CN1031642C - 6-取代的嘌呤基哌嗪衍生物的制备方法 - Google Patents
6-取代的嘌呤基哌嗪衍生物的制备方法 Download PDFInfo
- Publication number
- CN1031642C CN1031642C CN91103957A CN91103957A CN1031642C CN 1031642 C CN1031642 C CN 1031642C CN 91103957 A CN91103957 A CN 91103957A CN 91103957 A CN91103957 A CN 91103957A CN 1031642 C CN1031642 C CN 1031642C
- Authority
- CN
- China
- Prior art keywords
- purine
- compound
- propylthio
- piperazin
- bis
- 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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- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- -1 6-substituted purinyl piperazine Chemical class 0.000 title claims abstract description 15
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 30
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- 150000001805 chlorine compounds Chemical class 0.000 claims description 4
- 239000012312 sodium hydride Substances 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- SGCZKAZTLANUAF-UHFFFAOYSA-N [1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(7h-purin-6-ylsulfanyl)propan-2-yl] acetate Chemical compound COC1=CC=CC=C1N1CCN(CC(CSC=2C=3NC=NC=3N=CN=2)OC(C)=O)CC1 SGCZKAZTLANUAF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- RZGNXPCHOLHTKP-UHFFFAOYSA-N [1-(7h-purin-6-ylsulfanyl)-3-(4-pyridin-2-ylpiperazin-1-yl)propan-2-yl] acetate Chemical compound N=1C=NC=2N=CNC=2C=1SCC(OC(=O)C)CN(CC1)CCN1C1=CC=CC=N1 RZGNXPCHOLHTKP-UHFFFAOYSA-N 0.000 claims description 2
- WOXYWGWWLKEFQM-UHFFFAOYSA-N [1-[4-[bis(4-fluorophenyl)methyl]-1,4-diazepan-1-yl]-3-(7h-purin-6-ylsulfanyl)propan-2-yl] acetate Chemical compound N=1C=NC=2N=CNC=2C=1SCC(OC(=O)C)CN(CC1)CCCN1C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 WOXYWGWWLKEFQM-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- PEQFGXNLBPCOMW-UHFFFAOYSA-N 1-(7h-purin-6-ylsulfanyl)-3-(4-pyridin-2-ylpiperazin-1-yl)propan-2-ol;hydrate Chemical compound O.N=1C=NC=2N=CNC=2C=1SCC(O)CN(CC1)CCN1C1=CC=CC=N1 PEQFGXNLBPCOMW-UHFFFAOYSA-N 0.000 claims 1
- HTYPMIQXADGSKR-UHFFFAOYSA-N 1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(7h-purin-6-ylsulfanyl)propan-2-ol Chemical compound COC1=CC=CC=C1N1CCN(CC(O)CSC=2C=3NC=NC=3N=CN=2)CC1 HTYPMIQXADGSKR-UHFFFAOYSA-N 0.000 claims 1
- ZQMZVOCMPDOOFF-UHFFFAOYSA-N [1-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-3-(7h-purin-6-ylsulfanyl)propan-2-yl] hydrogen sulfate Chemical compound N=1C=NC=2N=CNC=2C=1SCC(OS(=O)(=O)O)CN(CC1)CCN1C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 ZQMZVOCMPDOOFF-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 1
- 239000003416 antiarrhythmic agent Substances 0.000 abstract description 4
- 239000000496 cardiotonic agent Substances 0.000 abstract description 3
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
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- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical class S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 14
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000012043 crude product Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
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- 238000001914 filtration Methods 0.000 description 7
- 229960001428 mercaptopurine Drugs 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- TTXIFFYPVGWLSE-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCNCC1 TTXIFFYPVGWLSE-UHFFFAOYSA-N 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
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- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical class C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 3
- ZJJVMOCDIGKVAK-UHFFFAOYSA-N 1-chloro-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-2-ol Chemical compound COC1=CC=CC=C1N1CCN(CC(O)CCl)CC1 ZJJVMOCDIGKVAK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/36—Sulfur atom
- C07D473/38—Sulfur atom attached in position 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (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)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52762590A | 1990-05-23 | 1990-05-23 | |
