DK142284B - Analogous Process for Preparation of Thiazole Derivatives. - Google Patents
Analogous Process for Preparation of Thiazole Derivatives. Download PDFInfo
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- DK142284B DK142284B DK58476AA DK58476A DK142284B DK 142284 B DK142284 B DK 142284B DK 58476A A DK58476A A DK 58476AA DK 58476 A DK58476 A DK 58476A DK 142284 B DK142284 B DK 142284B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
(11) FREMLÆGGELSESSKRIFT 142284 DANMARK (ευ int.ci.3 c- 07 • (21) Ansøgning nr. 584/76 (22) Indleveret den 13* fst). 1976 (24) Løbedag 13· feb. 1976 (44) Ansøgningen fremlagt og fremlæggelsesskrtftet offentliggjort den 6« Okt. ' 1980(11) PUBLICATION 142284 DENMARK (ευ int.ci.3 c- 07 • (21) Application No. 584/76 (22) Filed on 13 * fst). 1976 (24) Race day 13 · Feb. 1976 (44) The application submitted and the publication date published on 6 «Oct. 1980
Dl REKTORATET FOR .Dl THE RECTORATE FOR.
PATENT-OG VAREMÆRKEVÆSENET (30) Prioritet begæret fra denPATENT AND TRADE MARKET (30) Priority requested from it
14. feb. 1975a 7504627, PR 12. dec. 1975, 7558O6I, PRFeb 14 1975a 7504627, PR Dec 12 1975, 7558O6I, PR
(’i) ROUSSEL-UCLAF S.A., 35, Boulevard des Invalides, 75007 Paris, PR. .('I) ROUSSEL-UCLAF S.A., 35, Boulevard des Invalides, 75007 Paris, PR. .
(72) Opfinder: Andre Poittevin, 11, Allee des Tilleuls, Pare de 1'Aul= nay, 77360 ValnesT-sur-Marne, PR: Vesperto Torelli, 5, rue de la Convention, 94700 Maisons-Alfort, PR.(72) Inventor: Andre Poittevin, 11, Allee des Tilleuls, Pare de 1'Aul = nay, 77360 ValnesT-sur-Marne, PR: Vesperto Torelli, 5, rue de la Convention, 94700 Maisons-Alfort, PR.
(74) Fuldmsegtig under sagens behandling:(74) Plenipotentiary in the proceedings:
Patentagentflrmaet Magnus Jensens Eftf._ (54) Analogifremgangsmåde til fremstilling af thiasolderivater.Patent Agent Magnus Jensen's Eftf._ (54) Analogous process for the preparation of thiazole derivatives.
Opfindelsen angår en analogifremgangsmåde til fremstilling af hidtil ukendte thiazolderivater med den i kravets indledning angivne almene formel I, såvel som salte deraf, og fremgangsmåden er ejendommelig ved det i kravets kendetegnende del omhandlede.The invention relates to an analogous process for the preparation of novel thiazole derivatives having the general formula I as set forth in the preamble, as well as salts thereof, and the process is characterized by the characterizing part of the claim.
Udtrykket alkyl med 1-5 carbonatoaer kan f.eks. betegne · methyl, ethyl, propyl, n-butyl, isobutyl, tert.-butyl og pentyl.The term alkyl having 1-5 carbon atoms may e.g. denote methyl, ethyl, propyl, n-butyl, isobutyl, tert-butyl and pentyl.
Fremstillingen af saltene omfatter såvel fremstillingen af additionssalte med stærke mineralsyrer eller organiske syrer af forbindelserne.med formlen I som fremstillingen af alkalimetalsalte, jordalkalimetalsalte og aluminiumsalte deraf.The preparation of the salts comprises both the preparation of addition salts with strong mineral acids or organic acids of the compounds of formula I as well as the preparation of alkali metal salts, alkaline earth metal salts and aluminum salts thereof.
