NO309767B1 - Ny form av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2- fenyletoksy)-2-pyridinyl]-2-propensyre, anvendelse derav og farmasöytisk blanding inneholdende den - Google Patents
Ny form av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2- fenyletoksy)-2-pyridinyl]-2-propensyre, anvendelse derav og farmasöytisk blanding inneholdende den Download PDFInfo
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- NO309767B1 NO309767B1 NO974840A NO974840A NO309767B1 NO 309767 B1 NO309767 B1 NO 309767B1 NO 974840 A NO974840 A NO 974840A NO 974840 A NO974840 A NO 974840A NO 309767 B1 NO309767 B1 NO 309767B1
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- phenylethoxy
- dichlorophenyl
- pyridinyl
- thio
- methyl
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- ZJLFOOWTDISDIO-ZRDIBKRKSA-N (e)-3-[6-[(2,6-dichlorophenyl)sulfanylmethyl]-3-(2-phenylethoxy)pyridin-2-yl]prop-2-enoic acid Chemical compound C=1C=C(OCCC=2C=CC=CC=2)C(/C=C/C(=O)O)=NC=1CSC1=C(Cl)C=CC=C1Cl ZJLFOOWTDISDIO-ZRDIBKRKSA-N 0.000 title claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 7
- 238000010521 absorption reaction Methods 0.000 claims description 7
- 238000002441 X-ray diffraction Methods 0.000 claims description 6
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 6
- 230000008018 melting Effects 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- -1 2,6-dichlorophenyl Chemical group 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229910052724 xenon Inorganic materials 0.000 description 2
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical class [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- 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
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Description
Ny form av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre
Den foreliggende oppfinnelse vedrører en ny fysikalsk form av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre, farmasøytiske blandinger inneholdende den og dens anvendelse ved fremstilling av et medikament for behandling av psoriasis.
(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-
propensyre, dvs. forbindelse med den følgende struktur:
er tidligere kjent som en forbindelse som er anvendelig som en leukotrien-
antagonist. Spesielt er forbindelsen som er beskrevet i WO94/00437 anvendelig for. behandling av psoriasis. Pasienter som lider av psoriasis utsettes ofte for sollys som en del av terapien sin, og en slik eksponering kan potensielt forårsake nedbrytning av farmasøytisk aktive forbindelser. Det foreligger derfor et behov for topiske formuleringer som inneholder denne forbindelsen, hvilke er resistente mot eksponering for sollys.
(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)- 2-pyridinyl]-2-
propensyre kan foreligge i en rekke forskjellige fysikalske former (også kjent som
polymorfer).
Den foreliggende oppfinnelse tilveiebringer derfor i et første aspekt (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre i form II som identifiseres ved de følgende karakteristika:
infrarøde absorbsjonsbånd ved ca. 697, 743 og 884 cm"<1>.
• én eneste smelteendoterm som begynner på ca. 140°C (minimum ved 142,2°C) identifisert ved differensial-scanning kalorimetri. • røntgendiffraksjonsspredning (Cu kilde) ved 9,2, 16.4, 23,3, 26,8 & 27,3 grader.
For å unngå tvil, er infrarødt absorbsjonsbånd ovenfor de som oppnås med en nujol mølle.
(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre i den polymorfe form som er beskrevet i WO94/00437 har de følgende fysikalske
karakteristika:
• infrarøde absorbsjonsbånd ved ca. 704, 758 og 896 cm"<1>.
• en liten endoterm etterfulgt av en liten eksoterm fra 118°C til 138°C og en smelteendoterm med begynnelse på ca. 140°C identifisert ved differensial-scanning kalorimetri. • røntgendiffraksjonsspredning (Cu kilde) ved 10,1, 20,0, 23,0, 24,0 og 25,4 grader.
Den polymorfe form med de ovennevnte karakteristika kalles Form I.
(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre Form II har visse overraskende fordeler sammenlignet med de tidligere identifiserte
fysikalske former. For eksempel viser (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2- t fenyletoksy)-2-pyridinyl]-2-propensyre Form II meget høyere stabilitet mot lys sammenlignet med Form I polymorfe.