| US527,625 | 1990-05-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1057463A CN1057463A (zh) | 1992-01-01 |
| CN1031642C true CN1031642C (zh) | 1996-04-24 |
Family
ID=24102273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN91103957A Expired - Fee Related CN1031642C (zh) | 1990-05-23 | 1991-05-23 | 6-取代的嘌呤基哌嗪衍生物的制备方法 |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0458618A1 (enExample) |
| JP (1) | JPH04226986A (enExample) |
| KR (1) | KR910020011A (enExample) |
| CN (1) | CN1031642C (enExample) |
| AU (1) | AU636034B2 (enExample) |
| CA (1) | CA2042944A1 (enExample) |
| FI (1) | FI912486L (enExample) |
| HU (1) | HUT57768A (enExample) |
| IE (1) | IE911751A1 (enExample) |
| IL (1) | IL98224A (enExample) |
| MY (1) | MY106167A (enExample) |
| NO (1) | NO179909C (enExample) |
| NZ (1) | NZ238122A (enExample) |
| PT (1) | PT97741B (enExample) |
| TN (1) | TNSN91037A1 (enExample) |
| TW (1) | TW211012B (enExample) |
| ZA (1) | ZA913880B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU648070B2 (en) * | 1990-04-23 | 1994-04-14 | Ortho Pharmaceutical Corporation | Process for preparing optically active isomers of 6-substituted purinyl piperazine derivatives |
| JPH05255089A (ja) * | 1991-12-18 | 1993-10-05 | Sanwa Kagaku Kenkyusho Co Ltd | 抗ウイルス剤 |
| ATE311884T1 (de) | 1997-07-12 | 2005-12-15 | Cancer Rec Tech Ltd | Cyclin-abhängige-kinase inhibierende purinderivate |
| EP1746889B1 (en) * | 2004-05-12 | 2009-07-22 | Bayer CropScience AG | Plant growth regulation |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2334009A1 (de) * | 1973-07-04 | 1975-01-23 | Boehringer Mannheim Gmbh | Purin-derivate sowie verfahren zu ihrer herstellung |
| DE3703633A1 (de) * | 1986-02-14 | 1987-08-20 | Sandoz Ag | Purin-derivate, ihre herstellung und sie enthaltende arzneimittel |
| US4876257A (en) * | 1988-03-03 | 1989-10-24 | Ortho Pharmaceutical Corporation | 6-Substituted purinyl piperazine derivatives useful as cardiotonic and antiarrhythmic agents |
-
1991
- 1991-05-10 NZ NZ238122A patent/NZ238122A/en unknown
- 1991-05-21 MY MYPI91000860A patent/MY106167A/en unknown
- 1991-05-21 CA CA002042944A patent/CA2042944A1/en not_active Abandoned
- 1991-05-21 AU AU77233/91A patent/AU636034B2/en not_active Ceased
- 1991-05-22 KR KR1019910008205A patent/KR910020011A/ko not_active Ceased
- 1991-05-22 JP JP3145165A patent/JPH04226986A/ja active Pending
- 1991-05-22 NO NO911973A patent/NO179909C/no unknown
- 1991-05-22 PT PT97741A patent/PT97741B/pt not_active IP Right Cessation
- 1991-05-22 EP EP91304632A patent/EP0458618A1/en not_active Withdrawn
- 1991-05-22 FI FI912486A patent/FI912486L/fi not_active Application Discontinuation
- 1991-05-22 ZA ZA913880A patent/ZA913880B/xx unknown
- 1991-05-22 IL IL9822491A patent/IL98224A/en not_active IP Right Cessation
- 1991-05-22 HU HU911727A patent/HUT57768A/hu unknown
- 1991-05-22 IE IE175191A patent/IE911751A1/en unknown
- 1991-05-23 TN TNTNSN91037A patent/TNSN91037A1/fr unknown
- 1991-05-23 CN CN91103957A patent/CN1031642C/zh not_active Expired - Fee Related
- 1991-07-25 TW TW080105785A patent/TW211012B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| PT97741B (pt) | 1998-10-30 |
| PT97741A (pt) | 1992-02-28 |
| IL98224A (en) | 1995-07-31 |
| MY106167A (en) | 1995-03-31 |
| FI912486A7 (fi) | 1991-11-24 |
| IE911751A1 (en) | 1991-12-04 |
| HUT57768A (en) | 1991-12-30 |
| NO179909B (no) | 1996-09-30 |
| AU636034B2 (en) | 1993-04-08 |
| TW211012B (enExample) | 1993-08-11 |
| CN1057463A (zh) | 1992-01-01 |
| FI912486L (fi) | 1991-11-24 |
| NO911973L (no) | 1991-11-25 |
| KR910020011A (ko) | 1991-12-19 |
| IL98224A0 (en) | 1992-06-21 |
| EP0458618A1 (en) | 1991-11-27 |
| NO179909C (no) | 1997-01-08 |
| AU7723391A (en) | 1991-11-28 |
| TNSN91037A1 (fr) | 1992-10-25 |
| JPH04226986A (ja) | 1992-08-17 |
| ZA913880B (en) | 1993-01-27 |
| NO911973D0 (no) | 1991-05-22 |
| FI912486A0 (fi) | 1991-05-22 |
| CA2042944A1 (en) | 1991-11-24 |
| NZ238122A (en) | 1994-01-26 |
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| C14 | Grant of patent or utility model | ||
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| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |