NO152212B - Analogifremgangsmaate for fremstilling av terapeutisk aktive (d1)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive (d1)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater Download PDFInfo
- Publication number
- NO152212B NO152212B NO840258A NO840258A NO152212B NO 152212 B NO152212 B NO 152212B NO 840258 A NO840258 A NO 840258A NO 840258 A NO840258 A NO 840258A NO 152212 B NO152212 B NO 152212B
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- Prior art keywords
- phenoxy
- compounds
- keto
- preparation
- prostatriic
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
Foreliggende oppfinnelse angår fremstilling av nye terapeutisk virksomme 16-fenoksy- og 16-(o, m eller p)-substituerte fenoksyderivater av (dl)-9-keto-lla,15a-dihydroksy-17,18,19,20-tetranorprosta-4,5,13-trans-triensyre.
Prostaglandiner er klassisk blitt beskrevet som kjemisk nærstående 20 karbonkjedede hydroksyfettsyrer med et basis-skjelett slik man finner det i prostansyre:
Prostaglandiner som har en hydroksylgruppe i C-ll stillingen og en ketogruppe i C-9 stillingen, er kjent som PGE-seriene, mens de som har en hydroksylgruppe istedet for ketogruppen, er kjent som PGF-seriene, og blir ytterligere betegnet med et a- eller B-suffiks for å angi konfigura-sjonen på hydroksylgruppen i nevnte stilling. De naturlige forbindelser er a-hydroksysubstituerte forbindelser.
Det kan være forskjellige grader av umettethet i molekylet, da spesielt ved C-5, C-13 og C-17, og umettetheten blir også angitt ved hjelp av et suffiks. Således vil f.eks. PGF^ og PGE^ seriene referere seg til prostansyrer med transolefinbinding ved C-13 stillingen, mens PGF2 og PGE2 seriene refererer seg til prostadiensyrer med en cis-ole-finbinding i C-5 stillingen og en transolefinbinding ved C-13 stillingen. For en nærmere oversikt over prostaglandiner og definisjon av primære sådanne, se f.eks.
S. Bergstrøm, "Recent Progress in Hormone Research 22",
pp. 153-175 (1966) og "Science" 157, side 382 (1967) av samme forfatter.
Fremstillingen av derivater av prostansyre har vist seg
å bli stadig viktigere ettersom man har kunnet påvise at
naturlige prostaglandiner har en rekke interessante biologiske og farmakologiske aktiviteter.
Størstedelen av undersøkelsene er blitt fokusert på modi-fikasjonen av de to sidekjedene, eller modifikasjoner av substituentene knyttet til cyklopentangruppen (se f.eks. U.Axen et al., "Synthesis". vol. 1, John Wiley and Sons Inc., New York, N.Y. 1973 og P.H. Bently, "Chem. Soc. Reviews" 2, 29 (1973)). Det er bl.a. beskrevet syntesen av prostaglandinanaloger med en dietylenisk (allenisk) umettethet i karboksylsyrekjeden, se f.eks. US-patent nr. 3.879.438 utstede 22. april 1975 til Crabbe og Fried. Syntesen av flere prostaglandinanaloger hvor alkylkjeden knyttet- til.C-15 stillingen i de naturlige forbindelsene er blitt erstattet med en aryloksymetylengruppe, er bl.a. angitt i US-patentene nr. 3.864.387, 3.954.881 (9-keto-16-fenoksy-5,13-prostadienforbindelser), 3.985.791 (9a-hydroksy-16-fenoksy-4,5,13-prostatrienforbindelser) og belgisk patent nr. 806.995.
Ifølge oppfinnelsen fremstilles terapeutisk aktive forbindelser med formelen:
hvor X er hydrogen, o-, m- eller p-halogen (fluor, klor eller brom), o-, m- eller p-metyl, eller o-, m- eller p-metoksy.
Linjene som er vist i ovennevnte formel og i den nedenstå-ende formel som "" indikerer at substituentene er i en a-konfigurasjon, dvs. under planet i cyklopentanringen.
Dobbeltbindingen ved C-13 i forbindelser som fremstilles ifølge foreliggende oppfinnelse har samme konfigurasjon som i naturlige prostaglandiner av PGE og PGF-seriene,
dvs. i transkonfigurasjon.
De nye forbindelsene har asymmetriske sentra og kan således fremstilles som racemiske (dl) blandinger eller som individuelle 8R-antimerer. De racemiske blandinger kan opp-løses hvis dette er- ønskelig på passende syntesetrinn ved hjelp av fremgangsmåter som i seg selv er kjente, hvorved man får fremstilt de respektive individuelle antimerer.