Oppfinnelsen tilveiebringer også i et videre aspekt (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre Form II for anvendelse ved terapi, spesielt ved behandling av psoriasis. Brukt i terapi kan (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre Form II formuleres i en standard farmasøytisk blanding ved å bruke velkjente teknikker innenfor området farmasi.
I et videre aspekt tilveiebringer den foreliggende oppfinnelse en farmasøytisk blanding omfattende (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre Form II i forbindelse med en farmasøytisk bærer.
Det ville være klart for en fagmann på området at en farmasøytisk blanding omfattende(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre Formel II i hovedsakelig ren form vil vise de ovennevnte fordeler. Med «hovedsakelig ren form» menes minst 50% ren, fortrinnsvis 80-90% ren, og helst renere enn 95%.
Blandinger omfattende blandinger av Form I og Form II polymorfer utgjør et ytterligere aspekt av oppfinnelsen. Disse er særpreget ved at (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyren foreligger i form II som definert i krav 1 i tillegg til form I, og også som form I som identifiseres ved de følgende karakteristika:
<*>infrarøde absorbsjonsbånd ved ca. 704, 758 og 896 cm"<1>, ;<*>. en liten endoterm etterfulgt av en liten eksoterm fra 118°C til 138°C og en smeltende endoterm med begynnelse på ca. 140°C identifisert ved differensial-scanning kalorimetrii,
røntgendiffraksjonsspredning (Cu kilde) ved 10,1, 20,0, 23,0 og 25,4 grader.
I et videre aspekt tilveiebringer den foreliggende oppfinnelse bruken av
(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre Form II til fremstilling av et medikament for behandling av psoriasis
Doseringsområdet for forbindelsen ifølge den foreliggende oppfinnelse ventes å ligge i området fra ca. 5 til ca. 1000 mg daglig, fortrinnsvis ca. 10 til ca. 200 mg
daglig. For topisk bruk for anvendelse ved psoriasis, vil doseringsområdet avhenge av størrelsen til det påvirkede området og sykdomsgraden.
Når det administreres i henhold til oppfinnelsen, ventes ingen uakseptable toksikologiske virkninger med forbindelsen ifølge oppfinnelsen.
De følgende eksempler illustrerer oppfinnelsen.
Eksempel 1
En foliedekket 50 ml konisk kolbe ble fylt med rå (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre (fremstilt i henhold til fremgansmåten beskrevet i WO95/00487) (5,0 g) og propan-2-ol (25 ml). Suspensjonen ble oppvarmet til tilbakeløp, og den resulterende løsning ble filtrert gjennom papir under redusert trykk inn i et foliedekket glass inneholdende en magnetstav. Glasset ble tettet, og filtratet rørt i 3 timer og fikk kjøle til rom-temperatur. Det hvite, faste stoff ble filtrert, tømt godt for væske, toppvasket med dietyleter (3 ml) (se anmerkning) og tørket under vakuum og ga(E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre som et hvitt, fast stoff (4,36 g, 88% gjenvinning).
Anmerkning: Dietyleter ble brukt for å hjelpe vakuumtørkingen, men den kan utelates eller erstattes med en vask med kald propan-2-ol uten å påvirke utbyttet.
Produktet hadde de følgende karakteristika:
• infrarøde absorbsjonsbånd ved ca. 697, 743 og 884 cm"<1>.
• én eneste smelteendoterm som begynner på ca. 140°C (minimum ved 142,2°C) identifisert ved differensial-scanning kalorimetri. • røntgendiffraksjonsspredning (Cu kilde) ved 9,2, 16.4, 23,3, 26,8 & 27,3 grader.
Eksempel 2
Sammenligning av lysstabilitet av krystallinske former.
Prøver av Formel I og Formel II ble utsatt for xenonlys (85.000 lux) i et Heraeus Sun Test CPS lyskabinett i 4 timer. Prøvene ble analysert før og etter eksponering for lys med HPLC med hensyn til relativ respons og urenhetsprofil.
Dimeren refererer til en cyklobutandimer av ((E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre som er hovednedbrytnings- produktet av form l-forbindelsen. Resultatene viser tydelig at form II er betydelig mer stabil enn form I ved eksponering for xenonlys. Etter 4 timers eksponering nedbrytes form I nesten fullstendig.
Claims (5)
1. (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre,karakterisert vedat den foreligger i form II som identifiseres ved de følgende karakteristika: • infrarøde absorbsjonsbånd ved ca. 697, 743 og 884 cm"<1>. • én eneste smelteendoterm som begynner på ca. 140°C (minimum ved 142,2°C) identifisert ved differensial-scanning kalorimetri. • røntgendiffraksjonsspredning (Cu kilde) ved 9,2,16,4, 23,3, 26,8 & 27,3 grader.
2. Farmasøytisk blanding,karakterisert vedat den omfatter formen ((E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre som beskrevet i krav 1 i forbindelse med en farmasøytisk akseptabel bærer.
3. Kjemisk forbindelse for anvendelse som et terapeutisk middel,karakterisert vedat den har formen av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre som er beskrevet i krav 1.
4. Farmasøytisk blanding omfattende (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre i forbindelse med en farmasøytisk akseptabel bærer,karakterisert vedat (E)-3-[6-[[(2,6-diklorfenyl)- tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyren foreligger i form II som definert i krav 1 i tillegg til form I, og også som form I som identifiseres ved de følgende karakteristika:<*>infrarøde absorbsjonsbånd ved ca. 704, 758 og 896 cm"<1>,
<*>en liten endoterm etterfulgt av en liten eksoterm fra 118°C til 138°C og en smeltende endoterm med begynnelse på ca. 140°C identifisert ved differensial-scanning kalorimetri,
røntgendiffraksjonsspredning (Cu kilde) ved 10,1, 20,0, 23,0 og 25,4 grader.
5. Anvendelse av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2-fenyletoksy)-2-pyridinyl]-2-propensyre i form II som definert i krav 1 ved fremstilling av et medikament for behandling av psoriasis.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9508137.8A GB9508137D0 (en) | 1995-04-21 | 1995-04-21 | Formulation |
| PCT/EP1996/001466 WO1996033174A1 (en) | 1995-04-21 | 1996-04-02 | New form of (e)-3-[6-[[(2,6-dichlorophenyl)-thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic acid |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO974840L NO974840L (no) | 1997-10-20 |
| NO974840D0 NO974840D0 (no) | 1997-10-20 |
| NO309767B1 true NO309767B1 (no) | 2001-03-26 |
Family
ID=10773317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO974840A NO309767B1 (no) | 1995-04-21 | 1997-10-20 | Ny form av (E)-3-[6-[[(2,6-diklorfenyl)-tio]metyl]-3-(2- fenyletoksy)-2-pyridinyl]-2-propensyre, anvendelse derav og farmasöytisk blanding inneholdende den |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6093828A (no) |
| EP (1) | EP0821673B1 (no) |
| JP (1) | JPH11503737A (no) |
| KR (1) | KR19990007900A (no) |
| CN (1) | CN1182418A (no) |
| AT (1) | ATE198883T1 (no) |
| AU (1) | AU707089B2 (no) |
| BR (1) | BR9608003A (no) |
| CA (1) | CA2218322A1 (no) |
| CZ (1) | CZ333797A3 (no) |
| DE (1) | DE69611670T2 (no) |
| DK (1) | DK0821673T3 (no) |
| ES (1) | ES2154818T3 (no) |
| GB (1) | GB9508137D0 (no) |
| GR (1) | GR3035494T3 (no) |
| HU (1) | HUP9801574A3 (no) |
| NO (1) | NO309767B1 (no) |
| NZ (1) | NZ307493A (no) |
| PL (1) | PL322897A1 (no) |
| PT (1) | PT821673E (no) |
| TR (1) | TR199701213T1 (no) |
| WO (1) | WO1996033174A1 (no) |
| ZA (1) | ZA963134B (no) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9602675D0 (en) * | 1996-02-09 | 1996-04-10 | Smithkline Beecham Plc | Process |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993006085A1 (en) * | 1991-09-19 | 1993-04-01 | Smithkline Beecham Corporation | Pyridine compounds for treating leukotriene-related diseases |