Additionssalte med de stærke mineralsyrer eller organiske syrer kan f.eks. være de salte, som dannes med saltsyre, hy- 2 142284 drogenbromidsyre, hydrogeniodidsyre, salpetersyre, svovlsyre, phosphorsyre, alkylmonosulfonsyrer såsom methansulfonsyre, alky ld isulfonsyrer såsom methandisulfonsyre, α, β -ethandisulfonsyre, aiylmonoaulfonsyrer såsom benzensulfonsyre og aryldisulfon-syrer«Addition salts with the strong mineral acids or organic acids can e.g. be the salts formed with hydrochloric acid, hydrogen bromic acid, hydrogen iodide acid, nitric acid, sulfuric acid, phosphoric acid, alkyl monosulfonic acids such as methanesulfonic acid, alkyl isulfonic acids such as methanedisulfonic acid, α, β
Alkali- eller jorda?kalimetalsaltene kan f.eks. tære natrium-, kalium- eller calciumsalteme.The alkali or soil? tar the sodium, potassium or calcium salts.
Foretrukne betingelser for gennemførelsen af den beskrevne fremgangsmåde er følgende:Preferred conditions for carrying out the described process are the following:
Seaktionen af forbindelsen med formlen II med forbindelsen med formlen VI udføres i nærværelse af et organisk opløsningsmiddel.The section of the compound of formula II with the compound of formula VI is carried out in the presence of an organic solvent.
Set benyttede organiske opløsningsmiddel kan være dichlor-etfaan, benzen, toluen, tetrahydrofuran eller ethylether.The organic solvent used may be dichloroethane, benzene, toluene, tetrahydrofuran or ethyl ether.
Beaktionen udføres fortrinsvis ved reaktionsblandingens ti lbage svalings t empe ratur.Preferably, the reaction is carried out at the temperature of the reaction mixture's 10 o'clock swelling.
Hydrolysen af forbindelsen med formlen VII udføres ved indvirkning af en stærk base, som kan være et alkalimetalhydroxid såsom natrium- eller kaliumhydrid.The hydrolysis of the compound of formula VII is carried out by the action of a strong base which may be an alkali metal hydroxide such as sodium or potassium hydride.
Sen stærke syre, ved hvis hjælp decarboxyleringen af forbindelsen med formlen VIII udføres, kan f.eks. være saltsyre, svovlsyre^ eller phosphorsyre.Late strong acid, by means of which the decarboxylation of the compound of formula VIII is carried out, can e.g. be hydrochloric, sulfuric or phosphoric.
Eeaktionen udføres fortrinsvis i vandigt milieu og i varmen.The reaction is preferably carried out in an aqueous environment and in the heat.
Forbindelserne med formlen I samt deres salte, herunder additionssalte med stærke mineralsyrer eller organiske syrer samt alkali-, jordalkali- og aluminiumsalte deraf, har interessante farmakologiske egenskaber. Se bar især en udtalt antilipolytisk virkning. De formindsker blodplasmaets indhold af frie fede syrer.The compounds of formula I and their salts, including addition salts with strong mineral or organic acids, and their alkali, alkaline earth and aluminum salts, have interesting pharmacological properties. See especially a pronounced antilipolytic effect. They reduce the blood plasma content of free fatty acids.
Disse egenskaber retfærdiggør anvendelsen som medikamenter i terapien af ethvert af forbindelserne med formlen I samt deres additionssalte med stærke mineralsyrer eller organiske syrer, som er farmaceutisk acceptable, samt af alkali-, jordalkali-og aluminiumsaltene af forbindelserne med formlen I.These properties justify the use as drugs in the therapy of any of the compounds of formula I as well as their addition salts with strong mineral or organic acids which are pharmaceutically acceptable, as well as the alkali, alkaline earth and aluminum salts of the compounds of formula I.
De således definerede forbindelser udgør meget nyttige medikamenter i den humane terapi, især til behandling af akut eller kronisk hyperlipemi, coronarinsufficiens, hjerteinsufficiens af atheromatøs oprindelse og kroniske anginøse tilstande .The compounds thus defined constitute very useful drugs in the human therapy, especially for the treatment of acute or chronic hyperlipemia, coronary insufficiency, cardiac insufficiency of atheromatous origin, and chronic anginous conditions.
