FI107149B - Menetelmä (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitro-fenyyli)akryyliamidin stabiilin polymorfisen muodon valmistamiseksi - Google Patents
Menetelmä (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitro-fenyyli)akryyliamidin stabiilin polymorfisen muodon valmistamiseksi Download PDFInfo
- Publication number
- FI107149B FI107149B FI905198A FI905198A FI107149B FI 107149 B FI107149 B FI 107149B FI 905198 A FI905198 A FI 905198A FI 905198 A FI905198 A FI 905198A FI 107149 B FI107149 B FI 107149B
- Authority
- FI
- Finland
- Prior art keywords
- dihydroxy
- acrylamide
- cyano
- diethyl
- polymorphic form
- Prior art date
Links
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 15
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims abstract description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000019253 formic acid Nutrition 0.000 claims abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000003197 catalytic effect Effects 0.000 claims abstract description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 3
- 238000002329 infrared spectrum Methods 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims 2
- IZXCSWDOAKESAA-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enamide Chemical compound NC(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 IZXCSWDOAKESAA-UHFFFAOYSA-N 0.000 claims 1
- 102000006378 Catechol O-methyltransferase Human genes 0.000 abstract description 3
- 108020002739 Catechol O-methyltransferase Proteins 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- -1 (E) -N Chemical compound 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- JRURYQJSLYLRLN-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide Chemical compound CCN(CC)C(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002447 crystallographic data Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000002424 x-ray crystallography Methods 0.000 description 2
- RZWGTXHSYZGXKF-UHFFFAOYSA-N 2-(2-methylphenyl)acetic acid Chemical compound CC1=CC=CC=C1CC(O)=O RZWGTXHSYZGXKF-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Psychiatry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Description
107149
Menetelmä (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitro-fenyyli)akryyliamidin stabiilin polymorfisen muodon valmistamiseksi : Keksinnön kohteena on stabiili ja kristallografisesti
oleellisesti puhdas N,N-dietyyli-2-syano-3-{3,4-dihydroksi-i 5-nitrofenyyli)akryyliamidin E-isomeerin polymorfinen muoto A
• i « · ja menetelmä sen valmistamiseksi.
• · · « · · N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)-akryyliamidi, joka on kuvattu hakijan suomalaisessa patenttihakemuksessa FI 875229, on tehokas katekoli-O-metyylitransferaasientsyymin (COMT) estäjä, jota *... voidaan käyttää mm. Parkinsonin taudin hoidossa. Tämä » · ·.· yhdiste, jonka sulamispisteeksi hakemuksessa FI 875229 on . annettu 153-156°C, on osoittautunut kahden geometrisen • « · ____· isomeerin seokseksi (E-isomeeri 70-80% ja Z-isomeeri 30-20%). 1 · Nämä isomeerit voidaan esittää seuraavilla rakennekaavoilla: 2 107149 HO -.- /C; Hs 03 tbf C’«>
CN
E-isomeeri, s.p. 162-163°C HO-~~_ CN
H0-O)—\/ 11 02 1 j ^5
CON
\ c2h5
Z-isomeeri, s.p. 148-151°C
N,N-di etyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)- akrvyliamidin E-isomeeri, eli (E)-N,N-di etyyli-2-syano-3- ( 3 , 4-dihydroksi-5-nitrof enyyli )-ak ryyliamidi (I), voi .·;· röntgenkristallografiän perusteella esiintyä ainakin kahdessa ' i; polymorfisessa muodossa A ja B. Sekä Z-isomeeri että . . E-isomeerin polymorfinen muoto B ovat osoittautuneet epästabiileiksi. Z-isomeeri muuttuu E-isomeeriksi lämmön tai
’···* happojen vaikutuksesta. E-isomeerin polymorfinen muoto B
• · *.1 isomeroituu hitaasti polymorfiseen muotoon A huoneenlämmössä.
Uudelleenkiteytettäessä synteesin raakatuotetta tavanomaisista liuottimista kuten alemmista alifaattisista alkoholeista, estereistä tai hiilivedyistä, esim. etanolista, .*** 2-propanolista, etyyliasetaatista tai tolueenista, saadaan «·« .·.· yleensä hyvin komplisoitu seos eri geometrisiä isomeerejä » » *· · ja/tai polymorfisia muotoja. Tämä vaikeuttaa lääkeaineen *... karakterisointia ja standardointia. Polymorfismi ja geometrinen isomeria saattaa myös vaikuttaa lääkkeen • · · 3 107149 biologiseen käyttökelpoisuuteen, kuten tiedetään muiden lääkeaineiden tutkimuksista.
