NO850920L - PROCEDURE FOR THE PREPARATION OF PHENYL-ALKAN CARBOXYLIC ACID DERIVATIVES - Google Patents
PROCEDURE FOR THE PREPARATION OF PHENYL-ALKAN CARBOXYLIC ACID DERIVATIVESInfo
- Publication number
- NO850920L NO850920L NO850920A NO850920A NO850920L NO 850920 L NO850920 L NO 850920L NO 850920 A NO850920 A NO 850920A NO 850920 A NO850920 A NO 850920A NO 850920 L NO850920 L NO 850920L
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- alkyl
- preparation
- acid derivatives
- halogen atom
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- -1 2-hydroxy-phenyl Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 235000013312 flour Nutrition 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- AQVQBKUTLFBTFJ-UHFFFAOYSA-N (5-chloro-2-hydroxy-3-propylphenyl)-(4-methylphenyl)methanone Chemical compound CCCC1=CC(Cl)=CC(C(=O)C=2C=CC(C)=CC=2)=C1O AQVQBKUTLFBTFJ-UHFFFAOYSA-N 0.000 description 1
- QCVSDCHNBNFJDQ-UHFFFAOYSA-N 1-(4-chloro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1O QCVSDCHNBNFJDQ-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 210000001361 achilles tendon Anatomy 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001670 myorelaxant effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av terapeutisk aktive CU - 2-hydroksyfenyl) metylen-amino^]-fenyl-alkankarboksylsyrederivater med formel (I) The present invention relates to a method for the production of therapeutically active CU - 2-hydroxyphenyl) methylene-amino^]-phenyl-alkanecarboxylic acid derivatives of formula (I)
i in
hvori in which
og R- representerer hver uavhengig av hverandre et hydrogenatom, et halogenatom eller (C1_4)alkyl, and R- each independently represents a hydrogen atom, a halogen atom or (C1-4)alkyl,
R, representerer (C^_g)alkyl eller fenyl som kan bære et halogenatom eller (C^_^)alkyl, R, represents (C^_g)alkyl or phenyl which may bear a halogen atom or (C^_^)alkyl,
R^representerer et hydrogenatom eller halogenatom eller (C1_4alkyl, R^ represents a hydrogen atom or halogen atom or (C1-4 alkyl,
R,, representerer hydroksy, O-alkalimetall eller O-jordalkalimetall, (C^_^)alkoksy eller amino, og R,, represents hydroxy, O-alkali metal or O-alkaline earth metal, (C^_^)alkyl or amino, and
n og m representerer hver et helt tall 0,1 eller 2, og det karakteristiske ved oppfinnelsen er at en forbindelse med formel (II) n and m each represent an integer 0, 1 or 2, and the characteristic of the invention is that a compound of formula (II)
hvori in which
R^, R2 og R^har den ovennevnte betydning, omsettes medR^, R2 and R^ have the above meaning, are converted to
en forbindelse med formel (III)a compound of formula (III)
De ved oppfinnelsen fremstillbare forbindelser kan foreligge i form av racemater eller optiske isomerer. The compounds that can be prepared by the invention can exist in the form of racemates or optical isomers.
Skjematisk fremstilling reaksjonen ved følgende reaksjons-skjema Schematic presentation of the reaction in the following reaction scheme
I IN
I de ovenstående strukturformler er definisjonene for forbindelsene (II) og (III)' som tidligere anført. In the above structural formulas, the definitions for the compounds (II) and (III)' are as previously stated.
Reaksjonen mellom forbindelsen (II) og (III) gjennomføres i et løsningsmiddel som metanol, ved tilbakeløpstemperaturen for løsningsmidlet, i nærvær av et alkalimetallalkoholat. The reaction between the compound (II) and (III) is carried out in a solvent such as methanol, at the reflux temperature of the solvent, in the presence of an alkali metal alcoholate.
Forbindelsene (II) er beskrevet i litteraturen, eller beskrevet i franske patentskrifter 75 24065, 81 21559 og 82 19981. The compounds (II) are described in the literature, or described in French patent documents 75 24065, 81 21559 and 82 19981.
