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：US20070259867A1

公开(公告)日：2007-11-08

申请号：US11600391

申请日：2006-11-16

申请人： Yong Seo Cho ,  Hyunah Choo ,  Ae Nim Pae ,  Joo Hwan Cha ,  Hun Yeong Koh ,  Hwa-Sil Kim ,  Hyewhon Rhim ,  Seon Hee Seo

发明人： Yong Seo Cho ,  Hyunah Choo ,  Ae Nim Pae ,  Joo Hwan Cha ,  Hun Yeong Koh ,  Hwa-Sil Kim ,  Hyewhon Rhim ,  Seon Hee Seo

IPC分类号： A61K31/5377 ,  A61K31/496 ,  A61K31/454 ,  A61K31/4035 ,  C07D413/02 ,  C07D403/02

CPC分类号： C07D209/48

摘要： The present invention relates to 1,3-dioxoisoindole derivatives of Formula (1) or pharmaceutically acceptable salts thereof, a preparation method thereof and use thereof as a T-type calcium channel antagonist, based on the fact that 1,3-dioxoisoindole derivatives of Formula (1) show selective antagonistic activity against T-type calcium channel, thus being effective in treating brain diseases, cardiac diseases and neurogenic pains: wherein R1 is a phenyl or a benzyl group, optionally substituted with a moiety selected from the group consisting of a halogen atom, a C1-C6 alkoxy, a C1-C6 alkyl, and a cyano group; R2 is a heterocyclic group selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, and piperazinyl groups, wherein the heterocyclic group is optionally substituted with a C1-C6 alkyl group; and n is 1 or 2.

摘要翻译： 本发明涉及式（1）的1,3-二氧代异吲哚衍生物或其药学上可接受的盐，其制备方法及其作为T型钙通道拮抗剂的用途，基于以下事实： 式（1）表示对T型钙通道的选择性拮抗活性，因此有效治疗脑疾病，心脏病和神经源性疼痛：其中R 1是苯基或苄基，任选被 选自卤素原子，C 1 -C 6 - 烷氧基，C 1 -C 6烷氧基，C 1 -C 6 - 烷基和氰基; R 2是选自哌啶基，吡咯烷基，吗啉基和哌嗪基的杂环基，其中杂环基任选被C 1 -C 6烷基取代， C 1-6烷基; n为1或2。

公开(公告)号：US07319098B2

公开(公告)日：2008-01-15

申请号：US11600391

申请日：2006-11-16

申请人： Yong Seo Cho ,  Hyunah Choo ,  Ae Nim Pae ,  Joo Hwan Cha ,  Hun Yeong Koh ,  Hwa-Sil Kim ,  Hyewhon Rhim ,  Seon Hee Seo

发明人： Yong Seo Cho ,  Hyunah Choo ,  Ae Nim Pae ,  Joo Hwan Cha ,  Hun Yeong Koh ,  Hwa-Sil Kim ,  Hyewhon Rhim ,  Seon Hee Seo

IPC分类号： A61K31/5377 ,  A61K31/496 ,  A61K31/454 ,  A61K31/4025 ,  C07D413/12 ,  C07D403/12 ,  C07D401/12 ,  C07D207/06

CPC分类号： C07D209/48

摘要： The present invention relates to 1,3-dioxoisoindole derivatives of Formula (1) or pharmaceutically acceptable salts thereof, a preparation method thereof and use thereof as a T-type calcium channel antagonist, based on the fact that 1,3-dioxoisoindole derivatives of Formula (1) show selective antagonistic activity against T-type calcium channel, thus being effective in treating brain diseases, cardiac diseases and neurogenic pains: wherein R1 is a phenyl or a benzyl group, optionally substituted with a moiety selected from the group consisting of a halogen atom, a C1-C6 alkoxy, a C1-C6 alkyl, and a cyano group; R2 is a heterocyclic group selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, and piperazinyl groups, wherein the heterocyclic group is optionally substituted with a C1-C6 alkyl group; and n is 1 or 2.

