NL8002272A - PROCESS FOR PREPARING ISOPROPYLAMINOPYRIMIDINE HYDROXY DERIVATIVES. - Google Patents
PROCESS FOR PREPARING ISOPROPYLAMINOPYRIMIDINE HYDROXY DERIVATIVES. Download PDFInfo
- Publication number
- NL8002272A NL8002272A NL8002272A NL8002272A NL8002272A NL 8002272 A NL8002272 A NL 8002272A NL 8002272 A NL8002272 A NL 8002272A NL 8002272 A NL8002272 A NL 8002272A NL 8002272 A NL8002272 A NL 8002272A
- Authority
- NL
- Netherlands
- Prior art keywords
- hydrogen atom
- isopropylaminopyrimidine
- hydroxy derivatives
- isopropylamino
- groups
- Prior art date
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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
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- 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
\ / Jj <*· // f.\ / Yy <* // f.
' ή ί 1'ή ί 1
Werkwijze ter bereiding van isopropylaminopyrimidine-hydroxy-derivaten.Process for the preparation of isopropylaminopyrimidine-hydroxy derivatives.
De uitvinding heeft betrekking op een werkwijze ter bereiding van isopropylaminopyrimidinehydroxy-derivaten met een belangwekkende therapeutische werking en meer in het bijzonder op een werkwijze voorde behandeling van variërende neuropathie-5 ën en musculaire dystrofieën.The invention relates to a method of preparing isopropylaminopyrimidine hydroxy derivatives with an interesting therapeutic effect and more particularly to a method for the treatment of varying neuropathies and muscular dystrophies.
De volgens de werkwijze van de uitvinding bereide verbindingen bezitten de op het formuleblad aangegeven algemene formule I, waarin A^, en Ag een waterstofatoom of een hydroxy-groep voorstellen, waarbij tenminste dén van de groepen A^, A^ 10 en Ag geen waterstofatoom voorstelt.The compounds prepared according to the process of the invention have the general formula I indicated on the formula sheet, in which A ^, and Ag represent a hydrogen atom or a hydroxy group, at least one of the groups A ^, A ^ 10 and Ag not having a hydrogen atom proposes.
Deze verbindingen kunnen bijvoorbeeld worden bereid door reductie van het overeenkomstige 2-isopropylaminoaral-~~~ —'" kyloxy- of -alkyloxypyrimidine met waterstof onder druk en in tegenwoordigheid van een hydrogeneringskatalysator, zoals palla-15 dium, volgens het op het formuleblad aangegeven reactieschema, waarin A"^, A"g en A"g elk een waterstofatoom of een aralkyl-oxy- of alkyloxyrest voorstellen, waarbij tenminste een van de genoemde groepen geen waterstofatoom is.These compounds can be prepared, for example, by reduction of the corresponding 2-isopropylaminoaral- kyloxy- or -alkyloxypyrimidine with hydrogen under pressure and in the presence of a hydrogenation catalyst, such as palladium, according to the reaction scheme shown on the formula sheet wherein A "^, A" g and A "g each represent a hydrogen atom or an aralkyloxy or alkyloxy radical, wherein at least one of said groups is not a hydrogen atom.
De uitvinding wordt verder toegelicht maar niet 20 beperkt door de volgende voorbeelden.The invention is further illustrated but not limited by the following examples.
Voorbeeld IExample I
2-isopropylamino-5-hydroxypyrimidine.2-isopropylamino-5-hydroxypyrimidine.
In een onder druk gebrachte reactor met een capaciteit van 2 liter , bij voorkeur gespoeld met een stikstof-25 stroom, werden gebracht 0,8 g 2-isopropylamino-5-benzyloxypyri-midine, 40 ml methanol en 80 mg palladium-katalysator; de hydro-genering werd uitgevoerd gedurende 2 uren onder normale druk. Na de verwijdering van de katalysator door filtratie en afdamping 800 2 2 72 t 2 r van de methanol werd het produkt opgenomen in diethylether en de oplossing afgefiltreerd ter verwijdering van onoplosbaar materiaal. De diethylether werd afgedampt en het produkt werd eerst uit water en vervolgens uit ethylacetaat herkristalliseerd. Na de 5 droging verkreeg men 0,4 g (opbrengst 80 %) 2-isopropylamino-5-hydroxy-pyrimidine. De verwachte empirische formule C^HjjN^O bleek uit de elementair analyse; smeltpunt = 161°C (Tottoli).0.8 g of 2-isopropylamino-5-benzyloxypyrimine, 40 ml of methanol and 80 mg of palladium catalyst were introduced into a pressurized reactor with a capacity of 2 liters, preferably flushed with a nitrogen stream. the hydrogenation was carried out under normal pressure for 2 hours. After removal of the catalyst by filtration and evaporation of methanol, the product was taken up in diethyl ether and the solution filtered to remove insoluble material. The diethyl ether was evaporated and the product was recrystallized first from water and then from ethyl acetate. After drying, 0.4 g (yield 80%) of 2-isopropylamino-5-hydroxy-pyrimidine were obtained. The expected empirical formula C ^ HjjN ^ O was apparent from the elemental analysis; melting point = 161 ° C (Tottoli).
