公开(公告)号：US08372844B2

公开(公告)日：2013-02-12

申请号：US13454817

申请日：2012-04-24

申请人： Jae Yang Kong ,  Woo-Kyu Park ,  Heeyeong Cho ,  Daeyoung Jeong ,  Gildon Choi ,  Hun Yeong Koh ,  Sang Hee Kim ,  Ae Nim Pae ,  Yong Seo Cho ,  Joo Hwan Cha ,  Hyunah Choo ,  Sang Eun Chae ,  Hee-Yoon Lee

发明人： Jae Yang Kong ,  Woo-Kyu Park ,  Heeyeong Cho ,  Daeyoung Jeong ,  Gildon Choi ,  Hun Yeong Koh ,  Sang Hee Kim ,  Ae Nim Pae ,  Yong Seo Cho ,  Joo Hwan Cha ,  Hyunah Choo ,  Sang Eun Chae ,  Hee-Yoon Lee

IPC分类号： A61K31/496 ,  C07D231/12 ,  C07D401/04 ,  C07D409/04

CPC分类号： C07D403/06

摘要： The present invention relates to a novel piperazinyl-propyl-pyrazole derivative, a method of its preparation and a pharmaceutically acceptable composition comprising the same. The novel piperazinyl-propyl-pyrazole derivative of the present invention has superior selective affinity for dopamine D4 receptor, can effectively inhibit psychotic behavior (cage climbing) induced by apomorphine, and has relatively low adverse effects in mouse rotarod test. Therefore, it can be developed as a therapeutic agent for the treatment and prevention of central nervous system (CNS) disorders, in particular, schizophrenia, attention deficit hyperactivity disorder, depression, stress diseases, panic disorder, phobia, obsessive-compulsive disorder, posttraumatic stress disorder, cognitive disorder, Alzheimer's disease, Parkinson's disease, anxiety, paraphrenia, mania, seizure disorder, personality disorder, migraine, drug addiction, alcohol addiction, obesity, eating disorder, and sleeping disorder.

摘要翻译： 本发明涉及一种新的哌嗪基 - 丙基 - 吡唑衍生物，其制备方法和包含其的药学上可接受的组合物。 本发明的新型哌嗪基 - 丙基 - 吡唑衍生物对多巴胺D4受体具有优异的选择性亲和力，可有效抑制阿扑吗啡诱导的精神病性行为（笼养），并在小鼠旋转试验中具有较低的不良反应。 因此，它可以被开发为用于治疗和预防中枢神经系统（CNS）障碍，特别是精神分裂症，注意缺陷多动障碍，抑郁症，压力疾病，恐慌症，恐惧症，强迫症，创伤后疼痛的治疗剂 压力障碍，认知障碍，阿尔茨海默病，帕金森病，焦虑症，过敏性反应，躁狂症，癫痫发作，人格障碍，偏头痛，药物成瘾，酒精成瘾，肥胖，进食障碍和睡眠障碍。

公开(公告)号：US20120209001A1

公开(公告)日：2012-08-16

申请号：US13454817

申请日：2012-04-24

申请人： Jae Yang KONG ,  Park Woo-Kyu ,  Heeyeong CHO ,  Daeyoung JEONG ,  Gildon CHOI ,  Hun Yeong KOH ,  Sang Hee KIM ,  Ae Nim PAE ,  Yong Seo CHO ,  Joo Hwan CHA ,  Hyunah CHOO ,  Sang Eun CHAE ,  Hee-Yoon LEE

发明人： Jae Yang KONG ,  Park Woo-Kyu ,  Heeyeong CHO ,  Daeyoung JEONG ,  Gildon CHOI ,  Hun Yeong KOH ,  Sang Hee KIM ,  Ae Nim PAE ,  Yong Seo CHO ,  Joo Hwan CHA ,  Hyunah CHOO ,  Sang Eun CHAE ,  Hee-Yoon LEE

