NO159999B - Analogifremgangsmaate for fremstilling av farmakologisk aktive substituerte 2-fenyl-2-(pyridyloksy)-etylamin-derivater og isostere forbindelser. - Google Patents
Analogifremgangsmaate for fremstilling av farmakologisk aktive substituerte 2-fenyl-2-(pyridyloksy)-etylamin-derivater og isostere forbindelser. Download PDFInfo
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- NO159999B NO159999B NO823253A NO823253A NO159999B NO 159999 B NO159999 B NO 159999B NO 823253 A NO823253 A NO 823253A NO 823253 A NO823253 A NO 823253A NO 159999 B NO159999 B NO 159999B
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
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- C07—ORGANIC CHEMISTRY
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
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- C07—ORGANIC CHEMISTRY
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- C07D213/00—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
- C07D213/02—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
- 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
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Description
Denne oppfinnelse angår en analogifremgangsmåte for fremstilling av nye substituerte 2-fenyl-2-(pyridyloksy)-etyl-aminer og isostere forbindelser med den generelle formel
hvor
og R2# som kan være like eller forskjellige, betyr hydrogen, halogen, metyl, metoksy, amino eller nitro,
R^ betyr hydrogen, halogen eller metyl,
R4 og R^, som kan være like eller forskjellige, betyr hydrogen eller en alkylgruppe med 1 til 2 karbonatomer eller kan sammen med nitrogenatomet danne en pyrrolidino- eller morfolinoring, og X betyr 0, NH eller S,
og deres syreaddisjonssalter,
som kan anvendes som virkestoffer i legemidler.
De nye forbindelser fremstilles ifølge oppfinnelsen
ved at et fenyletylamin med den generelle formel
hvor R^, R^, R^ og R^ har de ovenfor angitte betydninger, og Y betyr et halogenatom eller en hydroksygruppe, eller st syreaddisjonssalt av denne forbindelse, omsettes med et pyridinderivat med den generelle formel
hver har den ovenfor angitte betydning, og Z betyr en hydroksy-, amino- eller merkaptogruppe.
Ved anvendelse av utgangsstoffer med den generelle
formel II hvor Y betyr en hydroksygruppe, skjer kondensasjonen med en forbindelse med den generelle formel III i et surt medium ved forhøyede temperaturer. Ved denne omsetning anvendes sterke uorganiske eller organiske syrer, f.eks. konsentrerte mineralsyrer så som saltsyre, bromhydrogensyre, svovelsyre, polyfosforsyre, og dessuten eddiksyreanhydrid, fosforpentoksyd eller trifluoreddiksyre.
Fenyletylaminer med den generelle formel II hvor Y betyr et halogenatom, omsettes fortrinnsvis under anvendelse av et basisk stoff og fortrinnsvis under fase-overførings-betingelser (dvs. under tilsetning av ett eller flere langkjedete,
tertiære aminer så som et benzyl-tributyl-ammonium-halogenid eller et tetrabutyl-ammonium-halogenid eller under tilsetning av benzyl-trifenylfosfoniumklorid) med pyridin-derivatet med den generelle formel III.
Som basiske stoffer kan f.eks. anvendes uorganiske baser
så som alkali- eller jordalkalihydroksyder eller -karbonater, organiske baser så som pyridin, piperidin, tertiære aminer eller også alkalialkoholater.
Forbindelser med den generelle formel I hvor R^ og/eller R^ betyr hydrogen, kan alkyleres på i og for seg kjent måte, f.eks. ved omsetning med et dialkylsulfat eller et alkyl-halogenid.
Utgangsmaterialene er vanlige kjemikalier som kan kjøpes eller som kan fremstilles ved vanlig kjente fremgangsmåter.
Sluttproduktene med den generelle formel I kan eventuelt overføres til sine fysiologisk godtagbare syreaddisjonssalter efter vanlige metoder.
Egnede syrer for dette formål er både uorganiske syrer
så som halogenhydrogensyrer, svovelsyre, fosforsyre og amino-sulfonsyre, og også organiske syrer så som maursyre, eddiksyre, propionsyre, melkesyre, glykolsyre, glukonsyre, maleinsyre, ravsyre, vinsyre, benzoesyre, salicylsyre, sitronsyre,
askorbinsyre, p-toluensulfonsyre eller oksyetansulfonsyre.