Forbindelsene (III) er beskrevet i litteraturen.The compounds (III) are described in the literature.
Fra syrene (I) kan tilsvarende amider (I) fremstilles hvoriFrom the acids (I) corresponding amides (I) can be prepared in which
Ri- erNH2, estere (I) hvori R5er (C1_4) alkoksy ogRi- is NH 2 , esters (I) in which R 5 is (C 1_4 ) alkoxy and
saltene (I) hvori R5er O-alkalimetall eller O-jordalkalimetall, ved hjelp av klassiske metoder. the salts (I) in which R5 is O-alkali metal or O-alkaline earth metal, using classical methods.
De etterfølgende eksempler illustrerer fremstillingen av forbindelsene og analyser og spektra IR og NMR bekrefter struk-turen av forbindelsene. The following examples illustrate the preparation of the compounds and analyzes and IR and NMR spectra confirm the structure of the compounds.
Eksempel 1 Example 1
4- £["( 5-klor-2-hydroksy-f enyl) me ty Ime tyl enj aminoj-3- ( 4-klor-fenyl)-butansyre. 4-£[(5-Chloro-2-hydroxy-phenyl)methyl-methyl-aminoj-3-(4-chloro-phenyl)-butanoic acid.
Man inndamper til tørrhet under redusert trykk en blanding av A mixture of is evaporated to dryness under reduced pressure
10 g (0,0586 mol) 4-klor-2-hydroksy-acetofenon, 12,5 g (0,0585 10 g (0.0586 mol) 4-chloro-2-hydroxy-acetophenone, 12.5 g (0.0585
mol) 4-amino-3-( 4-klor-f enyl) -butan-syre og 3,2 g (0,0592 mol) natriummetylat i 600 ml"metanol. mol) of 4-amino-3-(4-chloro-phenyl)-butanoic acid and 3.2 g (0.0592 mol) of sodium methylate in 600 ml of methanol.
Det avkjøles, resten oppløses i 1 liter vann og deretter sur-gjøres til pH 4 med sitronsyre. It is cooled, the residue is dissolved in 1 liter of water and then acidified to pH 4 with citric acid.
Produktet utfelles og man omrører i kort tid hvoretter man filtrerer på glassfilter, avsuger på filteret og produktet vaskes flere ganger med vann. Man avsuger på filteret og tør-ker i desikator i nærvær av P2O5" The product is precipitated and stirred for a short time, after which it is filtered on a glass filter, suction is applied to the filter and the product is washed several times with water. Suction is applied to the filter and dried in a desiccator in the presence of P2O5"
Produktet oppløses varmt i 1 liter CH2Cl2og 400 ml MeOH, blandingen behandles med aktivt karbon, filtreres gjennom papir, inndampes til 200 ml. Det utfelte produkt filtreres, avsuges på filter og vaskes flere ganger med eter. Produktet oppløses på nytt i 700 ml CH2Cl2og 400 ml MeOH (varm oppløsning). The product is dissolved hot in 1 liter of CH2Cl2 and 400 ml of MeOH, the mixture is treated with active carbon, filtered through paper, evaporated to 200 ml. The precipitated product is filtered, filtered off with suction and washed several times with ether. The product is redissolved in 700 ml CH2Cl2 and 400 ml MeOH (hot solution).
Det inndampes til å omtrent 150 ml. Produktet utfelles og filtreres, avsuges på filter og vaskes to ganger med 30 ml eter. Man avsuger på filter og tørker i desikator ved 80°C It is evaporated to approximately 150 ml. The product is precipitated and filtered, filtered off with suction and washed twice with 30 ml of ether. It is filtered off with suction and dried in a desiccator at 80°C
i nærvær av P^ 0^-in the presence of P^ 0^-
Den oppnådde forbindelse smelter ved 220-221°C.The obtained compound melts at 220-221°C.
Eksempel 2Example 2
4- f[( 5-klor-2-hydroksy-3-propyl-f enyl) ( 4-metyl-f enyl) rnetyl-enl aminoJ-3-(4-klor-fenyl)-butansyre. 4-[(5-chloro-2-hydroxy-3-propyl-phenyl)(4-methyl-phenyl)-methyl-enylamino]-3-(4-chloro-phenyl)-butanoic acid.
