NO148644B - Analogifremgangsmaate til fremstilling av terapeutisk aktive sukkerderivater - Google Patents
Analogifremgangsmaate til fremstilling av terapeutisk aktive sukkerderivater Download PDFInfo
- Publication number
- NO148644B NO148644B NO801862A NO801862A NO148644B NO 148644 B NO148644 B NO 148644B NO 801862 A NO801862 A NO 801862A NO 801862 A NO801862 A NO 801862A NO 148644 B NO148644 B NO 148644B
- Authority
- NO
- Norway
- Prior art keywords
- residue
- formula
- tetrahydro
- compound
- hydrogen
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 13
- 230000001225 therapeutic effect Effects 0.000 title claims 2
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- 125000003545 alkoxy group Chemical group 0.000 claims description 7
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
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- NLIUDONFMFYFRU-UHFFFAOYSA-M triphenyl-[1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethyl]phosphanium;bromide Chemical compound [Br-].C=1C=C(C(CCC2(C)C)(C)C)C2=CC=1C(C)[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 NLIUDONFMFYFRU-UHFFFAOYSA-M 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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Description
Foreliggende oppfinnelse vedrører en analogifremgangsmåte ved fremstilling av terapeutisk aktive forbindelser med formelen
1 6 7 hvori R er en rest -CH OH, -CH OR , COR eller -CONH , 2 3 4 R hydrogen eller lavere alkanoyl, R og R hydrogen, lavere-alkanoyl eller en rest R^, R^ lavere-alkoksy, en OR^ eller OR^, R^
7
R hydroksy, lavere-alkoksy eller OM og M et kation,
g
og R en rest med formelen
og når R 1 er en rest CH2OR 6 , er R 2 hydrogen, og en av restene R^ og R<4> hydrogen og den andre en rest R^ hvis R~<* >1 7
er lavere-alkoksy, og nar R er en rest -COR og
R2, R3 og R4 er lavere-alkanoyl, så er R5 en rest OR<6>, og når R1 er en rest -CH-OH, -COR<7> og CONH og R<2>, R3 og R<4 >hydrogen eller lavere-alkanoyl, så er R <5> en rest OR <8>.
En foretrukken gruppe av de fremstilte forbindelsene er forbindelsene med formel
51 31
hvori R er metoksy og en av restene R og R4^ er en rest R6 og den andre er hydrogen, og R6 har den ovenfor angitte betydning.
Særlig foretrukket er metyl-2, 6-bis-0- lp- [(E)-2-(5, 6 , 7 , 8-tetrahydro-5,5,8, 8-tetrametyl-2-naf tyl) -propenyl] -benzoyl] - <<-D-glukopyranosid.
Uttrykket "lavere" skal angi fortrinnsvis grupper med opp-til 7 C-atomer. Eksempler på lavere alkanoylgrupper er acetyl, propionyl, butyryl. Eksempler på lavere alkoksygrupper er metoksy, etoksy, propoksy og butoksy. Et kation i resten R<7> er fortrinnsvis et alkalimetallkation, spesielt en Na <+>.
Forbindelsene med formel I fremstilles ifølge oppfinnelsen ved at man
a) omsetter en forbindelse med formelen.
51
hvori R betyr lavere-alkoksy,
6 6
med syren R OH, hvor R har den ovenfor angitte betydning, eller et reaktivt derivat derav i nærvær av et vann- henholdsvis syrebindende middel, eller
b) deacetylerer en forbindelse med formelen
hvori Ac betyr acetyl og R g har den ovenfor angitte
betydning,
eller
c) behandler en forbindelse med formelen
med metanolisk ammoniakk, og om ønsket overfører en erholdt
forbindelse med formel I hvori R"*" er lavere-alkoksykarbonyl
i en forbindelse hvori R er karboksyl, eller i et salt av en slik forbindelse.