IPC分类号： C07D403/10 ,  C07D401/14

CPC分类号： C07D403/06

摘要： The present invention relates to a novel piperazinyl-propyl-pyrazole derivative, a method of its preparation and a pharmaceutically acceptable composition comprising the same. The novel piperazinyl-propyl-pyrazole derivative of the present invention has superior selective affinity for dopamine D4 receptor, can effectively inhibit psychotic behavior (cage climbing) induced by apomorphine, and has relatively low adverse effects in mouse rotarod test. Therefore, it can be developed as a therapeutic agent for the treatment and prevention of central nervous system (CNS) disorders, in particular, schizophrenia, attention deficit hyperactivity disorder, depression, stress diseases, panic disorder, phobia, obsessive-compulsive disorder, posttraumatic stress disorder, cognitive disorder, Alzheimer's disease, Parkinson's disease, anxiety, paraphrenia, mania, seizure disorder, personality disorder, migraine, drug addiction, alcohol addiction, obesity, eating disorder, and sleeping disorder.

摘要翻译： 本发明涉及一种新的哌嗪基 - 丙基 - 吡唑衍生物，其制备方法和包含其的药学上可接受的组合物。 本发明的新型哌嗪基 - 丙基 - 吡唑衍生物对多巴胺D4受体具有优异的选择性亲和力，可有效抑制阿扑吗啡诱导的精神病性行为（笼养），并在小鼠旋转试验中具有较低的不良反应。 因此，它可以被开发为用于治疗和预防中枢神经系统（CNS）障碍，特别是精神分裂症，注意缺陷多动障碍，抑郁症，压力疾病，恐慌症，恐惧症，强迫症，创伤后疼痛的治疗剂 压力障碍，认知障碍，阿尔茨海默病，帕金森病，焦虑症，过敏性反应，躁狂症，癫痫发作，人格障碍，偏头痛，药物成瘾，酒精成瘾，肥胖，进食障碍和睡眠障碍。

公开(公告)号：US20100063286A1

公开(公告)日：2010-03-11

申请号：US12530312

申请日：2007-07-13

申请人： Jae Yang Kong ,  Woo-Kyu Park ,  Heeyeong Cho ,  Daeyoung Jeong ,  Gildon Choi ,  Hun Yeong Koh ,  Sang Hee Kim ,  Ae Nim Pae ,  Yong Seo Cho ,  Joo Hwan Cha ,  Hyunah Choo ,  Sang Eun Chae ,  Hee-Yoon Lee

发明人： Jae Yang Kong ,  Woo-Kyu Park ,  Heeyeong Cho ,  Daeyoung Jeong ,  Gildon Choi ,  Hun Yeong Koh ,  Sang Hee Kim ,  Ae Nim Pae ,  Yong Seo Cho ,  Joo Hwan Cha ,  Hyunah Choo ,  Sang Eun Chae ,  Hee-Yoon Lee

IPC分类号： C07D403/06

CPC分类号： C07D403/06

摘要： The present invention relates to a novel piperazinyl-propyl-pyrazole derivative, a method of its preparation and a pharmaceutically acceptable composition comprising the same. The novel piperazinyl-propyl-pyrazole derivative of the present invention has superior selective affinity for dopamine D4 receptor, can effectively inhibit psychotic behavior (cage climbing) induced by apomorphine, and has relatively low adverse effects in mouse rotarod test. Therefore, it can be developed as a therapeutic agent for the treatment and prevention of central nervous system (CNS) disorders, in particular, schizophrenia, attention deficit hyperactivity disorder, depression, stress diseases, panic disorder, phobia, obsessive-compulsive disorder, posttraumatic stress disorder, cognitive disorder, Alzheimer's disease, Parkinson's disease, anxiety, paraphrenia, mania, seizure disorder, personality disorder, migraine, drug addiction, alcohol addiction, obesity, eating disorder, and sleeping disorder.