Nyt on havaittu, että uudelleenkiteytettäessä synteesin raakatuotetta alemmista alifaattisista karboksyylihapoista kuten muurahaishaposta tai etikkahaposta, johon on lisätty katalyyttinen määrä vetykloridia tai vetybromidia saadaan hyvällä saannolla kristallografisesti oleellisesti puhdasta ja stabiilia (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)akryyliamidin polymorfista muotoa A. Tällä menetelmällä voidaan valmistaa homogeenista ja kristallografisesti oleellisesti puhdasta (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)akryyliamidin polymorfista muotoa A teollisessa mittakaavassa riippumatta panoksen koosta tai jäähdytysnopeudesta.
"Kristallografisesti oleellisesti puhdas" tarkoittaa tässä (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)-akryyliamidin polymorfista muotoa A, joka sisältää korkeintaan 3%, mieluummin korkeintaan 2%, muita polymorfisia muotoja tai Z-isomeeria.
I I I
*:"· "Alempi alifaattinen karboksyylihappo" tarkoittaa tässä ; alifaattista karboksyylihappoa, joka sisältää 1-2 /·' hiiliatomia. Esimerkkejä näistä ovat muurahaishappo ja .·.· etikkahappo.
« · .
(E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)-akryyliamidin polymorfista muotoa A karakterisoidaan joko iR-spektroskopialla tai röntgenkristallografiällä.
IM
. ·... ( E)-N,N-dietyyli-2-syano-3-( 3,4-dihydr oksi-5-ni tr of enyyli )- « ♦ V akryyliamidin polymorfisen muodon A IR-spektri on esitetty « · . .*·* kuvassa 1 ja tyypilliset iR-absorptionauhat taulukossa 1.
ι*ι· 4 · * 4 4 107149 (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)-akryyliamidin polymorfisen muodon A röntgendiffraktogrammi on esitetty kuvassa 2 ja kristallografinen data taulukossa 2.
Taulukko 1. (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)akryyliamidin polymorfisen muodon A tunnusomaiset nauhat IR-spektrissä
Aaltoluvut ( cm-1) ja suhteelliset intensiteetit 3339 s 3092 w 3066 w 3039 w 2981 w 2938 w 2217 m 1628 s 1607 s 1580 sh 1544 s 1512 m 1441 s 1377 s 1298 s 1281 sh •' ' 1210m ‘ , 1165 m ·:1 1150 m . 800 sh :.: 779 m . ‘ 74 0 m 4 l t . .
• « » s = strong; m = medium; w = weak; sh = shoulder *♦» « »·» » 1 * m • · • ♦ • · · « * « · « · 107149 5
Taulukko 2. (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)akryyliamidin polymorfisen muodon A kristallografinen data.
No 2Θ d Rel I (%) 1 3.680 23.9905 0.8 2 9.040 9.7745 49.7 3 11.840 7.4685 9.9 4 13.541 6.5339 11.1 5 14.060 6.2939 11.6 6 15.820 5.5974 7.6 7 16.320 5.4270 3.9 8 18.220 4.8651 4.6 9 18.459 4.8027 8.7 10 18.720 4.7363 13.6 11 18.940 4.6818 5.5 12 20.041 4.4270 5.0 13 20.380 4.3541 11.1 14 21.140 4.1993 3.5 15 21.939 4.0481 58.3 16 22.901 3.8802 13.8 17 23.340 3.8082 100.0 18 23.960 3.7110 3.3 19 24.480 3.6334 2.9 20 26.343 3.3805 3.6 :.V Seuraava esimerkki kuvaa keksintöä.
* 4 · ·;··:' Esimerkki 1.