Som reaktivt derivat av syren R OH kommer spesielt halogen-idene, f.eks. kloridet, i betraktning. Omsetningen ifølge fremgangsmåtevariant a) skjer gjerne i et inert løsnings-middel. Eksempler på løsningsmidler er etere, f.eks. di-etyleter, tetrahydrofuran eller dioksan, eller vann, eller blandinger derav. Eksempler på egnede baser ved denne omsetningen er organiske baser så som pyridin, homologer derav og uorganiske baser så som alkalimetallkarbonater. Omsetningen utføres gjerne ved temperaturer fra 0° til romtemperatur .
Deacetylering ifølge fremgangsmåtevariant b) kan oppnås ved behandling med baser så som alkalimetallalkoksyder, f.eks. natriummetoksyd i metanol. Denne reaksjonen kan utføres ved romtemperatur.
Omsetningen ifølge fremgangsmåtevariant c) kan utføres ved behandling av en forbindelse med formel IV med metanolisk ammoniakk ved romtemperatur.
Omvandlingen av en alkoksykarbonylgruppe R^" i en forbindelse med formel I i karboksylgruppen hhv. karboksylatgruppen kan skje ved forsåpning, f.eks. med alkali så som alkoholis-ke alkalihydroksyder. De således erholdte salter kan ved nøytralisering, f.eks. med kationbyttere i H+<->form overfør-es i de frie syrer.
Utgangsmaterialene kan fremstilles som beskrevet i eksemp-lene eller analogt med disse.
Forbindelsene med formel I er verdifulle som virkestoffer for farmasøytika, f.eks. for behandling av neoplasmer, spesielt ved topisk administrering. De kan videre anvendes ved behandling av akne og psoriasis og ved behandling av betente og allergiske dermatoser. Forbindelsene utmerker ser ved god fordragelighet, f.eks. gir de ikke hudirritasjon
ved topisk administrering.
Den tumorhemmende virkning av forbindelsene ble prøvet på mus, ved hvilke papillomer i huden ble fremkalt ved dimetyl-benzantracen og krotonolje. Ved å gi forbindelsene med formel I observerte man en tilbakegang av <p>apillomene. For-søksresultatene fremgår av tabell I.
A: p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-p-D-glykopyranosid
B: p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-&-D-glykopyranosid-uronamid
C: Natrium-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetra-metyl-2-naftyl)-propenyl]-benzyl-3-D-glukopyranosid-uronat
D: Metyl-2,6-bis-0-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoyl]-a-D-glukopyranosid
E: Metyl-3,6-bis-0-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoyl]-a-D-glukopyranosid
F: Metyl-2,3,4-tri-O-acetyl-l-O-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoyl]-a-D-glukopyranuronat
G: Metyl-2,3,4-tri-O-acetyl-l-O-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramety1-2-naftyl)-propenyl]-benzoyl]-(3-D-glukopyranuronat
Forbindelsene med formel I kan anvendes som legemidler, f.eks. i form av farmasøytiske preparater. Preparatene som tjener for systemisk anvendelse kan f.eks. fremstilles ved at man tilfører en forbindelse med formel I som virksom bestanddel ikke-toksiske, inerte, i og for seg i slike preparater vanlige faste eller flytende bæremidler. Midlene kan gis enteralt eller parenteralt. For enteral applikasjon er midlene f.eks. egnet i form av tabletter, kapsler, drageer, sirups, suspensjoner, løsninger og suppositorier. Egnede midler for parenteral applikasjon er infusjons- eller injek-sjonsløsninger.
Doseringene som fremgangsmåteproduktene gis i kan variere avhengig av anvendelsestypen og anvendelsesveien og pasient-enes behov.
Fremgangsmåteproduktene kan gis i mengder på ca. 0,01 til ca. 5 mg daglig i en eller flere doser. En foretrukket admini-streringsform er kapsler med et innhold på ca. 0,1 mg til ca.
1 mg virkestoff.
