公开(公告)号：US06281355B1

公开(公告)日：2001-08-28

申请号：US09555570

申请日：2000-06-01

申请人： Atsuro Nakazato ,  Taketoshi Okubo ,  Toshihito Kumagai ,  Shigeyuki Chaki ,  Kazuyuki Tomisawa ,  Masashi Nagamine ,  Makoto Gotoh ,  Kuniaki Kondoh ,  Masanori Yoshida

发明人： Atsuro Nakazato ,  Taketoshi Okubo ,  Toshihito Kumagai ,  Shigeyuki Chaki ,  Kazuyuki Tomisawa ,  Masashi Nagamine ,  Makoto Gotoh ,  Kuniaki Kondoh ,  Masanori Yoshida

IPC分类号： A61K31403

CPC分类号： C07D471/04 ,  C07D495/04

摘要： A nitrogen-containing tetracyclic compound represented by the formula: wherein Y1—Y2—Y3 is N—C═N or a group represented by the formula: C═C—NR3 (wherein R3 is a hydrogen atom, a C1-5 alkyl group or a nitrogen-containing C2-10 alkyl group), Y4 is S, SO, SO2, CH2 or a group represented by the formula: NR4 (wherein R4 is a C1-5 alkanoyl group or a C1-5 alkyl group), R1 and R2 are the same or different, and are each a hydrogen atom, a C1-10 alkyl group, a C3-15 alkoxyalkyl group or a C3-15 alkylaminoalkyl group, or R1 and R2 taken together with the nitrogen atom to which they are attached form a cyclic amino group, X1 and X2 are the same or different, and are each a hydrogen atom, a C1-5 alkyl group, a C1-5 alkoxy group or a halogen atom, and n is 0, 1 or 2; or a pharmaceutically acceptable salt thereof.

摘要翻译： 一种由下式表示的含氮四环化合物：其中Y1-Y2-Y3为NC = N或由下式表示的基团：C = C-NR3（其中R3为氢原子，C1-5烷基或 含氮的C2-10烷基），Y4是S，SO，SO2，CH2或由下式表示的基团：NR4（其中R4是C1-5烷酰基或C1-5烷基），R1和R2 各自为氢原子，C 1-10烷基，C 3-15烷氧基烷基或C 3-15烷基氨基烷基，或者R 1和R 2与它们所连接的氮原子一起形成 环状氨基，X1和X2相同或不同，分别为氢原子，C1-5烷基，C1-5烷氧基或卤素原子，n为0,1或2; 或其药学上可接受的盐。

公开(公告)号：US08455511B2

公开(公告)日：2013-06-04

申请号：US12951556

申请日：2010-11-22

申请人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Mikako Yamaguchi ,  Tomoko Tamita ,  Ludo E. J. Kennis ,  Marcel F. L. De Bruyn ,  Jean-Pierre A. M. Bongartz ,  Frans M. A. Van Den Keybus ,  Yves E. M. Van Roosbroeck ,  Marcel G. M. Luyckx ,  Robert J. M. Hendrickx

发明人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Mikako Yamaguchi ,  Tomoko Tamita ,  Ludo E. J. Kennis ,  Marcel F. L. De Bruyn ,  Jean-Pierre A. M. Bongartz ,  Frans M. A. Van Den Keybus ,  Yves E. M. Van Roosbroeck ,  Marcel G. M. Luyckx ,  Robert J. M. Hendrickx

IPC分类号： C07D471/04 ,  A61K31/437 ,  C07D487/04 ,  A61K31/519 ,  A61P25/28 ,  A61P25/24 ,  A61P25/18

CPC分类号： C07D471/04 ,  C07D487/04 ,  C07F9/6561

摘要： An object of the present invention is to provide an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastric diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, etc. This problem can be solved with a pyrrolopyrimidine or pyrrolopyridine derivative substituted with a cyclic amino group represented by formula [I] below which has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

