公开(公告)号：US06723724B2

公开(公告)日：2004-04-20

申请号：US09839206

申请日：2001-04-23

Applicant: Hun Yeong Koh ,  Kyung Il Choi ,  Yong Seo Cho ,  Ae Nim Pae ,  Kyung Ho Kang ,  Mi Young Cha ,  Jae Yang Kong ,  Dae Young Jeong ,  Hee-Yoon Lee

Inventor： Hun Yeong Koh ,  Kyung Il Choi ,  Yong Seo Cho ,  Ae Nim Pae ,  Kyung Ho Kang ,  Mi Young Cha ,  Jae Yang Kong ,  Dae Young Jeong ,  Hee-Yoon Lee

IPC: A61K31496

CPC classification number: C07D413/04 ,  C07D261/08 ,  C07D413/14

Abstract: The present invention relates to isoxazolylalkylpiperazine derivatives having selective biological activity at dopamine D3 or D4 receptors represented by the following formula (1), and its preparation method through reductive amination reaction in the presence of reducing agent, wherein R1, R2, X and n are the same as defined in the specification.

Abstract translation: 本发明涉及在下列通式（1）表示的多巴胺D3或D4受体中具有选择性生物活性的异恶唑基烷基哌嗪衍生物及其还原胺还原反应的制备方法，其中R1，R2，X和n为 与说明书中定义的相同。

公开(公告)号：US5703246A

公开(公告)日：1997-12-30

申请号：US617755

申请日：1996-03-15

Applicant: Varinder Kumar Aggarwal ,  Hesham Nimer Hasan Abdel-Rahman ,  Hee Yoon Lee

Inventor： Varinder Kumar Aggarwal ,  Hesham Nimer Hasan Abdel-Rahman ,  Hee Yoon Lee

IPC: C07B37/10 ,  C07B41/00 ,  C07B43/00 ,  C07C2/86 ,  C07C13/04 ,  C07C13/28 ,  C07C45/68 ,  C07C49/293 ,  C07C69/743 ,  C07C69/753 ,  C07C211/16 ,  C07C303/30 ,  C07C303/34 ,  C07C303/40 ,  C07C315/04 ,  C07D203/02 ,  C07D203/22 ,  C07D203/24 ,  C07D301/02 ,  C07D303/04 ,  C07D303/08 ,  C07D303/16 ,  C07D303/40 ,  C07D303/46 ,  C07D407/04 ,  C07F9/564 ,  C07C203/00

CPC classification number: C07D203/22 ,  C07C2/868 ,  C07D203/02 ,  C07D203/24 ,  C07D301/02 ,  C07D303/04 ,  C07D303/08 ,  C07D303/16 ,  C07D303/40 ,  C07D303/46 ,  C07D407/04 ,  C07F9/564 ,  C07C2101/02

Abstract: A process for the preparation of an oxirane, aziridine or cyclopropane of formula (I) wherein, X is oxygen, NR.sup.4 or CHR.sup.5 ; R.sup.1 is hydrogen, alkyl, aryl, heteroaromatic, heterocyclic or cycloalkyl; R.sup.2 is hydrogen, alkyl, aryl, heteroaromatic, CO.sub.2 R.sup.8, CHR.sup.14 NHR.sup.13, heterocyclic or cycloalkyl; or R.sup.1 and R.sup.2 join together to form a cycloalkyl ring; R.sup.3 is hydrogen, alkyl, aryl, heteroaromatic, CO.sub.2 R.sup.8, R.sup.8.sub.3 Sn, CONR.sup.8 R.sup.9 or trimethylsilyl; R.sup.4 and R.sup.5 are, independently, alkyl, cycloalkyl, aryl, heteroaromatic, SO.sub.2 R.sup.8, SO.sub.3 R.sup.8, COR.sup.8, CO.sub.2 R.sup.8, CONR.sup.8 R.sup.9 or CN, or R.sup.4 can also be P(O)(aryl).sub.2 ; R.sup.8 and R.sup.9 are independently alkyl, aryl or arylalkyl; R.sup.13 and R.sup.14 are independently hydrogen, alkyl or aryl; the process comprising reacting a mixture of a compound of formula (II), wherein R.sup.1, R.sup.2 and X are as defined above, and a sulphide of formula SR.sup.6 R.sup.7, wherein R.sup.6 and R.sup.7 are independently alkyl, aryl or heteroaomatic, or R.sup.6 and R.sup.7 join together to form a cycloalkyl ring which optionally includes an additional heteroatom, with either (i) a metallocarbon obtainable by reacting an alkylmetal with a methane derivative of formula CHR.sup.3 X'X", wherein R.sup.3 is as defined above, and X' and X" are independently, a leaving group, or (ii) a metallocarbon obtainable by reacting a compound of formula (III), (wherein R.sup.3 may not be hydrogen) with a suitable organometallic or inorganic reagent.

Abstract translation: PCT No.PCT / GB94 / 02280第 371日期：1996年3月15日 102（e）1996年3月15日PCT 1994年10月19日PCT PCT。 公开号WO95 / 11230 日期：1995年04月27日制备式（I）的环氧乙烷，氮丙啶或环丙烷的方法，其中X是氧，NR 4或CHR 5; R 1是氢，烷基，芳基，杂芳族，杂环或环烷基; R2是氢，烷基，芳基，杂芳族，CO2R8，CHR14NHR13，杂环或环烷基; 或R 1和R 2连接在一起形成环烷基环; R3是氢，烷基，芳基，杂芳族，CO2R8，R83Sn，CONR8R9或三甲基甲硅烷基; R4和R5独立地是烷基，环烷基，芳基，杂芳族，SO2R8，SO3R8，COR8，CO2R8，CONR8R9或CN，或R4也可以是P（O）（芳基）2; R8和R9独立地是烷基，芳基或芳基烷基; R 13和R 14独立地是氢，烷基或芳基; 该方法包括使式（II）化合物（其中R 1，R 2和X如上所定义）和式SR 6 R 7的硫化物的混合物反应，其中R 6和R 7独立地为烷基，芳基或杂芳基，或R 6和R 7连接 一起形成任选地包括另外的杂原子的环烷基环，与（i）通过使烷基金属与式CHR 3 X'X“的甲烷衍生物反应得到的金属碳，其中R 3如上所定义，X'和X' 独立地是离去基团，或（ii）可通过使式（III）化合物（其中R 3可以不是氢）与合适的有机金属或无机试剂反应得到的金属碳。

公开(公告)号：US08372844B2

公开(公告)日：2013-02-12

申请号：US13454817

申请日：2012-04-24

Applicant: 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

Inventor： 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: A61K31/496 ,  C07D231/12 ,  C07D401/04 ,  C07D409/04

CPC classification number: C07D403/06

Abstract: 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.

Abstract translation: 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。