NO154056B - Analogifremgangsmaate for fremstilling av terapeutisk aktive isopropylamino-pyrimidin-hydroksy-derivater. - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive isopropylamino-pyrimidin-hydroksy-derivater. Download PDFInfo
- Publication number
- NO154056B NO154056B NO801235A NO801235A NO154056B NO 154056 B NO154056 B NO 154056B NO 801235 A NO801235 A NO 801235A NO 801235 A NO801235 A NO 801235A NO 154056 B NO154056 B NO 154056B
- Authority
- NO
- Norway
- Prior art keywords
- isopropylamino
- preparation
- pyrimidine
- hydroxy derivatives
- therapeutic active
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 5
- 230000001225 therapeutic effect Effects 0.000 title description 2
- -1 ISOPROPYLAMINO-PYRIMIDINE HYDROXY Chemical class 0.000 title 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- NOBMCJZUSXFKLM-UHFFFAOYSA-N 5-phenylmethoxy-N-propan-2-ylpyrimidin-2-amine Chemical compound C(C)(C)NC1=NC=C(C=N1)OCC1=CC=CC=C1 NOBMCJZUSXFKLM-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 210000003497 sciatic nerve Anatomy 0.000 description 3
- 238000002211 ultraviolet spectrum Methods 0.000 description 3
- UBGRSKXBCVWAOV-UHFFFAOYSA-N 2-(propan-2-ylamino)pyrimidin-5-ol Chemical compound CC(C)NC1=NC=C(O)C=N1 UBGRSKXBCVWAOV-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- VQEDGGYDPKEQGW-UHFFFAOYSA-N 2-(propan-2-ylamino)-1h-pyrimidin-6-one Chemical compound CC(C)NC1=NC=CC(O)=N1 VQEDGGYDPKEQGW-UHFFFAOYSA-N 0.000 description 1
- ZRNBGIUZXJKFBD-UHFFFAOYSA-N 4,6-bis(phenylmethoxy)-N-propan-2-ylpyrimidin-2-amine Chemical compound C(C)(C)NC1=NC(=CC(=N1)OCC1=CC=CC=C1)OCC1=CC=CC=C1 ZRNBGIUZXJKFBD-UHFFFAOYSA-N 0.000 description 1
- YCHCKOKZMYMYMP-UHFFFAOYSA-N 4-ethoxy-N-propan-2-ylpyrimidin-2-amine Chemical compound C(C)(C)NC1=NC=CC(=N1)OCC YCHCKOKZMYMYMP-UHFFFAOYSA-N 0.000 description 1
- BKDYEBFKDKOMQE-UHFFFAOYSA-N 4-hydroxy-2-(propan-2-ylamino)-1h-pyrimidin-6-one Chemical compound CC(C)NC1=NC(O)=CC(=O)N1 BKDYEBFKDKOMQE-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Denne oppfinnelse angår en analogifremgangsmåte for fremstilling av isopropylaminopyrimidin-hydroksy-derivater med interessante terapeutiske egenskaper, særlig for behandling av forskjellige neuropatier og muskeldystrofier.
Den generelle formel for disse derivater er:
hvor hver av A^, Aj- og A^ betyr:
- et hydrogenatom eller
- en hydroksygruppe,
med det forbehold at minst én av A^ , Aj- og Ag ikke er et hydrogenatom.
Disse forbindelser kan fremstilles ved reduksjon av det tilsvarende 2-isopropylamino-aralkyloksy- eller alkyloksy-pyrimidin med hydrogen under trykk og i nærvær av en hydrogeneringskatalysator som f.eks. palladium, i henhold til følgende skjema:
hvor A"4, A"5 og A"6 hver betyr et hydrogenatom eller et aralkyloksy- eller alkyloksyradikal, med samme forbehold som ovenfor.
Med forbindelsene fremstilt ifølge foreliggende oppfinnelse oppnås en noe bedre virkning på nervevekst-regenereringen med lavere doser enn de doser som anvendes for forbindelsen ifølge britisk patent 1 525 995. Som konklusjon kan man si at forbindelsene fremstilt ifølge foreliggende oppfinnelse er omtrentlig 9 ganger så aktive som forbindelsene ifølge teknikkens stand.