摘要翻译： 本发明的目的是提供一种抗CRF受体的拮抗剂，其作为治疗或预防药物是有效的，其涉及CRF被认为涉及的疾病，例如抑郁症，焦虑症，阿尔茨海默氏病，帕金森病，亨廷顿氏舞蹈病，进食 疾病，高血压，胃疾病，药物依赖，癫痫，脑梗塞，脑缺血，脑水肿，头部外伤，炎症，免疫相关疾病，脱发，肠易激综合征，睡眠障碍，癫痫，皮肤病，精神分裂症等。 可以用由以下式[I]表示的环氨基取代的吡咯并嘧啶或吡咯并吡啶衍生物来解决问题，其具有对CRF受体的高亲和力，并且对于CRF被认为涉及的疾病是有效的。

公开(公告)号：US08106194B2

公开(公告)日：2012-01-31

申请号：US10584946

申请日：2005-01-06

申请人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Tomoko Tamita ,  Ludo E. J. Kennis

发明人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Tomoko Tamita ,  Ludo E. J. Kennis

IPC分类号： C07D251/02 ,  C07D251/42 ,  C07D239/70

CPC分类号： C07D487/04

摘要： An object of the present invention is to provide an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastral diseases, drug dependence, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alpecia, irritable bowel syndrome, sleep disorders, dermatitides, schizophrenia, pain, etc. A pyrrolopyrimidine or pyrrolotriazine derivative substituted with a carbamoyl group represented by the following formula [I]: has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

摘要翻译： 本发明的目的是提供一种抗CRF受体的拮抗剂，其作为治疗或预防药物是有效的，其涉及CRF被认为涉及的疾病，例如抑郁症，焦虑症，阿尔茨海默氏病，帕金森病，亨廷顿氏舞蹈病，进食 疾病，高血压，胃疾病，药物依赖，癫痫，脑梗塞，脑缺血，脑水肿，头部外伤，炎症，免疫相关疾病，特异性，肠易激综合征，睡眠障碍，皮肤病，精神分裂症，疼痛等。 由下式[I]表示的氨基甲酰基取代的吡咯并嘧啶或吡咯并三嗪衍生物：对CRF受体具有高亲和力，并且对于认为涉及CRF的疾病是有效的。

公开(公告)号：US08076502B2

公开(公告)日：2011-12-13

申请号：US12847392

申请日：2010-07-30

申请人： Akito Yasuhara ,  Kazunari Sakagami ,  Hiroshi Ohta ,  Atsuro Nakazato

发明人： Akito Yasuhara ,  Kazunari Sakagami ,  Hiroshi Ohta ,  Atsuro Nakazato

IPC分类号： C07C69/74 ,  C07C61/12

CPC分类号： C07C229/50 ,  C07D307/88

摘要： A drug effective for the treatment and prevention of psychiatric disorders such as schizophrenia, anxiety and related ailments thereof, depression, bipolar disorder and epilepsy. The drug antagonizes the action of group II metabotropic glutamate receptors and shows high activity in oral administrationA 2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic ester derivative represented by formula [I] [wherein R1 and R2 are identical or different, and each represents a hydrogen atom, a C1-10alkyl group or the like; X represents a hydrogen atom or a fluorine atom; Y represents —OCHR3R4 or the like (wherein R3 and R4 are identical or different, and each represents a hydrogen atom, a C1-10alkyl group or the like; and n represents integer 1 or 2)], a pharmaceutically acceptable salt thereof or a hydrate thereof.