摘要翻译： 本发明涉及式（1）的1,3-二氧代异吲哚衍生物或其药学上可接受的盐，其制备方法及其作为T型钙通道拮抗剂的用途，基于以下事实： 式（1）表示对T型钙通道的选择性拮抗活性，因此有效治疗脑疾病，心脏病和神经源性疼痛：其中R 1是苯基或苄基，任选被 选自卤素原子，C 1 -C 6烷氧基，C 1 -C 6烷基的部分 烷基和氰基; R 2是选自哌啶基，吡咯烷基，吗啉基和哌嗪基的杂环基，其中杂环基任选被C 1 -C 6烷基取代， C 1-6烷基; n为1或2。

公开(公告)号：US07223874B2

公开(公告)日：2007-05-29

申请号：US11303125

申请日：2005-12-15

申请人： Yong Seo Cho ,  Joo Hwan Cha ,  Ae Nim Pae ,  Hun Yeong Koh ,  Chul Shin

发明人： Yong Seo Cho ,  Joo Hwan Cha ,  Ae Nim Pae ,  Hun Yeong Koh ,  Chul Shin

IPC分类号： C07D493/00 ,  C07D311/02

CPC分类号： C07D493/02

摘要： The present invention relates to bicyclic tetrahydrofuran lactone derivatives of Formula (1) and a preparation method thereof, and particularly it relates to a process of preparing compounds of Formula (1) by performing an intramolecular cyclization of tetrahydrofuran-allenic acid derivatives in the presence of a phenyl halide, a palladium catalyst and a base: wherein n is 1 or 2, and R is phenyl optionally substituted with C1–C6 alkyl, C1–C6 alkoxy, hydroxyl or C1–C6 hydroxyalkyl group.

公开(公告)号：US07241906B2

公开(公告)日：2007-07-10

申请号：US11300966

申请日：2005-12-15

申请人： Yong Seo Cho ,  Ae Nim Pae ,  Joo Hwan Cha ,  Hun Yeong Koh ,  Chul Shin

发明人： Yong Seo Cho ,  Ae Nim Pae ,  Joo Hwan Cha ,  Hun Yeong Koh ,  Chul Shin

IPC分类号： C07D493/02

CPC分类号： C07D493/04

摘要： The present invention relates to bicyclic tetrahydrofuran derivatives of Formula (1) and a preparation method thereof, and particularly it relates to a process of preparing compounds of Formula (1) by performing an intramolecular cyclization of tetrahydrofuran-allenol derivatives in the presence of alcohol compound, transitional metal catalyst and carbon monoxide: wherein n is 1 or 2; R is phenyl optionally substituted with C1-C6 alkyl, C1-C6 alkoxy, hydroxyl or C1-C6 hydroxyalkyl group; and R1 is C1-C6 alkyl group.

摘要翻译： 本发明涉及式（1）的二环四氢呋喃衍生物及其制备方法，特别涉及通过在醇化合物存在下进行四氢呋喃 - 联苯酚衍生物的分子内环化制备式（1）化合物的方法 过渡金属催化剂和一氧化碳，其中n为1或2; R是任选被C 1 -C 6烷基，C 1 -C 6烷基，羟基或C 1 -C 6烷基取代的苯基 C 1 -C 6羟烷基; 且R 1是C 1 -C 6烷基。

公开(公告)号：US07094908B2

公开(公告)日：2006-08-22

申请号：US10327793

申请日：2002-12-23

申请人： Hun Yeong Koh ,  Kyung Il Choi ,  Yong Seo Cho ,  Ae Nim Pae ,  Joo Hwan Cha ,  Ye Sun Han ,  Jong Soo Lee ,  Hong Chul Yun

发明人： Hun Yeong Koh ,  Kyung Il Choi ,  Yong Seo Cho ,  Ae Nim Pae ,  Joo Hwan Cha ,  Ye Sun Han ,  Jong Soo Lee ,  Hong Chul Yun

IPC分类号： C20D209/48

CPC分类号： C07D209/48

摘要： A compound represented by a general formula (Ia) or (Ib) and a stereo-selective preparation method thereof using a carbonyl reductase which is separated from Kluyveromyces marxianus. The compound can be prepared by reduction of substituted β-keto ester and can be used as an intermediate in preparing β-lactam group antibiotics.