| MA22926A1 (fr) * | 1992-06-30 | 1994-04-01 | Smithkline Beecham Corp | Procede pour la preparation de nouveaux composes. |
| WO1994000433A1 (en) * | 1992-06-30 | 1994-01-06 | Smithkline Beecham Corporation | Process for making phenylthiomethylpyridinylalkenoates |
| GB9313145D0 (en) * | 1993-06-25 | 1993-08-11 | Smithkline Beecham Plc | Process |
-
1995
- 1995-04-21 GB GBGB9508137.8A patent/GB9508137D0/en active Pending
-
1996
- 1996-04-02 CN CN96193405A patent/CN1182418A/zh active Pending
- 1996-04-02 HU HU9801574A patent/HUP9801574A3/hu unknown
- 1996-04-02 KR KR1019970707423A patent/KR19990007900A/ko not_active Application Discontinuation
- 1996-04-02 CZ CZ973337A patent/CZ333797A3/cs unknown
- 1996-04-02 US US08/945,372 patent/US6093828A/en not_active Expired - Fee Related
- 1996-04-02 AT AT96914877T patent/ATE198883T1/de active
- 1996-04-02 JP JP8531444A patent/JPH11503737A/ja active Pending
- 1996-04-02 CA CA002218322A patent/CA2218322A1/en not_active Abandoned
- 1996-04-02 TR TR97/01213T patent/TR199701213T1/xx unknown
- 1996-04-02 DK DK96914877T patent/DK0821673T3/da active
- 1996-04-02 PL PL96322897A patent/PL322897A1/xx unknown
- 1996-04-02 AU AU56859/96A patent/AU707089B2/en not_active Ceased
- 1996-04-02 EP EP96914877A patent/EP0821673B1/en not_active Expired - Lifetime
- 1996-04-02 BR BR9608003A patent/BR9608003A/pt active Search and Examination
- 1996-04-02 WO PCT/EP1996/001466 patent/WO1996033174A1/en not_active Application Discontinuation
- 1996-04-02 ES ES96914877T patent/ES2154818T3/es not_active Expired - Lifetime
- 1996-04-02 NZ NZ307493A patent/NZ307493A/en unknown
- 1996-04-02 DE DE69611670T patent/DE69611670T2/de not_active Expired - Fee Related
- 1996-04-02 PT PT96914877T patent/PT821673E/pt unknown
- 1996-04-19 ZA ZA9603134A patent/ZA963134B/xx unknown
-
1997
- 1997-10-20 NO NO974840A patent/NO309767B1/no not_active IP Right Cessation
-
2001
- 2001-02-28 GR GR20010400337T patent/GR3035494T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR19990007900A (ko) | 1999-01-25 |
| US6093828A (en) | 2000-07-25 |
| AU5685996A (en) | 1996-11-07 |
| CN1182418A (zh) | 1998-05-20 |
| NO974840L (no) | 1997-10-20 |
| CA2218322A1 (en) | 1996-10-24 |
| HUP9801574A3 (en) | 1998-12-28 |
| DK0821673T3 (da) | 2001-06-18 |
| ZA963134B (en) | 1997-02-14 |
| BR9608003A (pt) | 1999-01-05 |
| NZ307493A (en) | 1998-07-28 |
| TR199701213T1 (no) | 1998-03-21 |
| HUP9801574A2 (hu) | 1998-11-30 |
| NO974840D0 (no) | 1997-10-20 |
| GB9508137D0 (en) | 1995-06-07 |
| CZ333797A3 (cs) | 1999-01-13 |
| ATE198883T1 (de) | 2001-02-15 |
| AU707089B2 (en) | 1999-07-01 |
| EP0821673A1 (en) | 1998-02-04 |
| JPH11503737A (ja) | 1999-03-30 |
| ES2154818T3 (es) | 2001-04-16 |
| EP0821673B1 (en) | 2001-01-24 |
| GR3035494T3 (en) | 2001-05-31 |
| DE69611670D1 (en) | 2001-03-01 |
| WO1996033174A1 (en) | 1996-10-24 |
| PL322897A1 (en) | 1998-03-02 |
| PT821673E (pt) | 2001-05-31 |
| DE69611670T2 (de) | 2001-08-23 |
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| Date | Code | Title | Description |
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| MM1K | Lapsed by not paying the annual fees |
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