摘要翻译： 一种有效治疗和预防精神疾病如精神分裂症，焦虑及其相关疾病，抑郁症，双相情感障碍和癫痫的药物。 该药物拮抗II型代谢型谷氨酸受体的作用，并且在口服给药中表现出高活性。由式[I]表示的2-氨基 - 双环[3.1.0]己烷-2,6-二羧酸酯衍生物[其中R1和R2为 相同或不同，并且各自表示氢原子，C 1-10烷基等; X表示氢原子或氟原子; Y表示-OCHR 3 R 4等（其中R 3和R 4相同或不同，并且各自表示氢原子，C 1-10烷基等; n表示1或2的整数）]，其药学上可接受的盐或 水合物。

公开(公告)号：US07951811B2

公开(公告)日：2011-05-31

申请号：US11630042

申请日：2005-06-24

申请人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Tomoko Tamita ,  Ludo E. J. Kennis

发明人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Tomoko Tamita ,  Ludo E. J. Kennis

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P25/24 ,  A61P25/28 ,  A61P25/16 ,  A61P29/00

CPC分类号： C07D471/04 ,  C07D487/04

摘要： [PROBLEM TO BE SOLVED]An object of the present invention is to provide an antagonist against CRF receptors and/or an agonist for δ receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal diseases, drug dependence, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, pain, etc.[SOLUTION]A pyrrolopyrimidine or pyrrolopyridine derivative substituted with a cyclic amino group represented by the following a [I] has a high affinity for CRF receptors and/or δ receptors, and is effective against diseases in which CRF is considered to be involved.

摘要翻译： [待解决的问题]本发明的目的是提供一种抗CRF受体拮抗剂和/或对δ受体的激动剂，其有效作为涉及CRF的疾病的治疗或预防剂，例如 抑郁症，焦虑症，阿尔茨海默氏病，帕金森病，亨廷顿氏舞蹈病，进食障碍，高血压，胃肠道疾病，药物依赖，脑梗塞，脑缺血，脑水肿，头部外伤，炎症，免疫相关疾病，脱发，肠易激综合征， 睡眠障碍，癫痫，皮肤病，精神分裂症，疼痛等。解决方案：由以下[I]表示的环状氨基取代的吡咯并嘧啶或吡咯并吡啶衍生物对CRF受体和/或δ受体具有高亲和性，并且是 对抗CRF被认为参与的疾病有效。

公开(公告)号：US20090306408A1

公开(公告)日：2009-12-10

申请号：US12511482

申请日：2009-07-29

申请人： Akito YASUHARA ,  Kazunari Sakagami ,  Hiroshi Ohta ,  Atsuro Nakazato

发明人： Akito YASUHARA ,  Kazunari Sakagami ,  Hiroshi Ohta ,  Atsuro Nakazato

IPC分类号： C07D317/18 ,  C07C69/753 ,  C07D305/12

CPC分类号： C07C229/50 ,  C07D307/88

摘要： A drug effective for the treatment and prevention of psychiatric disorders such as schizophrenia, anxiety and related ailments thereof, depression, bipolar disorder and epilepsy. The drug antagonizes the action of group II metabotropic glutamate receptors and shows high activity in oral administrationA 2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic ester derivative represented by formula [I] [wherein R1 and R2 are identical or different, and each represents a hydrogen atom, a C1-10alkyl group or the like; X represents a hydrogen atom or a fluorine atom; Y represents —OCHR3R4 or the like (wherein R3 and R4 are identical or different, and each represents a hydrogen atom, a C1-10alkyl group or the like; and n represents integer 1 or 2)], a pharmaceutically acceptable salt thereof or a hydrate thereof.

摘要翻译： 一种有效治疗和预防精神疾病如精神分裂症，焦虑及其相关疾病，抑郁症，双相情感障碍和癫痫的药物。 该药物拮抗II型代谢型谷氨酸受体的作用，并且在口服给药中表现出高活性。由式[I]表示的2-氨基 - 双环[3.1.0]己烷-2,6-二羧酸酯衍生物[其中R1和R2为 相同或不同，并且各自表示氢原子，C 1-10烷基等; X表示氢原子或氟原子; Y表示-OCHR 3 R 4等（其中R 3和R 4相同或不同，并且各自表示氢原子，C 1-10烷基等; n表示1或2的整数）]，其药学上可接受的盐或 水合物。