摘要翻译： 本发明涉及一种新的哌嗪基 - 丙基 - 吡唑衍生物，其制备方法和包含其的药学上可接受的组合物。 本发明的新型哌嗪基 - 丙基 - 吡唑衍生物对多巴胺D4受体具有优异的选择性亲和力，可有效抑制阿扑吗啡诱导的精神病性行为（笼养），并在小鼠旋转试验中具有较低的不良反应。 因此，它可以被开发为用于治疗和预防中枢神经系统（CNS）障碍，特别是精神分裂症，注意缺陷多动障碍，抑郁症，压力疾病，恐慌症，恐惧症，强迫症，创伤后疼痛的治疗剂 压力障碍，认知障碍，阿尔茨海默病，帕金森病，焦虑症，过敏性反应，躁狂症，癫痫发作，人格障碍，偏头痛，药物成瘾，酒精成瘾，肥胖，进食障碍和睡眠障碍。

公开(公告)号：US08236806B2

公开(公告)日：2012-08-07

申请号：US12530312

申请日：2007-07-13

申请人： Jae Yang Kong ,  Woo-Kyu Park ,  Heeyeong Cho ,  Daeyoung Jeong ,  Gildon Choi ,  Hun Yeong Koh ,  Sang Hee Kim ,  Ae Nim Pae ,  Yong Seo Cho ,  Joo Hwan Cha ,  Hyunah Choo ,  Sang Eun Chae ,  Hee-Yoon Lee

发明人： Jae Yang Kong ,  Woo-Kyu Park ,  Heeyeong Cho ,  Daeyoung Jeong ,  Gildon Choi ,  Hun Yeong Koh ,  Sang Hee Kim ,  Ae Nim Pae ,  Yong Seo Cho ,  Joo Hwan Cha ,  Hyunah Choo ,  Sang Eun Chae ,  Hee-Yoon Lee

IPC分类号： A61K31/496 ,  C07D231/12 ,  C07D401/04 ,  C07D409/04

CPC分类号： C07D403/06

摘要： The present invention relates to a novel piperazinyl-propyl-pyrazole derivative, a method of its preparation and a pharmaceutically acceptable composition comprising the same. The novel piperazinyl-propyl-pyrazole derivative of the present invention has superior selective affinity for dopamine D4 receptor, can effectively inhibit psychotic behavior (cage climbing) induced by apomorphine, and has relatively low adverse effects in mouse rotarod test. Therefore, it can be developed as a therapeutic agent for the treatment and prevention of central nervous system (CNS) disorders, in particular, schizophrenia, attention deficit hyperactivity disorder, depression, stress diseases, panic disorder, phobia, obsessive-compulsive disorder, posttraumatic stress disorder, cognitive disorder, Alzheimer's disease, Parkinson's disease, anxiety, paraphrenia, mania, seizure disorder, personality disorder, migraine, drug addiction, alcohol addiction, obesity, eating disorder, and sleeping disorder.

摘要翻译： 本发明涉及一种新的哌嗪基 - 丙基 - 吡唑衍生物，其制备方法和包含其的药学上可接受的组合物。 本发明的新型哌嗪基 - 丙基 - 吡唑衍生物对多巴胺D4受体具有优异的选择性亲和力，可有效抑制阿扑吗啡诱导的精神病性行为（笼养），并在小鼠旋转试验中具有较低的不良反应。 因此，它可以被开发为用于治疗和预防中枢神经系统（CNS）障碍，特别是精神分裂症，注意缺陷多动障碍，抑郁症，压力疾病，恐慌症，恐惧症，强迫症，创伤后疼痛的治疗剂 压力障碍，认知障碍，阿尔茨海默病，帕金森病，焦虑症，过敏性反应，躁狂症，癫痫发作，人格障碍，偏头痛，药物成瘾，酒精成瘾，肥胖，进食障碍和睡眠障碍。

公开(公告)号：US20100145043A1

公开(公告)日：2010-06-10

申请号：US12570492

申请日：2009-09-30

申请人： Young-Dae Gong ,  Taeho Lee ,  Moon-Kook Jeon ,  Heeyeong Cho ,  Jae Yang Kong ,  Gildon Choi ,  Dae Young Jeong ,  Soon-Hee Hwang

发明人： Young-Dae Gong ,  Taeho Lee ,  Moon-Kook Jeon ,  Heeyeong Cho ,  Jae Yang Kong ,  Gildon Choi ,  Dae Young Jeong ,  Soon-Hee Hwang

