FI106860B - Förfarande för framställning av en kristallin dihydratförening och kristallin mellanprodukt - Google Patents
Förfarande för framställning av en kristallin dihydratförening och kristallin mellanprodukt Download PDFInfo
- Publication number
- FI106860B FI106860B FI20000353A FI20000353A FI106860B FI 106860 B FI106860 B FI 106860B FI 20000353 A FI20000353 A FI 20000353A FI 20000353 A FI20000353 A FI 20000353A FI 106860 B FI106860 B FI 106860B
- Authority
- FI
- Finland
- Prior art keywords
- acid
- crystalline
- alkyl
- compound
- dimethyl
- Prior art date
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- -1 dihydrate compound Chemical class 0.000 title claims description 19
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 28
- 230000008569 process Effects 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 18
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- HPOKESDSMZRZLC-UHFFFAOYSA-N propan-2-one;hydrochloride Chemical compound Cl.CC(C)=O HPOKESDSMZRZLC-UHFFFAOYSA-N 0.000 claims description 4
- 229940049920 malate Drugs 0.000 claims description 3
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
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- 239000000543 intermediate Substances 0.000 abstract description 10
- 239000000039 congener Substances 0.000 abstract 1
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- 125000000217 alkyl group Chemical group 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
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- 239000000243 solution Substances 0.000 description 30
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- 239000000047 product Substances 0.000 description 25
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 22
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 19
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- 238000005481 NMR spectroscopy Methods 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
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- 239000001257 hydrogen Substances 0.000 description 14
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- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
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- 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 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
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- 239000002002 slurry Substances 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 8
- 150000004683 dihydrates Chemical class 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- 229940116298 l- malic acid Drugs 0.000 description 7
- 230000002093 peripheral effect Effects 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
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- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
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- 238000010992 reflux Methods 0.000 description 6
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- 206010012735 Diarrhoea Diseases 0.000 description 5
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- 125000003342 alkenyl group Chemical group 0.000 description 5
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
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- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
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- NTBIYBAYFBNTCD-UHFFFAOYSA-N dibenzoyl 2,3-dihydroxybutanedioate Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-UHFFFAOYSA-N 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (5)
1. Förfarande för framställning av en kristallin dihydratförening med formeln 5 ©· 10 Λ 0 y^·' Ph H (5) kännetecknat därav, att man hydrolyserar en förening med formeln 4 20 OH [pj : 25 ·· ΥΎ' Ph (4) 35 väri R1 är Cx.6-alkyl, och därefter slacker reaktionen med hjälp av en syra. 106860 38
2. Förfarande enligt patentkrav 1, kanne-t e c k n a t därav, att föreningen med formeln 4 är ett salt, vilket valts ur gruppen som omfattar hydroklo-ridacetonmonosolvat, malat (1:1) och seskvimalat (3:2). :
3. Kristallin mellanprodukt med formeln 4 (§r rV VYy*1 Ph (4) 20 väri R1 är C^-alkyl, vilken förening är ett sait, vilket valts ur gruppen som omfattar hydrokloridacetonmonosolvat, malat (1:1) och seskvimalat (3:2).
4. Kristallin mellanprodukt enligt patentkrav 3, vilken mellanprodukt är ett sait av 2-metylpropylester av \ 25 (2S,3R,4R) [ [2-[ [4-(3-hydroxifenyl)-3,4-dimetyl-l-piperi- dinyl] metyl]-l-oxo-3-fenylpropyl]amino]ättiksyra.
5. Kristallin mellanprodukt enligt patentkrav 3, vilken mellanprodukt är ett malat av 2-metylpropylester av (2S,3R,4R)[(2-[[4-(3-hydroxifenyl)-3,4-dimetyl-l-piperi- 30 dinyl]metyl]-l-oxo-3-fenylpropyl]amino]ättiksyra. • ·
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16407493 | 1993-12-08 | ||
