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：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：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。

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：US07662810B2

公开(公告)日：2010-02-16

申请号：US11578007

申请日：2005-02-24

申请人： Bong-Jin Kim ,  Jae-Hak Kim ,  Jae-Yang Kong ,  Heeyeong Cho ,  Young-Ro Choi ,  Chang-Seob Kim

发明人： Bong-Jin Kim ,  Jae-Hak Kim ,  Jae-Yang Kong ,  Heeyeong Cho ,  Young-Ro Choi ,  Chang-Seob Kim

IPC分类号： C07D477/20 ,  A61K31/407 ,  A61P31/04 ,  C07D205/04 ,  C07F9/572

CPC分类号： C07D477/20

摘要： A 2-arylmethylazetidine carbapenem derivative of formula (I) or a pharmaceutically acceptable salt thereof exhibits a wide spectrum of antibacterial activities against Gram-positive and Gram-negative bacteria and excellent antibacterial activities against resistant bacteria such as methicillinresistant Staphylococcus aureus (MRSA) and quinolone-resistant strains (QRS):

摘要翻译： 式（I）的2-芳基甲基氮杂环丁烷碳青霉烯衍生物或其药学上可接受的盐对抗革兰氏阳性和革兰氏阴性细菌具有广谱的抗菌活性，对耐甲氧西林金黄色葡萄球菌（MRSA）和喹诺酮类抗性细菌具有优异的抗菌活性 抗性菌株（QRS）：

公开(公告)号：US20070244089A1

公开(公告)日：2007-10-18

申请号：US11578007

申请日：2005-02-24

申请人： Bong-Jin Kim ,  Jae-Hak Kim ,  Jae-Yang Kong ,  Heeyeong Cho ,  Young-Ro Choi ,  Chang-Seob Kim

发明人： Bong-Jin Kim ,  Jae-Hak Kim ,  Jae-Yang Kong ,  Heeyeong Cho ,  Young-Ro Choi ,  Chang-Seob Kim

IPC分类号： C07D477/20 ,  A61K31/407

CPC分类号： C07D477/20

摘要： A 2-arylmethylazetidine carbapenem derivative of formula (I) or a pharmaceutically acceptable salt thereof exhibits a wide spectrum of antibacterial activities against Gram-positive and Gram-negative bacteria and excellent antibacterial activities against resistant bacteria such as methicillinresistant Staphylococcus aureus (MRSA) and quinolone-resistant strains (QRS).

摘要翻译： 式（I）的2-芳基甲基氮杂环丁烷碳青霉烯衍生物或其药学上可接受的盐对抗革兰氏阳性和革兰氏阴性细菌具有广谱的抗菌活性，对耐甲氧西林金黄色葡萄球菌（MRSA）和喹诺酮类抗性细菌具有优异的抗菌活性 抗性菌株（QRS）。

公开(公告)号：US20110118229A1

公开(公告)日：2011-05-19

申请号：US12742966

申请日：2008-11-18

申请人： Young-Ro Choi ,  Bong-Jin Kim ,  Bok-Ju Song ,  Bum-Soo Lee ,  Dong-Woo Lee ,  Dong-Geun Seo ,  Young-Cheol Jeong ,  Si-Min Kim ,  Jee-Woong Kwon ,  Jae-Yang Kong ,  Heeyeong Cho

发明人： Young-Ro Choi ,  Bong-Jin Kim ,  Bok-Ju Song ,  Bum-Soo Lee ,  Dong-Woo Lee ,  Dong-Geun Seo ,  Young-Cheol Jeong ,  Si-Min Kim ,  Jee-Woong Kwon ,  Jae-Yang Kong ,  Heeyeong Cho

IPC分类号： A61K31/407 ,  C07D477/20 ,  C07D477/08 ,  C07D477/06 ,  A61P31/04

CPC分类号： C07D477/20

摘要： The present invention provides a 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives or their pharmaceutically acceptable salts show high oral absorption rate, and thus can be orally administered. The active metabolites thereof have a broad spectrum of antibacterial activities against Gram-positive and Gram-negative bacteria and excellent antibacterial activities against methicillin-resistant Staphylococcus aurus (MRSA) and quinolone-resistant strains (QRS). In particular, the acid addition salts of the 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives are obtained in crystalline forms having excellent stability.

摘要翻译： 本发明提供2-芳基甲基氮杂环丁烷 - 碳青霉烯-3-羧酸酯衍生物或其药学上可接受的盐，其制备方法和包含其的药物组合物。 2-芳基甲基氮杂环丁烷 - 碳青霉烯-3-羧酸酯衍生物或其药学上可接受的盐显示出高的口服吸收率，因此可以口服给药。 其活性代谢物对革兰氏阳性和革兰氏阴性菌具有广谱的抗菌活性，对耐甲氧西林金黄色葡萄球菌（MRSA）和喹诺酮耐药菌株（QRS）具有优异的抗菌活性。 特别地，2-芳基甲基氮杂环丁烷 - 碳青霉烯-3-羧酸酯衍生物的酸加成盐以稳定性优异的结晶形式得到。