NO138000B - Fremgangsm}te for fremstilling av 19-nortestosteron og 19-nor-9beta, 10alfa-testosteron henholdsvis 17beta-tert.-butyleter derav - Google Patents
Fremgangsm}te for fremstilling av 19-nortestosteron og 19-nor-9beta, 10alfa-testosteron henholdsvis 17beta-tert.-butyleter derav Download PDFInfo
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- NO138000B NO138000B NO2099/72A NO209972A NO138000B NO 138000 B NO138000 B NO 138000B NO 2099/72 A NO2099/72 A NO 2099/72A NO 209972 A NO209972 A NO 209972A NO 138000 B NO138000 B NO 138000B
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- Prior art keywords
- acid
- nortestosterone
- tert
- optically active
- butyleter
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- 238000000034 method Methods 0.000 title claims description 7
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- NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 title claims description 4
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- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 2
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
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- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
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- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
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- C07C45/66—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups by dehydration
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/69—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to carbon-to-carbon double or triple bonds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/73—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with hydrogenation
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/385—Saturated compounds containing a keto group being part of a ring
- C07C49/487—Saturated compounds containing a keto group being part of a ring containing hydroxy groups
- C07C49/507—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic
- C07C49/513—Saturated compounds containing a keto group being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/16—Benz[e]indenes; Hydrogenated benz[e]indenes
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Catching Or Destruction (AREA)
Description
Nærværende-oppfinnelse vedrører en ny fremgangsmåte for fremstilling av optisk aktivt 19-nortestosteron og 19-nor-9f3, 10a-testosteron henholdsvis deres 17|3-tertiær-butyletere karakterisert ved at man behandler rasemisk 3&-tert.-butoksy-6(3-oksobutyl)-3a3-metyl-perhydrobenz[e]-indan 7-on i et protisk eller aprotisk løsningsmiddel, eventuelt i nærvær av en syre, med en optisk aktiv a-aminosyre, behandler reaksjonsproduktet som erholdes ved å arbeide i et aprotisk løsnings-middel og i fravær av en syre med syre og eventuelt avspalter den tertiære butylgruppen i reaksjonsproduktet.
Eksempler på optisk aktive a- eller 3-aminosyrer er alanin, serin, threonin, valin, leucin, isoleucin, fenylalanin, tyrosin, L-azetidin-2-karboksylsyre eller prolin, særlig (S)-(-)-prolin, og (S)-(-)-4-trans-hydroksy-prolin. Spesielt egnét er (S)-(-)-prolin.
Fremgangsmåten ifolge oppfinnelsen kan gjennomfores i nærvær av protislce eller fortrinnsvis aprotiske opplosningsmidler eller også i fravær av slike opplosningsmidler. En foretrukken grup-pe av protiske opplosningsmidler er de lavere alkanoler som etanol, butanol, isopropanol og tert.-butanol. Det har vist seg at det optiske utbytte ved anvendelse av lavere alkanoler i rek-kefølgen primær, sekundær, tertiær tiltar. Derfor er isopropa-i noi og tertiær-butanol foretrukne opplosningsmidler. Det har videre vist seg at ved anvendelse av protiske opplosningsmidler eller ved å arbeide i nærvær av en organisk eller uorganisk syre som HCl, Hio,, HClO. eller p-toluensulfonsyre erholdes sluttproduktet direkte. Eksempler på aprotiske opplosningsmidler er benzen, tetrahydro-furan, acetonitril og dimetylformamid. Her er det for oppnåelse av et hoyst mulig optisk utbytte igjen onskelig at opplosningsmidlet har relativt stor polaritet. Ved anvendelse av aprotiske opplosningsmidler oppnås cykliske sluttprodukter, som for den overveiende dels vedkommende består av 4,5-mettede 5-hydroksy-19-nor-androsteroner (ketoner) og bare i mindre grad av det ønskede testosteronderivat. Ketonene kan lett overføres ved dehydratisering etter kjente metoder til de tilsvarende enoner f.eks. ved behandling med en syre, f.eks. med p-toluensulfonsyre, i et inert, organisk oppløsningsmiddel som benzen under tilbakeløpskjøling.