« 4 · .·*. Raaka synteesituote (3 kg), joka oli valmistettu suomalaisessa patenttihakemuksessa FI 875229 kuvatulla menetelmällä, liuotettiin 8,0 kg:aan etikkahappoa (98-100%) (tai muurahaishappoa), joka sisälsi 80 g vetybromidia (tai 40 g vetykloridia), kuumentamalla 90°C:een. Liuos jäähdytettiin hitaasti 20°C:een, sekoitettiin 20 tuntia 20°C:ssa ja lopuksi 6 tuntia 15°C:ssa. Kiteinen tuote suodatettiin ja pestiin huolellisesti ensin 1 1:11a kylmää (4°C) tolueeni-etikkahappo .···' seosta (1:1 til/til) ja sen jälkeen kylmällä tolueenilla (1 1). Tuote kuivattiin vakuumissa 45°C:ssa.
4 4 4 4 « · 6 107149 (E)—N,N—dietyyli—2—syano—3—(3,4-dihydroksi-5-nitrofenyyli)-akryyliamidin kristallografisesti puhtaan polymorfisen muodon A saanto oli 2,4 kg (80%), s.p. 162-163°C.
Claims (3)
1. Menetelmä kristallografisesti oleellisesti puhtaan farmaseuttisesti aktiivisen (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitrofenyyli)akryyliamidin polymorfisen muodon A valmistamiseksi, jonka infrapunaspektri kaliumbromidissa osoittaa seuraavat absorptionauhat: Aaltoluku Aaltoluku (cm-1) (cm-1) 3339 1512 3092 1441 3066 1377 3039 1298 2981 1281 2938 1210 2217 1165 1628 1150 1607 800 1580 779 . . 1544 740 • · · t · · • · i « · • · · tunnettu siitä, että kiteytetään raaka N,N-dietyyli-. . 2-syano-3-(3,4-dihydroksi-5-nitrofenyyli) akryyliamidi alemmasta alifaattisesta karboksyylihaposta, joka sisältää katalyyttisen määrän vetykloridia tai vetybromidia. • · · • i »
2. Vaatimuksen 1 mukainen menetelmä tunnettu siitä, että alempi alifaattinen karboksyylihappo on etikkahappo. ♦ · · • » I • · « « . .·1.
3. Vaatimuksen 1 mukainen menetelmä tunnettu siitä, • · · ’ • · *..! että alempi alifaattinen karboksyylihappo on muurahaishappo. • · • · ♦ ♦ · • « · · 107149
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8924838 | 1989-11-03 | ||
| GB8924838A GB2238047B (en) | 1989-11-03 | 1989-11-03 | Stable polymorphic form of (e)-n,n-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide and the process for its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FI905198A0 FI905198A0 (fi) | 1990-10-23 |
| FI107149B true FI107149B (fi) | 2001-06-15 |
Family
ID=10665678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI905198A FI107149B (fi) | 1989-11-03 | 1990-10-23 | Menetelmä (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitro-fenyyli)akryyliamidin stabiilin polymorfisen muodon valmistamiseksi |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5135950A (fi) |
| EP (1) | EP0426468B1 (fi) |
| JP (1) | JP2823680B2 (fi) |
| AT (1) | ATE127447T1 (fi) |
| BR (1) | BR1100289A (fi) |
| DE (2) | DE69022166T2 (fi) |
| DK (1) | DK0426468T3 (fi) |
| ES (1) | ES2075885T3 (fi) |
| FI (1) | FI107149B (fi) |
| GB (1) | GB2238047B (fi) |
| GR (1) | GR3017526T3 (fi) |
| LU (1) | LU91071I2 (fi) |
| NL (1) | NL300147I1 (fi) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5283352A (en) * | 1986-11-28 | 1994-02-01 | Orion-Yhtyma Oy | Pharmacologically active compounds, methods for the preparation thereof and compositions containing the same |
| GB9113431D0 (en) * | 1991-06-20 | 1991-08-07 | Orion Yhytma Oy | Method for the preparation of 3,4-dihydroxy-5-nitrobenzaldehyde |
| CA2080554A1 (en) * | 1991-10-15 | 1993-04-16 | Mitsubishi Chemical Corporation | Styrene derivatives |
| JPH05301838A (ja) * | 1991-10-15 | 1993-11-16 | Mitsubishi Kasei Corp | スチレン誘導体 |
