CN1140524C - 用于治疗精神疾病的3-四氢吡啶-4-基吲哚 - Google Patents
用于治疗精神疾病的3-四氢吡啶-4-基吲哚 Download PDFInfo
- Publication number
- CN1140524C CN1140524C CNB998135801A CN99813580A CN1140524C CN 1140524 C CN1140524 C CN 1140524C CN B998135801 A CNB998135801 A CN B998135801A CN 99813580 A CN99813580 A CN 99813580A CN 1140524 C CN1140524 C CN 1140524C
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- alkyl
- alkali
- indoles
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- 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
- A61P25/18—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明涉及一组新的具有有用的药理特性的3-四氢吡啶-4-基吲哚。这些化合物及其盐具有通式(I)结构,其中R1为卤素、CF3、C1-3烷基、C1-3氧基、CN或SCH3;m为0、1或2; R2为H或C1-3烷基;n为3、4、5或6;R3为卤素、C1-4烷基;或C1-4烷氧基;p为0、1或2。
Description
本发明涉及一组新的式(I)化合物3-四氢吡啶-4-基吲哚衍生物及其盐:其中:
R1为卤素、CF3、C1-3烷基、C1-3烷氧基、CN或SCH3-m为0、1或2-R2为H或C1-3烷基-n为3、4、5或6-R3为卤素、C1-4烷基或C1-4烷氧基-p为0、1或2
已发现式(I)化合物对多巴胺D2-受体有高度的亲和力并且是很好的5-羟色胺再摄取抑制剂(SRI′S)。
本发明化合物优选的式(I)化合物及其盐是,其中R1为H(即m=0)或F、Cl、CH3、或CN,和m=1,R2为H或CH3,n=4,R3为H(即p=0),或F或烷基C1-4,p=1。特别优选式(I)化合物及其盐中的(R1)m为F,R2为H,n=4和p=0。
已经发现本发明化合物对多巴胺D2-受体和5-羟色胺再摄取位点均有高度的亲和力。这种联合作用对于治疗精神***症和其他精神疾病是有用的,并且可确保对所有疾病症状(例如阳性症状和阴性症状)能进行更彻底的治疗。
化合物在小鼠中有潜力对抗由阿扑***诱导的爬行行为,显示了其对多巴胺D2-受体有拮抗剂的活性。化合物加强了小鼠的5-HTP(5-羟色胺)诱导的行为,也显示了其对5-羟色胺再摄取有抑制剂活性。
化合物在对临床上相关的抗精神病药(例如,条件化躲避反应(Theconditioned avoidance response);Van der Heyden和Bradford,脑行为学研究(Behav.Brain.Res.),1988,31:61-67)和抗抑郁药或抗焦虑药(Suppression of stress-induced vocolization;vander Poel等.,精神药理学(Psychoharmacology),1989,97:147-148)敏感的治疗模型具有活性。
与临床上相关的多巴胺D2-受体拮抗剂相反的是,在此所描述的化合物对啮齿动物具有较低的僵住症诱导趋势,并且与现有抗精神病药相比,化合物的锥体外系副反应较低。
这些化合物对抗抑郁药或抗焦虑药敏感的行为模型的治疗效果表明,这种疗效可能是化合物所固有的对5-羟色胺再摄取的抑制活性所致。化合物可用于由多巴胺能或5-羟色胺能***紊乱所致的中枢神经***病变或疾病,例如:攻击、焦虑症、孤独症、眩晕、抑郁、识别或记忆失调和尤其是精神***症和其他精神疾病。
用于与本发明化合物形成适宜酸加成盐的药理可接受的酸包括如盐酸、硫酸、磷酸、硝酸,和有机酸如柠檬酸、富马酸、马来酸、酒石酸、乙酸、苯甲酸、对甲苯磺酸、甲磺酸和萘磺酸。
通过用辅助物质如液体和固体载体材料处理,可将化合物及其酸加成盐制成适于给药的形式。因此本发明进一步涉及一种药用组合物,其中含有至少一种式(I)的化合物或其药理上可接受的酸加成盐。本发明还涉及式(I)的化合物或其药理上可接受的酸加成盐用于制备治疗中枢神经***疾病的药物的用途。
按下述获得式(I)化合物:
a)式(II)化合物与式(III)化合物反应,其中的符号含义同上并且L是所谓的离去基团,例如溴基。
回流温度下,于三乙胺或K2CO3和KI存在下的溶剂如乙腈中进行反应,或
b)(i)将式(IV)化合物中的氰基还原成-(CH2)n-NH2 其中A代表-(CH2)n-1-CN基团;和
(ii)将所得的胺与任选取代的邻苯二甲酸酐式(V)化合物反应式中所用符号含义同上。
反应步骤b(i)可用如LiAlH4在有机溶剂如四氢呋喃中于回流温度下进行。
反应步骤(ii)可例如在有机溶剂如四氢呋喃和甲苯中于回流温度下进行。
采用本领域已知方法,用4-哌啶酮与任选取代的吲哚衍生物反应可获得方法a)中的式(II)起始化合物。
采用本领域已知方法,用式(II)化合物与式Br-(CH2)n-1-CN的溴烷基腈反应可获得方法b)中式(IV)的起始化合物。
下述实施例将详细描述式(I)化合物的制备。实施例1
1-甲基-3-(1,2,3,6-四氢吡啶-4-基)吲哚的制备于室温下,向含4-哌啶酮·H2O·盐酸盐(50g,0.32mol)的100ml乙酸和150ml三氟乙酸溶液中滴加1-甲基吲哚(11.5ml,0.09mol,于100ml乙酸中)。反应混合物搅拌1小时后浓缩(真空,约30℃)、加水,加碳酸钾碱化并且用乙酸乙酯提取。分离有机层,干燥并用硅胶柱色谱(二氯甲烷/甲醇/氢氧化铵=85/15/1)纯化获得9g(47%)标题所示化合物。实施例2