Reaksjonen gjennomføres på egnet måte ved en temperatur på -5 til +100°C, fortrinnsvis ved 18-85°C. Det arbeides mest mulig under inertgassatmosfære, f.eks. under nitrogen eller en edel-gass som helium eller argon. Generelt er reaksjonstiden 3 timer til 3 uker, fortrinnsvis 16 timer til 6 dager. En forlen-gelse av reaksjonstiden utover nevnte tidspunkt er ikke for-delaktig på grunn av uonskede bireaksjoner.
På grunn av de overordentlig hoye optiske utbytter som oppnås når det arbeides i nærvær av optisk aktivt prolin, er denne optisk aktive forbindelse den valgte reagens. Utover dette oppnås ved anvendelse av (S)-(-)-prolin i overveiende mengde optisk aktive forbindelser med en slik absolutt konfigura-* sjon, som tilsvarer den for de naturlige steroider.-
Det er videre å fastslå at ved anvendelse av andre enantiomerer av den optisk aktive forbindelse oppnås et speilbilledlig oppbygget sluttprodukt.
Forbindelsene med formel I som oppnås ifølge oppfinnelsen er farmakologisk aktive og kan anvendes som legemidler eller omvandles til sådanne.
Eksempel 1.
En blanding av 348 mg (-) - 3(3-tert .-butoksy-6- ( 3-oksobutyl) - 3a(3-metyl-perhydro-benz[e]indan-7-on, 17,5 mg (S)-prolin og 1,0 ml vannfritt N,N-dimetylformamid blé omrort 24 timer ved 20-23°C under argon-atmosfære. Etter å ha fortynnet blandingen med 10 ml eter filtrerte man, og filtratet ble inndampet ved et trykk på ca. 0,1 mm kvikksolv ved 35°C til 268 mg (77%) av en mork olje, som ved hjelp av preparativ tynnfilmskromatogra-
fi ble delt i to fraksjoner. Den forste fraksjonen var et delvis krystallinsk produkt (36,2 mg = 10,4%) med [or ]^ <=><->4,8°
(c=l,00% i kloroform), IR-maksima i kloroform ved 3550, 3500-3350, 1710, 1385 og 1355 cm"'''. Den andre fraksjonen var en ol-
je (73,3 mg = 21%), som var tynnfilmskromatografisk homogen,
r -i 25
og som oppviste en dreieverdi LaJD = -3,0 (c = 2,0% i kloroform) . Ved siden av det onskede sluttproduktet forekom ikke-om-satt utgangsmateriale, og dette viste ved UV-spektroskopi: ^ maks <=> 238 ~ 239 ^ ^= 5930) 5 IR-maksima i kloroform ved 3550, 3500-3350, 1710, 1660, 1620, 1380 og 1355 cm<-1>.
33,5 mg av den delvis krystallinske forste fraksjonen ble opp-varmet 5 timer under tilbakelop og i nitrogen-atmosfære i 5 ml av en l:l-blanding av 2-N saltsyre og metanol, hvorved dehy-drering og hydrolyse av den tertiære butylgruppen fant sted. Reaksjonsblandingen ble avkjolt i et isbad og noytralisert med vandig natriumhydroksyd. Opplosningsmidlet ble fjernet ved 30°
og et trykk på 0,05 mm kvikksolv. Den torre resten ble tatt opp i etylacetat, losningen filtrert og filtratet inndampet under redusert trykk til 26,3 mg olje (100%). Rensingen av dette råproduktet ved preparativ tynnfilmskromatografi med si-likagel ga 5,2 mg (19,8%) (-)-19-nortestosteron i form av en olje, [a]<25> = -22,4° (c = 0,433% i kloroform) , ^ Jjj^S = 239 nm
(£ = 11,730), maksima i IR-spektrum ved 3675, 3550-3350, 1665 og 1620 cm<->"'". Produktet var ifolge tynnfilms-kromatografisk metode homogent og viste en med autentisk 19-nortestosteron identisk Rf-verdi. Optisk renhet: 38,2%, optisk utbytte 55,4%
(beregnet på grunnlag av UV-spektroskopi.).
I en annen fraksjon erholdt man 4,2 mg (16%) av et krystallinsk
r n25 produkt,som ble identifisert som (-)-19-rior-9p, lOor-testosteron LocJD = -17,7° (c = 0,35% i kloroform) X <EtOH> = 2U ^ (£ = 13)95o)> IR-maksima i kloroform ved 3650, 3550-3350, 1660 og 1620 cm<-1>. Optisk renhet 16,9%, optisk utbytte 20,9% (beregnet på grunnlag av UV-spelctroskopi) .