公开(公告)号：US20070293670A1

公开(公告)日：2007-12-20

申请号：US11630041

申请日：2005-06-24

申请人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Ludo Kennis ,  Marcel De Bruyn

发明人： Atsuro Nakazato ,  Taketoshi Okubo ,  Dai Nozawa ,  Ludo Kennis ,  Marcel De Bruyn

IPC分类号： C07D487/04

CPC分类号： C07D487/04 ,  C07D471/04

摘要： [PROBLEM TO BE SOLVED]An object of the present invention is to provide an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal diseases, drug dependence, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alopecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, pain, etc. [SOLUTION]A pyrrolopyrimidine or pyrrolopyridine derivative substituted with tetrahydropyridine represented by the following formula [I]: has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

摘要翻译： [待解决的问题]本发明的目的是提供一种抗CRF受体的拮抗剂，其作为治疗或预防药物是有效的，其涉及CRF被认为涉及的疾病，例如抑郁症，焦虑症，阿尔茨海默病，帕金森病 疾病，亨廷顿氏舞蹈病，饮食失调，高血压，胃肠道疾病，药物依赖，脑梗死，脑缺血，脑水肿，头部外伤，炎症，免疫相关疾病，脱发，肠易激综合征，睡眠障碍，癫痫，皮肤病，精神分裂症 ，疼痛等。[解决方案]由下式[I]表示的用四氢吡啶取代的吡咯并嘧啶或吡咯并吡啶衍生物对CRF受体具有高亲和力，并且对于被认为涉及CRF的疾病是有效的。

公开(公告)号：US20070270588A1

公开(公告)日：2007-11-22

申请号：US10591765

申请日：2005-03-04

申请人： Francois Bischoff ,  Ludo Kennis ,  Mirielle Braeken ,  Gaston Diels ,  Atsuro Nakazato

发明人： Francois Bischoff ,  Ludo Kennis ,  Mirielle Braeken ,  Gaston Diels ,  Atsuro Nakazato

IPC分类号： C07D487/04

CPC分类号： C07D487/04

摘要： According to the present invention, there is provided an antagonist against CRF receptors which is effective as a therapeutic or prophylactic agent for diseases in which CRF is considered to be involved, such as depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastro-intestinal diseases, drug dependence, cerebral infarction, cerebral ischemia, cerebral edema, cephalic external wound, inflammation, immunity-related diseases, alpecia, irritable bowel syndrome, sleep disorders, epilepsy, dermatitides, schizophrenia, pain, etc. A pyrrolopyrimidine derivative represented by the following formula [I]: has a high affinity for CRF receptors and is effective against diseases in which CRF is considered to be involved.

摘要翻译： 根据本发明，提供了一种抗CRF受体的拮抗剂，其作为治疗或预防药物是有效的，其涉及CRF被认为涉及的疾病，例如抑郁症，焦虑症，阿尔茨海默氏病，帕金森病，亨廷顿氏舞蹈病，进食 疾病，高血压，胃肠疾病，药物依赖，脑梗塞，脑缺血，脑水肿，头部外伤，炎症，免疫相关疾病，特异性，肠易激综合征，睡眠障碍，癫痫，皮肤病，精神分裂症，疼痛等 由下式[I]表示的吡咯并嘧啶衍生物对CRF受体具有高亲和力，并且对于涉及CRF的疾病有效。

公开(公告)号：US20050119345A1

公开(公告)日：2005-06-02

申请号：US10500101

申请日：2002-12-26

申请人： Atsuro Nakazato ,  Shigeyuki Chaki ,  Kazunari Sakagami ,  Ryoko Dean ,  Hiroshi Ohta ,  Shiho Hirota ,  Akito Yasuhara

发明人： Atsuro Nakazato ,  Shigeyuki Chaki ,  Kazunari Sakagami ,  Ryoko Dean ,  Hiroshi Ohta ,  Shiho Hirota ,  Akito Yasuhara

