CN1463269A - 新颖苯基哌嗪 - Google Patents
新颖苯基哌嗪 Download PDFInfo
- Publication number
- CN1463269A CN1463269A CN02801684A CN02801684A CN1463269A CN 1463269 A CN1463269 A CN 1463269A CN 02801684 A CN02801684 A CN 02801684A CN 02801684 A CN02801684 A CN 02801684A CN 1463269 A CN1463269 A CN 1463269A
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- milliliters
- acid
- grams
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明是关于式(1)的新颖苯基哌嗪衍生物，其中，R代表说明书中所述的取代基(a)或(b)。本化合物是(部分)D2受体的激动剂，且有益于治疗中枢神经系统疾病，尤其是帕金森氏症。
Description
本发明涉及式(1)的新颖苯基哌嗪衍生物
其中：
R是式为(a)或(b)的基团
及其盐。
目前已发现本发明所述的化合物与多巴胺D2受体及五羟色胺再吸收位皆具有高亲和力。此组合可用于治疗精神疾病如精神分裂症(包括正向及负向症状)以及其他精神疾病。
本化合物具有(部分)激动剂的作用，故亦适用于治疗帕金森氏症。
本化合物具有拮抗多巴胺D2受体的活性，因此能拮抗阿朴吗啡所引起的老鼠爬抓行为。本化合物亦具有五羟色胺再吸收抑制剂的活性，因此能加强5-HTP在老鼠身上所导致的行为反应。
本化合物用于那些对临床使用的抗精神病药物(如：条件性回避反应；Van der Heyden & Bradford，Behav.Brain Res.，1988，31：61-67)及抗抑郁药物或抗焦虑药物(如：抑制压力引起的发声行为；Van der Poel等，《精神药理学》(Psychopharmacology)，1989，97：147-148)敏感的治疗模型有显著效用。
本化合物用于帕金森氏症的临床相关模型有显著效用(如：改变大鼠的行为；U.Ungerstedt，Acta1 Physiol.Scand.，1971，82(suppl.367)：69-93)。
不同于临床使用的多巴胺D2受体拮抗剂，本化合物于啮齿类动物上引起强直性昏厥倾向较小，因此可能比目前既有的抗精神病药物引起较少的锥体外神经系的副作用。
在那些对抗抑郁药物或抗焦虑药物敏感的行为模型上所观察到的治疗效果可能是因为本化合物所具有的五羟色胺再吸收活性。
本化合物可以用来治疗因多巴胺能或五羟色胺能系统障碍所导致的中枢神经系统异常或疾病，例如：攻击性、焦虑症、孤癖、晕眩、抑郁、认知或记忆障碍、帕金森氏症及精神分裂症和其他精神疾病。
药理学上可使用的酸包括氢氯酸(盐酸)、硫酸、磷酸、硝酸、及有机酸像柠檬酸、延胡索酸(反丁烯二酸)、马来酸、酒石酸、乙酸、苯甲酸、对甲苯磺酸、甲磺酸和萘磺酸，本发明化合物能与这些酸形成适合的酸加成盐类。
本化合物及其酸加成盐能通过辅助的物质像液态及固态载体材料，经过合适的工艺手段制成适于给药的形式。
具有式(1)的化合物可由式II化合物
在碱性条件下与式为
L-(a)或L-(b)
的化合物进行反应来制备；其中式(a)和(b)同前文所定义，且L是所谓的离去离基例如卤素原子或甲磺酸酯基团。
具有式(2)的哌嗪化合物可依欧洲专利0189612所述的方法制得。
式L-(a)的起始原料可依下列反应流程制得：
流程A
化合物1p2可由1pl得到，其获得方式与由化合物2p3得到化合物2p4的相同，也就是化合物L-(b)，其中L是甲磺酰基团(见下列流程B)。
流程B
本发明通过下列实施例加以举例说明。实施例1
将18.1克(0.1摩尔)的2pl溶于250毫升的CH2Cl2并置于0℃，再将由50毫升浓硫酸倒进200克的冰所配成的溶液加入此CH2Cl2溶液，所得混和物通过冰/丙酮冷却浴以保持于0℃。接着将8.3克(0.12摩尔)NaNO2溶于50毫升水所配成的溶液滴加入该溶液中，并且过程中温度保持在2℃以下，持续搅拌1小时。然后有机层分离后，水层再萃取(CH2Cl2)一次，将合并后的有机层部分以MgSO4干燥。将干燥剂过滤移除并以真空浓缩滤液后得到17.8克(99％)的深黄色2p2粗产物。
在氮气保护环境下，将由17.8克(0.099摩尔)2p2于100毫升无水THF中的溶液，小心地滴入LiAlH4(9.75克，244毫摩尔)于回流的无水THF的悬浮液中。完全加入后，让最后的混合物继续反应40分钟。然后将反应物置于室温，再进一步以冰/乙醇冷却浴冷却。接着加入9.75毫升水/THF(1/1)、18.5毫升的2N NaOH(水溶液)及18.5毫升的水，并保持所得混合物继续回流20分钟。待冷却下来后，将此反应混合物过滤(Hyflo)，得到的滤液经由真空浓缩可得到15.9克的残余物。将此残余物溶于98毫升的1N HCl/EtOAc，其所产生的沉淀物经过滤后得到17.5克(87％)的2p3.HCl。
将17.5克(86毫摩尔)的2p3.HCl溶于190毫升乙二醇和90毫升水的混合物中，所得溶液加热到95℃。接着，将7.96克(94.6毫摩尔)的(3，4)-二氢-2H-吡喃小心地逐滴加入。完全加入后，在95℃继续搅拌3小时。当反应混合物温度降到室温后，加入水及一些盐水并以EtOAc进行萃取(3次)。将合并的有机层部分依序用水、NaHSO3(水溶液)、水、NaHCO3(水溶液)、NaCl(水溶液)冲洗，的后将此有机层部分以Na2SO4干燥。将干燥剂与溶剂去除所得到的残余物，经由柱层析(SiO2，洗脱剂为MeOH/CH2Cl2(3/97))纯化后得到12克(63％)的深红色油状物，其中含有2p4的对应醇，放置后固化。接着以标准步骤(MsCl，二异丙基乙胺，于CH2Cl2中，0℃)将所得到的醇转化成其甲磺酸酯而得到2p4(产率98％)。