Claims (3)
1. Fremgangsmåte ved fremstilling av optisk aktivt 19-nortestosteron og 19-nor-93, 10a-testosteron henholdsvis deres 173-tertiær-butyletere^karakterisert ved at man behandler rasemisk 33-tert.-butoksy-6(3-oksobutyl)-3 aft-metyl-perhydrobenz[e]-indan 7-on i et protisk eller aprotisk løsningsmiddel, eventuelt i nærvær av en syre, med en optisk aktiv a-aminosyre, behandler reaksjonsproduktet som erholdes ved å arbeide i et aprotisk løsningsmiddel og i fravær av en syre med syre og eventuelt avspalter den tertiære butylgruppen i reaksjonsproduktet.
2. Fremgangsmåte ifølge krav 1, karakterisert ved at det som optisk aktiv aminosyre anvendes (S)-(-)-prolin.
3. Fremgangsmåte ifølge et av kravene 1 eller 2, karakterisert ved at man arbeider i nærvær av en uorganisk eller organisk:: syre.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US476270A | 1970-01-21 | 1970-01-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO138000B true NO138000B (no) | 1978-02-27 |
| NO138000C NO138000C (no) | 1978-06-07 |
Family
ID=27421984
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO200/71A NO134983C (no) | 1970-01-21 | 1971-01-20 | |
| NO2099/72A NO138000C (no) | 1970-01-21 | 1972-06-13 | Fremgangsmaate for fremstilling av 19-nortestosteron og 19-nor-9beta, 10alfa-testosteron henholdsvis 17beta-tert.-butyleter derav |
| NO2098/72A NO134371C (no) | 1970-01-21 | 1972-06-13 | |
| NO761104A NO761104L (no) | 1970-01-21 | 1976-03-30 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO200/71A NO134983C (no) | 1970-01-21 | 1971-01-20 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2098/72A NO134371C (no) | 1970-01-21 | 1972-06-13 | |
| NO761104A NO761104L (no) | 1970-01-21 | 1976-03-30 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US3975440A (no) |
| JP (2) | JPS5737573B1 (no) |
| AT (4) | AT316533B (no) |
| BE (1) | BE761783A (no) |
| CA (2) | CA993878A (no) |
| CH (3) | CH597129A5 (no) |
| DE (3) | DE2102623C2 (no) |
| DK (2) | DK146717C (no) |
| ES (2) | ES387449A1 (no) |
| FI (2) | FI53450C (no) |
| FR (2) | FR2077253B1 (no) |
| GB (2) | GB1325631A (no) |
| HU (2) | HU166419B (no) |
| IE (3) | IE35093B1 (no) |
| IL (1) | IL35985A (no) |
| NL (2) | NL164267C (no) |
| NO (4) | NO134983C (no) |
| PH (2) | PH12661A (no) |
| SE (2) | SE393798B (no) |
| YU (1) | YU35332B (no) |
| ZA (1) | ZA7120B (no) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4201869A (en) * | 1970-12-21 | 1980-05-06 | Hoffmann-La Roche Inc. | Intermediates for steroid total synthesis process utilizing asymmetric induction |
| ZA814972B (en) * | 1980-07-30 | 1982-07-28 | Beecham Group Plc | Reduced naphthalenes,their preparation and use |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2668858A (en) * | 1954-02-09 | Process for their preparation | ||
| US2407673A (en) * | 1941-06-20 | 1946-09-17 | Research Corp | Process for the synthesis of 1-keto-8-methylhexahydroindanol-1 |
| US2833694A (en) * | 1955-08-25 | 1958-05-06 | Ciba Pharm Prod Inc | Process for splitting racemates |
| NL130309C (no) * | 1963-11-29 | |||
| NL131552C (no) * | 1965-04-28 | |||
| AT278767B (de) * | 1965-10-13 | 1970-02-10 | Hoffmann La Roche | Verfahren zur herstellung von neuen indanderivaten |
| US3501479A (en) * | 1967-05-19 | 1970-03-17 | American Cyanamid Co | Dihydroquinolines and substituted dihydroquinolines and method of preparing the same |
