FI112213B - Menetelmä terapeuttisesti käyttökelpoisten trifluorimetyylimerkaptaani- ja merkaptoasyylijohdannaisten valmistamiseksi - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten trifluorimetyylimerkaptaani- ja merkaptoasyylijohdannaisten valmistamiseksi Download PDFInfo
- Publication number
- FI112213B FI112213B FI911399A FI911399A FI112213B FI 112213 B FI112213 B FI 112213B FI 911399 A FI911399 A FI 911399A FI 911399 A FI911399 A FI 911399A FI 112213 B FI112213 B FI 112213B
- Authority
- FI
- Finland
- Prior art keywords
- ethyl acetate
- mmol
- give
- mixture
- product
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims description 6
- MFLLMKMFWIUACU-UHFFFAOYSA-N trifluoromethanethiol Chemical compound FC(F)(F)S MFLLMKMFWIUACU-UHFFFAOYSA-N 0.000 title claims 2
- -1 4,5-dihydrothiazolyl Chemical group 0.000 claims abstract description 115
- 150000001875 compounds Chemical class 0.000 claims abstract description 98
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 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 description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000002792 enkephalinase inhibitor Substances 0.000 abstract description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 8
- 239000002327 cardiovascular agent Substances 0.000 abstract description 2
- 229940125692 cardiovascular agent Drugs 0.000 abstract description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 2
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 abstract 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 abstract 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 abstract 1
- 125000002883 imidazolyl group Chemical group 0.000 abstract 1
- 125000000842 isoxazolyl group Chemical group 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 125000002971 oxazolyl group Chemical group 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- 125000000335 thiazolyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 815
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 466
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 384
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
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- 239000000047 product Substances 0.000 description 147
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 132
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 68
- 238000004458 analytical method Methods 0.000 description 64
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 44
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 41
- 229910052786 argon Inorganic materials 0.000 description 40
- 239000012044 organic layer Substances 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 37
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
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- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 32
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 31
- RZYHXKLKJRGJGP-UHFFFAOYSA-N 2,2,2-trifluoro-n,n-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)N([Si](C)(C)C)C(=O)C(F)(F)F RZYHXKLKJRGJGP-UHFFFAOYSA-N 0.000 description 30
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 29
- 239000000908 ammonium hydroxide Substances 0.000 description 29
- 238000003818 flash chromatography Methods 0.000 description 28
- 239000010410 layer Substances 0.000 description 25
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 25
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 239000002024 ethyl acetate extract Substances 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 17
- SJFZYZLRGKXXPW-UHFFFAOYSA-N 4-oxo-2-(trifluoromethyl)pentanethioyl chloride Chemical compound CC(=O)CC(C(Cl)=S)C(F)(F)F SJFZYZLRGKXXPW-UHFFFAOYSA-N 0.000 description 16
- 239000007789 gas Substances 0.000 description 16
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- 239000003480 eluent Substances 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
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- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical class CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 10
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
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- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
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- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—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
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49738690A | 1990-03-22 | 1990-03-22 | |
| US49738690 | 1990-03-22 | ||
| SG165394A SG165394G (en) | 1990-03-22 | 1994-11-16 | Mercapto-or acylthio-trifluoromethyl amide derivatives and their use |
| SG165394 | 1994-11-16 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI911399A0 FI911399A0 (fi) | 1991-03-22 |
| FI911399L FI911399L (fi) | 1991-09-23 |
| FI112213B true FI112213B (fi) | 2003-11-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| FI911399A FI112213B (fi) | 1990-03-22 | 1991-03-22 | Menetelmä terapeuttisesti käyttökelpoisten trifluorimetyylimerkaptaani- ja merkaptoasyylijohdannaisten valmistamiseksi |
Country Status (27)
| Country | Link |
|---|---|
| EP (1) | EP0449523B1 (cs) |
| JP (1) | JP2955051B2 (cs) |
| KR (1) | KR0184876B1 (cs) |
| CN (1) | CN1038505C (cs) |
| AT (1) | ATE110056T1 (cs) |
| AU (1) | AU632408B2 (cs) |
| CA (1) | CA2038379C (cs) |
| CY (1) | CY1820A (cs) |
| CZ (1) | CZ281165B6 (cs) |
| DE (1) | DE69103454T2 (cs) |
| DK (1) | DK0449523T3 (cs) |
| EG (1) | EG19711A (cs) |
| ES (1) | ES2057761T3 (cs) |
| FI (1) | FI112213B (cs) |
| HK (1) | HK24295A (cs) |
| HU (1) | HU210313B (cs) |
| IE (1) | IE65539B1 (cs) |
| IL (1) | IL97626A (cs) |
| MX (1) | MX25035A (cs) |
| NO (1) | NO175147C (cs) |
| NZ (1) | NZ237534A (cs) |
| PL (1) | PL165153B1 (cs) |
| PT (1) | PT97121B (cs) |
| RU (1) | RU2024504C1 (cs) |
| SG (1) | SG165394G (cs) |
| SK (1) | SK279617B6 (cs) |
| ZA (1) | ZA912133B (cs) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1273455B (it) * | 1995-01-27 | 1997-07-08 | Zambon Spa | Derivati tiolici ad attivita' inibitrice delle metallopeptidasi |
| IT1277736B1 (it) * | 1995-12-28 | 1997-11-12 | Zambon Spa | Derivati tiolici ad attivita' inibitrice delle metallopeptidasi |
| FR2805259B1 (fr) * | 2000-02-17 | 2002-03-29 | Inst Nat Sante Rech Med | Nouveaux derives d'aminoacides n-mercaptoacyles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE429374B (sv) * | 1980-04-15 | 1983-08-29 | Luxor Ab | Feste |
| FR2480747A1 (fr) * | 1980-04-17 | 1981-10-23 | Roques Bernard | Derives d'acides amines et leur application therapeutique |
| US4333943A (en) * | 1980-04-24 | 1982-06-08 | Miles Laboratories, Inc. | Ethyl 3-(3-indolyl)-3-(5-tetrazolyl) propionate compounds used as anti-hypertensive agents |
| BE890948A (fr) * | 1981-10-30 | 1982-02-15 | Luitpold Werk Chem Pharm | Derives de l'acide anthranilique |
| EP0361365A1 (en) * | 1988-09-30 | 1990-04-04 | E.R. SQUIBB & SONS, INC. | Aminobenzoic and aminocyclohexane-carboylic acid compounds, compositions, and their method of use |
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1991
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- 1991-03-21 ZA ZA912133A patent/ZA912133B/xx unknown
- 1991-03-21 CZ CS91765A patent/CZ281165B6/cs not_active IP Right Cessation
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- 1991-03-22 CN CN91102697A patent/CN1038505C/zh not_active Expired - Fee Related
- 1991-03-22 DE DE69103454T patent/DE69103454T2/de not_active Expired - Fee Related
- 1991-03-22 AT AT91302508T patent/ATE110056T1/de not_active IP Right Cessation
- 1991-03-22 RU SU914895195A patent/RU2024504C1/ru active
- 1991-03-22 MX MX2503591A patent/MX25035A/es unknown
- 1991-03-22 PL PL91289549A patent/PL165153B1/pl not_active IP Right Cessation
- 1991-03-22 FI FI911399A patent/FI112213B/fi active
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- 1991-03-22 JP JP3083522A patent/JP2955051B2/ja not_active Expired - Fee Related
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1994
- 1994-11-16 SG SG165394A patent/SG165394G/en unknown
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1995
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- 1995-10-20 CY CY182095A patent/CY1820A/xx unknown
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