En blanding av 5 g (0,0173 mol) (5-klor-2-hydroksy-3-n-propyl-fenyl)(4-metyl-fenyl)metanon, 3,69 g (0,0173 mol) 4-amino-3-(4-klor-fenyl)-butansyre, 1 g (0,0185 mol) natriummetylat og 600 ml metanol inndampes til tørrhet under redusert trykk. A mixture of 5 g (0.0173 mol) (5-chloro-2-hydroxy-3-n-propyl-phenyl)(4-methyl-phenyl)methanone, 3.69 g (0.0173 mol) 4-amino -3-(4-chloro-phenyl)-butanoic acid, 1 g (0.0185 mol) of sodium methylate and 600 ml of methanol are evaporated to dryness under reduced pressure.
Blandingen oppløst i 500 ml metanol inndampes 6 ganger, resten oppløses i 1,2 1 vann og 0,200 1 CH2Cl2og deretter sur-gjøres til pH 4 med si.tronsyre. Man ekstraherer deretter med 3 ganger 500 ml CH2Cl2, den organiske fase vaskes med vann, avsettes, tørkes over MgSO^filreres og inndampes til tørrhet. Det utfelte produkt overføres på glassfilter med 100 ml petroleter og avsuges på filter. Produktet oppløses i 300 ml eter og inndampes til 100 ml. Produktet krystalliseres, filtreres, avsuges på filter og tørkes i desikator. Den oppnådde forbindelse smelter ved 195-196°C. The mixture dissolved in 500 ml methanol is evaporated 6 times, the residue is dissolved in 1.2 1 water and 0.200 1 CH2Cl2 and then acidified to pH 4 with citric acid. It is then extracted with 3 times 500 ml of CH2Cl2, the organic phase is washed with water, deposited, dried over MgSO4, filtered and evaporated to dryness. The precipitated product is transferred onto a glass filter with 100 ml of petroleum ether and filtered off with suction. The product is dissolved in 300 ml of ether and evaporated to 100 ml. The product is crystallized, filtered, filtered and dried in a desiccator. The obtained compound melts at 195-196°C.
Forbindelsene ble underkastet farmakologiske forsøk som viser deres aktivitet på det sentrale nervesystem. The compounds were subjected to pharmacological tests showing their activity on the central nervous system.
Den akutte giftighet av forbindelsene ble bestemt i mus ved oral tilførsel. Letal dose 50 er må mer enn 1000 mg/kg. The acute toxicity of the compounds was determined in mice by oral administration. Lethal dose 50 is must more than 1000 mg/kg.
Aktiviteten av forbindelsene på fleksionrefleksen ble studert i hannrotter Spraque-Dawley som var spinalbedøvet (Charles River, Frankrike) og som veide 200 til 240 g. 24 timer før testen ble rottene bedøvet med klorahydrat (400 mg/kg i.p.) og deres ryggmarg ble avkuttet i høyde med 6. - 8. toraks-virvel. The activity of the compounds on the flexion reflex was studied in spinally anesthetized male Spraque-Dawley rats (Charles River, France) weighing 200 to 240 g. 24 h before the test, the rats were anesthetized with chloral hydrate (400 mg/kg i.p.) and their spinal cords were severed at the height of the 6th - 8th thoracic vertebra.
For testen ble de spinalbedøvede rotter festet på et lite bord idet den venstre pote hvilte på en bærer.Achilles senen i For the test, the spinally anesthetized rats were fixed on a small table with the left paw resting on a support. The Achilles tendon in
denne pote er forbundet med en tråd (under 5 g strekk) til en strekkmåler som er knyttet til en skriveinnretning. this paw is connected by a wire (under 5 g stretch) to a strain gauge which is connected to a writing device.