| US20060013875A1 (en) * | 2002-05-29 | 2006-01-19 | Impax Laboratories, Inc. | Combination immediate release controlled release levodopa/carbidopa dosage forms |
| US7094427B2 (en) * | 2002-05-29 | 2006-08-22 | Impax Laboratories, Inc. | Combination immediate release controlled release levodopa/carbidopa dosage forms |
| KR100814737B1 (ko) * | 2003-12-19 | 2008-03-19 | 에프. 호프만-라 로슈 아게 | Ｃｏｍｔ 억제제 |
| WO2005070881A1 (en) * | 2003-12-24 | 2005-08-04 | Wockhardt Limited | An efficient process for the manufacture of (e)-entacapone polymorphic form a |
| EP1701937A4 (en) * | 2003-12-29 | 2007-05-02 | Wockhardt Ltd | STABLE POLYMORPHS OF (E) -N, N-DIETHYL-2-CYANO-3- (3,4-DIHYDROXY-5-NITROPHENYL) ACRYLAMIDE |
| US20080076825A1 (en) * | 2003-12-31 | 2008-03-27 | Thomas Bader | Novel Crystalline Forms of Entacapone and Production Thereof |
| AU2003287844A1 (en) * | 2003-12-31 | 2005-07-21 | Cilag Ag | Novel crystalline forms of entacapone, and production thereof |
| EP1577289A1 (en) | 2004-03-18 | 2005-09-21 | Revotar Biopharmaceuticals AG | Non-glycosylated/-glycosidic/-peptidic small molecule selectin inhibitors for the treament of inflammatory disorders |
| WO2006002082A2 (en) * | 2004-06-16 | 2006-01-05 | Jack Arbiser | Carbazole formulations for the treatment of psoriasis and angiogenesis |
| US20060173074A1 (en) | 2004-11-10 | 2006-08-03 | Juha Ellmen | Treatment of restless legs syndrome |
| EP2335696A1 (en) | 2005-06-08 | 2011-06-22 | Orion Corporation | An entacapone-containing oral dosage form |
| US20070148238A1 (en) * | 2005-06-23 | 2007-06-28 | Spherics, Inc. | Dosage forms for movement disorder treatment |
| EP1764095A1 (en) | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel nitrocatechol derivatives having selectin ligand activity |
| EP1764096A1 (en) | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel phloroglucinol derivatives having selectin ligand activity |
| EP1764093A1 (en) | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel aromatic compounds and their use in medical applications |
| ATE445591T1 (de) * | 2005-11-09 | 2009-10-15 | Usv Ltd | Verfahren zur herstellung von hochreinem (e)-n,n- diethyl-2-cyano-3-(3,4-dihydro-5- nitrophenyl)acrylamid (entacapon) |
| EP1976824A1 (en) * | 2006-01-02 | 2008-10-08 | Actavis Group PTC EHF | A process for the preparation of entacapone form-a |
| HRP20120445T1 (hr) * | 2006-02-06 | 2012-06-30 | Orion Corporation | Postupak proizvodnje entakapona |
| WO2007094007A1 (en) * | 2006-02-13 | 2007-08-23 | Suven Life Sciences Ltd., | An improved process for the preparation of entacapone |
| WO2007113845A1 (en) * | 2006-04-03 | 2007-10-11 | Alembic Limited | A process for the preparation of (e)-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl)-n, n-diethyl-2-propenamide (entacapone) |
| GB0610207D0 (en) * | 2006-05-23 | 2006-07-05 | Pliva Istrazivanje I Razvoj D | New forms of active pharmaceutical ingredient |
| US20080131492A1 (en) * | 2006-06-23 | 2008-06-05 | Spherics, Inc. | Dosage forms for movement disorder treatment |
| US20080004343A1 (en) * | 2006-06-29 | 2008-01-03 | Wockhardt Limited | Stable polymorphs of (E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide |
| GB0613826D0 (en) * | 2006-07-12 | 2006-08-23 | Pliva Istrazivanje I Razvoj D | Process and product |