摘要翻译： 由通式（Ia）或（Ib）表示的化合物及其使用与马克斯克鲁维酵母分离的羰基还原酶的立体选择性制备方法。 该化合物可以通过还原取代的β-酮酯制备，并且可以用作制备β-内酰胺类抗生素的中间体。

公开(公告)号：US07388101B1

公开(公告)日：2008-06-17

申请号：US11732602

申请日：2007-04-04

申请人： Yong Seo Cho ,  Hyunah Choo ,  Joo Hwan Cha ,  Ae Nim Pae ,  Satish N. Chavre ,  Kyung Il Choi

发明人： Yong Seo Cho ,  Hyunah Choo ,  Joo Hwan Cha ,  Ae Nim Pae ,  Satish N. Chavre ,  Kyung Il Choi

IPC分类号： C07D307/02

CPC分类号： C07D307/12

摘要： The present invention relates to a tetrahydrofuran compound having cis substituents, the derivatives thereof and a process for preparing the same, and in particular relates to a dihydrofuran-3-ylidene triflate compound having cis substituents at C2 and C5 positions prepared through Prins-type cyclization using a homopropargylic alcohol derivative as a starting material in the presence of Lewis acid catalyst, a tetrahydrofuran compound having cis substituents at C2, C3 and C5 positions prepared through the hydrolysis of triflate group in the derivatives of the dihydrofuran-3-ylidene triflate compound, and a preparation method thereof.The derivatives and the target tetrahydrofuran compound prepared according to the present invention are hydrofuran compounds with novel structures having cis substituents at C2, C3 and/or C5 positions, which are useful as a derivative for synthesizing drugs such as an antagonist for neurokinin receptor.

摘要翻译： 本发明涉及具有顺式取代基的四氢​​呋喃化合物及其衍生物及其制备方法，特别涉及在C 2上具有顺式取代基的二氢呋喃-3-亚基三氟甲磺酸酯化合物和 在路易斯酸催化剂存在下，使用均二炔醇衍生物作为起始原料，在C 2 N 2上具有顺式取代基的四氢​​呋喃化合物，通过Prins-型环化制备的C 5 H 3位， 通过在二氢呋喃-3-亚基三氟甲磺酸酯化合物的衍生物中水解三氟甲磺酸酯基制备的C 3和C 5 H 3位及其制备方法。 根据本发明制备的衍生物和目标四氢呋喃化合物是具有在C 2，C 3和/或C 5上具有顺式取代基的新结构的氢呋喃化合物 其可用作合成药物的衍生物，例如用于神经激肽受体的拮抗剂。

公开(公告)号：US06955904B2

公开(公告)日：2005-10-18

申请号：US10306651

申请日：2002-11-26

申请人： Ye Sun Han ,  Hun Yeoung Koh ,  Hyewhon Rhim ,  Joo Hwan Cha ,  Wook Hyun Kim ,  Jung Ho Back

发明人： Ye Sun Han ,  Hun Yeoung Koh ,  Hyewhon Rhim ,  Joo Hwan Cha ,  Wook Hyun Kim ,  Jung Ho Back

IPC分类号： C12N15/09 ,  C12N1/21 ,  C12N9/02 ,  C12N15/53 ,  C12R1/645 ,  C07H21/04 ,  C12N1/20 ,  C12N15/00 ,  C12P21/04

CPC分类号： C12N9/0036

摘要： The invention is a gene coding for a quinone oxidoreductase from Kluyveromyces marxianus and a protein having an amino acid sequence expressed therefrom, which can be advantageously used in a reduction reaction of a quinone compound and synthesis of intermediates for a biologically active compound.

摘要翻译： 本发明是编码马克斯克鲁维酵母的醌氧化还原酶的基因和具有由其表达的氨基酸序列的蛋白质，其可有利地用于醌化合物的还原反应和合成生物活性化合物的中间体。