Preparatene kan inneholde inerte eller også farmakodynamisk aktive tilsetninger. Tabletter eller granulater kan f.eks. inneholde forskjellige bindemidler, fyllstoffer, bærestoffer eller fortynningsmidler. Flytende preparater kan f.eks. foreligge i form av en steril vannblandbar løsning. Kapsler kan foruten virkestoffet også inneholde et fyllmateriale eller fortykningsmiddel. Videre kan smaksbedrende tilsetninger samt de vanlige anvendte stoffer som konserverings-, stabiliserings-, fuktighetsbevarende, og emulgerende midler, videre også salter for endring av det osmotiske trykk, puff-
ere og andre tilsetninger være tilstede.
De foran nevnte bæresubstanser og fortynningsmidler kan be-stå av organiske eller uorganiske stoffer, f.eks. av vann, gelatin, melkesukker, stivelse, magnesiumstearat, talkum, gummi arabicum, polyalkylenglykoler og lignende. Forutset-ning er at alle hjelpestoffene som anvendes ved fremstilling av preparatene er ugiftige.
For topisk anvendelse anvendes fremgangsmåteproduktene hensiktsmessig i form av salver, tinkturer, kremer, løsninger,, lotioner, sprays, suspensjoner og lignende. Fortrinnsvis anvendes salver og kremer samt løsninger. Disse preparatene som er bestemt for topisk anvendelse kan fremstilles ved at man blander fremgangsmåteproduktene som virksom bestanddel til ikke-toksiske, inerte og for topisk behandling egnede,
i og for seg i slike preparater vanlige faste eller flytende bæremidler.
For topisk anvendelse er hensiktsmessig ca. 0,01 til 0,3%-ig, fortrinnsvis 0,02 til 0,1%-ig løsninger samt ca. 0,05 til 5%-ige, fortrinnsvis ca. 0,05 til 1%-ige salver og kremer egnet.
Preparatene kan eventuelt tilsettes et antibksydasjonsmiddel, f.eks. tokoferol, N-metyl-y-tokoferamin samt butylert hydro-ksyanisol eller butylert hydroksytoluen.
De følgende eksempler skal videre belyse oppfinnelsen.
EKSEMPEL 1'
En løsning av 3,4 g metyl-2,3,4-tri-O-acetyl-a-D-glukopyranu-ronat i 40 ml pyridin ble omsatt ved 0° med en løsning av p-[(E)-2-(5,6,7,8-tetrariydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoylklorid i 70 ml eter. Blandingen ble rørt natten over ved romtemperatur, inndampet til tørrhet og resten kromatografert på kiselgel med heksan-etylacetat.
Man fikk metyl-2,3,4-tri-O-acetyl-l-O-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoyl]-D-glukopyranuronat som blanding av [3- og cx-anomerer (ca. 4:1). Smp. 149-150° (etanol), [a]<25> =3° (c = 1 i kloroform).
Syrekloridet som anvendes som utgangsmateriale kan fremstilles som følger: p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzosyreetylester forsåpes med vandig etanolisk kalilut ved 55° i 18 timer til den tilsvarende karboksylsyre og syren overføres med tionylklorid i pyridin og N,N-dimetyl-formamid i syrekloridet.
EKSEMPEL 2
En blanding av 3,5 g p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzosyre, 1,05 g N,N-di-cykloheksylkarbodiimid og 0,6 5 g 4-dimetylaminopyridin i 4 50 ml diklormetan ble holdt 5 timer ved romtemperatur. Di-cykloheksylurinstoffet ble frafiltrert, filtratet blandet med 1,7 g metyl-2,3,4-tri-O-acetyl-a-D-glukopyranuronat,
1,05 g N,N'-dicykloheksylkarbodiimid og 0,65 g 4-dimetylaminopyridin og fikk stå natten over ved romtemperatur. Blandingen ble så filtrert, filtratet inndampet og resten kromatografert. Man fikk en blanding av det a- og p-anomerer (ca. 3:2), som ble adskilt ved kromatografi på en kiselgel-søyle (Merck, heksan-etylacetat). Man fikk metyl-2,3,4-tri-O-acetyl-l-O- [p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramet-yl-2-naftyl)-propenyl]-benzoyl]-a-D-glukopyranuronat, smp. 172° (etanol), [a]<25> = +104,1° (c = 1 i kloroform) og den tilsvarende (3-anomer , smp. 161° (etanol), [c]^<5> = -24,6°
(c = 1 i kloroform).