5-氟-3-(1,2,3,6-四氢吡啶-4-基)吲哚的制备
向1000ml含钠(60g,2.6mol)的甲醇溶液中加入5-氟吲哚(49g,0.36mol)和4-哌啶酮·H2O·盐酸盐(170g,1.11mol)。混合物回流加热18小时后浓缩、加水,用乙酸乙酯提取。合并的有机层用硫酸钠干燥并浓缩。所得固体用甲醇(约200ml)溶解并用水(约1000-1500ml)稀释。收集沉淀并用水和石油醚洗涤,然后于真空下60℃烘干。获得74g(95%)黄色固体物。实施例3
N-[4-[4-[(5-氟-1H-吲哚-3-基)-1,2,3,6-四氢吡啶-1-基]丁基]-邻苯二甲酰亚胺·盐酸盐(化合物1)的制备
5-氟-3-(1,2,3,6-四氢吡啶-4-基)吲哚(7.5g,34.7mmol)、N-(4-溴丁基)邻苯二甲酰亚胺(10.8g,38.3mmol)、三乙胺(4.5ml)和碘化钾(5.5g)在150ml乙腈中的溶液回流加热18小时。反应混合物浓缩并用硅胶柱色谱(二氯甲烷/甲醇/氢氧化铵=92/7.5/0.5)纯化获得8.3g标题所示的游离碱化合物,熔点为186℃。将该游离碱溶于20ml1MHCl乙醇中制得其盐酸盐。浓缩溶液并用醚洗涤所得固体。获得8.4g(54%)化合物1,熔点为224℃(分解)。实施例4
5-氟-3-[1-(3-氰丙基)-(1,2,3,6-四氢吡啶-4-基)吲哚的制备
将5-氟-3-(1,2,3,6-四氢吡啶-4-基)吲哚(10g,46mmol)、4-溴丁腈(5.6ml,56mmol)、碳酸钾(6.3g)和碘化钾(7.6g)在100ml乙腈中的溶液回流加热18小时。过滤混合物并用84/15/1的二氯甲烷/甲醇/氢氧化铵冲洗滤器中的残余物。浓缩有机层得到10.9g(83%)标题所示的化合物,熔点为152℃。实施例5
5-氟-3-[1-(4-氨基丁基)-1,2,3,6-四氢吡啶-4-基]吲哚的制备
向含有5-氟-3-[1-(3-氰丙基)-1,2,3,6-四氢吡啶-4-基]吲哚(10g,35mmol)的300ml干THF溶液中缓慢加入LiAlH4(2.0g)。搅拌混合物并加热回流18小时。然后冷却反应混合物并依次缓慢加入含水(1.9ml)的THF(10ml)和2N氢氧化钠(1.9ml)。混合物加热回流0.25小时,用hyflo过滤和浓缩获得8.76g(88%)标题所示化合物。实施例6
N-[4-[4-[(5-氟-1H-吲哚-3-基)-1,2,3,6-四氢吡啶-1-基]丁基]-4-氟邻苯二甲酰亚胺(化合物19)的制备
向含有5-氟-3-[1-(4-氨基丁基)-1,2,3,6-四氢吡啶-4-基]吲哚(1.46g,5mmol)的20ml THF溶液中加入4-氟邻苯二甲酸酐和50ml甲苯。蒸馏除去THF并将所得混合物加热回流18小时,共沸除去水。反应混合物浓缩并用硅胶柱色谱(二氯甲烷/甲醇/氢氧化铵=92/7.5/0.5)纯化获得1.52g(69%)标题所示的化合物19,熔点为197-199℃。
按实施例1-3所示的方法a),或按实施例4-6所示的方法b)制备下表所示化合物:
表
化合物编号 | (R1)m | R2 | n | (R3)p | 盐/碱 | 熔点℃ |
1 | 5-F | H | 4 | H | HCl | 224(分解) |
2 | H | H | 4 | H | 碱 | 193-4 |
3 | H | H | 3 | H | 碱 | 190-2 |
4 | H | CH3 | 4 | H | HCl | 230 |
5 | 7-CH3 | H | 4 | H | 碱 | 175-8 |
6 | 5-F | H | 3 | H | 碱 | 174-6 |
7 | H | H | 4 | 3-F | 碱 | 173-4 |
8 | H | H | 4 | 3-CH3 | 碱 | 184-5 |
9 | H | H | 4 | 4-CH3 | 碱 | 195-8 |
10 | 5-CN | H | 3 | H | 碱 | 无定形 |
11 | 5-CN | H | 4 | H | 碱 | 无定形 |
12 | 5-Cl | H | 4 | H | 碱 | 无定形 |
13 | H | H | 4 | 4-F | 碱 | 197-8 |
14 | H | H | 4 | 4-t.C4H9 | 富马酸盐 | 243-5 |
15 | 5-F | H | 4 | 4-t.C4H9 | 富马酸盐 | 193-5 |
16 | 5-F | H | 4 | 3-CH3 | 碱 | 167-8 |
17 | 5-F | H | 4 | 4-CH3 | 碱 | 199-200 |
18 | 5-F | H | 4 | 3-F | 碱 | 188-190 |
19 | 5-F | H | 4 | 4-F | 碱 | 197-9 |
20 | H | H | 6 | H | 碱 | 196-7 |
21 | 5-F | H | 6 | H | 碱 | 170-2 |
22 | 5-F | H | 4 | 4.5-二氯 | 碱 | 216-8 |
23 | H | H | 4 | 4,5-二氯 | 碱 | 217-8 |
24 | 5-F | H | 5 | H | 碱 | 194-8 |
25 | 5-F | H | 4 | 4-Cl | 碱 | 186-8 |
26 | H | H | 4 | 4-Cl | 碱 | 209-215 |
Claims (6)
1.式(I)化合物及其药理可接受的酸加成盐,其中:-R1为卤素、CF3、C1-3烷基或CN-m为0、1或2-R2为H或C1-3烷基-n为3、4、5或6-R3为卤素、C1-4烷基-p为0、1或2。
2.如权利要求1的化合物及其药理可接受的酸加成盐,其中R1为F、Cl、CH3或CN,m=0或1,R2为H或CH3,n=4,R3为F或C1-4烷基而p=0或1。
3.如权利要求1的化合物及其药理可接受的酸加成盐,其中R1为F,m=0或1,R2为H,n=4而p=0。