| ES2306587B1 (es) * | 2006-11-15 | 2009-08-07 | Quimica Sintetica, S.A. | Nueva forma cristalina de entacapona y procedimiento para su obtencion. |
| ITMI20062450A1 (it) * | 2006-12-19 | 2008-06-20 | Dipharma Spa | Procedimento per la preparazione di entacapone |
| EP2063867A2 (en) * | 2006-12-22 | 2009-06-03 | Combinatorx, Incorporated | Pharmaceutical compositions for treatment of parkinson's disease and related disorders |
| ES2319024B1 (es) * | 2007-02-13 | 2009-12-11 | Quimica Sintetica, S.A. | Procedimiento para la obtencion de entacapona sustancialmente libre de isomero z, sus intermedios de sintesis y nueva forma cristalina. |
| WO2009084031A2 (en) * | 2007-12-03 | 2009-07-09 | Neuland Laboratories Ltd | An improved process for preparation of (2e)-2-cyano-3-(3,4- dihydroxy-5-nitrophenyl)n,n-diethyl-2-propenamide polymorphic form a |
| EP2251323B1 (en) | 2009-05-14 | 2014-04-23 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Method for the purification of entacapone |
| EP2542220B1 (en) | 2010-03-04 | 2016-11-02 | Orion Corporation | Use of levodopa, carbidopa and entacapone for treating parkinson's disease |
| CN103845317B (zh) | 2012-11-28 | 2018-05-08 | 北京生命科学研究所 | 恩他卡朋在预防或治疗肥胖等代谢综合征中的应用 |
| JP6506271B2 (ja) | 2013-10-07 | 2019-04-24 | インパックス ラボラトリーズ、 インコーポレイテッドＩｍｐａｘ Ｌａｂｏｒａｔｏｒｉｅｓ， Ｉｎｃ． | レボドパ及び／又はレボドパのエステルの粘膜付着性制御放出配合物、並びにその使用 |
| US10987313B2 (en) | 2013-10-07 | 2021-04-27 | Impax Laboratories, Llc | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof |
| CN104402764A (zh) * | 2014-11-26 | 2015-03-11 | 千辉药业（安徽）有限责任公司 | 一种恩他卡朋的制备方法 |
| US11986449B2 (en) | 2020-12-22 | 2024-05-21 | Amneal Pharmaceuticals Llc | Levodopa dosing regimen |
| WO2022140448A1 (en) | 2020-12-22 | 2022-06-30 | Amneal Pharmaceuticals Llc | Levodopa dosing regimen |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU213587A (en) * | 1986-11-28 | 1989-06-30 | Orion Yhtymae Oy | Process for obtaining new pharmacologic active cateholic derivatives |
| JP2539504B2 (ja) * | 1987-03-11 | 1996-10-02 | 鐘淵化学工業株式会社 | ヒドロキシスチレン誘導体 |
| KR900016098A (ko) * | 1988-04-28 | 1990-11-12 | 사하루 게이 죠오 | 카페인산의 유도체 및 이를 함유하는 약제학적 조성물 |
| GB8813762D0 (en) | 1988-06-10 | 1988-07-13 | Orion Yhtymae Oy | Catechol derivatives for use in cancer treatment |
| JP2535058B2 (ja) * | 1988-07-29 | 1996-09-18 | 富士通株式会社 | 半導体装置の製造方法 |
-
1989
- 1989-11-03 GB GB8924838A patent/GB2238047B/en not_active Revoked
-
1990
- 1990-10-23 FI FI905198A patent/FI107149B/fi not_active IP Right Cessation
- 1990-10-31 US US07/606,717 patent/US5135950A/en not_active Expired - Lifetime
- 1990-11-01 EP EP90311963A patent/EP0426468B1/en not_active Expired - Lifetime
- 1990-11-01 DK DK90311963.4T patent/DK0426468T3/da active
- 1990-11-01 DE DE69022166T patent/DE69022166T2/de not_active Expired - Lifetime
- 1990-11-01 ES ES90311963T patent/ES2075885T3/es not_active Expired - Lifetime
- 1990-11-01 DE DE200412000014 patent/DE122004000014I1/de active Pending
- 1990-11-01 AT AT90311963T patent/ATE127447T1/de active
- 1990-11-02 JP JP2298708A patent/JP2823680B2/ja not_active Expired - Lifetime
-
1995
- 1995-09-26 GR GR950402644T patent/GR3017526T3/el unknown
-
1997
- 1997-04-15 BR BR1100289-1A patent/BR1100289A/pt active IP Right Grant
-
2004
- 2004-04-09 LU LU91071C patent/LU91071I2/fr unknown
- 2004-04-16 NL NL300147C patent/NL300147I1/nl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| LU91071I2 (fr) | 2005-06-21 |
| EP0426468A2 (en) | 1991-05-08 |