Oppfinnelsen illustreres ved hjelp av de følgende
eksempler.
Eksempel 1
2- isopropylamino- 5- hydroksy- pyrimidin
I en trykkreaktor med kapasitet på 2 liter, fortrinnsvis klargjort ved hjelp av en nitrogenstrøm, ble innført 0,8 g 2-isopropylamino-5-benzyloksy-pyrimidin, 40 ml metanol og 80 mg palladiumkatalysator, og hydrogenering ble foretatt i 2 timer ved normaltrykk. Efter frafiltrering av katalysatoren og avdampning av metanolen, ble produktet opptatt i dietyleter, og oppløsningen ble filtrert for å fjerne uoppløselig materiale. Dietyleteren ble avdampet, og produktet ble omkrystallisert, først fra vann og derefter fra etylacetat. Efter tørring fikk man 0,4 g (utbytte 80%) 2-isopropylamino-5-hydroksy-pyrimidin. Elementæranalyse viste den ventede empiriske formel C^H^N^O. Smeltepunkt 161°C (Tottoli) . UV-sjpektrum bekrefter strukturen.
Eksempel 2
2- isopropylamino- 4- hydroksy- pyrimidin
Fremgangsmåten beskrevet i eksempel 1 ble anvendt på 2-isopropylamino-4-etoksy-pyrimidin istedenfor 2-isopropylamino-5-benzyloksy-pyrimidin. Utbyttet var 83% av et hvitt, krystallinsk produkt som smeltet ved 140°C (Tottoli), og analysen viste fullkommen overensstemmelse med formelen C^H^N^O. UV-spekteret bekrefter strukturen.
Eksempel 3
2- isopropylamino- 4, 6- dihydroksy- pyrimidin
Fremgangsmåten beskrevet i eksempel 1 ble anvendt på 2-isopropylamino-4,6-dibenzyloksy-pyrimidin istedenfor 2-isopropylamino-5-benzyloksy-pyrimidin. Utbyttet var 78% av et hvitt krystallinsk produkt (hydroklorid) med smeltepunkt 218-221°C (Tottoli), med spaltning, og analysen viste fullkommen overensstemmelse med formelen <C>7<H>^N302-HC1.
UV-spekteret bekrefter strukturen.
T oksisitet
Den akutte toksisitet (mg/kg) for forbindelsene fremstilt ifølge oppfinnelsen ble bestemt på mus i.p. og per os, og verdiene er angitt i den følgende tabell:
Farmakologi
Den farmakologiske aktivitet for forbindelsene fremstilt ifølge oppfinnelsen er undersøkt ved hjelp av følgende sammen-lignings forsøk som ble gjort for å undersøke regenereringen av hoftenerven hos voksne hannrotter (Wistar).
En skade frembringes på hoftenerven hos rottene ved anvendelse av termolyd ved -20°C i 20 minutter på nerven. Rottene behandles derefter i.p. med referanseproduktet eller med forbindelsene fremstilt ifølge oppfinnelsen over et fastsatt tidsrom. Ved slutten av behandlingen avlives rottene, hofte-nervene tas ut og anbringes i kontakt med en serie av 70 tynne parallelle platinatråder (avstand 1 mm), og et elektrisk signal påsettes ovenfor skadepunktet og undersøkes på platinatrådene: Den fjerneste tråd hvor signalet kan påvises, gir den regenererte lengde.
For hvert undersøkte preparat og for hver behandlings-varighet anvendes en gruppe på 8 rotter.
Fire preparater er undersøkt i.p.: Eksempel 1-forbindelse, Eksempel 2-forbindeIse, Eksempel 3-forbindelse, alle med en i.p. dose på 10 mg/kg, og som referanse, en blanding av vitaminer Bl (500 mg/kg), B6 (500 mg/kg) og B12 (5 mg/kg) som er kjent for å være det mest effektive preparat på dette området. Kontrollene fikk ingen behandling i det hele tatt. Fem grupper pn hver 8 dyr ble anvendt for hver varighet (7, 11, 14, 17 og 21 dager) enten for kontroller eller for forbindelser 1, 2, 3 eller referansepreparatet.