5.一种药用组合物,其中含有至少一种如权利要求1的化合物作为活性成分。
6.权利要求1-3任一项的化合物用于制备治疗中枢神经***疾病的药物的用途。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98203499.3 | 1998-10-16 | ||
EP98203499 | 1998-10-16 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1328553A CN1328553A (zh) | 2001-12-26 |
CN1140524C true CN1140524C (zh) | 2004-03-03 |
Family
ID=8234230
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998135801A Expired - Fee Related CN1140524C (zh) | 1998-10-16 | 1999-10-15 | 用于治疗精神疾病的3-四氢吡啶-4-基吲哚 |
Country Status (29)
Country | Link |
---|---|
US (1) | US6391896B1 (zh) |
EP (1) | EP1121356B1 (zh) |
JP (1) | JP4659984B2 (zh) |
KR (1) | KR100619464B1 (zh) |
CN (1) | CN1140524C (zh) |
AR (1) | AR020773A1 (zh) |
AT (1) | ATE230741T1 (zh) |
AU (1) | AU750811B2 (zh) |
BR (1) | BR9914582A (zh) |
CA (1) | CA2346896C (zh) |
CZ (1) | CZ20011353A3 (zh) |
DE (1) | DE69904849T2 (zh) |
DK (1) | DK1121356T3 (zh) |
DZ (1) | DZ2917A1 (zh) |
ES (1) | ES2188260T3 (zh) |
HK (1) | HK1039333A1 (zh) |
HU (1) | HUP0104701A3 (zh) |
IL (2) | IL142589A0 (zh) |
NO (1) | NO320531B1 (zh) |
NZ (1) | NZ511289A (zh) |
PL (1) | PL195734B1 (zh) |
RU (1) | RU2222535C2 (zh) |
SI (1) | SI1121356T1 (zh) |
SK (1) | SK285764B6 (zh) |
TR (1) | TR200101808T2 (zh) |
TW (1) | TW577884B (zh) |
UA (1) | UA66888C2 (zh) |
WO (1) | WO2000023441A1 (zh) |
ZA (1) | ZA200103251B (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU4552200A (en) * | 1999-05-12 | 2000-12-05 | Solvay Pharmaceuticals B.V. | Method of treating psychotic disorders |
TR200200460T2 (tr) | 1999-08-23 | 2002-06-21 | Solvay Pharmaceuticals B.V. | Yeni fenilpiperazinler |
AR032711A1 (es) * | 2001-02-21 | 2003-11-19 | Solvay Pharm Bv | Derivados de fenilpiperazina, un metodo para la preparacion de los mismos y una composicion farmaceutica que los contiene |
AR032712A1 (es) * | 2001-02-21 | 2003-11-19 | Solvay Pharm Bv | Un mesilato de derivados de fenilpiperazina y composiciones farmaceuticas que lo contienen |
US7371769B2 (en) | 2004-12-07 | 2008-05-13 | Solvay Pharmaceuticals B.V. | Tetrahydropyridin-4-yl indoles with a combination of affinity for dopamine-D2 receptors and serotonin reuptake sites |
US20070072870A2 (en) | 2004-12-08 | 2007-03-29 | Solvay Pharmeceuticals B.V. | Phenylpiperazine derivatives with a combination of partial dopamine-d2 receptor agonism and serotonin reuptake inhibition |
US20060227421A1 (en) | 2005-04-06 | 2006-10-12 | Stover Carl A | Optical bodies including strippable boundary layers |
EP1890869B1 (en) | 2005-04-06 | 2008-10-15 | 3M Innovative Properties Company | Optical bodies including rough strippable boundary layers and asymmetric surface structures |
