CN1199974C - 作为甘氨酸转运抑制剂的螺(2h-1-苯并吡喃-2,4’-哌啶)衍生物 - Google Patents
作为甘氨酸转运抑制剂的螺(2h-1-苯并吡喃-2,4’-哌啶)衍生物 Download PDFInfo
- Publication number
- CN1199974C CN1199974C CNB008157901A CN00815790A CN1199974C CN 1199974 C CN1199974 C CN 1199974C CN B008157901 A CNB008157901 A CN B008157901A CN 00815790 A CN00815790 A CN 00815790A CN 1199974 C CN1199974 C CN 1199974C
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- Prior art keywords
- chromene
- piperidines
- spiral shell
- phenyl
- carboxymethyl
- 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.)
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- 239000003112 inhibitor Substances 0.000 title description 2
- 125000003003 spiro group Chemical group 0.000 title 1
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- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- -1 tetralyl Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
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- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
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- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
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- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
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- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
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- 239000010410 layer Substances 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
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- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
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- 238000003345 scintillation counting Methods 0.000 description 1
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- 238000012163 sequencing technique Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
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- 230000005062 synaptic transmission Effects 0.000 description 1
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- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- 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
- A61P25/24—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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
实施例 | 化合物 | plC50 |
2 | 1’-羧甲基-4-(4-氯代苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.0 |
4 | 1’-羧甲基-4-(4-甲基苯基)螺[2H-1-苯并吡喃-2,4-哌啶]盐酸盐 | 6.3 |
8 | 1’-羧甲基-4-(4-氯代-3-氟代苯基)螺[2H-1-苯并吡喃-2,4’哌啶]盐酸盐 | 6.3 |
10 | 1’-羧甲基-4-(2-萘基)螺[2H-1-苯并吡喃-2,4-哌啶]盐酸盐 | 6.2 |
11 | 1’-羧甲基-4-(3-氟代-4-甲氧基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.2 |
12 | 1’-羧甲基-4-(4-叔丁基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.4 |
14 | 4-(1,3-苯并间二氧杂环戊烯)-1’-羧甲基螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.1 |
24 | 1’-羧甲基-4-[4-(N,N-二甲基氨基)苯基]螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.2 |
28 | 1’-羧甲基-4-(3-氟代-4-甲基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.5 |
33 | 1’-羧甲基-4-(2,2-二氟-1,3-苯并间二氧杂环戊烯)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.2 |
35 | 1’-羧甲基-7-氯代-4-(3-氟代-4-甲基苯基)螺[2H-1-苯并吡喃-2,4’哌啶]盐酸盐 | 6.3 |
36 | 1’-羧甲基-4-(3,5-二氟-4-甲氧基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.4 |
37 | 1’-羧甲基-4-(4-二甲基氨基-3-氟代苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.4 |
38 | 1’-羧甲基-4-(3,5-二氟-4-二甲基氨基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.6 |
39 | 4-(4-溴代-3-氟代苯基)-1’-羧甲基螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.1 |
48 | 1’-羧甲基-4-(3-氟代-4-正丙氧基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.3 |
49 | 1’-羧甲基-4-(3-氟代4-正丁氧基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.1 |
55 | 4-(4-烯丙氧基-3,5-二氟代苯基)-1’-羧甲基螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.6 |
57 | 1’-羧甲基-4-(3,5-二氟-4-炔丙氧基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.6 |
59 | 1’-羧甲基-4-(3,5-二氟-4-三氟乙氧基苯基)螺[2H-1-苯并吡喃-2,4’-哌啶]盐酸盐 | 6.6 |
Claims (7)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99309137.0 | 1999-11-17 | ||
EP99309137 | 1999-11-17 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1390221A CN1390221A (zh) | 2003-01-08 |
CN1199974C true CN1199974C (zh) | 2005-05-04 |
Family
ID=8241739
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB008157901A Expired - Fee Related CN1199974C (zh) | 1999-11-17 | 2000-11-13 | 作为甘氨酸转运抑制剂的螺(2h-1-苯并吡喃-2,4’-哌啶)衍生物 |
Country Status (29)
Country | Link |
---|---|
US (2) | US6645973B1 (zh) |
EP (1) | EP1232160B1 (zh) |
JP (1) | JP4825386B2 (zh) |
KR (1) | KR100776226B1 (zh) |
CN (1) | CN1199974C (zh) |
AR (1) | AR026487A1 (zh) |
AT (1) | ATE398622T1 (zh) |
AU (1) | AU779518B2 (zh) |
BR (1) | BR0015586A (zh) |
CA (1) | CA2389491C (zh) |
CO (1) | CO5261618A1 (zh) |
CY (1) | CY1108339T1 (zh) |
CZ (1) | CZ293920B6 (zh) |
DE (1) | DE60039247D1 (zh) |
DK (1) | DK1232160T3 (zh) |
ES (1) | ES2307536T3 (zh) |
HK (1) | HK1047282B (zh) |
HU (1) | HUP0204162A3 (zh) |
IL (2) | IL149286A0 (zh) |
NO (1) | NO327743B1 (zh) |
NZ (1) | NZ518671A (zh) |
PE (1) | PE20010750A1 (zh) |
PL (1) | PL206071B1 (zh) |
PT (1) | PT1232160E (zh) |
RU (1) | RU2250211C2 (zh) |
SK (1) | SK287040B6 (zh) |
TW (1) | TWI243173B (zh) |
WO (1) | WO2001036423A1 (zh) |
ZA (1) | ZA200203320B (zh) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI243173B (en) * | 1999-11-17 | 2005-11-11 | Akzo Nobel Nv | Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives |
FR2842804B1 (fr) * | 2002-07-29 | 2004-09-03 | Sanofi Synthelabo | Derives de n-[phenyl(piperidin-2-yl)methyl]benzamide, leur preparation et leur application en therapeutique |
KR20140015122A (ko) * | 2003-10-01 | 2014-02-06 | 아돌로 코포레이션 | 스피로시클릭 헤테로시클릭 유도체 및 이의 사용 방법 |
RU2351599C2 (ru) * | 2004-01-08 | 2009-04-10 | Ф.Хоффманн-Ля Рош Аг | Диазаспиропиперидиновые производные в качестве ингибиторов глицинового переносчика 1 и глицинового переносчика 2 |
EP1720873B1 (en) * | 2004-01-08 | 2011-02-23 | F. Hoffmann-La Roche AG | Diaza-spiropiperidine derivatives |
CA2609972C (en) * | 2004-03-22 | 2013-05-14 | Apkarian Technologies Llc | Method and compositions for treatment of chronic neuropathic pain |
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