EKSEMPEL 3
En løsning av 100 mmol p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoylklorid i 450 ml eter ble under røring ved 0° i løpet av 1 time satt til en løs-ning av 19,5 g metyl-a-D-glukopyranosid i 500 ml pyridin. Blandingen ble rørt ytterligere 4 timer ved 0° og 16 timer ved romtemperatur og så inndampet til tørrhet. Resten ble løst i etylacetat og ekstraktet vasket med 3N HC1, vann, mettet, vandig natriumbikarbonatløsning og vann. Etter-tørking over natriumsulfat ble den organiske fasen inndampet og resten kromatografert på kiselgel (heksan-etylacetat) hvorved man fikk metyl-2,6-bis-O-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoyl]-a-D-glukopyranosid, smp. 203-204° (etylacetat), fct]<2>^ = +27,4°
(c = 1 i kloroform) og metyl-3,6-bis-O-[p-[(E)-2-(5,6 , 7 , 8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzoyl]-ct-D-glukopyranosid, smp. 128-129° (under spaltning, fra metanol), ta]^ +13<*>5° (c = 1 i kloroform).
EKSEMPEL 4
En løsning av 3,9 g p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-2,3,4,6-tetra-O-acetyl-(3-D-glukopyranosid i 150 ml 0, IN natriummetoksyd i metanol ble holdt 3 0 min. ved romtemperatur, nøytralisert med Amberlite IR-120 kationbytter (H-form) og inndampet. Omkrystallisering fra 2-propanol ga p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-p-D-glukopyranosid, smp. 156-157°, [a]^ = -23,8° (c = 1 "i" pyridin).
Fremstilling av utgangsstoffet: 5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-naftalin ble omsatt med acetylklorid og AlCl^ i nitrobenzen til (5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-metylketon. Reduksjonen av ketonet med litiumaluminiumhydrid i eter gir 5,6,7,8-tetrahydro-a-5,5,8,8-pentametyl-2-naftalin-metanol som med fosfortribromid i eter/heksan i nærvær av lite pyridin over-føres i 2-brometyl-5 , 6., 7 ,8-tetrahydro-5, 5 , 8 , 8-tetrametyl-
naftalin. Brometylforbindelsen gir trifenylfosfin i xylen under oppvarming i 12 timer [ 1-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-etyl]-trifenylfosfoniumbromid, som i en Wittig-reaksjon med 4-etoksykarbonyl-benzaldehyd gir p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzosyre-etylester, smp. 90-91°. Esteren redu-seres med LiAlH4 i eter/tetrahydrofuran til p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramety1-2-naftyl)-propenyl]-benzylalkohol, smp. 123-124° (fra metanol).
En blanding av 5 g av denne alkoholen, 6,3 g 2,3,4,6-tetra-O-acetyl-a-D-glukopyranosylbromid og 1,5 g kvikksølv-II-cyanid oppvarmes i 2 50 ml toluen 5 timer ved tilbakeløp. Saltene filtreres fra og løsningen vaskes med mettet natriumhydrogen-karbonatløsning og vann, tørkes og inndampes. Omkrystallisering fra metanol gir p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-2,3,4,6-tetra-O-acetyl-(3-D-glukopyranosid, smp. 134-135° (fra metanol).
