine, (4-chloro-benzyl)-(1H-imidazol-2-yl)-amine, or (2-chloro-benzyl)-(1H-imidazol-2-yl)-amine. The invention relates also to a pharmaceutically-acceptable acid-addition salt of such a compound, processes for making the compound, and a composition comprising such a compound.

摘要翻译： 本发明涉及式I化合物，其中X是-CH 2 - 或-NH-; Y是-CH（低级烷氧基） - ， - CH（低级烷基） - ， - O - ， - S - ， - S（O） - ， - S（O） 2 - ; 并且Ar是苯基或萘基，该环任选地被一个或两个选自卤素，低级烷氧基，低级烷基和被卤素取代的低级烷基的取代基取代; 或其药学上可接受的酸加成盐; 条件是当X是-NH-时，Y是-CH（低级烷基） - 或-CH 2 - 。 另外的条件是该化合物不是2-苯乙基-1H-咪唑盐酸盐，2-（3,4-二氯 - 苯氧基甲基）-1H-咪唑盐酸盐，2-（2-氯 - 苯氧基甲基）-1H-咪唑盐酸盐， 2-（2,3-二氯 - 苯氧基甲基）-1H-咪唑，苄基 - （1H-咪唑-2-基） - 胺，（4-氯 - 苄基） - （1H-咪唑-2-基） - 胺， 或（2-氯 - 苄基） - （1H-咪唑-2-基） - 胺。 本发明还涉及这种化合物的药学上可接受的酸加成盐，制备该化合物的方法和包含这种化合物的组合物。

公开(公告)号：US20080139533A1

公开(公告)日：2008-06-12

申请号：US11938801

申请日：2007-11-13

申请人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

发明人： Guido Galley ,  Katrin Groebke Zbinden ,  Roger Norcross ,  Henri Stalder

IPC分类号： A61K31/55 ,  C07D233/61 ,  C07D401/06 ,  C07D413/06 ,  C07D403/06 ,  A61K31/4164 ,  A61K31/4709 ,  A61K31/5377

CPC分类号： C07D401/06 ,  C07D403/06 ,  C07D413/06

摘要： The present invention relates to a compound of formula I, wherein R1 is selected from the group consisting of hydrogen and lower alkyl; each R2 is independently selected from the group consisting of hydrogen and lower alkyl; each R3 is independently selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, phenyloxy, benzyloxy, halogen and lower alkyl substituted by halogen; R4 is selected from the group consisting of hydrogen and lower alkyl; X is selected from the group consisting of —CH2—, —CH— and —O—; Y is selected from the group consisting of —CH2—, —CH2CH2—, —CH— and a bond; with the proviso that, when X is —O—, Y is —CH2—; Z is selected from the group consisting of —CH2— and —CH—; m is 1 or 2; and n is 1 or 2. The invention relates also to a pharmaceutically-acceptable acid-addition salt of such a compound, methods for making the compound, and a composition comprising such a compound.It has been found that the compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1.

摘要翻译： 本发明涉及式I化合物，其中R 1选自氢和低级烷基; 每个R 2独立地选自氢和低级烷基; 每个R 3独立地选自氢，低级烷基，低级烷氧基，苯氧基，苄氧基，卤素和被卤素取代的低级烷基; R 4选自氢和低级烷基; X选自-CH 2 - ， - CH-和-O-; Y选自-CH 2 - ， - CH 2 CH 2 - ， - CH-和键; 条件是当X是-O-时，Y是-CH 2 - 。 Z选自-CH 2 - 和-CH-; m为1或2; 本发明还涉及这种化合物的药学上可接受的酸加成盐，制备该化合物的方法和包含这种化合物的组合物。 已经发现，式I化合物对微量胺相关受体（TAAR）具有良好的亲和力，特别是对于TAAR1。