将具有式(2)的苯基哌嗪依照欧洲专利0900792中所述的步骤与2p4反应，即得到其中R为式(b)基团的化合物(1)；(熔点：182-5℃)。实施例2
类似2p4制备(于实施例1中)，将1p1转化成1p2。
依照RajanBabu等人所述的步骤(RajanBabu等，J.Org.Chem.51，(1986)，1704，再将1p2转化成1p3(98％))。
在氮气保护下，将31.9克(103毫摩尔)的1p3溶解于49毫升DMF中，将此溶液缓慢加入另一含有5.88克(134毫摩尔，1.3当量)的油状悬浮液中(此悬浮液为148毫升DMF含有55％NaH)，的后在室温下搅拌持续1小时，然后将反应混合物冷却下来(冰/水)。接着，将由8.34毫升(19.02克，134毫摩尔，1.3当量)的MeI稀释于49毫升DMF中配成的溶液逐滴地加入该溶液中。此反应混合物于室温下再持续搅拌16小时。然后加入水并进行萃取；萃取Et2O(2次)后，将有机层部分以水(2次)及盐水(1次)洗涤，最后以MgSO4干燥。将干燥剂及溶剂真空去除后，剩下的残余物通过柱层析(SiO2，洗脱剂：CH2Cl2/己烷(3/1))纯化后得到26.2克(79％)的浅黄色油状的1p4。
在氮气保护下，将25.03克(78毫摩尔)的1p4溶于110毫升的THF，接着加入配于THF中的1N(nBut)4N+F-，93毫升(0.93毫摩尔，1.2当量)。搅拌1小时后，加入Et2O，得到的混合物以水(3次)及盐水(1次)洗涤。此有机层以Na2SO4干燥。除去干燥剂及溶剂后，剩下的残余物溶于甲苯中并接着真空浓缩以去除少量的(叔)丁基-三甲基-甲硅烷基氟，透过闪极色谱纯化(SiO2，洗脱剂为Et2O)后，最后得到14.8克(92％)的1p5。
将1.69克(6.45毫摩尔)的PPh3和0.44克(6.44毫摩尔)的咪唑溶于20毫升的CH2Cl2，然后将1.64克(6.45毫摩尔)的碘分次加入。此反应混合物于室温下再搅拌30分钟。接着将1.07克(5.16毫摩尔)1p5溶于10毫升CH2Cl2中的混合物，缓慢加入混合物中。30分钟后将反应混合物以NaHCO3(水溶液)、NaHSO3(水溶液)及盐水洗涤，剩余的有机层部分以Na2SO4干燥。将干燥剂及溶剂真空去除后，将剩下的残余物溶于Et2O中，其中形成(Ph3PO)的沉淀物以过滤方式除去。将滤液真空浓缩后，残余物以闪极色谱(SiO2，洗脱剂为CH2Cl2/己烷(1/1))纯化后，得到1.45克(88％)所需碘化物1p6。
使具有式(2)的苯基哌嗪依照欧洲专利0900792中所述的步骤与1p6反应，得到其中R为基团(a)的化合物(1)；(熔点：202-4℃)。
Claims (5)
1.具有式(1)的苯基哌嗪衍生物
其中R是式(a)或(b)的基团
及其盐。
2.制备权利要求1的化合物的方法，其特征在于在碱性条件下式(2)化合物
与式
L-(a)或L-(b)
的化合物进行反应，其中式L是离去基，而(a)及(b)的定义同权利要求1所述。
3.一种药物组合物，含有至少一种权利要求1所述的化合物作为有效成分。
4.一种治疗帕金森氏症的方法，其特征在于使用权利要求1所述的化合物。
5.一种治疗CNS-失调，如精神分裂症、焦虑症、抑郁症的方法，其特征在于使用权利要求1所述的化合物。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01200609.4 | 2001-02-21 | ||
| EP01200609 | 2001-02-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1463269A true CN1463269A (zh) | 2003-12-24 |
| CN1190433C CN1190433C (zh) | 2005-02-23 |
Family
ID=8179908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB02801684XA Expired - Fee Related CN1190433C (zh) | 2001-02-21 | 2002-02-19 | 新颖苯基哌嗪 |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US6828325B2 (zh) |
| EP (1) | EP1395583B1 (zh) |
| JP (1) | JP4178033B2 (zh) |
| KR (1) | KR100848482B1 (zh) |
| CN (1) | CN1190433C (zh) |
| AR (1) | AR032711A1 (zh) |
| AT (1) | ATE289604T1 (zh) |
| AU (1) | AU2002253043B2 (zh) |
| BR (1) | BR0205220A (zh) |
| CA (1) | CA2411973A1 (zh) |
| CZ (1) | CZ299487B6 (zh) |
| DE (1) | DE60203042T2 (zh) |
| DK (1) | DK1395583T3 (zh) |
| DZ (1) | DZ3441A1 (zh) |
| ES (1) | ES2235029T3 (zh) |
| HK (1) | HK1059781A1 (zh) |
| HU (1) | HUP0303329A3 (zh) |
| IL (1) | IL153176A (zh) |
| MX (1) | MXPA03004242A (zh) |
| NO (1) | NO323781B1 (zh) |
| NZ (1) | NZ523135A (zh) |
| PL (1) | PL359650A1 (zh) |
| PT (1) | PT1395583E (zh) |
| RU (1) | RU2279431C2 (zh) |
| SI (1) | SI1395583T1 (zh) |
| SK (1) | SK286064B6 (zh) |