EKSEMPEL 5
En løsning av 2,8 g metyl-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-2,3,4-tri-O-acetyl-3-D-glukopyranosid]-uronat i 100 ml metanolisk ammoniakk (nesten mettet ved 0°) fikk stå 3 dager ved romtemperatur og ble så inndampet. Omkrystallisering fra etanol ga p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naf tyl) -propenyl] -benzyl-|3-D-glukopyranosid-uronamid, smp. 194°, [et]<25> = -380 (c = 1 i pyridin).
EKSEMPEL 6
Fra n-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naf-tyl)-propenyl]-benzylalkohol og metyl-2,3,4-tri-O-acetyl-a-D-glukopyranosylbromid-uronat får man metyl-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-2,3,4-tri-0-acetyl-3-D-glukopyranosid]-uronat, smp. 162-163°
(etanol), [<*]^ = -59,7° (c = 1 i kloroform).
EKSEMPEL 7
Analogt med eksempel 4 får man ut fra metyl-[p-[(E)-2-
(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-2,3,4-tri-O-acetyl-fJ-D-glukopyranosid]-uronat metyl-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-|3-D-glukopyranosid]-uronat, smp. 103-104°
(spaltning fra isopropyleter), [a]25 = -65,6° (c = 1 i kloroform) .
EKSEMPEL 8
1,9 g metyl-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-3-D-glukopyranosid]-uronat oppvarmes i 190 ml metanol med 10,8 ml lN-metanolisk NaOH 1 time ved tilbakeløp. Etter tilsetning av 2-propanol inntil uklar-het og avkjøling krystalliserte natrium-p-[(E)-2-(5,6,7,8-tetrahydro-5 , 5,8, 8-tetramety 1-2-naf tyl) -propenyl] -benzyl-13-D-glukopyranosid-uronat, smp. 240-242° (spaltning), [et]25 = -44,1° (c = 1 i H20).
EKSEMPEL 9
En løsning av 4,3 metyl-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8, 8-tetrametyl-2-naf tyl) -propenyl] -benzyl-(3-D-glukopyranosid]-uronat ble oppvarmet i 430 ml metanol med 24,5 ml lN-metanolisk NaOH 1 time ved tilbakeløp og så inndampet. Resten ble løst i 100 ml vann, løsningen nøytralisert med Amberlite IR-120 (H<+>)-harpiks og frysetørket. Man fikk p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrametyl-2-naftyl)-propenyl]-benzyl-p-D-glukopyranosid-uronsyre, smp. 174-175° 25 o
(spaltning fra metanol-benzen) , [ct]D = -28 (c = 1 i pyridin) .
Claims (3)
1. Analogifremgangsmåte ved fremstilling av terapeutisk
aktive forbindelser med formel
hvori R1 er en rest -CH-OH, -CH OR6, -COR7 eller -CONH.,; 2 3 4 R hydrogen eller lavere-alkanoyl; R og R hydrogen,
lavere-alkanoyl eller en rest R ; R<5> lavere-alkoksy, 6 8 6
en rest OR eller OR ; R en rest med formel
r<7> hydroksy, lavere-alkoksy eller OM, og M et kation og R en rest med formelen
og når R er en rest CH-.OR , er R hydrogen, og en av 3 4 1 6 restene R oq R hydrogen og den andre en rest R hvis
R5 er lavere-alkoksy; og når R er en rest -COR , og 2 3 4 " 5 6 R , R og R er lavere-alkanoyl, så er R en rest OR ;
og når R<1> er en rest -CH„OH, -COR<7> eller -CONH og R<2>, 3 4 z z5 R og R hydrogen eller lavere-alkanoyl,så er R en 8
rest OR, karakterisert ved at man a) omsetter en forbindelse med formel
hvori R<51> betyr lavere-alkoksy, med syren R<6>OH, hvor R<6> har den ovenfor angitte betydning, eller et reaktivt derivat derav i nærvær av et vann- hh. syrebindende middel, eller b) deacetylerer en forbindelse med formelen
hvori Ac betyr acetyl og R g har den foran angitte betydning, eller c) behandler en forbindelse med formelen med metanolisk ammoniakk, og om ønsket overfører en erholdt forbindelse med formel I hvori R er lavere alkoksykarbonyl i en forbindelse hvori R"<*>" er karboksyl eller i et salt av en slik forbindelse.
