CS268534B2 - Method of ergolen derivatives production - Google Patents
Method of ergolen derivatives production Download PDFInfo
- Publication number
- CS268534B2 CS268534B2 CS872920A CS292087A CS268534B2 CS 268534 B2 CS268534 B2 CS 268534B2 CS 872920 A CS872920 A CS 872920A CS 292087 A CS292087 A CS 292087A CS 268534 B2 CS268534 B2 CS 268534B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- group
- derivative
- acyl
- ergolene
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 20
- 125000002252 acyl group Chemical group 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- 150000008065 acid anhydrides Chemical class 0.000 claims description 12
- 239000000010 aprotic solvent Substances 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 150000001266 acyl halides Chemical class 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 238000009835 boiling Methods 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 230000010933 acylation Effects 0.000 claims description 6
- 238000005917 acylation reaction Methods 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 16
- DAVNRFCJMIONPO-UHFFFAOYSA-N (7-methyl-6,6a,8,10a-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl)methanol Chemical compound C1=CC(C2C=C(CO)CN(C2C2)C)=C3C2=CNC3=C1 DAVNRFCJMIONPO-UHFFFAOYSA-N 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- -1 phenyl acetyl Chemical group 0.000 description 10
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- BIXJFIJYBLJTMK-MEBBXXQBSA-N lysergol Chemical compound C1=CC(C2=C[C@@H](CO)CN([C@@H]2C2)C)=C3C2=CNC3=C1 BIXJFIJYBLJTMK-MEBBXXQBSA-N 0.000 description 6
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- 230000000561 anti-psychotic effect Effects 0.000 description 5
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- 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 208000009132 Catalepsy Diseases 0.000 description 4
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- 206010047853 Waxy flexibility Diseases 0.000 description 4
- UDIJSKHBACNYIE-YMTOWFKASA-N [(6ar,9r)-5-chloro-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl]methanol Chemical compound C1=CC(C2=C[C@@H](CO)CN([C@@H]2C2)C)=C3C2=C(Cl)NC3=C1 UDIJSKHBACNYIE-YMTOWFKASA-N 0.000 description 4
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- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 4
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- 238000004440 column chromatography Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000000141 anti-hypoxic effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
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- 230000004083 survival effect Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010002660 Anoxia Diseases 0.000 description 2
- 241000976983 Anoxia Species 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
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- 125000000623 heterocyclic group Chemical group 0.000 description 2
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- 230000002631 hypothermal effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
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- 231100000820 toxicity test Toxicity 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
- 230000009466 transformation Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/02—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid with hydrocarbon or substituted hydrocarbon radicals, attached in position 8
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU861719A HU196598B (en) | 1986-04-25 | 1986-04-25 | Process for producing 1- and/or 8-substituted 2-halogenated ergoline derivatives and pharmaceutics comprising such compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS292087A2 CS292087A2 (en) | 1989-06-13 |
| CS268534B2 true CS268534B2 (en) | 1990-03-14 |
Family
ID=10955843
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS872920A CS268534B2 (en) | 1986-04-25 | 1987-04-24 | Method of ergolen derivatives production |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US4859682A (en]) |
| JP (1) | JPS62258379A (en]) |
| KR (1) | KR920008167B1 (en]) |
| CN (1) | CN87102944A (en]) |
| AT (1) | AT391472B (en]) |
| AU (1) | AU592637B2 (en]) |
| BE (1) | BE1001159A4 (en]) |
| CH (1) | CH669791A5 (en]) |
| CS (1) | CS268534B2 (en]) |
| DD (1) | DD256133A5 (en]) |
| DE (1) | DE3713768A1 (en]) |
| DK (1) | DK208887A (en]) |
| EG (1) | EG18272A (en]) |
| ES (1) | ES2007339A6 (en]) |
| FI (1) | FI871128A7 (en]) |
| FR (1) | FR2597869B1 (en]) |
| GB (1) | GB2189487B (en]) |
| GR (1) | GR870645B (en]) |
| HU (1) | HU196598B (en]) |
| IL (1) | IL82324A0 (en]) |
| IN (1) | IN165245B (en]) |
| IT (1) | IT1203976B (en]) |
| LU (1) | LU86853A1 (en]) |
| NL (1) | NL8700966A (en]) |
| NO (1) | NO165800C (en]) |
| PL (1) | PL152619B1 (en]) |
| PT (1) | PT84739B (en]) |
| SE (1) | SE466401B (en]) |