US9709700B2 (en) | 2005-04-06 | 2017-07-18 | 3M Innovative Properties Company | Optical bodies including rough strippable boundary layers |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4414113A1 (de) | 1994-04-22 | 1995-10-26 | Merck Patent Gmbh | 3-Indolylpiperidine |
US5576321A (en) * | 1995-01-17 | 1996-11-19 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
ZA9711376B (en) * | 1996-12-20 | 1998-07-21 | Lundbeck & Co As H | Indole or dihydroindole derivatives |
-
1999
- 1999-10-12 AR ARP990105138A patent/AR020773A1/es active IP Right Grant
- 1999-10-13 TW TW088117668A patent/TW577884B/zh not_active IP Right Cessation
- 1999-10-15 TR TR2001/01808T patent/TR200101808T2/xx unknown
- 1999-10-15 WO PCT/EP1999/007912 patent/WO2000023441A1/en active IP Right Grant
- 1999-10-15 DE DE69904849T patent/DE69904849T2/de not_active Expired - Lifetime
- 1999-10-15 SK SK512-2001A patent/SK285764B6/sk not_active IP Right Cessation
- 1999-10-15 IL IL14258999A patent/IL142589A0/xx active IP Right Grant
- 1999-10-15 UA UA2001053312A patent/UA66888C2/uk unknown
- 1999-10-15 PL PL99347329A patent/PL195734B1/pl not_active IP Right Cessation
- 1999-10-15 KR KR1020017004764A patent/KR100619464B1/ko not_active IP Right Cessation
- 1999-10-15 NZ NZ511289A patent/NZ511289A/xx not_active IP Right Cessation
- 1999-10-15 AT AT99952604T patent/ATE230741T1/de active
- 1999-10-15 CA CA002346896A patent/CA2346896C/en not_active Expired - Fee Related
- 1999-10-15 BR BR9914582-0A patent/BR9914582A/pt active Search and Examination
- 1999-10-15 DK DK99952604T patent/DK1121356T3/da active
- 1999-10-15 CN CNB998135801A patent/CN1140524C/zh not_active Expired - Fee Related
- 1999-10-15 US US09/807,408 patent/US6391896B1/en not_active Expired - Lifetime
- 1999-10-15 CZ CZ20011353A patent/CZ20011353A3/cs unknown
- 1999-10-15 JP JP2000577167A patent/JP4659984B2/ja not_active Expired - Fee Related
- 1999-10-15 AU AU64741/99A patent/AU750811B2/en not_active Ceased
- 1999-10-15 HU HU0104701A patent/HUP0104701A3/hu unknown
- 1999-10-15 SI SI9930196T patent/SI1121356T1/xx unknown
- 1999-10-15 ES ES99952604T patent/ES2188260T3/es not_active Expired - Lifetime
- 1999-10-15 EP EP99952604A patent/EP1121356B1/en not_active Expired - Lifetime
- 1999-10-15 RU RU2001113272/04A patent/RU2222535C2/ru not_active IP Right Cessation
- 1999-10-16 DZ DZ990217A patent/DZ2917A1/xx active
-
2001
- 2001-04-15 IL IL142589A patent/IL142589A/en not_active IP Right Cessation