| BR1100289A (pt) | 1999-10-05 |
| JP2823680B2 (ja) | 1998-11-11 |
| DE69022166T2 (de) | 1996-02-15 |
| US5135950A (en) | 1992-08-04 |
| JPH03169844A (ja) | 1991-07-23 |
| DK0426468T3 (da) | 1995-10-23 |
| ATE127447T1 (de) | 1995-09-15 |
| GB2238047B (en) | 1993-02-10 |
| DE122004000014I1 (de) | 2004-08-12 |
| EP0426468B1 (en) | 1995-09-06 |
| GR3017526T3 (en) | 1995-12-31 |
| DE69022166D1 (de) | 1995-10-12 |
| EP0426468A3 (en) | 1992-05-06 |
| FI905198A0 (fi) | 1990-10-23 |
| ES2075885T3 (es) | 1995-10-16 |
| GB8924838D0 (en) | 1989-12-20 |
| NL300147I1 (nl) | 2004-07-01 |
| GB2238047A (en) | 1991-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI107149B (fi) | Menetelmä (E)-N,N-dietyyli-2-syano-3-(3,4-dihydroksi-5-nitro-fenyyli)akryyliamidin stabiilin polymorfisen muodon valmistamiseksi | |
| JP4928727B2 (ja) | 脂肪酸アミドの製造方法 | |
| JP5112399B2 (ja) | アゴメラチン合成の新規な方法 | |
| JP2682705B2 (ja) | ２，６−ジクロロフェニルアミノベンゼン酢酸誘導体及びジフェニルアミン誘導体の製造方法。 | |
| HU201523B (en) | Process for producing retinoyl chlorides | |
| AU2003288712A1 (en) | Alternative process for the preparation of entacapone | |
| DE69006345T2 (de) | Totale Synthese von Erbstatin-Analogen. | |
| CN113316573B (zh) | 用于制备i型吡虫啉多晶型体的方法 | |
| DE60021410T2 (de) | Verfahren zur herstellung von ketiminen | |
| AU2003292465A1 (en) | Stable polymorphs of (e)-n,n-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide | |
| AU615521B2 (en) | Compounds used in the preparation of nifedipine | |
| WO2006064296A1 (en) | Process for the preparation of (e)-n,n-diethyl-2-cyano-3(3,4-dihydroxy-5-nitro-phenyl)-acrylamide in stable polymorphic form and intermediates of the process | |
| CA2327056C (en) | Phosphine reduction of azides to amides | |
| CA2042854A1 (en) | Process for the synthesis of n-vinyl amides | |
| US6235935B1 (en) | Method of manufacturing high purity oximes from aqueous hydroxylamine and ketones | |
| US20080300420A1 (en) | Process for the Preparation of Entacapone Form-A | |
| GB2061257A (en) | Method for the preparation of 2-chlorobenzoyl chloride, and its uses | |
| US5631403A (en) | Process for the preparation of hydroxycarboxanilides | |
| SK77894A3 (en) | Method of producing of nitriles of aminopropione acid | |
| US5231215A (en) | Method of manufacturing substituted monoamides of dicarboxylic-acid monoalkyl esters | |
| JPS5931748A (ja) | α−シアノアクリル酸エステルの製造法 | |
| US5973205A (en) | Process for the preparation of 1, 3-diaminopropane derivatives and intermediates useful in this process | |
| HU218599B (hu) | Eljárás 4-(3,4-diklór-fenil)-3,4-dihidro-1-(2H)-naftalin-1-on előállítására | |
| KR820002043B1 (ko) | β-이소부티릴 아미노크로톤산 아미드의 제조방법 | |
| JPH0757744B2 (ja) | ４‐ブロモアニリン臭化水素酸塩の製法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SPCF | Supplementary protection certificate application filed |
Spc suppl protection certif: L20020006 |
|
| SPCF | Supplementary protection certificate application filed |
Spc suppl protection certif: L20040007 |
|
| FG | Patent granted |
Owner name: ORION-YHTYMAE OY |
|
| PC | Transfer of assignment of patent |
Owner name: ORION CORPORATION Free format text: ORION CORPORATION |
|
| SPCG | Supplementary protection certificate granted |
Spc suppl protection certif: 221 Extension date: 20151023 |
|
| SPCR | Lapse or expiry of a supplementary protection certificate |
Spc suppl protection certif: 221 Effective date: 20140311 |