IPC分类号： C07D417/14 ,  C07D417/04 ,  C07D277/56

CPC分类号： C07D277/56 ,  C07D417/04 ,  C07D417/12

摘要： Disclosed herein are 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole derivatives, a preparation method thereof, and a therapeutic agent for treating inflammatory diseases induced by SPC, which contains the derivative as an active ingredient. The anti-inflammatory effect of the 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole derivatives was analyzed through a test employing human dermal cells and an animal test using mice and, as a result, it was found that the derivatives showed excellent inhibitory activity on SPC receptor compared to thiazole derivatives known in the prior art. Thus, the 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole derivatives or pharmaceutically acceptable salts thereof are useful as active ingredients in therapeutic agents for treating inflammatory diseases, such as inflammation, pruritus and skin infection, which appear in atopic dermatitis and other diseases induced by SPC activity. wherein R1, R2, R3 and R4 are as defined in the specification.

摘要翻译： 本文公开了2,4-二取代-5-氨基羰基-1,3-噻唑衍生物，其制备方法和用于治疗由SPC诱导的炎症性疾病的治疗剂，其含有该衍生物作为活性成分。 通过使用人真皮细胞的试验和使用小鼠的动物试验分析2,4-二取代-5-氨基羰基-1,3-噻唑衍生物的抗炎作用，结果发现衍生物 与现有技术中已知的噻唑衍生物相比，对SPC受体显示出优异的抑制活性。 因此，2,4-二取代-5-氨基羰基-1,3-噻唑衍生物或其药学上可接受的盐可用作用于治疗炎性疾病如炎症，瘙痒和皮肤感染的治疗剂中的活性成分，其出现在特应性 皮炎和其他由SPC活动引起的疾病。 其中R1，R2，R3和R4如说明书中所定义。

公开(公告)号：US07915405B2

公开(公告)日：2011-03-29

申请号：US12570492

申请日：2009-09-30

申请人： Young-Dae Gong ,  Taeho Lee ,  Moon-Kook Jeon ,  Heeyeong Cho ,  Jae Yang Kong ,  Gildon Choi ,  Dae Young Jeong ,  Soon-Hee Hwang

发明人： Young-Dae Gong ,  Taeho Lee ,  Moon-Kook Jeon ,  Heeyeong Cho ,  Jae Yang Kong ,  Gildon Choi ,  Dae Young Jeong ,  Soon-Hee Hwang

IPC分类号： C07D413/14 ,  C07D413/10 ,  C07D417/10 ,  C07D417/14 ,  C07D277/54 ,  A61K31/5377 ,  A61K31/497 ,  A61K31/454 ,  A61K31/431

CPC分类号： C07D277/56 ,  C07D417/04 ,  C07D417/12

摘要： Disclosed herein are 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole derivatives, a preparation method thereof, and a therapeutic agent for treating inflammatory diseases induced by SPC, which contains the derivative as an active ingredient. The anti-inflammatory effect of the 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole derivatives was analyzed through a test employing human dermal cells and an animal test using mice and, as a result, it was found that the derivatives showed excellent inhibitory activity on SPC receptor compared to thiazole derivatives known in the prior art. Thus, the 2,4-disubstituted-5-aminocarbonyl-1,3-thiazole derivatives or pharmaceutically acceptable salts thereof are useful as active ingredients in therapeutic agents for treating inflammatory diseases, such as inflammation, pruritus and skin infection, which appear in atopic dermatitis and other diseases induced by SPC activity. wherein R1, R2, R3 and R4 are as defined in the specification.

摘要翻译： 本文公开了2,4-二取代-5-氨基羰基-1,3-噻唑衍生物，其制备方法和用于治疗由SPC诱导的炎症性疾病的治疗剂，其含有该衍生物作为活性成分。 通过使用人真皮细胞的试验和使用小鼠的动物试验分析2,4-二取代-5-氨基羰基-1,3-噻唑衍生物的抗炎作用，结果发现衍生物 与现有技术中已知的噻唑衍生物相比，对SPC受体显示出优异的抑制活性。 因此，2,4-二取代-5-氨基羰基-1,3-噻唑衍生物或其药学上可接受的盐可用作用于治疗炎性疾病如炎症，瘙痒和皮肤感染的治疗剂中的活性成分，其出现在特应性 皮炎和其他由SPC活动引起的疾病。 其中R1，R2，R3和R4如说明书中所定义。