De nye forbindelser med den generelle formel I og deres syreaddisjonssalter representerer verdifulle farmasøytiske forbindelser. De er godt virksomme i de biokjemiske og farmakologiske testanordninger som er spesifikke for anti-depressiva. Således har de evnen til å hemme den ptose som fremkalles hos mus ved hjelp av tetrabenzain, og ED50 ligger ved størrelsesorden 1 mg/kg. Denne test tjener som standard-test på antidepressive egenskaper (International Journal of Neuropharmacology 8, 73 (1969)).
Også ved testen på reserpinantagonisme, en opphevelse
av den hypotermiske effekt som forårsakes av reserpin, ved hjelp av en antidepressiv aktiv forbindelse, har forbindelsene fremstilt ifølge oppfinnelsen vist seg å ha en særdeles gunstig virkning. Dessuten har det vist seg at de hemmer gjenopptagelsen av serotonin og adrenalin i neuronene.
De nye forbindelser er særlig verdifulle da de har en struktur som adskiller seg fra strukturen hos kjent anti-depressiva og dessuten er de likeverdige med eller bedre enn kjente handelsprodukter med hensyn til virkning og lav toksisitet.
Særlig skal fremheves slike forbindelser med den generelle formel I hvor R^ betyr et bromatom i p-stilling, X betyr et oksygenatom eller en aminogruppe, R2 betyr hydrogen, og R, og R^ betyr metylgrupper. Spesielt skal følgende forbindelser fremheves: 2-(p-bromfenyl)-2-(pyridyl-(3)-oksy)-N,N-dimetyl-etylamin, 2-(p-bromfenyl-2-(pyridyl-(2)-amino)-N,N-dimetyl-etylamin, 2-(p-bromfenyl)-2-(pyridyl-(3)-amino)-N,N-dimetyl-etylamin.
Fra TJS-patent 3.471.501 er det kjent forbindelser som f.eks. N,N-dimetyl-N<1->fenyl-N'-(2-pyridylmetyl)-etylendiamin. Disse forbindelser har hostestillende egenskaper. Struktur-messig er disse forbindelser vesentlig forskjellige fra forbindelsene som fremstilles ifølge oppfinnelsen. De kjente forbindelser inneholder således to tertiære aminogrupper, hvor fenylresten er bundet direkte til nitrogenatomet, mens pyridylresten er bundet over CH2. I de anti-depressivt virkende forbindelser fremstilt ifølge oppfinnelsen er derimot fenylgruppen bundet til et C-atom i etylendiamin, og pyridylresten er bundet direkte til nitrogen (hvis X er NH; når X
er 0 eller S, er forskjellen enda større), slik at de nye forbindelser da inneholder en sekundær aminogruppe.
De følgende eksempler skal tjene til å illustrere oppfinnelsen ytterligere: E ksempel 1
2- p- bromfenyl- 2-( 3- pyridyloksy)- N, N- dimetyl- etylamin-d ihydroklorid
29,9 g 2-klor-2-p-bromf enyl-N ,N-dimetyl-etylan;in-hydroklorid (0,1 mol) og 14,3 g 3-hydroksypyridin (0,15 mol)
i 150 ml 25%ig natronlut og 150 ml toluen oppvarmes til kokning under tilbakeløpskjøling i 16 timer sammen med 0,5 g benzyltrifenylfosfoniumklorid. Efter avdestillering av oppløsningsmidlet fra den organiske fase blir tilbake et residuum som oppløses i alkohol. Med saltsyre dannes dihydrokloridet av tittelforbindelsen. For rensning behandles titelforbindelsen i cykloheksan med aktivt kull og kiselgur. Utbyttet av dihydroklorid er 20 g (44% av det teoretiske). Sm.p. 128-129°C (etanol).