Resultatene av dette forsak er oppsummert i den følgende t.abe.ll sammen med verdiene som ble oppnådd for kontrolldyrene. Lengden av de regenererte nerver er angitt i mm i det respektive daq-spalter som'en gjennomsnittlig verdi for de lengder som ble målt for alle dyrene j hver gruppe. Når ingen tall er angitt (17 og 21 dager) betyr dette at den regenererte lengde oversteg lengden av den uttatte prøve.
Claims (1)
- Analogifremgangsmåte for fremstilling av terapeutisk aktive isopropylamino-pyrimidin-hydroksy-derivater med formelen:hvor hver av , A,- og Ag betyr - et hydrogenatom, eller - en hydroksygruppe,med det forbehold at minst én av A^, Aj. og Ag ikke er et hydrogenatom, karakterisert ved reduksjon av det tilsvarende 2-isopropylamino-aralkyloksy- eller -alkyloksy-pyrimidin med hydrogen under trykk og i nærvær av en hydrogeneringskatalysator som f.eks. palladium, i henhold til følgende skjema:hvor A"4, A"5 og A"g hver betyr et hydrogenatom eller et aralkyloksy- eller alkyloksyradikal, med samme forbehold som ovenfor.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7914987 | 1979-04-30 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO801235L NO801235L (no) | 1980-10-31 |
| NO154056B true NO154056B (no) | 1986-04-01 |
| NO154056C NO154056C (no) | 1986-07-09 |
Family
ID=10504858
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO801235A NO154056C (no) | 1979-04-30 | 1980-04-28 | Analogifremgangsmaate for fremstilling av terapeutisk aktive isopropylamino-pyrimidin-hydroksy-derivater. |
| NO801234A NO154055C (no) | 1979-04-30 | 1980-04-28 | Analogifremgangsmaate for fremstilling av terapeutisk aktive isopropylamino-pyrimidin-hydroksy-derivater. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO801234A NO154055C (no) | 1979-04-30 | 1980-04-28 | Analogifremgangsmaate for fremstilling av terapeutisk aktive isopropylamino-pyrimidin-hydroksy-derivater. |
Country Status (26)
| Country | Link |
|---|---|
| JP (2) | JPS55145670A (no) |
| AR (2) | AR222870A1 (no) |
| AT (2) | AT380012B (no) |
| BE (2) | BE882593A (no) |
| CH (2) | CH645633A5 (no) |
| DK (2) | DK183880A (no) |
| EG (2) | EG14259A (no) |
| ES (2) | ES8103060A1 (no) |
| FI (2) | FI66359C (no) |
| FR (2) | FR2455589A1 (no) |
| GB (2) | GB2054556B (no) |
| HK (2) | HK55583A (no) |
| IE (2) | IE49709B1 (no) |
| IN (2) | IN154067B (no) |
| IT (2) | IT1141487B (no) |
| LU (2) | LU82333A1 (no) |
| MA (1) | MA18824A1 (no) |
| MX (2) | MX5878E (no) |
| MY (2) | MY8400204A (no) |
| NL (2) | NL8002271A (no) |
| NO (2) | NO154056C (no) |
| NZ (2) | NZ193422A (no) |
| OA (2) | OA06527A (no) |
| PT (2) | PT71155A (no) |
| SG (2) | SG22283G (no) |
| ZA (2) | ZA801958B (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63145595U (no) * | 1987-03-13 | 1988-09-26 | ||
| JPS645795U (no) * | 1987-06-26 | 1989-01-13 | ||
| JPH01100695U (no) * | 1987-12-21 | 1989-07-06 | ||
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| US5264435A (en) * | 1988-12-29 | 1993-11-23 | Mitsui Petrochemical Industries, Ltd. | Pyrimidines and their pharmaceutical acceptable salts, and their use as medicines |
-
1980