Het ultraviolet spectrum bevestigt de structuur.The ultraviolet spectrum confirms the structure.
Voorbeeld IIExample II
10 2-isopropylamino-4-hydroxypyrimidine.2-isopropylamino-4-hydroxypyrimidine.
De in voorbeeld I beschreven werkwijze werd toegepast op 2-isopropylamino-4-ethoxypyrimidine in plaats van 2-iso-propylamino-5-benzyloxypyrimidine. Het produkt werd verkregen in een opbrengst van 83 % in de vorm van een witte kristallijne 15 stof met een smeltpunt van 140°C (Tottoli); uit de analyse blijkt de perfecte overeenkomst met de formule C^HjjN^O. Het ultraviolet spectrum bevestigt de structuur.The method described in Example I was applied to 2-isopropylamino-4-ethoxypyrimidine instead of 2-iso-propylamino-5-benzyloxypyrimidine. The product was obtained in a yield of 83% in the form of a white crystalline substance with a melting point of 140 ° C (Tottoli); the analysis shows the perfect agreement with the formula C ^ HjjN ^ O. The ultraviolet spectrum confirms the structure.
Voorbeeld IIIExample III
2-isopropylamino-4.6-dihydroxypyrimidine.2-isopropylamino-4,6-dihydroxypyrimidine.
20 De in voorbeeld I beschreven werkwijze werd toegepast op 2-iso- propylamino-4.6-dibenzyloxypyrimidine in plaats van 2-iso-propyl-amino-5-benzyloxypyrimidine. Het produkt werd verkregen in een opbrengst van 78 % in de vorm van een witte kristallijne stof (hydrochloride) met een smeltpunt van 218-221°C (Tottoli) onder 25 ontleding; uit de analyse van het produkt blijkt de perfecte overeenkomst met de formule C^Hj jN-^-HCl. Het ultraviolet spectrum bevestigt de structuur.The method described in Example I was applied to 2-isopropylamino-4,6-dibenzyloxypyrimidine instead of 2-iso-propyl-amino-5-benzyloxypyrimidine. The product was obtained in a yield of 78% in the form of a white crystalline substance (hydrochloride), mp 218-221 ° C (Tottoli) under decomposition; the analysis of the product shows the perfect agreement with the formula C 2 H 2 N 2 - HCl. The ultraviolet spectrum confirms the structure.
ToxiciteitToxicity
De acute toxiciteit (mg/kg) van de verbindingen 30 vo-lgens de uitvinding werd bepaald bij muizen onder intraperitonea-le en orale toedieningen de verkregen waarden zijn aangegeven in onderstaande tabel.The acute toxicity (mg / kg) of the compounds of the invention was determined in mice under intraperitoneal and oral administrations, the values obtained are shown in the table below.
35 800 2 2 72 ' * & 3 ' ^‘^'—-^Verbinding Voorbeeld Voorbeid Voorbeeld35 800 2 2 72 '* & 3' ^ "^" —- ^ Connection Example Prepared Example
Toediening ^_I_II_III_ intraperitoneaal_200 _240_260_ oraal___ 205_355_285_ 5 Farmacologie.Administration ^ _I_II_III_ intraperitoneal_200 _240_260_ oral___ 205_355_285_ 5 Pharmacology.
De farmacologische activiteit van de verbindingen volgens de uitvinding werd onderzocht onder gebruikmaking van de onderstaande vergelijkende proeven, die uitgevoerd worden op de regeneratie van de heupzenuw van de volwassen mannetjesrat (Wistar).The pharmacological activity of the compounds of the invention was investigated using the comparative tests below, which are performed on the regeneration of the sciatic nerve of the adult male rat (Wistar).