3 1422843 142284
Den nyttige dosis, som afhænger af den benyttede forbindelse, den behandlede patient og den pågældende lidelse, kan f.eks. være 0,1-2,5 g pr. dag hos voksne af oral vej.The useful dose, which depends on the compound used, the patient being treated and the disorder in question, can e.g. be 0.1-2.5 g per day in adults by oral route.
Forbindelserne med formlen II kan fremstilles efter den fremgangsmåde, som er beskrevet af Gilbert og Ej. anowaki, C.A, 6£, 20 020 e.The compounds of formula II can be prepared according to the process described by Gilbert and Ej. anowaki, C.A, £ 6, 20 020 e.
Forbindelserne med formlen VI, hvor hal betegner et bromatom, kan fremstilles ved indvirkning af brom på forbindelserne med formlenThe compounds of formula VI wherein hal represents a bromine atom can be prepared by the action of bromine on the compounds of the formula
HH
tt
OsC-CHg-CHg-CH-COOR1' COOR1' hvor R1’ betegner en alkylgruppe med 1-5 earbonatomer, i et organisk opløsningsmiddel.OsC-CHg-CHg-CH-COOR1 'COOR1' wherein R1 'represents an alkyl group of 1-5 earbone atoms, in an organic solvent.
En udførelsesform for en sådan præparation er angivet nedenfor i eksemplerne.An embodiment of such a preparation is set forth below in the Examples.
Forbindelserne med formlen VI, hvor hal betegner et chloratom, kan fremstilles ved indvirkning af gasformet chlor på produkterne med formlenThe compounds of formula VI, wherein hal represents a chlorine atom, can be prepared by the action of gaseous chlorine on the products of formula
HH
t O-C-CHg-CHg-CH-COOR1' COOR1' 1» hvor R har samme betydning som ovenfor, idet man fortrinsvis arbejder i et organisk opløsningsmiddel.wherein O has the same meaning as above, preferably working in an organic solvent.
γ,γ-dicarbethoxybutyraldehyd, der benyttes som udgangsprodukt ved præparationen nedenfor, er beskrevet i J.Am.The γ, γ-dicarbethoxybutyraldehyde used as the starting product in the preparation below is described in J.Am.
Soc. 22, 3 470.Soc. 22, 3 470.
Esterne med formlenThe esters of formula
HH
» 0=C-CH2-CH2-CH-C00R1’ COOR1' kan, når de ikke er kendte, fremstilles ud fra et derivat af malonsyre og acrolein efter en fremgangsmåde, som er analog med den, som er beskrevet i ovennævnte artikel vedrørende fremstillingen af γ,γ-dicarbethoxybutyraldehyd.'0 = C-CH2-CH2-CH-C00R1' COOR1 ', when not known, can be prepared from a derivative of malonic acid and acrolein following a method analogous to that described in the above article relating to the preparation of γ, γ-dicarbethoxybutyraldehyde.
c U 2284 4c U 2284 4
Eksempel 2-meth.yl-5-thiazolpropans.yre.Example 2-Methyl-5-thiazole propanoic acid.
Trin A: C(2-meth.vl-5-thiazolyl)-methyl)-prouandisyredlethylester.Step A: C (2-Methyl-5-thiazolyl) methyl) propanedioic acid ethyl ester.
Man blander 108 g a-brom-Y,Y-dicarbethoxybutyraldehyd, 500 ml vandfrit dlchlorethan og 27 g thioacetamid, opvarmer til tilbagesvaling i 6 timer, idet man langsomt lader afdestillere ca. 200 ml dichlorethan, og idet man tilsætter blandingen samme mængde dichlorethan, hvorefter man bringer på stuetemperatur, tilsætter 500 ml iskoldt vand og en opløsning af koncentreret ammoniakvand indtil en pH-værdi på 10-12, hvorefter man dekanterer, ekstraherer med methylenchlorid og tørrer de organiske ekstrakter over magnesiumsulfat, filtrerer, inddamper og får 110 g ((2-methyl--5-thiazolyl)-methyl)-propand isyrediethylester.108 g of α-bromo-Y, Y-dicarbethoxybutyraldehyde, 500 ml of anhydrous dichloroethane and 27 g of thioacetamide are heated to reflux for 6 hours, slowly allowing to distill off for approx. 200 ml of dichloroethane, adding to the mixture the same amount of dichloroethane, then bringing to room temperature, adding 500 ml of ice-cold water and a solution of concentrated ammonia water to a pH of 10-12, then decanting, extracting with methylene chloride and drying. organic extracts over magnesium sulfate, filter, evaporate and give 110 g of ((2-methyl-5-thiazolyl) methyl) -propanedioic acid diethyl ester.