| US3897460A (en) * | 1968-10-04 | 1975-07-29 | Hoffmann La Roche | 3{62 -Tertiarybutoxy-decahydro-benz{8 E{9 indenes |
| DE2016750A1 (de) * | 1970-04-04 | 1971-10-14 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von 2,2 disubstituierten Cycloalkan 1,3 dionen |
-
1970
- 1970-12-09 US US05/096,597 patent/US3975440A/en not_active Expired - Lifetime
-
1971
- 1971-01-04 ZA ZA710020A patent/ZA7120B/xx unknown
- 1971-01-07 CH CH638775A patent/CH597129A5/xx not_active IP Right Cessation
- 1971-01-07 CH CH18571A patent/CH588434A5/xx not_active IP Right Cessation
- 1971-01-10 PH PH12122A patent/PH12661A/en unknown
- 1971-01-12 IL IL35985A patent/IL35985A/xx unknown
- 1971-01-14 IE IE42/71A patent/IE35093B1/xx unknown
- 1971-01-14 IE IE1796/73A patent/IE35094B1/xx unknown
- 1971-01-14 IE IE1797/73A patent/IE35095B1/xx unknown
- 1971-01-19 YU YU117/71A patent/YU35332B/xx unknown
- 1971-01-19 GB GB257171A patent/GB1325631A/en not_active Expired
- 1971-01-19 GB GB4688172A patent/GB1325632A/en not_active Expired
- 1971-01-20 DE DE2102623A patent/DE2102623C2/de not_active Expired
- 1971-01-20 BE BE761783A patent/BE761783A/xx not_active IP Right Cessation
- 1971-01-20 FR FR717101825A patent/FR2077253B1/fr not_active Expired
- 1971-01-20 FI FI152/71A patent/FI53450C/fi active
- 1971-01-20 AT AT392372A patent/AT316533B/de not_active IP Right Cessation
- 1971-01-20 ES ES387449A patent/ES387449A1/es not_active Expired
- 1971-01-20 DE DE2166994A patent/DE2166994C3/de not_active Expired
- 1971-01-20 NO NO200/71A patent/NO134983C/no unknown
- 1971-01-20 DE DE19712166993 patent/DE2166993A1/de active Pending
- 1971-01-20 AT AT392272A patent/AT315142B/de not_active IP Right Cessation
- 1971-01-20 AT AT45571A patent/AT308087B/de active
- 1971-01-21 DK DK25571A patent/DK146717C/da not_active IP Right Cessation
- 1971-01-21 CA CA103,278A patent/CA993878A/en not_active Expired
- 1971-01-21 NL NL7100813.A patent/NL164267C/xx not_active IP Right Cessation
- 1971-01-21 SE SE7100704A patent/SE393798B/xx unknown
- 1971-01-21 HU HUHO1647A patent/HU166419B/hu unknown
- 1971-01-21 JP JP177971A patent/JPS5737573B1/ja active Pending
- 1971-01-21 HU HUHO1349A patent/HU166411B/hu unknown
- 1971-09-08 ES ES394882A patent/ES394882A1/es not_active Expired
- 1971-11-05 FR FR717139725A patent/FR2112170B1/fr not_active Expired
-
1972
- 1972-05-05 AT AT392472A patent/AT348150B/de not_active IP Right Cessation
- 1972-06-13 NO NO2099/72A patent/NO138000C/no unknown
- 1972-06-13 NO NO2098/72A patent/NO134371C/no unknown
-
1973
- 1973-12-28 SE SE7317592A patent/SE404607B/xx unknown
-
1975
- 1975-08-04 PH PH17445A patent/PH11206A/en unknown
-
1976
- 1976-01-07 CH CH1535676A patent/CH589024A5/xx not_active IP Right Cessation
- 1976-03-04 CA CA247,076A patent/CA1013752A/en not_active Expired
- 1976-03-30 NO NO761104A patent/NO761104L/no unknown
-
1977
- 1977-05-23 FI FI771632A patent/FI771632A7/fi not_active Application Discontinuation
- 1977-11-11 JP JP13556877A patent/JPS5373541A/ja active Granted
-
1978
- 1978-06-12 US US05/914,840 patent/US4189447A/en not_active Expired - Lifetime
-
1979
- 1979-07-16 DK DK298479A patent/DK298479A/da not_active Application Discontinuation
- 1979-10-02 NL NL7907334A patent/NL7907334A/nl unknown
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