10 Een letsel wordt veroorzaakt aan de heupzenuw van de ratten door op de zenuw gedurende 20 minuten bij -20°C een thermosonde aan te brengen. De ratten worden vervolgens intraperitoneaal behandeld met het referentie-produkt of met de verbindingen volgens de uitvinding gedurende een van te voren bepaalde 15 tijdsduur. Na afloop van de behandeling worden de ratten gedood, de heupzenuwen weggenomen en in contact gebracht met een serie van 70 dunne evenwijdige platina-draden (tussenruimte 1 mm) en een elektrisch signaal, aangebracht stroomopwaarts ten opzichte van de plaats van het letsel, wordt gezocht op de platina-draden; de 20 meest verwijderde draad, waarbij het signaal kan worden verzameld, geeft de geregenereerde lengte.An injury is caused to the sciatic nerve of the rats by applying a thermoprobe to the nerve for 20 minutes at -20 ° C. The rats are then treated intraperitoneally with the reference product or with the compounds of the invention for a predetermined period of time. At the end of the treatment, the rats are killed, the sciatic nerves are removed and contacted with a series of 70 thin parallel platinum wires (1 mm spacing) and an electrical signal applied upstream of the injury site is searched on the platinum wires; the 20 most distant wire, where the signal can be collected, gives the regenerated length.
Voorelk onderzocht produkt en voor elke behande-lingsduur werd een aantal van 8 ratten gebruikt.A number of 8 rats were used for each product tested and for each treatment period.
Vier produkten werden intraperitoneaal onder-25 zocht: de verbinding van voorbeeld I, de verbinding van voorbeeld II, de verbinding van voorbeeld III, alle bij een intraperitoneale dosis van 10 mg/kg, en, als referentie-produkt, een mengsel van vitaminen BI (500 mg/kg), B6 (500 mg/kg) en B12 (5 mg/kg), welk mengsel in de techniek bekend is als het meest doeltreffende pro-30 dukt op dit gebied. De controle-ratten ontvingen in het geheel geen behandeling. Vijf charges van 8 dieren werden gebruikt voor elke behandelingsduur (7, 11, 14, 17 en 21 dagen) voor de controles, voor de verbindingen I, II en III of voor het referentie-mengsel.Four products were examined intraperitoneally: the compound of example I, the compound of example II, the compound of example III, all at an intraperitoneal dose of 10 mg / kg, and, as a reference product, a mixture of vitamins B1 (500 mg / kg), B6 (500 mg / kg) and B12 (5 mg / kg), which mixture is known in the art as the most effective product in this field. The control rats received no treatment at all. Five batches of 8 animals were used for each treatment duration (7, 11, 14, 17 and 21 days) for the controls, for compounds I, II and III or for the reference mixture.
De resultaten van deze proeven zijn aangegeven 35 in onderstaande tabel, samen met de voor de controle-dieren ver- 800 22 72 c 4 kregen waarden. De lengten van de geregenereerde zenuwen zijn aangegeven in mm bij de respectievelijke dag-kolommen als een gemiddelde waarde van de lengten, gemeten voor alle dieren van elke charge. Wanneer geen waarde is aangegeven (17 en 21 dagen) 5 betekent dit dat de geregenereerde lengte de lengte van het genomen monster overtrof.The results of these experiments are shown in the table below, together with the values obtained for the control animals. The lengths of the regenerated nerves are indicated in mm at the respective day columns as an average value of the lengths measured for all animals of each batch. If no value is indicated (17 and 21 days) 5 this means that the regenerated length exceeded the length of the sample taken.
' ——___Duur(dagen) 7 11 14 17 21Duration (days) 7 11 14 17 21
Verbinding en dosis i7pT~~ 1—-____ 15 Controles 5,1 10,2 12,8 17,8 22,4Compound and Dose i7pT ~~ 1 —-____ 15 Controls 5.1 10.2 12.8 17.8 22.4
Voorbeeld IExample I
10 mg/kg 6,6 14,1 26,310 mg / kg 6.6 14.1 26.3
Voorbeeld IIExample II
10 mg/kg 6,8 14,4 26,110 mg / kg 6.8 14.4 26.1
20 Voorbeeld IIIExample III
10 mg/kg 6,7 15,6 26,7 BI, B6, B12 8,8 13,4 15,8 20,4 23,7 500 mg/kg, 500 mg/kg en 5 mg/kg10 mg / kg 6.7 15.6 26.7 CI, B6, B12 8.8 13.4 15.8 20.4 23.7 500 mg / kg, 500 mg / kg and 5 mg / kg
Preparaatvormen en dosering.Preparation forms and dosage.