2. Fremgangsmåte ifølge krav 1 ved fremstilling av for
bindelser med formel 51 „31 hvori R er metoksy og en av restene R og R er en rest K<6> og den andre hydrogen og R har den i krav 1 angitte betydning, karakterisert ved at man anvender tilsvarende substituerte utgangsmaterialer.
3. Fremgangsmåte ifølge krav 1 ved fremstilling av metyl-2,6-bis-O-[p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8,-tetra-metyl-2-naftyl)-propenyl]-benzoyl]-a-D-glukopyranosid, karakteri"sert ved at man anvender tilsvarende substituerte utgangsmaterialer.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH580879 | 1979-06-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO801862L NO801862L (no) | 1980-12-22 |
| NO148644B true NO148644B (no) | 1983-08-08 |
| NO148644C NO148644C (no) | 1983-11-16 |
Family
ID=4299652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO801862A NO148644C (no) | 1979-06-21 | 1980-06-20 | Analogifremgangsmaate til fremstilling av terapeutisk aktive sukkerderivater. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US4316983A (no) |
| EP (1) | EP0021339B1 (no) |
| JP (1) | JPS567798A (no) |
| KR (2) | KR840000678B1 (no) |
| AR (2) | AR225312A1 (no) |
| AT (1) | ATE2434T1 (no) |
| AU (1) | AU530478B2 (no) |
| CA (1) | CA1134819A (no) |
| DE (1) | DE3061891D1 (no) |
| DK (1) | DK154650C (no) |
| ES (2) | ES8104322A1 (no) |
| FI (1) | FI67386C (no) |
| GR (1) | GR69283B (no) |
| HU (1) | HU184915B (no) |
| IE (1) | IE50463B1 (no) |
| IL (1) | IL60324A (no) |
| MC (1) | MC1338A1 (no) |
| NO (1) | NO148644C (no) |
| NZ (1) | NZ194061A (no) |
| PH (1) | PH16243A (no) |
| PT (1) | PT71435B (no) |
| ZA (1) | ZA803538B (no) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4987223A (en) * | 1981-12-23 | 1991-01-22 | Choay S.A. | Derivatives of the uronic acid |
| US4388457A (en) * | 1982-02-11 | 1983-06-14 | University Patents, Inc. | Phyllanthostatin compounds |
| CH661516A5 (de) * | 1983-12-08 | 1987-07-31 | Hoffmann La Roche | Phenylnonatetraenoylzuckerderivate. |
| AU582758B2 (en) * | 1984-06-28 | 1989-04-13 | Mect Corporation | Sialic acid derivatives, galactose derivatives and method for producing the same |
| CH667868A5 (fr) * | 1984-09-05 | 1988-11-15 | Oreal | Derives du benzonorbornene, leurs procedes de preparation et compositions medicamenteuse et cosmetique les contenant. |
| LU85726A1 (fr) * | 1985-01-10 | 1986-08-04 | Cird | Nouveaux derives naphtaleniques du benzonorbornene,leur procede de preparation et compositions medicamenteuse et cosmetique les contenant |
| EP0249008B1 (de) * | 1986-05-09 | 1993-09-15 | Pulverer, Gerhard, Prof. Dr.Dr.h.c. | Verwendung von spezifischen Monosacchariden zur Herstellung eines Arzneimittels zur Verhinderung von Metastasen maligner Tumore |
| JPH03502327A (ja) * | 1988-01-19 | 1991-05-30 | ボード・オブ・リージェンツ，ザ・ユニバーシティ・オブ・テキサス・システム | ３’‐デアミノドキソルビシンのエステル体、そのリポソーム組成物およびその使用方法 |