IPC分类号： A61K45/00 ,  A61K31/00 ,  A61K31/196 ,  A61K31/198 ,  A61K31/381 ,  A61P25/18 ,  A61P43/00 ,  C07C229/50 ,  C07C237/04 ,  C07C237/26 ,  C07C255/54 ,  C07D333/16 ,  A61K31/195 ,  C07C229/32

CPC分类号： A61K31/381 ,  A61K31/00 ,  A61K31/196 ,  A61K31/198 ,  C07C229/50 ,  C07C237/04 ,  C07C237/26 ,  C07C255/54 ,  C07C2601/08 ,  C07C2602/18 ,  C07D333/16

摘要： An antidepressant comprising, as an active ingredient, a compound having an antagonistic effect on group II metabotropic glutamate receptors, as well as a 2-amino-3-alkoxy-6-fluoro-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative of Formula [I]: [wherein R1 and R2, which may be the same or different, each represent a hydroxyl group, a C1-10 alkoxy group, etc.; R3 represents a C1-10 acyl group, a C1-6 alkoxy-C1-6 acyl group, etc.; and R4 and R5, which may be the same or different, each represent a hydrogen atom, a C1-10 alkyl group, etc.] or a pharmaceutically acceptable salt or hydrate thereof.

摘要翻译： 作为活性成分的抗抑郁药，其具有对II型代谢型谷氨酸受体具有拮抗作用的化合物，以及2-氨基-3-烷氧基-6-氟 - 双环[3.1.0]己烷-2,6-二 式[I]的二羧酸衍生物：其中R 1和R 2可以相同或不同，各自表示羟基，C 1〜 1-10个烷氧基等; R 3表示C 1-10烷基酰基，C 1-6烷氧基-C 1-6烷基， 酰基等; 和R 4和R 5可以相同或不同，各自表示氢原子，C 1-10烷基， 等]或其药学上可接受的盐或水合物。

公开(公告)号：US06600038B1

公开(公告)日：2003-07-29

申请号：US09914534

申请日：2001-08-30

申请人： Atsuro Nakazato ,  Taketoshi Okubo ,  Toshihito Kumagai ,  Kazuyuki Tomisawa

发明人： Atsuro Nakazato ,  Taketoshi Okubo ,  Toshihito Kumagai ,  Kazuyuki Tomisawa

IPC分类号： C07D47334

CPC分类号： A61K31/519 ,  C07D473/00 ,  C07D487/04

摘要： Carbamoyl tetrahydropyridine derivatives represented by the formula: [in the formula, R1 and R2 are identical or different, and each represents a hydrogen atom, a C1-C5 alkyl group, or the like; Y1-Y2 represents (R4)C═C(R5), (R6)C═N, N═N, (R7)N—CO, or N═C(R8); X1, X2, and X3 are identical or different, and each represents a hydrogen atom, a halogen atom, or the like; R3, R4, R5, and R6 are identical or different, and each represents a hydrogen atom or an alkyl group; R7 represents a hydrogen atom, a C1-C5 alkyl group, or the like; and R8 represents a hydrogen atom or a carbamoyl group] or a pharmaceutically acceptable salt thereof, and intermediates for the preparation thereof are provided. The derivatives described above are effective for diseases which are believed to involve CRF.

摘要翻译： 由下式表示的氨基甲酰基四氢吡啶衍生物：[式中，R 1和R 2相同或不同，各自表示氢原子，C 1 -C 5烷基等; Y1-Y2表示（R4）C = C（R5），（R6）C = N，N = N，（R7）N-CO或N = C（R8） X1，X2和X3相同或不同，各自表示氢原子，卤素原子等; R3，R4，R5和R6相同或不同，各自表示氢原子或烷基; R7表示氢原子，C1-C5烷基等; 并且R8表示氢原子或氨基甲酰基]或其药学上可接受的盐，并且提供其制备的中间体。上述衍生物对于被认为涉及CRF的疾病是有效的。