Eksempel 2
2- p- bromfenyl- 2-( 2- pyridylamino)- N, N- dimety1- etylamin- dioksalat
24,5 g 2-p-bromfenyl-N,N-dimetyletanolamin (0,1 mol)
og 11 g'2-aminopyridin (0,11 mol) oppvarmes i 50 ml metan-sulfonsyre i 30 minutter til 60°C. Den ennu varme reaksjons-blanding helles på is, gjøres alkalisk med ammoniakk og ekstraheres med etylacetat. Rensningen foretas kolonne-kromatografisk over silikagel/metylenklorid-etylacetat-metanol. Ved tilsetning av alkoholisk oksalsyre dannes det krystallinske dioksalat av tittelforbindelsen.
Utbyttet utgjør 21 g (42% av det teoretiske).
Sm.p. 170-171°C.
Ifølge den ovenfor beskrevne fremgangsmåte ble de følgende forbindelser med den generelle formel I fremstilt:
Claims (4)
1. Analogifremgangsmåte for fremstilling av farmakologisk aktive substituerte 2^fenyl-2-(pyridyloksy)-etylaminer og
deres isostere forbindelser med den generelle formel
hvor
og R2/ som kan være like eller forskjellige, betyr hydrogen, halogen, metyl, metoksy, amino eller nitro, R, betyr hydrogen, halogen eller metyl,
R4 og R,-, som kan være like eller forskjellige, betyr hydrogen eller en alkylgruppe med 1 til 2 karbonatomer eller kan sammen med nitrogenatomet danne en pyrrolidino- eller morfolinoring, og X betyr 0, NH eller S,
og deres fysiologisk forlikelige syreaddisjonssalter, karakterisert ved at et fenyletylamin med
den generelle formel
hvor R^, R2, R^ og R^ har den ovenfor angitte betydning, og V betyr et halogenatom eller en hydroksygruppe, resp. et <sy>readdisjonssalt av denne forbindelse, omsettes med et pyridinderivat med den generelle formel
hvor betyr hydrogen, et halogenatom eller en metylgruppe,
og Z betyr en hydroksy-, amino- eller merkaptogruppe,
og det således oppnådde sluttprodukt overføres eventuelt til et fysiologisk forlikelig syreaddisjonssalt.
2. Fremgangsmåte ifølge krav 1 for fremstilling av 2-(p-brcmfenyl)-2-(pyridyl-(3)-oksy)-N,N-dimetyl-etylamin, karakterisert ved at det anvendes utgangs-materialer hvor R, er hydrogen, R., er p-brom, R^ er hydrogen, R4 og R^ er hver metyl, og Z er en hydroksygruppe i 3-stilling.
3. Fremgangsmåte ifølge krav 1 for fremstilling av 2-(p-bromfenyl)-2-(pyridyl-(2)-amino)-N,N-dimetyl-etylamin, karakterisert ved at det anvendes utgangs-materialer hvor R^ er hydrogen, R-, er p-brom, R^ er hydrogen, R. og R^ er hver metyl, og Z er en aminogruppe i 2-stilling.
4. Fremgangsmåte ifølge krav 1 for fremstilling av 2- (p-brcmfenyl)-2-(pyridyl-(3)-amino)-N,N-dimetyl-etylamin, karakterisert ved at det anvendes utgangs-materialer hvor R^ er hydrogen, R2 er p-brom, R^ er hydrogen, R. og Rj. er hver metyl, og Z er en aminogruppe i 3-stilling.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813138550 DE3138550A1 (de) | 1981-09-28 | 1981-09-28 | Substituierte 2-phenyl-2-(pyridyloxy)-ethylamine und isostere verbindungen, verfahren zu ihrer herstellung und verwendung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO823253L NO823253L (no) | 1983-03-29 |
| NO159999B true NO159999B (no) | 1988-11-21 |
| NO159999C NO159999C (no) | 1989-03-01 |
Family
ID=6142812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO823253A NO159999C (no) | 1981-09-28 | 1982-09-27 | Analogifremgangsmaate for fremstilling av farmakologisk aktive substituerte 2-fenyl-2-(pyridyloksy)-etylamin-derivater og isostere forbindelser. |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4666910A (no) |
| EP (1) | EP0075752B1 (no) |
| JP (1) | JPS5869865A (no) |
| KR (1) | KR880002705B1 (no) |