| SE462229B (sv) * | 1988-01-19 | 1990-05-21 | Exma Extern Marknadsfoering Ab | Laasanordning foer ett roerligt organ som aer svaengbart i foerhaallande till ett annat organ |
| US4943563A (en) * | 1988-10-03 | 1990-07-24 | Cornell Research Foundation, Inc. | 2,3,4-triacylhexose insect repellants |
| DE3929355A1 (de) * | 1989-09-04 | 1991-03-07 | Boehringer Mannheim Gmbh | Verfahren zur spezifischen bestimmung von pankreas-(alpha)-amylase |
| JP2674843B2 (ja) * | 1989-10-31 | 1997-11-12 | 新日本製鐵株式会社 | 鋳鉄用被覆アーク溶接棒 |
| US5523398A (en) * | 1994-08-31 | 1996-06-04 | The Center For Innovative Technology | Cellulose derivatives with a low degree of substitution |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3629238A (en) * | 1968-09-20 | 1971-12-21 | Sumitomo Chemical Co | Novel glucuronides of 3-indolylaliphatic acid derivatives |
| FR2141532B1 (no) * | 1971-06-14 | 1974-08-23 | Anvar | |
| FR2307820A1 (fr) * | 1975-04-17 | 1976-11-12 | Hayashibara Seibutsu Chem Inst | Glycosides d'echinatine et leur preparation |
| JPS51125362A (en) * | 1975-04-17 | 1976-11-01 | Hayashibara Biochem Lab Inc | Process for synthesizing echinatin glycosides |
| LU77254A1 (no) * | 1977-05-04 | 1979-01-18 | ||
| DK159967C (da) * | 1977-12-22 | 1991-06-03 | Hoffmann La Roche | Analogifremgangsmaade til fremstilling af terapeutisk aktive stilbenderivater |
-
1980
- 1980-05-07 FI FI801472A patent/FI67386C/fi not_active IP Right Cessation
- 1980-06-02 CA CA000353189A patent/CA1134819A/en not_active Expired
- 1980-06-04 AU AU59029/80A patent/AU530478B2/en not_active Ceased
- 1980-06-06 NZ NZ194061A patent/NZ194061A/xx unknown
- 1980-06-12 US US06/158,678 patent/US4316983A/en not_active Expired - Lifetime
- 1980-06-13 ZA ZA00803538A patent/ZA803538B/xx unknown
- 1980-06-16 IL IL60324A patent/IL60324A/xx unknown
- 1980-06-18 HU HU801510A patent/HU184915B/hu not_active IP Right Cessation
- 1980-06-18 AT AT80103397T patent/ATE2434T1/de not_active IP Right Cessation
- 1980-06-18 DE DE8080103397T patent/DE3061891D1/de not_active Expired
- 1980-06-18 EP EP80103397A patent/EP0021339B1/de not_active Expired
- 1980-06-19 GR GR62258A patent/GR69283B/el unknown
- 1980-06-19 JP JP8221680A patent/JPS567798A/ja active Granted
- 1980-06-19 AR AR281472A patent/AR225312A1/es active
- 1980-06-19 DK DK262480A patent/DK154650C/da not_active IP Right Cessation
- 1980-06-19 MC MC801455A patent/MC1338A1/xx unknown
- 1980-06-20 IE IE1280/80A patent/IE50463B1/en not_active IP Right Cessation
- 1980-06-20 NO NO801862A patent/NO148644C/no unknown
- 1980-06-20 PH PH24170A patent/PH16243A/en unknown
- 1980-06-20 ES ES492616A patent/ES8104322A1/es not_active Expired
- 1980-06-20 PT PT71435A patent/PT71435B/pt unknown
- 1980-06-20 KR KR1019800002441A patent/KR840000678B1/ko active
-
1981
- 1981-01-19 ES ES498607A patent/ES498607A0/es active Granted
- 1981-07-22 AR AR286172A patent/AR229247A1/es active
-
1984
- 1984-04-09 KR KR1019840001868A patent/KR840000850B1/ko not_active IP Right Cessation
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