| UA (1) | UA74426C2 (zh) |
| WO (1) | WO2002066472A1 (zh) |
| ZA (1) | ZA200209897B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1212320T1 (en) * | 1999-08-23 | 2005-10-31 | Solvay Pharmaceuticals B.V. | Phenylpiperazines as serotonin reuptake inhibitors |
| AR032712A1 (es) | 2001-02-21 | 2003-11-19 | Solvay Pharm Bv | Un mesilato de derivados de fenilpiperazina y composiciones farmaceuticas que lo contienen |
| JP5080716B2 (ja) | 2001-07-20 | 2012-11-21 | サイコジェニックス・インコーポレーテッド | 注意欠陥・多動性障害の治療 |
| EP1683790A1 (en) * | 2005-01-24 | 2006-07-26 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | 3,4-dihydro-2-naphthamide derivatives as selective dopamine D3 ligands |
| GB0708818D0 (en) * | 2007-05-08 | 2007-06-13 | Portela & Ca Sa | Compounds |
| WO2011082266A2 (en) | 2009-12-30 | 2011-07-07 | Arqule, Inc. | Substituted heterocyclic compounds |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0900792B1 (en) * | 1997-09-02 | 2003-10-29 | Duphar International Research B.V | Piperazine and piperidine derivatives as 5-HT1A and dopamine D2-receptor (ant)agonists |
| NZ508506A (en) * | 1998-06-19 | 2004-01-30 | H | 4,5,6 and 7-indole and indoline derivatives, their preparation and use |
| AR020773A1 (es) * | 1998-10-16 | 2002-05-29 | Duphar Int Res | Compuesto derivados de 3-(tetrahidropiridin-4-il)indol, metodo para prepararlo, una composicion farmaceutica que los contiene, metodo para preparar dicha composicion y uso del compuesto |
| SI1212320T1 (en) | 1999-08-23 | 2005-10-31 | Solvay Pharmaceuticals B.V. | Phenylpiperazines as serotonin reuptake inhibitors |
| EP1336406A1 (en) | 2002-02-14 | 2003-08-20 | Solvay Pharmaceuticals B.V. | Partial dopamine-D2 receptor agonist plus serotonin and/or noradrenaline inhibitory activity |
-
2002
- 2002-02-18 AR ARP020100547A patent/AR032711A1/es active IP Right Grant
- 2002-02-19 DE DE60203042T patent/DE60203042T2/de not_active Expired - Lifetime
- 2002-02-19 KR KR1020027016845A patent/KR100848482B1/ko not_active IP Right Cessation
- 2002-02-19 SK SK1805-2002A patent/SK286064B6/sk not_active IP Right Cessation
- 2002-02-19 CZ CZ20023933A patent/CZ299487B6/cs not_active IP Right Cessation
- 2002-02-19 HU HU0303329A patent/HUP0303329A3/hu unknown
- 2002-02-19 PL PL02359650A patent/PL359650A1/xx not_active IP Right Cessation
- 2002-02-19 SI SI200230087T patent/SI1395583T1/xx unknown
- 2002-02-19 DK DK02722107T patent/DK1395583T3/da active
- 2002-02-19 DZ DZ023441A patent/DZ3441A1/fr active
- 2002-02-19 JP JP2002565986A patent/JP4178033B2/ja not_active Expired - Fee Related
- 2002-02-19 CA CA002411973A patent/CA2411973A1/en not_active Abandoned
