CA2362303A1 - Growth hormone secretagogues - Google Patents
Growth hormone secretagogues Download PDFInfo
- Publication number
- CA2362303A1 CA2362303A1 CA002362303A CA2362303A CA2362303A1 CA 2362303 A1 CA2362303 A1 CA 2362303A1 CA 002362303 A CA002362303 A CA 002362303A CA 2362303 A CA2362303 A CA 2362303A CA 2362303 A1 CA2362303 A1 CA 2362303A1
- Authority
- CA
- Canada
- Prior art keywords
- mmol
- preparation
- product
- nmr
- anal
- 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.)
- Abandoned
Links
- 239000003324 growth hormone secretagogue Substances 0.000 title abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000012453 solvate Substances 0.000 claims abstract description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 5
- 125000006302 indol-3-yl methyl group Chemical group [H]N1C([H])=C(C2=C([H])C([H])=C([H])C([H])=C12)C([H])([H])* 0.000 claims abstract description 5
- 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 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 182
- -1 4-methyl piperidinyl Chemical group 0.000 claims description 82
- 238000000034 method Methods 0.000 claims description 33
- 239000000122 growth hormone Substances 0.000 claims description 32
- 102000018997 Growth Hormone Human genes 0.000 claims description 31
- 108010051696 Growth Hormone Proteins 0.000 claims description 31
- 239000004480 active ingredient Substances 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 241001465754 Metazoa Species 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
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- 150000004663 bisphosphonates Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract description 9
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- 239000012044 organic layer Substances 0.000 description 25
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- 238000009472 formulation Methods 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
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- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 23
- 239000012047 saturated solution Substances 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
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- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 22
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 229960000208 pralmorelin Drugs 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000979 retarding 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
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 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
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical group 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- COAZGNJFDSQYTL-UHFFFAOYSA-N tert-butyl n-(1-amino-2-methyl-1-oxopropan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(N)=O COAZGNJFDSQYTL-UHFFFAOYSA-N 0.000 description 1
- PXLDCIVHVKRQRS-FDOABKJOSA-N tert-butyl n-[1-[[(2r)-3-(1h-indol-3-yl)-1-[[1-[2-(4-methylpiperidin-1-yl)-2-oxo-1-phenylethyl]imidazol-4-yl]amino]-1-oxopropan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]carbamate Chemical compound C1CC(C)CCN1C(=O)C(N1C=C(NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)C(C)(C)NC(=O)OC(C)(C)C)N=C1)C1=CC=CC=C1 PXLDCIVHVKRQRS-FDOABKJOSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12081399P | 1999-02-19 | 1999-02-19 | |
| US60/120,813 | 1999-02-19 | ||
| PCT/US2000/004274 WO2000049037A1 (en) | 1999-02-19 | 2000-02-18 | Growth hormone secretagogues |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2362303A1 true CA2362303A1 (en) | 2000-08-24 |
Family
ID=22392709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002362303A Abandoned CA2362303A1 (en) | 1999-02-19 | 2000-02-18 | Growth hormone secretagogues |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1153034B1 (https=) |
| JP (1) | JP2002539089A (https=) |
| CN (1) | CN1179972C (https=) |
| AR (1) | AR023369A1 (https=) |
| AT (1) | ATE375996T1 (https=) |
| AU (1) | AU765642B2 (https=) |
| BR (1) | BR0008321A (https=) |
| CA (1) | CA2362303A1 (https=) |
| CO (1) | CO5160260A1 (https=) |
| DE (1) | DE60036785D1 (https=) |
| IL (1) | IL144350A0 (https=) |
| PE (1) | PE20001468A1 (https=) |
| WO (1) | WO2000049037A1 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6639076B1 (en) | 1998-08-18 | 2003-10-28 | Eli Lilly And Company | Growth hormone secretagogues |