En prøve af dette produkt rektificeres. Kp, 102°C/0,02 mm Hg.A sample of this product is rectified. Bp, 102 ° C / 0.02 mm Hg.
Trin B; 2-methvl-5-thiazolpropansyre.Step B; 2-methyl-5-thiazolpropansyre.
Man blander 110 g ((2-methyl-5-thiazolyl)-methyl)-propan-disyrediethylester og 250 ml af en 4 1 natriumhydroxidopløsning, holder under omrøring ved stuetemperatur i 16 timer, filtrerer, vasker filtratet med ethylacetat, ekstraherer den organiske fase med vand og fqrener de vandige faser, som indeholder ((2-methyl-5--thiazolyl)-methyl)-propandisyre. Man behandler den opnåede vandige fase med 100 ml koncentreret saltsyre indtil en pH-værdi på 1, tilbagesvaler i 5 timer, bringer på stuetemperatur, isafkøler, tilsætter en koncentreret ammoniumhydroxidopløsning indtil en pH-værdi på 10-12, bobler svovldioxid igennem indtil en pH-værdi på 4-5, mætter med natriumchlorid og ekstraherer med ethylacetat, tørrer ekstrakten over magnesiumsulfat, filtrerer, inddamper til tørhed og får 43 g af det krystallinske produkt, som man omkrystalliserer af ethylacetat, hvorved man får 29 g 2-methyl-5-thiazolpropansyre med smp. 130°C.110 g ((2-methyl-5-thiazolyl) methyl) propane diacetic diethyl ester and 250 ml of a 4 L sodium hydroxide solution are stirred at room temperature for 16 hours, filtered, the filtrate is washed with ethyl acetate, extracted the organic phase with water and purify the aqueous phases containing ((2-methyl-5-thiazolyl) -methyl) -propanedioic acid. The aqueous phase obtained is treated with 100 ml of concentrated hydrochloric acid until a pH of 1, reflux for 5 hours, brought to room temperature, ice-cooled, a concentrated ammonium hydroxide solution added to a pH of 10-12, bubbles of sulfur dioxide through to a pH - value of 4-5, saturates with sodium chloride and extracts with ethyl acetate, dries the extract over magnesium sulfate, filters, evaporates to dryness and gives 43 g of the crystalline product which is recrystallized from ethyl acetate to give 29 g of 2-methyl-5 -thiazole propanoic acid, m.p. 130 ° C.
Analyse: CyH^DOgSAnalysis: CyH 2 DOgS
beregnet: 49,0 Hfc 5,30 8,18 Sf6 18,73 fundet: 49,1 5,3 7,9 18,3calculated: 49.0 Hfc 5.30 8.18 Sf6 18.73 found: 49.1 5.3 7.9 18.3
Det a-brom-Y,Y-dicarbethoxybutyraldehyd, som benyttes som udgangsprodukt ved fremstillingen af 3-methyl-5-thiazolpropansyre, kan fremstilles på følgende måde: lian blander 150 g γ,γ-dicarbethoxybutyraldehyd, 900 ml _ 142284 o vandfri ethylether og 8,5 ml dioxan, omrører og tilsætter derefter dråbevis ved 20°C 2 ml brom, afkøler til 5°C og tilsætter dråbevis 33,5 ml brom, tilsætter en mættet vandig natriumcarbonatopløsning, lader dekantere, samler etberfasen og vasker den med vand, tørrer, filtrerer, inddamper til tørhed og får 207 g af en brun olie, som rektificeres under vakuum, Be·»· fås 171 g a-brom-y,Y~dicarbethoxy-butyraldehyd. Kp, l08°C/0,02 mm Hg.The α-bromo-Y, Y-dicarbethoxybutyraldehyde used as the starting product in the preparation of 3-methyl-5-thiazole propanoic acid can be prepared as follows: lian mixes 150 g of γ, γ-dicarbethoxybutyraldehyde, 900 ml of anhydrous ethyl ether and 8.5 ml dioxane, then stir and then add dropwise at 20 ° C 2 ml bromine, cool to 5 ° C and drop dropwise 33.5 ml bromine, add a saturated aqueous sodium carbonate solution, decant, collect the ether phase and wash it with water, dries, filters, evaporates to dryness and yields 207 g of a brown oil which is rectified in vacuo. Be obtain 171 g of α-bromo-γ, Y Kp, 108 ° C / 0.02 mm Hg.