| SU (1) | SU1500161A3 (en]) |
| ZA (1) | ZA872931B (en]) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU196394B (en) * | 1986-06-27 | 1988-11-28 | Richter Gedeon Vegyeszet | Process for preparing 2-halogenated ergoline derivatives |
| KR20040104677A (ko) * | 2002-04-30 | 2004-12-10 | 비오갈 기오기스제르갸르 알티. | 신규의 온단세트론 결정 형태, 그 제조 방법, 그 신규의결정 형태를 함유하는 약학 조성물 및 이들을 이용한구역질 치료 방법 |
| US20240343692A1 (en) * | 2021-08-09 | 2024-10-17 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Selective psychedelic compounds |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE237837C (en]) * | ||||
| DE1936410A1 (de) * | 1969-07-17 | 1971-02-11 | Hoechst Ag | O-Acyl-lysergole und Verfahren zu ihrer Herstellung |
| AR206772A1 (es) * | 1972-07-21 | 1976-08-23 | Lilly Co Eli | Procedimiento para preparar una nueva d-2-halo-6-metil-8-ciano(carboxamido)metil ergolina |
| US3992385A (en) * | 1975-01-20 | 1976-11-16 | Eli Lilly And Company | 2,3-Dihydroergolines |
| CH619709A5 (en) * | 1975-03-14 | 1980-10-15 | Siphar Sa | Process for the preparation of carbamates of 2-halogenoergolines and 2-halogenoergolenes |
| DE2656344A1 (de) * | 1975-12-23 | 1977-07-07 | Sandoz Ag | Ergolinderivate, ihre verwendung und herstellung |
| US4035094A (en) * | 1976-03-11 | 1977-07-12 | Trw Inc. | Ball and socket joint |
| DK75177A (da) * | 1976-04-27 | 1977-10-28 | Sandoz Ag | Fremgangsmade til fremstilling af prostaglandiner |
| US4098790A (en) * | 1976-09-15 | 1978-07-04 | Eli Lilly And Company | Ergoline chlorination process |
| DE3001752A1 (de) * | 1980-01-16 | 1981-07-30 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | Verfahren zur herstellung von 8(alpha)-substituierten 6-methylergolinen |
| DE3151912A1 (de) * | 1981-12-23 | 1983-06-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue ergolin-aminoderivate, verfahren zu ihrer herstellung und deren verwendung als arzneimittel |
| DD237837A1 (de) * | 1983-11-29 | 1986-07-30 | 1086 Berlin,Otto-Nuscke-Str. 2/23,Dd | Verfahren zur herstellung von 2-bromergolinen |
| DE3403067A1 (de) * | 1984-01-30 | 1985-08-14 | Eckart Prof. Dr. 6500 Mainz Eich | Ergolin-derivate, verfahren zu ihrer herstellung, sie enthaltende arzneimittel und deren verwendung |
| DE3413657A1 (de) * | 1984-04-09 | 1985-10-17 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue ergoline |
| HU193781B (en) * | 1985-06-21 | 1987-11-30 | Richter Gedeon Vegyeszet | Process for producing 10alpha-methoxy-6-methylergoline derivatives and acid additional salts thereof |
| US4782152A (en) * | 1985-08-16 | 1988-11-01 | Eli Lilly And Company | Decyanation of pergolide intermediate |
| HU196394B (en) * | 1986-06-27 | 1988-11-28 | Richter Gedeon Vegyeszet | Process for preparing 2-halogenated ergoline derivatives |
-
1986
- 1986-04-25 HU HU861719A patent/HU196598B/hu not_active IP Right Cessation
-
1987
- 1987-03-13 FI FI871128A patent/FI871128A7/fi not_active Application Discontinuation
- 1987-04-21 US US07/040,938 patent/US4859682A/en not_active Expired - Fee Related
- 1987-04-22 PT PT84739A patent/PT84739B/pt not_active IP Right Cessation
- 1987-04-23 CN CN87102944A patent/CN87102944A/zh active Pending
- 1987-04-23 EG EG238/87A patent/EG18272A/xx active
- 1987-04-24 CH CH1577/87A patent/CH669791A5/de not_active IP Right Cessation
- 1987-04-24 DD DD87302104A patent/DD256133A5/de not_active IP Right Cessation
- 1987-04-24 PL PL1987265357A patent/PL152619B1/pl unknown
- 1987-04-24 CS CS872920A patent/CS268534B2/cs unknown
- 1987-04-24 LU LU86853A patent/LU86853A1/de unknown
- 1987-04-24 GR GR870645A patent/GR870645B/el unknown
- 1987-04-24 NL NL8700966A patent/NL8700966A/nl not_active Application Discontinuation
- 1987-04-24 ES ES8701211A patent/ES2007339A6/es not_active Expired
- 1987-04-24 SU SU874202410A patent/SU1500161A3/ru active
- 1987-04-24 NO NO871721A patent/NO165800C/no unknown
- 1987-04-24 IL IL82324A patent/IL82324A0/xx not_active IP Right Cessation
- 1987-04-24 BE BE8700445A patent/BE1001159A4/fr not_active IP Right Cessation
- 1987-04-24 IN IN326/CAL/87A patent/IN165245B/en unknown
- 1987-04-24 AU AU71945/87A patent/AU592637B2/en not_active Ceased
- 1987-04-24 FR FR878705838A patent/FR2597869B1/fr not_active Expired - Lifetime
- 1987-04-24 JP JP62100224A patent/JPS62258379A/ja active Granted
- 1987-04-24 AT AT0102287A patent/AT391472B/de active
- 1987-04-24 DK DK208887A patent/DK208887A/da not_active Application Discontinuation
- 1987-04-24 DE DE19873713768 patent/DE3713768A1/de not_active Withdrawn
- 1987-04-24 IT IT20271/87A patent/IT1203976B/it active
- 1987-04-24 ZA ZA872931A patent/ZA872931B/xx unknown
- 1987-04-24 SE SE8701700A patent/SE466401B/sv not_active IP Right Cessation
- 1987-04-24 KR KR1019870003970A patent/KR920008167B1/ko not_active Expired
- 1987-04-27 GB GB8709893A patent/GB2189487B/en not_active Expired - Lifetime
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