25 De genoemde derivaten kunnen worden gebracht in een willekeurige therapeutisch aanvaardbare vorm, bijvoorbeeld in de vorm van tabletten of gelatine-capsules, bevatten 5 mg per doseringseenheid, samen met een excipiëns; voor een injecteerbare vorm kan het produkt worden afgevuld in flesjes, bevattende ten-30 minste 1 mg actief bestanddeel in de vorm van het hydrochloride daarvan, opgelost in water. Ten aanzien van de dosering voor mensen geldt dat de orale toediening 20 mg tot 1 g per dag vereist, terwijl een injecteerbare vorm kan wor.den toegediend in doses van 1-50 mg per dag.The said derivatives can be put in any therapeutically acceptable form, for example in the form of tablets or gelatin capsules, containing 5 mg per dosage unit, together with an excipient; for an injectable form, the product can be filled into vials containing at least 1 mg of the active ingredient in the form of its hydrochloride dissolved in water. Regarding the dosage for humans, the oral administration requires 20 mg to 1 g per day, while an injectable form can be administered in doses of 1-50 mg per day.
35 Een voorbeeld van de samenstelling van een tablet- is hieronder aangegeven.An example of the composition of a tablet is shown below.
800 22 72 5800 22 72 5
Verbinding volgens voorbeelden 5 mgCompound according to examples 5 mg
Lactose .. 70 mgLactose .. 70 mg
Talk 20 mgTalc 20 mg
Magnesiumstearaat 5 mg 5 100 mg 800 22 72Magnesium stearate 5 mg 5 100 mg 800 22 72
Claims (4)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7914987 | 1979-04-30 | ||
| GB7914987 | 1979-04-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8002272A true NL8002272A (en) | 1980-11-03 |
Family
ID=10504858
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8002272A NL8002272A (en) | 1979-04-30 | 1980-04-18 | PROCESS FOR PREPARING ISOPROPYLAMINOPYRIMIDINE HYDROXY DERIVATIVES. |
| NL8002271A NL8002271A (en) | 1979-04-30 | 1980-04-18 | PROCESS FOR PREPARING ISOPROPYLAMINOPYRIMIDINE HYDROXY DERIVATIVES. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8002271A NL8002271A (en) | 1979-04-30 | 1980-04-18 | PROCESS FOR PREPARING ISOPROPYLAMINOPYRIMIDINE HYDROXY DERIVATIVES. |
Country Status (26)
| Country | Link |
|---|---|
| JP (2) | JPS55145670A (en) |
| AR (2) | AR222870A1 (en) |
| AT (2) | AT380013B (en) |
| BE (2) | BE882593A (en) |
| CH (2) | CH645361A5 (en) |
| DK (2) | DK183880A (en) |
| EG (2) | EG14284A (en) |
| ES (2) | ES8103060A1 (en) |
| FI (2) | FI66358C (en) |
| FR (2) | FR2455588A1 (en) |
| GB (2) | GB2054556B (en) |
| HK (2) | HK55583A (en) |
| IE (2) | IE49709B1 (en) |
| IN (2) | IN154066B (en) |
| IT (2) | IT1141487B (en) |
| LU (2) | LU82333A1 (en) |
| MA (1) | MA18824A1 (en) |
| MX (2) | MX5878E (en) |
| MY (2) | MY8400203A (en) |
| NL (2) | NL8002272A (en) |
| NO (2) | NO154056C (en) |
| NZ (2) | NZ193422A (en) |
| OA (2) | OA06527A (en) |
| PT (2) | PT71154A (en) |
| SG (2) | SG22583G (en) |
| ZA (2) | ZA801958B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63145595U (en) * | 1987-03-13 | 1988-09-26 | ||
| JPS645795U (en) * | 1987-06-26 | 1989-01-13 | ||
| JPH01100695U (en) * | 1987-12-21 | 1989-07-06 | ||