Farmakologisk undersøgelse.Pharmacological study.
1) Bestemmelse af akut toksicitet.1) Determination of acute toxicity.
Ben akutte toksicitet bestemmes på hold på 10 mus på 18-22 g. Produktet indgives i suspension i carboxymethylcellulose ad in-traperitoneal vej.Bone acute toxicity is determined in 10 mice of 18-22 g. The product is administered in suspension in carboxymethyl cellulose by intra-traperitoneal route.
Byrene holdes under observation i 1 uge.The cities are kept under observation for 1 week.
Man bestemmer den dødelige dosis 50, BL,-q, °S °Pn&ede resultater er som følger:The lethal dose 50, BL, -q, ° S ° Pn and results are determined as follows:
Forbindelse ifølge eksemplet DL^q mg/&£: ca. 600 2) Bestemmelse af antilipolytisk virkning.Compound of Example DL 600 2) Determination of antilipolytic effect.
Bestemmelse af frie fede syrer i plasma.Determination of free fatty acids in plasma.
Hanrotter af stammen Sprague Dawley S.P.F. på 180-200 g, som har været fastende i 24 timer, modtager forbindelsen ad oral vej. 1 time efter indgiften aflives dyrene ved carotis-snit, og på de udtagne blodprøver bestemmes indholdet af frie fede syrer.Male rats of the strain Sprague Dawley S.P.F. of 180-200 g, which has been fasting for 24 hours, receives the compound by oral route. At 1 hour after administration, the animals are sacrificed by carotid incision and the content of free fatty acids is determined on the blood samples taken.
Ekstraktionen af frie fede syrer udføres ifølge W.P.The extraction of free fatty acids is carried out according to W.P.
Dole (J. Clin. Invest, ^8, 1544-1554, (1959)), modificeret af D.L, Trout, H.H. Esters jr. og S.J. Friedberg (J, Lipid, Res.Dole (J. Clin. Invest, 8, 1544-1554, (1959)), modified by D.L., Trout, H.H. Esters jr. and S.J. Friedberg (J, Lipid, Res.
1960, 1, 199-202)).1960, 1, 199-202)).
Den for phosphorlipider befriede plasmaekstrakt bestemmes kolorimetrisk ifølge A. Antonis (J. Lipid. Res. 1965, 6, 307-312).The phosphorus lipid-free plasma extract is determined colorimetrically according to A. Antonis (J. Lipid. Res. 1965, 6, 307-312).
Man bestemmer de doser af forbindelsen, som under forsøgsbetingelserne formindsker indholdet af frie fede syrer hos de behandlede dyr med 50% i forhold til kontroldyrene (°α^0)·The doses of the compound are determined which, under the experimental conditions, reduce the free fatty acids content of the treated animals by 50% over the control animals (° α α0) ·
Man får følgende resultater:You get the following results:
Forbindelse ifølge eksemplet DA^q mg/kg: ca. 1,5 142284 6Compound of Example DA 2 mg / kg: approx. 1.5 142284 6
Konklusion.Conclusion.