I US-patent 3.985.791 beskrives beslektede prostatriensyre-derivater og hovedforskjellen mellom disse og de som fremstilles ifølge oppfinnelsen finnes ved 9-stillingen, idet disse forbindelsene har en ketogruppe, mens forbindelsene i nevnte US-patent har en hydroksylgruppe.
Videre anvendes forbindelsene i foreliggende oppfinnelse hovedsakelig for behandling og hindring av sår i magesekken og i tolvfingertarmen, mens forbindelsene i nevnte US-patent er særlig egnet som luteolytiske midler hos pattedyr av hunnkjønn.
De ovenfor angitte terapeutisk virksomme syreforbindelsene fremstilles ifølge foreliggende oppfinnelse ved at man surgjør en forbindelse med formelen:
hvor R er et kation og X har den ovenfor angitte betydning.
Saltene som anvendes som utgangsmaterialer kan være salter avledet fra uorganiske baser, slik som natrium-, kalium-, litium-, ammonium-, kalsium-, magnesium-, toverdig jern-, sink-, kobber-, mangan-, aluminium-, treverdig jern-, mangansalter o.l. Videre kan det anvendes salter av primære, sekundære og tertiære aminer, substituerte aminer således naturlig forekommende substituerte aminer, cykliske aminer og basiske ioneutbytningsharpikser, så som isopropylamin, trimetylamin, dietylamin, trietylamin, tripropylamin, etanolamin, 2-dimetylaminoetanol, 2-dietylaminoetanol, trometamin, lysin, arginin, histidin, kaffein, prokain, hydrabamin, kolin, betain, etylendiamin, glukoseamin, N-metylglukamin, teobromin, puriner, piperazin, piperidin, N-etylpiperidin, polyaminharpikser o.l.
Ved fremgangsmåten behandles de respektive saltene i det minste med støkiometriske mengder av en sterk syre, fortrinnsvis en uorganisk syre, slik som saltsyre, svovelsyre o.l., i et organisk oppløsningsmiddel, slik som en alkohol, fortrinnsvis metanol eller etanol.
Forbindelser fremstilt ifølge foreliggende oppfinnelse
har prostaglandin-lignende biologiske aktiviteter, og kan således brukes ved behandlingen av pattedyr, hvor det er ønskelig med bruk av prostaglandiner. Således kan forbindelsene brukes for kontroll av astma-anfall, fordi de er bronkodilatorer og fordi at de dessuten viser anti-allergiske egenskaper ved at de hemmer en mediatorfrigjør-ing. I tillegg til dette kan de brukes for behandling av bronkierkramper hos pattedyr, eller alle de steder hvor det er ønskelig med bronkodilatorer. Forbindelsene viser også vasodilaterende egenskaper og kan derfor brukes for å kontrollere eller å lindre for høyt blodtrykk hos pattedyr, foruten at de har en sentralnervesystemdepressiv akti-vitet hos pattedyr, og kan således brukes som beroligende midler.
Mer spesielt og overraskende har det vist seg at de fremstilte forbindelsene er sterkere hemmere for magesaftut-skillelse og følgelig sterkere midler mot magesårdannelse enn de tilsvarende 9-keto-16-fenoksy-5,13-prostadien-forbindelser. Således vil de fremstilte forbindelsene være meget verdifulle ved behandlingen av og å hindre magesår både i magesekken og i tolvfingertarmen.
Forbindelsene kan tilføres i en rekke forskjellige doserings-former, enten alene eller i kombinasjon med andre farmasøy-tisk forenlige preparater, og kan brukes i form av farma-søytiske preparater som er regnet for oral eller parente-ral tilførsel eller som innhalering i forbindelse med bronkodilatorer. Typisk vil de tilføres som farmasøytiske preparater inneholdende i alt vesentlig en fri syre, et salt eller en ester av forbindelsen og en farmasøytisk bærer.
Den farmasøytiske bærer kan enten være et fast materiale,
en væske eller en aerosol, hvor forbindelsen er oppløst, dispergert eller suspendert, og kan dessuten inneholde mindre mengder av konserverende midler og/eller buffermidler for justering av pH. Som egnede konserveringsmidler kan man f.eks. bruke benzylalkohol o.l. Egnede buffere innbefatter f.eks. natriumacetat og farmasøytiske fosfatsalter o.l.