| US5264435A (en) * | 1988-12-29 | 1993-11-23 | Mitsui Petrochemical Industries, Ltd. | Pyrimidines and their pharmaceutical acceptable salts, and their use as medicines |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
-
1980
- 1980-04-02 BE BE0/200083A patent/BE882593A/en not_active IP Right Cessation
- 1980-04-02 ZA ZA00801958A patent/ZA801958B/en unknown
- 1980-04-02 ZA ZA00801960A patent/ZA801960B/en unknown
- 1980-04-02 BE BE0/200084A patent/BE882594A/en not_active IP Right Cessation
- 1980-04-03 LU LU82333A patent/LU82333A1/en unknown
- 1980-04-03 FI FI801083A patent/FI66358C/en not_active IP Right Cessation
- 1980-04-03 FI FI801084A patent/FI66359C/en not_active IP Right Cessation
- 1980-04-03 LU LU82332A patent/LU82332A1/en unknown
- 1980-04-07 IN IN253/DEL/80A patent/IN154066B/en unknown
- 1980-04-07 IN IN254/DEL/80A patent/IN154067B/en unknown
- 1980-04-08 CH CH269080A patent/CH645361A5/en not_active IP Right Cessation
- 1980-04-08 CH CH268980A patent/CH645633A5/en not_active IP Right Cessation
- 1980-04-11 NZ NZ193422A patent/NZ193422A/en unknown
- 1980-04-11 NZ NZ193421A patent/NZ193421A/en 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 NL8002272A patent/NL8002272A/en not_active Application Discontinuation
- 1980-04-18 NL NL8002271A patent/NL8002271A/en unknown
- 1980-04-22 MA MA19019A patent/MA18824A1/en unknown
- 1980-04-22 IT IT21542/80A patent/IT1141487B/en active
- 1980-04-22 IT IT21543/80A patent/IT1141296B/en active
- 1980-04-24 AT AT0221680A patent/AT380013B/en not_active IP Right Cessation
- 1980-04-24 AT AT0221580A patent/AT380012B/en not_active IP Right Cessation
- 1980-04-25 AR AR280811A patent/AR222870A1/en active
- 1980-04-25 AR AR280810A patent/AR222869A1/en active
- 1980-04-28 JP JP5557480A patent/JPS55145670A/en active Granted
- 1980-04-28 PT PT71154A patent/PT71154A/en unknown
- 1980-04-28 MX MX808786U patent/MX5878E/en unknown
- 1980-04-28 NO NO801235A patent/NO154056C/en unknown
- 1980-04-28 MX MX808783U patent/MX6514E/en unknown
- 1980-04-28 IE IE865/80A patent/IE49709B1/en unknown
- 1980-04-28 PT PT71155A patent/PT71155A/en unknown
- 1980-04-28 NO NO801234A patent/NO154055C/en unknown
- 1980-04-28 JP JP5557580A patent/JPS55145671A/en active Granted
- 1980-04-28 IE IE864/80A patent/IE49591B1/en unknown
- 1980-04-29 DK DK183880A patent/DK183880A/en unknown
- 1980-04-29 ES ES490999A patent/ES8103060A1/en not_active Expired
- 1980-04-29 DK DK183780A patent/DK183780A/en unknown
- 1980-04-29 ES ES491000A patent/ES491000A0/en active Granted
- 1980-04-29 EG EG257/80A patent/EG14284A/en active
- 1980-04-29 EG EG258/80A patent/EG14259A/en active
- 1980-04-30 OA OA57103A patent/OA06527A/en unknown
- 1980-04-30 FR FR8009732A patent/FR2455588A1/en active Granted
- 1980-04-30 OA OA57101A patent/OA06525A/en unknown
- 1980-04-30 FR FR8009733A patent/FR2455589A1/en active Granted
-
1983
- 1983-04-28 SG SG225/83A patent/SG22583G/en unknown
- 1983-04-28 SG SG222/83A patent/SG22283G/en unknown
- 1983-11-17 HK HK555/83A patent/HK55583A/en unknown
- 1983-11-17 HK HK556/83A patent/HK55683A/en unknown
-
1984
- 1984-12-30 MY MY203/84A patent/MY8400203A/en unknown
- 1984-12-30 MY MY204/84A patent/MY8400204A/en unknown
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