| US6828331B1 (en) | 1999-02-19 | 2004-12-07 | Eli Lilly And Company | Growth hormone secretagogues |
| JP2003534377A (ja) | 2000-05-30 | 2003-11-18 | メルク エンド カムパニー インコーポレーテッド | メラノコルチン受容体作働薬 |
| US6756385B2 (en) * | 2000-07-31 | 2004-06-29 | Pfizer Inc. | Imidazole derivatives |
| GT200100147A (es) * | 2000-07-31 | 2002-06-25 | Derivados de imidazol | |
| US20040106665A1 (en) * | 2000-10-13 | 2004-06-03 | Kress Thomas Joseph | Resolution process for preparation of substantially pure (r) and (s) enantiomers of 2-(4-nitroimidazolyl)-4-methodxyphenylpropionic acid and salts thereof |
| US7560490B2 (en) * | 2001-01-23 | 2009-07-14 | Gador S.A. | Composition comprising bisphosphonates for prevention and/or treatment of metabolic diseases of bones, process for preparing such composition and use thereof |
| US7125840B2 (en) | 2001-10-09 | 2006-10-24 | Eli Lilly And Company | Substituted dipeptides as growth hormone secretagogues |
| US7396846B2 (en) | 2002-04-09 | 2008-07-08 | Eli Lilly And Company | Growth hormone secretagogues |
| DK1730119T3 (da) * | 2004-03-23 | 2008-08-11 | Pfizer Prod Inc | Imidazolforbindelser til behandling af neurodegenerative forstyrrelser |
| AU2006293619A1 (en) | 2005-09-22 | 2007-03-29 | Pfizer Products Inc. | Imidazole compounds for the treatment of neurological disorders |
| PL4010322T3 (pl) | 2019-08-09 | 2026-02-16 | Pfizer Inc. | Stałe postacie (s)-2-(((s)-6,8-difluoro-1,2,3,4-tetrahydronaftalen-2-ylo)amino)-n-(1-(2-metylo-1-(neopentyloamino)propan-2-ylo)-1h-imidazol-4-ilo)pentanamidu i ich zastosowanie |
| US11884634B2 (en) | 2019-08-09 | 2024-01-30 | Pfizer Inc. | Compositions of solid forms of (S)-2-(((S)-6,8-difluoro-1,2,3,4- tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide |
| AU2022339841A1 (en) | 2021-09-01 | 2024-03-28 | Springworks Therapeutics, Inc. | Synthesis of nirogacestat |
| US11504354B1 (en) | 2021-09-08 | 2022-11-22 | SpringWorks Therapeutics Inc.. | Chlorinated tetralin compounds and pharmaceutical compositions |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL107836A (en) * | 1992-12-11 | 1998-01-04 | Merck & Co Inc | Spiro piperidines and homologues, their preparation and pharmaceutical preparations containing them |
| WO1994013696A1 (en) * | 1992-12-11 | 1994-06-23 | Merck & Co., Inc. | Spiro piperidines and homologs which promote release of growth hormone |
| US5721250A (en) * | 1993-12-23 | 1998-02-24 | Merck & Co. Inc. | Di-and tri-substituted piperidines, pyrrolidines and hexahydro-1H-azepines promote release of growth hormone |
| WO1998016527A1 (en) * | 1996-10-15 | 1998-04-23 | Fujisawa Pharmaceutical Co., Ltd. | Benzoxepine derivatives which promote release of growth hormone |
| ZA987383B (en) * | 1997-08-19 | 2000-02-17 | Lilly Co Eli | Treatment of congestive heart failure with growth hormone secretagogues. |
| ZA987385B (en) * | 1997-08-19 | 2000-04-18 | Lilly Co Eli | Growth hormone secretagogues. |
-
2000
- 2000-02-17 CO CO00011043A patent/CO5160260A1/es unknown
- 2000-02-18 AU AU34968/00A patent/AU765642B2/en not_active Ceased
- 2000-02-18 IL IL14435000A patent/IL144350A0/xx unknown
- 2000-02-18 CA CA002362303A patent/CA2362303A1/en not_active Abandoned
- 2000-02-18 JP JP2000599774A patent/JP2002539089A/ja active Pending
- 2000-02-18 DE DE60036785T patent/DE60036785D1/de not_active Expired - Lifetime
- 2000-02-18 PE PE2000000127A patent/PE20001468A1/es not_active Application Discontinuation
- 2000-02-18 AR ARP000100708A patent/AR023369A1/es unknown
- 2000-02-18 AT AT00913536T patent/ATE375996T1/de not_active IP Right Cessation
- 2000-02-18 EP EP00913536A patent/EP1153034B1/en not_active Expired - Lifetime
- 2000-02-18 BR BR0008321-6A patent/BR0008321A/pt not_active IP Right Cessation
- 2000-02-18 WO PCT/US2000/004274 patent/WO2000049037A1/en not_active Ceased
- 2000-02-18 CN CNB008037035A patent/CN1179972C/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000049037A1 (en) | 2000-08-24 |
| CO5160260A1 (es) | 2002-05-30 |
| AU3496800A (en) | 2000-09-04 |
| AU765642B2 (en) | 2003-09-25 |
| EP1153034B1 (en) | 2007-10-17 |
| AR023369A1 (es) | 2002-09-04 |
| IL144350A0 (en) | 2002-05-23 |
| BR0008321A (pt) | 2002-01-29 |
| PE20001468A1 (es) | 2000-12-20 |
| EP1153034A1 (en) | 2001-11-14 |
| DE60036785D1 (de) | 2007-11-29 |
| CN1179972C (zh) | 2004-12-15 |
| JP2002539089A (ja) | 2002-11-19 |
| CN1347420A (zh) | 2002-05-01 |
| ATE375996T1 (de) | 2007-11-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |