CA2480026C - Ester derivatives of a decahydroisoquinoline-3-carboxylic acid as analgesics - Google Patents
Ester derivatives of a decahydroisoquinoline-3-carboxylic acid as analgesics Download PDFInfo
- Publication number
- CA2480026C CA2480026C CA2480026A CA2480026A CA2480026C CA 2480026 C CA2480026 C CA 2480026C CA 2480026 A CA2480026 A CA 2480026A CA 2480026 A CA2480026 A CA 2480026A CA 2480026 C CA2480026 C CA 2480026C
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- Canada
- Prior art keywords
- compound
- ethyl
- carboxylic acid
- refers
- alkyl
- 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
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- 150000002148 esters Chemical class 0.000 title description 11
- NSENYWQRQUNUGD-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinolin-2-ium-3-carboxylate Chemical compound C1CCCC2CNC(C(=O)O)CC21 NSENYWQRQUNUGD-UHFFFAOYSA-N 0.000 title description 2
- 239000000730 antalgic agent Substances 0.000 title description 2
- 229940035676 analgesics Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 81
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 208000002193 Pain Diseases 0.000 claims abstract description 16
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- 206010027599 migraine Diseases 0.000 claims abstract description 11
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- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
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- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims 1
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- LNDYQNTTYXLTNH-UHFFFAOYSA-N 6-[2-(2h-tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrate Chemical compound O.C1CC2CNC(C(=O)O)CC2CC1CCC1=NN=NN1 LNDYQNTTYXLTNH-UHFFFAOYSA-N 0.000 description 3
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- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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- 230000000069 prophylactic effect Effects 0.000 description 1
- LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
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- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
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- 208000018198 spasticity Diseases 0.000 description 1
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- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
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- 230000002459 sustained effect Effects 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 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
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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
- C07D401/02—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 two hetero rings
- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37612002P | 2002-04-26 | 2002-04-26 | |
| US60/376,120 | 2002-04-26 | ||
| PCT/US2003/010466 WO2003091243A1 (en) | 2002-04-26 | 2003-04-14 | Ester derivatives of a decahydroisoquinoline-3-carboxylic acid as analgestics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2480026A1 CA2480026A1 (en) | 2003-11-06 |
| CA2480026C true CA2480026C (en) | 2011-06-07 |
Family
ID=29270765
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2480026A Expired - Fee Related CA2480026C (en) | 2002-04-26 | 2003-04-14 | Ester derivatives of a decahydroisoquinoline-3-carboxylic acid as analgesics |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US7247644B2 (https=) |
| EP (1) | EP1511741B1 (https=) |
| JP (2) | JP2005529892A (https=) |
| KR (1) | KR100757787B1 (https=) |
| CN (1) | CN100436446C (https=) |
| AU (1) | AU2003226277B2 (https=) |
| BR (1) | BR0308911A (https=) |
| CA (1) | CA2480026C (https=) |
| DK (1) | DK1511741T3 (https=) |
| EA (1) | EA009526B1 (https=) |
| ES (1) | ES2398225T3 (https=) |
| IL (1) | IL164773A (https=) |
| MX (1) | MXPA04009857A (https=) |
| NZ (1) | NZ535245A (https=) |
| PT (1) | PT1511741E (https=) |
| SI (1) | SI1511741T1 (https=) |
| WO (1) | WO2003091243A1 (https=) |
| ZA (1) | ZA200409552B (https=) |
Families Citing this family (5)
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|---|---|---|---|---|
| KR100757787B1 (ko) * | 2002-04-26 | 2007-09-11 | 일라이 릴리 앤드 캄파니 | 진통제로서의 데카히드로이소퀴놀린-3-카르복실산의 에스테르 유도체 |
| US8603980B2 (en) | 2007-01-16 | 2013-12-10 | The Johns Hopkins University | Glutamate receptor antagonists and methods of use |
| MX2022016223A (es) | 2020-07-02 | 2023-02-23 | Sea Pharmaceuticals Llc | Composiciones farmaceuticas de acido 6-(2-(2h-tetrazol-5-il)etil)- 6-fluorodecahidroisoquinolina-3-carboxilico y derivados de ester del mismo. |
| WO2022261287A1 (en) * | 2021-06-09 | 2022-12-15 | Proniras Corporation | Methods of treating nerve agent-induced seizures |