- 2001-04-17 NO NO20011892A patent/NO320531B1/no not_active IP Right Cessation
- 2001-04-20 ZA ZA200103251A patent/ZA200103251B/en unknown
-
2002
- 2002-02-05 HK HK02100870A patent/HK1039333A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5071859A (en) | N-substituted azaheterocyclic carboxylic acids and pharmaceutical uses | |
CN1140524C (zh) | 用于治疗精神疾病的3-四氢吡啶-4-基吲哚 | |
WO2001087874A1 (fr) | Procede de production d'un cristal | |
FR2476088A2 (fr) | Nouveaux derives du nor-tropane, leur procede de preparation et leur application en therapeutique | |
EP2038271A1 (en) | Process for the preparation of optically pure or optically enriched enantiomers of sulphoxide compounds | |
EP0538080A1 (fr) | Dérivés de l'aminométhyl-4 pipéridine, leur préparation et leur application en thérapeutique | |
AU771234B2 (en) | Antidepressant heterocyclic compounds | |
JPH04217663A (ja) | 4−アミノメチルピペリジン誘導体 | |
EP0351255A2 (fr) | Dérivés de [(pipéridinyl-4)méthyl]-2 tétrahydro-1,2,3,4 isoquinoléine, leur préparation et leur application en thérapeutique | |
EP1603899B1 (en) | Heterocyclic urea derivatives for the treatment of pain | |
EP0175452B1 (en) | 1,3-disubstituted piperidine compounds as neuroleptic agents | |
JP4324382B2 (ja) | テトラヒドロピリジル−アルキル−複素環、その製造方法およびそれを含む医薬組成物 | |
CN1183769A (zh) | α-(取代的烷基苯基)-4-(羟基二苯基甲基)-1-哌啶丁醇衍生物,其制备和其用作抗组胺剂、抗变应性剂和支气管扩张药的用途 | |
EP1804796A2 (en) | Amino substituted aryloxybenzylpiperidine derivatives | |
CN113651745A (zh) | 布瓦西坦中间体及其制备方法和纯化方法 | |
JP2918002B2 (ja) | アミノメチル アリール化合物;ドーパミンレセプター亜型選択性リガンド | |
EA005403B1 (ru) | Соединения бензолсульфонамида, способ их получения и фармацевтические композиции их содержащие | |
KR101001646B1 (ko) | (r)-(+)-란소프라졸의 제조방법 및 이에 사용되는 중간체 | |
WO2006041635A2 (en) | Arylthiobenzylpiperidine derivatives | |
US6465490B1 (en) | Sulfuric acid mono-[3({1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}-hydroxy-methyl)-2-methoxy-phenyl]ester | |
JPH11507064A (ja) | 新規n―アミノアルキル―2―アントラセンカルボキサミド;新規ドーパミン受容体サブタイプ特異的リガンド | |
US20050256150A1 (en) | Enantioselective acyl transfer catalysts and their use in kinetic resolution of alcohols and desymmetrization of meso-diols | |
US5214057A (en) | N-substituted azaheterocyclic carboxylic acids | |
US20060079524A1 (en) | Amino substituted aryloxybenzylpiperidine derivatives | |
WO2006083538A1 (en) | Aminoalkylphenyl indolone derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
C10 | Entry into substantive examination | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
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: 20040303 Termination date: 20111015 |