- 1980-04-02 ZA ZA00801958A patent/ZA801958B/xx unknown
- 1980-04-02 BE BE0/200083A patent/BE882593A/fr not_active IP Right Cessation
- 1980-04-02 BE BE0/200084A patent/BE882594A/fr not_active IP Right Cessation
- 1980-04-02 ZA ZA00801960A patent/ZA801960B/xx unknown
- 1980-04-03 LU LU82333A patent/LU82333A1/fr unknown
- 1980-04-03 LU LU82332A patent/LU82332A1/fr unknown
- 1980-04-03 FI FI801084A patent/FI66359C/fi not_active IP Right Cessation
- 1980-04-03 FI FI801083A patent/FI66358C/fi not_active IP Right Cessation
- 1980-04-07 IN IN254/DEL/80A patent/IN154067B/en unknown
- 1980-04-07 IN IN253/DEL/80A patent/IN154066B/en unknown
- 1980-04-08 CH CH268980A patent/CH645633A5/fr not_active IP Right Cessation
- 1980-04-08 CH CH269080A patent/CH645361A5/fr not_active IP Right Cessation
- 1980-04-11 NZ NZ193422A patent/NZ193422A/xx unknown
- 1980-04-11 NZ NZ193421A patent/NZ193421A/xx unknown
- 1980-04-15 GB GB8012349A patent/GB2054556B/en not_active Expired
- 1980-04-15 GB GB8012351A patent/GB2055801B/en not_active Expired
- 1980-04-18 NL NL8002271A patent/NL8002271A/nl unknown
- 1980-04-18 NL NL8002272A patent/NL8002272A/nl not_active Application Discontinuation
- 1980-04-22 MA MA19019A patent/MA18824A1/fr unknown
- 1980-04-22 IT IT21542/80A patent/IT1141487B/it active
- 1980-04-22 IT IT21543/80A patent/IT1141296B/it active
- 1980-04-24 AT AT0221580A patent/AT380012B/de not_active IP Right Cessation
- 1980-04-24 AT AT0221680A patent/AT380013B/de not_active IP Right Cessation
- 1980-04-25 AR AR280811A patent/AR222870A1/es active
- 1980-04-25 AR AR280810A patent/AR222869A1/es active
- 1980-04-28 IE IE865/80A patent/IE49709B1/en unknown
- 1980-04-28 JP JP5557480A patent/JPS55145670A/ja active Granted
- 1980-04-28 PT PT71155A patent/PT71155A/pt unknown
- 1980-04-28 IE IE864/80A patent/IE49591B1/en unknown
- 1980-04-28 JP JP5557580A patent/JPS55145671A/ja active Granted
- 1980-04-28 NO NO801235A patent/NO154056C/no unknown
- 1980-04-28 NO NO801234A patent/NO154055C/no unknown
- 1980-04-28 MX MX808786U patent/MX5878E/es unknown
- 1980-04-28 MX MX808783U patent/MX6514E/es unknown
- 1980-04-28 PT PT71154A patent/PT71154A/pt unknown
- 1980-04-29 ES ES490999A patent/ES8103060A1/es not_active Expired
- 1980-04-29 DK DK183880A patent/DK183880A/da unknown
- 1980-04-29 ES ES491000A patent/ES491000A0/es active Granted
- 1980-04-29 EG EG258/80A patent/EG14259A/xx active
- 1980-04-29 EG EG257/80A patent/EG14284A/xx active
- 1980-04-29 DK DK183780A patent/DK183780A/da unknown
- 1980-04-30 FR FR8009733A patent/FR2455589A1/fr active Granted
- 1980-04-30 FR FR8009732A patent/FR2455588A1/fr active Granted
- 1980-04-30 OA OA57103A patent/OA06527A/xx unknown
- 1980-04-30 OA OA57101A patent/OA06525A/xx unknown
-
1983
- 1983-04-28 SG SG222/83A patent/SG22283G/en unknown
- 1983-04-28 SG SG225/83A patent/SG22583G/en unknown
- 1983-11-17 HK HK555/83A patent/HK55583A/xx unknown
- 1983-11-17 HK HK556/83A patent/HK55683A/xx unknown
-
1984
- 1984-12-30 MY MY204/84A patent/MY8400204A/xx unknown
- 1984-12-30 MY MY203/84A patent/MY8400203A/xx unknown
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