| WO2023130008A2 (en) * | 2022-01-01 | 2023-07-06 | Sea Pharmaceuticals Llc | Pharmaceutical compositions of 6-(2-(2h-tetrazol-5-yl)ethyl)decahydroisoquinoline-3-carboxylic acid and derivatives thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK406686D0 (da) * | 1986-08-26 | 1986-08-26 | Hans Bundgaard | Carboxylsyrederivater |
| US4902695A (en) * | 1989-02-13 | 1990-02-20 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
| US5284957A (en) * | 1992-09-03 | 1994-02-08 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
| US5356902A (en) | 1992-11-06 | 1994-10-18 | Eli Lilly And Company | Decahydroisoquinoline compounds as excitatory amino acid receptor antagonists |
| US5446051A (en) | 1994-05-31 | 1995-08-29 | Eli Lilly And Company | Aryl-spaced decahydroisoquinoline-3-carboxylic acids as excitatory amino acid receptor antagonists |
| US5767117A (en) | 1994-11-18 | 1998-06-16 | The General Hospital Corporation | Method for treating vascular headaches |
| HUP0002030A3 (en) | 1997-04-07 | 2002-01-28 | Lilly Co Eli | Use of glur5 receptorantagonists for the treatment of pain |
| EP1200073B1 (en) | 1999-07-06 | 2007-01-10 | Eli Lilly And Company | SELECTIVE iGluR 5? RECEPTOR ANTAGONISTS FOR THE TREATMENT OF MIGRAINE |
| WO2001002367A2 (en) * | 1999-07-06 | 2001-01-11 | Eli Lilly And Company | Diester prodrugs of a decahydroisoquinoline-3-carboxylic acid |
| AU2574801A (en) | 1999-12-22 | 2001-07-03 | Eli Lilly And Company | Selective iGLUR5 receptor antagonists |
| WO2002053556A2 (en) | 2001-01-05 | 2002-07-11 | Eli Lilly And Company | Pyrrolidinylmethyl substituted decahydroisoquinolines as excitatory amino acid receptor antagonists |
| WO2003024453A1 (en) | 2001-01-05 | 2003-03-27 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
| AU2002227020A1 (en) | 2001-01-05 | 2002-07-16 | Eli Lilly And Company | Pyrrolidinylmethyl- and piperidinyl substituted decahydroisoquinolines as excitatory amino acid receptor antagonists |
| WO2003024934A2 (en) | 2001-01-05 | 2003-03-27 | Eli Lilly And Company | Derivatives of the (3s, 4ar, 6s, 8ar) 6-phenylamino-1, 2, 3, 4, 4a, 5, 6, 7, 8, 8a-decahydro isoquinoline-3-carboxylic acid as excitatory amino acid receptor antagonists for the treatment of neurological disorders and neurodegenerative diseases |
| WO2003082856A1 (en) | 2002-03-22 | 2003-10-09 | Eli Lilly And Company | Isoquinoline-3-carboxylic acid derivatives as excitatory amino acid receptor antagonists |
| KR100757787B1 (ko) * | 2002-04-26 | 2007-09-11 | 일라이 릴리 앤드 캄파니 | 진통제로서의 데카히드로이소퀴놀린-3-카르복실산의 에스테르 유도체 |
-
2003
- 2003-04-14 KR KR1020047017143A patent/KR100757787B1/ko not_active Expired - Fee Related
- 2003-04-14 CN CNB038094606A patent/CN100436446C/zh not_active Expired - Fee Related
- 2003-04-14 JP JP2003587801A patent/JP2005529892A/ja active Pending
- 2003-04-14 NZ NZ535245A patent/NZ535245A/en not_active IP Right Cessation
- 2003-04-14 US US10/511,452 patent/US7247644B2/en not_active Expired - Fee Related
- 2003-04-14 WO PCT/US2003/010466 patent/WO2003091243A1/en not_active Ceased
- 2003-04-14 AU AU2003226277A patent/AU2003226277B2/en not_active Ceased
- 2003-04-14 CA CA2480026A patent/CA2480026C/en not_active Expired - Fee Related
- 2003-04-14 MX MXPA04009857A patent/MXPA04009857A/es active IP Right Grant
- 2003-04-14 PT PT37472693T patent/PT1511741E/pt unknown
- 2003-04-14 EA EA200401432A patent/EA009526B1/ru not_active IP Right Cessation
- 2003-04-14 BR BR0308911-8A patent/BR0308911A/pt active Search and Examination
- 2003-04-14 SI SI200332227T patent/SI1511741T1/sl unknown
- 2003-04-14 EP EP03747269A patent/EP1511741B1/en not_active Expired - Lifetime
- 2003-04-14 DK DK03747269.3T patent/DK1511741T3/da active
- 2003-04-14 ES ES03747269T patent/ES2398225T3/es not_active Expired - Lifetime
-
2004
- 2004-10-21 IL IL164773A patent/IL164773A/en not_active IP Right Cessation
- 2004-11-25 ZA ZA200409552A patent/ZA200409552B/xx unknown
-
2010
- 2010-06-23 JP JP2010142881A patent/JP2010235623A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003091243A8 (en) | 2005-03-31 |
| CN1649862A (zh) | 2005-08-03 |
| ZA200409552B (en) | 2006-02-22 |
| IL164773A (en) | 2011-08-31 |
| NZ535245A (en) | 2007-11-30 |
| PT1511741E (pt) | 2013-02-05 |
| JP2010235623A (ja) | 2010-10-21 |
| AU2003226277A1 (en) | 2003-11-10 |
| IL164773A0 (en) | 2005-12-18 |
| DK1511741T3 (da) | 2013-01-21 |
| KR20040102171A (ko) | 2004-12-03 |
| EA009526B1 (ru) | 2008-02-28 |
| CA2480026A1 (en) | 2003-11-06 |
| SI1511741T1 (sl) | 2013-02-28 |
| WO2003091243A1 (en) | 2003-11-06 |
| US7247644B2 (en) | 2007-07-24 |
| KR100757787B1 (ko) | 2007-09-11 |
| EP1511741B1 (en) | 2012-12-26 |
| MXPA04009857A (es) | 2004-12-07 |
| AU2003226277B2 (en) | 2009-03-26 |
| US20050256155A1 (en) | 2005-11-17 |
| EP1511741A1 (en) | 2005-03-09 |
| JP2005529892A (ja) | 2005-10-06 |
| CN100436446C (zh) | 2008-11-26 |
| BR0308911A (pt) | 2005-01-04 |
| ES2398225T3 (es) | 2013-03-14 |
| EA200401432A1 (ru) | 2005-04-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160414 |