De flytende preparatene kan f.eks. være i form av oppløs-ninger, emulsjoner, suspensjoner, siruper o.l. De faste preparatene kan være i form av. tabletter, pulvere, kapsler, piller o.l., fortrinnsvis i enhetsdoseringsform for enkel tilførsel eller mer nøyaktig dosering. Egnede faste bærere innbefatter f.eks. farmasøytisk kvalitet av stivelse, lak-tose, natriumsakkarin, talkum, natriumbisulfit o.l.
For innhalering kan de frie syrene tilføres som en aerosol som innbefatter forbindelsene eller saltene i et inert drivmiddel sammen med et samoppløsningsmiddel, f.eks. metanol, sammen med eventuelle konserveringsmidler og buffere. Ytterligere informasjon angående innhaleringstilførsel
av aerosoler kan finnes i US-patentene 2.868.691 og 3.095.355.
Forbindelsene fremstilt ifølge foreliggende oppfinnelse
vil typisk tilføres i doser på 1-100 ug pr. kg kroppsvekt. Den presise effektive dose vil selvsagt være avhengig av tilførselsmåten, den tilstand som skal behandles samt pasi-entens. For f.eks. å oppnå en bronkodilatering vil man måtte tilføre 1-10 \ xg pr. kg kroppsvekt i en aerosol,
og for å hemme magesyreutskillelse må man tilføre 1-50
\ iq pr. kg kroppsvekt oralt.
Det er underforstått at isolering av de her beskrevne forbindelser kan utføres på mange egnede måter hva angår ut-separering og rensing, f.eks. ekstraksjon, fordampning, filtrering, destillasjon, krystalliseririg, tynnsjiktskroma-tografi, høytrykks væskekromatografi eller kolonnekroma-tografi eller ved en kombinasjon av disse fremgangsmåter. Følgende eksempel illustrerer oppfinnelsen.
Eksempel.
Til en oppløsning av 100 mg av natriumsaltet av (dl)-9-keto-lla,15a-dihyroksy-17,18,19,2 0-tetranorprosta-4,5,13-trans-triensyre i 10 ml vandig metanol, tilsettes 1,0 molar-ekvivalenter av IN HCl under opprettholdelse av pH-verdien ved 4-4,5, og blandingen omrøres ved romtemperatur i 1 time. Reaksjonsblandingen ekstraheres deretter med etylace-tat (2 x 5 ml), tørkes (MgSO^) og inndampes til tørrhet under redusert trykk for oppnåelse av (dl)-9-keto-lla,15a-dihyroksy-17,18,19,20-tetranorprosta-4,5,13-trans-triensyre som en olje med følgende fysikalske konstanter:
Claims (1)
- Analogifremgangsmåte for fremstilling av en terapeutisk aktiv forbindelse med formelen:hvor X er hydrogen, o-, m- eller p-halogen (fluor, klor eller brom), o-, m- eller p-metyl, eller o-, m- eller p-metoksy, karakterisert ved at man surgjør en forbindelse med formelen:hvor R er et kation og X har den ovenfor angitte betydning.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/922,957 US4178457A (en) | 1978-07-10 | 1978-07-10 | (dl)-16-Phenoxy- and 16-substituted phenoxy-9-keto prostatrienoic acid derivatives and processes for the production thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO840258L NO840258L (no) | 1980-01-11 |
| NO152212B true NO152212B (no) | 1985-05-13 |
| NO152212C NO152212C (no) | 1985-08-21 |
Family
ID=25447871
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO792283A NO150836C (no) | 1978-07-10 | 1979-07-09 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (dl)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater |
| NO840257A NO152211C (no) | 1978-07-10 | 1984-01-24 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (d1)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater |
| NO840258A NO152212C (no) | 1978-07-10 | 1984-01-24 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (d1)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater |
| NO840256A NO152296C (no) | 1978-07-10 | 1984-01-24 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (dl)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyre-derivater |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO792283A NO150836C (no) | 1978-07-10 | 1979-07-09 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (dl)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater |
| NO840257A NO152211C (no) | 1978-07-10 | 1984-01-24 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (d1)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyrederivater |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO840256A NO152296C (no) | 1978-07-10 | 1984-01-24 | Analogifremgangsmaate for fremstilling av terapeutisk aktive (dl)-16-fenoksy- og 16-substituerte fenoksy-9-keto-prostatriensyre-derivater |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US4178457A (no) |
| EP (1) | EP0008003B1 (no) |
| JP (1) | JPS5513282A (no) |
| KR (1) | KR890002773B1 (no) |
| AT (1) | ATE2427T1 (no) |
| AU (1) | AU527516B2 (no) |
| CA (1) | CA1149802A (no) |
| CS (1) | CS209927B2 (no) |
| DD (1) | DD146179A5 (no) |
| DE (2) | DE2927715A1 (no) |
| DK (1) | DK157753C (no) |
| ES (1) | ES482330A1 (no) |
| FI (1) | FI69061C (no) |
| FR (1) | FR2430939A1 (no) |
| GB (1) | GB2025413B (no) |
| HK (1) | HK41384A (no) |
| HU (1) | HU184185B (no) |
| IT (1) | IT1121462B (no) |
| MY (1) | MY8500576A (no) |
| NO (4) | NO150836C (no) |
| NZ (1) | NZ190924A (no) |
| PL (4) | PL121778B1 (no) |
| SG (1) | SG82483G (no) |
| SU (1) | SU1031407A3 (no) |
| YU (3) | YU41870B (no) |
| ZA (1) | ZA793293B (no) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4328245A (en) * | 1981-02-13 | 1982-05-04 | Syntex (U.S.A.) Inc. | Carbonate diester solutions of PGE-type compounds |
| US4358603A (en) * | 1981-04-16 | 1982-11-09 | Syntex (U.S.A.) Inc. | Acetal stabilized prostaglandin compositions |
| US4409239A (en) * | 1982-01-21 | 1983-10-11 | Syntex (U.S.A.) Inc. | Propylene glycol diester solutions of PGE-type compounds |
| US4912235A (en) * | 1983-12-22 | 1990-03-27 | Syntex (U.S.A.) Inc. | Processes and intermediates for making 16-phenoxy- and 16-substituted phenoxy-prostatrienoic acid derivatives and their stereoisomers |
| US4600785A (en) * | 1983-12-22 | 1986-07-15 | Syntex (U.S.A.) Inc. | Processes and intermediates for making 16-phenoxy and 16-substituted phenoxy-prostatrienoic acid derivatives |
| US4804787A (en) * | 1983-12-22 | 1989-02-14 | Syntex (U.S.A.) Inc. | Processes and intermediates for making 16-phenoxy and 16-substituted phenoxy-prostatrienoic acid derivatives |
| DE3414509A1 (de) * | 1984-04-13 | 1985-10-24 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue 9-halogen-prostaglandine |
| HU196174B (en) * | 1984-07-31 | 1988-10-28 | Syntex Inc | Process for preparing new prostaglandin derivatives and pharmaceutical compositions containing such active substance |
| US4792617A (en) * | 1984-07-31 | 1988-12-20 | Syntex (U.S.A.) Inc. | 11-substituted-16-phenoxy and 16-substituted phenoxy-prostatrienioc acid derivatives |
| US5057621A (en) * | 1984-07-31 | 1991-10-15 | Syntex (U.S.A.) Inc. | 11-substituted-16-phenoxy and 16-substituted phenoxy-prostatrienoic acid derivatives |
| US4618696A (en) * | 1984-07-31 | 1986-10-21 | Syntex (U.S.A.) Inc. | 9-oxo-15α-hydroxy-16-phenoxy and 16-substituted phenoxy 17,18,19,20-tetranorprosta-4,5,13,(E)-trienoates |
| US4778904A (en) * | 1985-09-13 | 1988-10-18 | Syntex (U.S.A.) Inc. | Intermediates for making 16-phenoxy- and 16-(substituted phenoxy)-prostatrienoic acid derivatives |
| JPS62267231A (ja) * | 1986-04-11 | 1987-11-19 | シンテツクス（ユ−・エス・エイ） インコ−ポレイテツド | 脂肪および炭水化物代謝調節剤エンプロスチル型プロスタグランジン類 |
| US4755531A (en) * | 1986-08-11 | 1988-07-05 | Syntex (U.S.A.) Inc. | Thiol esters of 4,5-allenyl prostaglandins and use thereof as antigastric secretion agents |
| GB8625321D0 (en) * | 1986-10-22 | 1986-11-26 | Glaxo Group Ltd | Chemical compounds |