- 2002-02-19 MX MXPA03004242A patent/MXPA03004242A/es active IP Right Grant
- 2002-02-19 AU AU2002253043A patent/AU2002253043B2/en not_active Ceased
- 2002-02-19 ES ES02722107T patent/ES2235029T3/es not_active Expired - Lifetime
- 2002-02-19 US US10/343,232 patent/US6828325B2/en not_active Expired - Fee Related
- 2002-02-19 UA UA2003098663A patent/UA74426C2/uk unknown
- 2002-02-19 NZ NZ523135A patent/NZ523135A/en unknown
- 2002-02-19 AT AT02722107T patent/ATE289604T1/de active
- 2002-02-19 CN CNB02801684XA patent/CN1190433C/zh not_active Expired - Fee Related
- 2002-02-19 WO PCT/EP2002/001793 patent/WO2002066472A1/en active IP Right Grant
- 2002-02-19 EP EP02722107A patent/EP1395583B1/en not_active Expired - Lifetime
- 2002-02-19 PT PT02722107T patent/PT1395583E/pt unknown
- 2002-02-19 RU RU2003106194/04A patent/RU2279431C2/ru not_active IP Right Cessation
- 2002-02-19 IL IL153176A patent/IL153176A/en not_active IP Right Cessation
- 2002-02-19 BR BR0205220-2A patent/BR0205220A/pt not_active Application Discontinuation
- 2002-12-05 ZA ZA200209897A patent/ZA200209897B/en unknown
- 2002-12-09 NO NO20025902A patent/NO323781B1/no not_active IP Right Cessation
-
2004
- 2004-04-15 HK HK04102632A patent/HK1059781A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2015528478A (ja) | 三環式キノリンおよびキノキサリン誘導体 | |
| CN1155596C (zh) | 新的苯基哌嗪 | |
| KR20020093974A (ko) | 아자비시클릭 카르밤산염 및 알파-７ 니코틴작용아세틸콜린 수용체 아고니스트로서의 이의 용도 | |
| CN1190433C (zh) | 新颖苯基哌嗪 | |
| EP3116873B1 (en) | Hexahydrodiazepinoquinolines carrying a cyclic radical | |
| CN1284780C (zh) | 对多巴胺d2受体和5－羟色胺重摄取位点有高亲和力的8－{4－[3－(5－氟－1h－吲哚－3－基)丙基]－哌嗪－1－基}－2－甲基－4h－苯并[1,4]噁嗪－3－酮甲磺酸盐 | |
| AU2002253043A1 (en) | New phenylpiperazines | |
| AU2002253043A2 (en) | New phenylpiperazines | |
| CN1304409A (zh) | 用于治疗抑郁症的吲哚－3－基－环己胺衍生物(5－ht1受体拮抗剂) | |
| EP3116874B1 (en) | Hexahydrodiazepinoquinolines carrying a substituted alkyl radical | |
| WO2017157929A1 (en) | Quinoline compounds suitable for treating disorders that respond to the modulation of the serotonin 5-ht6 receptor | |
| TWI225487B (en) | New phenylpiperazines | |
| JPH0637495B2 (ja) | アミノ置換された架橋アザビシクロキノロンカルボン酸およびエステル | |
| JP2018095656A (ja) | 三環式キノリンおよびキノキサリン誘導体 | |
| AU4720499A (en) | 6-(4-arylalkylpiperazin-1-yl)benzodioxane and 6-(4-arylalkylpiperazin-1-yl)chromane derivatives: dopamine receptor subtype specific ligands | |
| JPH05194427A (ja) | ベンゾキノキサリン類 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1059781 Country of ref document: HK |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20050223 Termination date: 20120219 |