| US08/164,074 US5434171A (en) | 1993-12-08 | 1993-12-08 | Preparation of 3,4,4-trisubstituted-piperidinyl-N-alkylcarboxylates and intermediates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FI20000353L FI20000353L (sv) | 2000-02-17 |
| FI106860B true FI106860B (sv) | 2001-04-30 |
Family
ID=22592858
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI945703A FI106455B (sv) | 1993-12-08 | 1994-12-02 | Förfarande för framställning av kristallin (alfaS,3R,4R)-4-(3-hydroxifenyl)-3,4-dimetyl-alfa-(fenylmetyl)-1-piperidinpropionsyramonohydrat och kristallina mellanprodukter |
| FI20000353A FI106860B (sv) | 1993-12-08 | 2000-02-17 | Förfarande för framställning av en kristallin dihydratförening och kristallin mellanprodukt |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI945703A FI106455B (sv) | 1993-12-08 | 1994-12-02 | Förfarande för framställning av kristallin (alfaS,3R,4R)-4-(3-hydroxifenyl)-3,4-dimetyl-alfa-(fenylmetyl)-1-piperidinpropionsyramonohydrat och kristallina mellanprodukter |
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| EP (3) | EP0657428B1 (sv) |
| JP (2) | JP3834075B2 (sv) |
| KR (1) | KR100356239B1 (sv) |
| CN (2) | CN1057294C (sv) |
| AT (1) | ATE200279T1 (sv) |
| AU (1) | AU681198B2 (sv) |
| BR (1) | BR9404842A (sv) |
| CA (1) | CA2137221C (sv) |
| CO (1) | CO4290427A1 (sv) |
| CZ (1) | CZ290559B6 (sv) |
| DE (1) | DE69427017T2 (sv) |
| DK (1) | DK0657428T3 (sv) |
| ES (1) | ES2155844T3 (sv) |
| FI (2) | FI106455B (sv) |
| GR (1) | GR3036136T3 (sv) |
| HU (1) | HUT71489A (sv) |
| IL (1) | IL111843A (sv) |
| MY (1) | MY121543A (sv) |
| NO (1) | NO302884B1 (sv) |
| NZ (1) | NZ270039A (sv) |
| PE (1) | PE41495A1 (sv) |
| PL (1) | PL181734B1 (sv) |
| PT (1) | PT657428E (sv) |
| RU (1) | RU2145958C1 (sv) |
| SI (1) | SI0657428T1 (sv) |
| TW (1) | TW290540B (sv) |
| UA (1) | UA52577C2 (sv) |
| YU (2) | YU49312B (sv) |
| ZA (1) | ZA949584B (sv) |
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| GB9912413D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912416D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9912411D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
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-
1993
- 1993-12-08 US US08/164,074 patent/US5434171A/en not_active Expired - Lifetime
-
1994
- 1994-12-01 JP JP29835694A patent/JP3834075B2/ja not_active Expired - Fee Related
- 1994-12-01 AU AU79170/94A patent/AU681198B2/en not_active Ceased
- 1994-12-01 TW TW083111189A patent/TW290540B/zh not_active IP Right Cessation
- 1994-12-01 PL PL94306068A patent/PL181734B1/pl not_active IP Right Cessation
- 1994-12-01 PE PE1994256135A patent/PE41495A1/es not_active Application Discontinuation
- 1994-12-01 IL IL11184394A patent/IL111843A/xx not_active IP Right Cessation
- 1994-12-01 NZ NZ270039A patent/NZ270039A/en not_active IP Right Cessation
- 1994-12-01 ZA ZA949584A patent/ZA949584B/xx unknown
- 1994-12-01 CZ CZ19942992A patent/CZ290559B6/cs not_active IP Right Cessation
- 1994-12-02 YU YU70294A patent/YU49312B/sh unknown
- 1994-12-02 CA CA2137221A patent/CA2137221C/en not_active Expired - Fee Related
- 1994-12-02 DE DE69427017T patent/DE69427017T2/de not_active Expired - Lifetime
- 1994-12-02 CO CO94055028A patent/CO4290427A1/es unknown
- 1994-12-02 RU RU94042903A patent/RU2145958C1/ru not_active IP Right Cessation
- 1994-12-02 HU HU9403466A patent/HUT71489A/hu unknown
- 1994-12-02 AT AT94308951T patent/ATE200279T1/de not_active IP Right Cessation
- 1994-12-02 EP EP94308951A patent/EP0657428B1/en not_active Expired - Lifetime
- 1994-12-02 PT PT94308951T patent/PT657428E/pt unknown
- 1994-12-02 DK DK94308951T patent/DK0657428T3/da active
- 1994-12-02 BR BR9404842A patent/BR9404842A/pt not_active Application Discontinuation
- 1994-12-02 NO NO944644A patent/NO302884B1/no not_active IP Right Cessation
- 1994-12-02 YU YU82304A patent/YU82304A/sh unknown
- 1994-12-02 FI FI945703A patent/FI106455B/sv not_active IP Right Cessation
- 1994-12-02 UA UA94129124A patent/UA52577C2/uk unknown
- 1994-12-02 EP EP05077072A patent/EP1607387A3/en not_active Withdrawn
- 1994-12-02 ES ES94308951T patent/ES2155844T3/es not_active Expired - Lifetime
- 1994-12-02 EP EP99203390A patent/EP0984004A3/en not_active Withdrawn
- 1994-12-02 SI SI9430367T patent/SI0657428T1/xx unknown
- 1994-12-03 CN CN94119376A patent/CN1057294C/zh not_active Expired - Fee Related
- 1994-12-05 KR KR1019940032794A patent/KR100356239B1/ko not_active Expired - Fee Related
- 1994-12-05 MY MYPI94003238A patent/MY121543A/en unknown
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1998
- 1998-12-03 CN CN98123069A patent/CN1121387C/zh not_active Expired - Fee Related
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2000
- 2000-02-17 FI FI20000353A patent/FI106860B/sv not_active IP Right Cessation
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2001
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2005
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