| US4689419A (en) * | 1986-11-14 | 1987-08-25 | G. D. Searle & Co. | Novel intermediate compounds in a process for producing 16-phenoxy- and 16-substituted phenoxy-9-keto-prostatrienoic acid derivatives |
| US6103765A (en) * | 1997-07-09 | 2000-08-15 | Androsolutions, Inc. | Methods for treating male erectile dysfunction |
| JP2001509480A (ja) | 1997-07-09 | 2001-07-24 | アンドロソリューションズ，インク． | 男性勃起機能不全を治療するための改良された方法及び組成物 |
| US20020037914A1 (en) | 2000-03-31 | 2002-03-28 | Delong Mitchell Anthony | Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins |
| US20020013294A1 (en) | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
| US20020172693A1 (en) | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
| US8966971B2 (en) * | 2008-07-28 | 2015-03-03 | Ford Global Technologies, Llc | Vehicle engine with fluid measuring system |
| US8623918B2 (en) | 2008-10-29 | 2014-01-07 | Novaer Holdings, Inc. | Amino acid salts of prostaglandins |
| CA2739571A1 (en) * | 2008-10-29 | 2010-08-26 | Aerie Pharmaceuticals, Inc. | Amino acid salts of prostaglandins |
| US8722739B2 (en) | 2008-10-29 | 2014-05-13 | Novaer Holdings, Inc. | Amino acid salts of prostaglandins |
| US20110293549A1 (en) | 2009-02-03 | 2011-12-01 | Athena Cosmetics, Inc. | Composition, method and kit for enhancing hair |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES449162A1 (es) * | 1975-06-23 | 1977-12-16 | Syntex Inc | Un procedimiento para la preparacion de un compuesto racemi-co u 8r-antimerico. |
-
1978
- 1978-07-10 US US05/922,957 patent/US4178457A/en not_active Expired - Lifetime
-
1979
- 1979-07-03 ZA ZA793293A patent/ZA793293B/xx unknown
- 1979-07-04 AU AU48641/79A patent/AU527516B2/en not_active Ceased
- 1979-07-05 CS CS794752A patent/CS209927B2/cs unknown
- 1979-07-05 NZ NZ190924A patent/NZ190924A/xx unknown
- 1979-07-06 JP JP8511679A patent/JPS5513282A/ja active Granted
- 1979-07-06 CA CA000331348A patent/CA1149802A/en not_active Expired
- 1979-07-06 FI FI792149A patent/FI69061C/fi not_active IP Right Cessation
- 1979-07-09 GB GB7923914A patent/GB2025413B/en not_active Expired
- 1979-07-09 DK DK288879A patent/DK157753C/da not_active IP Right Cessation
- 1979-07-09 ES ES482330A patent/ES482330A1/es not_active Expired
- 1979-07-09 DE DE19792927715 patent/DE2927715A1/de active Granted
- 1979-07-09 NO NO792283A patent/NO150836C/no unknown
- 1979-07-09 DE DE7979102349T patent/DE2964709D1/de not_active Expired
- 1979-07-09 IT IT68428/79A patent/IT1121462B/it active
- 1979-07-09 DD DD214202A patent/DD146179A5/de unknown
- 1979-07-09 AT AT79102349T patent/ATE2427T1/de not_active IP Right Cessation
- 1979-07-09 EP EP79102349A patent/EP0008003B1/en not_active Expired
- 1979-07-09 SU SU792786000A patent/SU1031407A3/ru active
- 1979-07-09 FR FR7917796A patent/FR2430939A1/fr active Granted
- 1979-07-10 YU YU1685/79A patent/YU41870B/xx unknown
- 1979-07-10 PL PL1979217001A patent/PL121778B1/pl unknown
- 1979-07-10 PL PL1979224555A patent/PL120604B1/pl unknown
- 1979-07-10 PL PL1979224557A patent/PL120632B1/pl unknown
- 1979-07-10 PL PL1979224556A patent/PL120633B1/pl unknown
- 1979-07-10 HU HU79SI1706A patent/HU184185B/hu unknown
-
1982
- 1982-01-29 KR KR8200378A patent/KR890002773B1/ko active
-
1983
- 1983-12-27 SG SG824/83A patent/SG82483G/en unknown
-
1984
- 1984-01-24 NO NO840257A patent/NO152211C/no unknown
- 1984-01-24 NO NO840258A patent/NO152212C/no unknown
- 1984-01-24 NO NO840256A patent/NO152296C/no unknown
- 1984-05-10 HK HK413/84A patent/HK41384A/xx unknown
-
1985
- 1985-12-30 MY MY576/85A patent/MY8500576A/xx unknown
-
1986
- 1986-05-08 YU YU735/86A patent/YU44553B/xx unknown
- 1986-05-08 YU YU736/86A patent/YU44554B/xx unknown
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