| AR (1) | AR231534A1 (no) |
| AT (1) | ATE18551T1 (no) |
| AU (1) | AU550614B2 (no) |
| CA (1) | CA1171086A (no) |
| DE (2) | DE3138550A1 (no) |
| DK (1) | DK156718C (no) |
| ES (1) | ES8308543A1 (no) |
| FI (1) | FI78074C (no) |
| GB (1) | GB2106902B (no) |
| GR (1) | GR77657B (no) |
| IE (1) | IE53959B1 (no) |
| IL (1) | IL66870A (no) |
| NO (1) | NO159999C (no) |
| NZ (1) | NZ202015A (no) |
| PH (1) | PH23219A (no) |
| PT (1) | PT75611B (no) |
| ZA (1) | ZA827055B (no) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8320699D0 (en) * | 1983-08-01 | 1983-09-01 | Wellcome Found | Ethylenediamines |
| GB0004153D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004152D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| AR035700A1 (es) * | 2001-05-08 | 2004-06-23 | Astrazeneca Ab | Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados |
| SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102639D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| SE0102640D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| US6800652B2 (en) | 2002-08-16 | 2004-10-05 | Pfizer Inc. | Diaryl compounds |
| GB0219154D0 (en) * | 2002-08-16 | 2002-09-25 | Pfizer Ltd | Diaryl compounds |
| SE0203304D0 (sv) * | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Coumpounds |
| CN1886398A (zh) * | 2003-10-09 | 2006-12-27 | 米伦纽姆医药公司 | 作为Xa因子抑制剂的经硫醚取代的苯甲酰胺 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2734845A (en) * | 1956-02-14 | Aqueous suspension of procaine penicil- | ||
| US2734846A (en) * | 1956-02-14 | Aqueous suspension of procaine penicil- | ||
| FR1511398A (fr) * | 1966-02-16 | 1968-01-26 | Takeda Chemical Industries Ltd | Procédé de préparation de nouveaux dérivés de picoline |
| BE790592A (no) * | 1971-10-28 | 1973-04-26 | Oreal | |
| US4011324A (en) * | 1976-01-20 | 1977-03-08 | Pfizer Inc. | Esters and amides of pyrimido[4,5-b]quinolin-4(3H)-one-2-carboxylic acids as antiulcer agents |
-
1981
- 1981-09-28 DE DE19813138550 patent/DE3138550A1/de not_active Withdrawn
-
1982
- 1982-09-06 AT AT82108196T patent/ATE18551T1/de not_active IP Right Cessation
- 1982-09-06 DE DE8282108196T patent/DE3269839D1/de not_active Expired
- 1982-09-06 EP EP82108196A patent/EP0075752B1/de not_active Expired
- 1982-09-22 FI FI823246A patent/FI78074C/fi not_active IP Right Cessation
- 1982-09-24 IL IL66870A patent/IL66870A/xx unknown
- 1982-09-24 AR AR290759A patent/AR231534A1/es active
- 1982-09-27 JP JP57168221A patent/JPS5869865A/ja active Granted
- 1982-09-27 NO NO823253A patent/NO159999C/no unknown
- 1982-09-27 IE IE2330/82A patent/IE53959B1/en not_active IP Right Cessation
- 1982-09-27 CA CA000412268A patent/CA1171086A/en not_active Expired
- 1982-09-27 DK DK428582A patent/DK156718C/da not_active IP Right Cessation
- 1982-09-27 ES ES515972A patent/ES8308543A1/es not_active Expired
- 1982-09-27 NZ NZ202015A patent/NZ202015A/en unknown
- 1982-09-27 KR KR8204342A patent/KR880002705B1/ko not_active Expired
- 1982-09-27 ZA ZA827055A patent/ZA827055B/xx unknown
- 1982-09-27 AU AU88738/82A patent/AU550614B2/en not_active Ceased
- 1982-09-27 GB GB08227449A patent/GB2106902B/en not_active Expired
- 1982-09-27 PT PT75611A patent/PT75611B/pt not_active IP Right Cessation
- 1982-09-28 GR GR69383A patent/GR77657B/el unknown
-
1984
- 1984-08-28 US US06/645,007 patent/US4666910A/en not_active Expired - Fee Related
-
1985
- 1985-03-07 PH PH31952A patent/PH23219A/en unknown
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