Forbindelsen ifølge eksemplet viser en klar antilipoly-tisk aktivitet, 1The compound of the example shows a clear antilipolitic activity, 1
Claims (1)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7504627 | 1975-02-14 | ||
| FR7504627A FR2300562A1 (en) | 1975-02-14 | 1975-02-14 | 2-Alkyl-thiazolyl-alkanols and their esters - have antilicpolytic activity |
| FR7538061A FR2334353A1 (en) | 1975-12-12 | 1975-12-12 | NEW THIAZOLIC DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND THEIR APPLICATION AS MEDICINAL PRODUCTS |
| FR7538061 | 1975-12-12 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK58476A DK58476A (en) | 1976-08-15 |
| DK142284B true DK142284B (en) | 1980-10-06 |
| DK142284C DK142284C (en) | 1981-03-02 |
Family
ID=26218733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK58476AA DK142284B (en) | 1975-02-14 | 1976-02-13 | Analogous Process for Preparation of Thiazole Derivatives. |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS51105056A (en) |
| AR (1) | AR219277A1 (en) |
| AU (1) | AU498142B2 (en) |
| BE (1) | BE838488A (en) |
| CA (1) | CA1082715A (en) |
| CH (1) | CH609974A5 (en) |
| DD (1) | DD124981A5 (en) |
| DE (1) | DE2605838A1 (en) |
| DK (1) | DK142284B (en) |
| ES (1) | ES445148A1 (en) |
| HU (1) | HU171950B (en) |
| IL (1) | IL48968A (en) |
| LU (1) | LU74338A1 (en) |
| NL (1) | NL7601561A (en) |
| PT (1) | PT64801B (en) |
| SE (1) | SE417510B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1042362B (en) * | 1953-06-20 | 1958-10-30 | Mindener Molkerei E G M B H | Milk pasteurizer |
-
1976
- 1976-02-04 IL IL48968A patent/IL48968A/en unknown
- 1976-02-05 HU HU76RO00000874A patent/HU171950B/en unknown
- 1976-02-11 AR AR262221A patent/AR219277A1/en active
- 1976-02-12 SE SE7601589A patent/SE417510B/en unknown
- 1976-02-12 CA CA245,873A patent/CA1082715A/en not_active Expired
- 1976-02-12 LU LU74338A patent/LU74338A1/xx unknown
- 1976-02-12 BE BE164262A patent/BE838488A/en unknown
- 1976-02-12 DD DD191209A patent/DD124981A5/xx unknown
- 1976-02-13 ES ES445148A patent/ES445148A1/en not_active Expired
- 1976-02-13 DK DK58476AA patent/DK142284B/en unknown
- 1976-02-13 PT PT64801A patent/PT64801B/en unknown
- 1976-02-13 CH CH181176A patent/CH609974A5/en not_active IP Right Cessation
- 1976-02-13 JP JP51014118A patent/JPS51105056A/ja active Pending
- 1976-02-13 DE DE19762605838 patent/DE2605838A1/en not_active Withdrawn
- 1976-02-13 AU AU11105/76A patent/AU498142B2/en not_active Expired
- 1976-02-16 NL NL7601561A patent/NL7601561A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DD124981A5 (en) | 1977-03-23 |
| AR219277A1 (en) | 1980-08-15 |
| NL7601561A (en) | 1976-08-17 |
| HU171950B (en) | 1978-04-28 |
| SE417510B (en) | 1981-03-23 |
| PT64801B (en) | 1978-02-06 |
| JPS51105056A (en) | 1976-09-17 |
| LU74338A1 (en) | 1976-12-31 |
| DK142284C (en) | 1981-03-02 |
| ES445148A1 (en) | 1977-09-16 |
| IL48968A (en) | 1978-08-31 |
| CA1082715A (en) | 1980-07-29 |
| AU498142B2 (en) | 1979-02-15 |
| IL48968A0 (en) | 1976-04-30 |
| CH609974A5 (en) | 1979-03-30 |
| PT64801A (en) | 1976-03-01 |
| AU1110576A (en) | 1977-08-18 |
| DE2605838A1 (en) | 1976-08-26 |
| BE838488A (en) | 1976-08-12 |
| SE7601589L (en) | 1976-08-15 |
| DK58476A (en) | 1976-08-15 |
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