En elektrode av rustfritt stål innføres subkutant i fothvelv-ingen. Refleksen frembringes med rekker av elektriske stimu-lasjoner med intensitet 7 mA med varighet med 200 ms, med fre-kvens 50 Hz hver 5 sekunder, i ett minutt ved hjelp av en elektrisk stimulator GRASS S-48. A stainless steel electrode is inserted subcutaneously into the arch of the foot. The reflex is produced with series of electrical stimulations with an intensity of 7 mA with a duration of 200 ms, with a frequency of 50 Hz every 5 seconds, for one minute using an electrical stimulator GRASS S-48.
Produktene som studeres injiseres intravenøst i form av en suspensjon fremstilt i fysiologisk serum tilsatt 0, 1% "Tween 80". ED 50, tilsvarende den dose som nedsetter reflekskraften med 50% i forhold til kontrollperioden, varierer fra 1 til 10 mg/kg i.v. The products under study are injected intravenously in the form of a suspension prepared in physiological serum to which 0.1% "Tween 80" has been added. ED 50, corresponding to the dose which reduces the reflex power by 50% in relation to the control period, varies from 1 to 10 mg/kg i.v.
Den myorelakserende og sedative virkning ble likeledes bedømt ved testen med trekktråden. Ved denne test blir en kontroll-rotte eller kontroll-mus opphengt i en tråd i forlabbene, tilbakeført til minst en av baklabbene på tråden i minst 10 sekunder. The myorelaxant and sedative effect was also assessed by the pulling wire test. In this test, a control rat or control mouse is suspended by a wire in the front paws, returned to at least one of the hind paws on the wire for at least 10 seconds.
Hvis behandlingen med en forbindelse påvirker dyrets evne til å holde baklabbene på tråden i mindre enn 10 sekunder betrak-tes virkningen som myorelakserende-sedativ. If the treatment with a compound affects the animal's ability to keep its hind paws on the wire for less than 10 seconds, the effect is considered to be myorelaxant-sedative.
Til grupper på 6 rotter injiseres intravenøst variable doser av forbindelser fremstilt i samsvar med oppfinnelsen, i suspensjon i "Tween 80" (0,1%) og man noterer deres myorelakserende virkning hver 10 minutter i 2 timer. Den prosentvise del av dyrene som ikke kan klatre beregnes for hver dose og hver tidsperiode. Groups of 6 rats are injected intravenously with variable doses of compounds prepared in accordance with the invention, in suspension in "Tween 80" (0.1%) and their muscle relaxant effect is noted every 10 minutes for 2 hours. The percentage of animals unable to climb is calculated for each dose and each time period.
For forbindelser fremstilt i samsvar med oppfinnelsen er ED 50 (den dose som hindrer 50% av dyrene å klatre på tråden), over 10 mg/kg som viser at forbindelsene fremstilt i samsvar med oppfinnelsen ikke har sedativ-rnyorelakserende virkning. For compounds produced in accordance with the invention, the ED 50 (the dose that prevents 50% of the animals from climbing the wire) is over 10 mg/kg, which shows that the compounds produced in accordance with the invention do not have a sedative-rnyorelaxant effect.
Forbindelsene fremstilt i henhold til oppfinnelsén kan anven-des for behandling av spastiske tilstander og bevegelsesprob-lemer. The compounds produced according to the invention can be used for the treatment of spastic conditions and movement problems.
Forbindelsene fremstilt i samsvar med oppfinnelsen kan tilfør-es i vanlige former passende for oral eller parenteral tilfør-sel og daglig dose kan være fra 10 til 200 mg. The compounds produced in accordance with the invention can be administered in usual forms suitable for oral or parenteral administration and the daily dose can be from 10 to 200 mg.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8403686A FR2560871B1 (en) | 1984-03-09 | 1984-03-09 | O - ((HYDROXY-2 PHENYL) METHYLENE-AMINO) -PHENYL-ALKANECARBOXYLIC ACID DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Publications (1)
Publication Number | Publication Date |
---|---|
NO850920L true NO850920L (en) | 1985-09-10 |
Family
ID=9301886
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO850920A NO850920L (en) | 1984-03-09 | 1985-03-08 | PROCEDURE FOR THE PREPARATION OF PHENYL-ALKAN CARBOXYLIC ACID DERIVATIVES |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0160582A1 (en) |
JP (1) | JPS60204751A (en) |
AU (1) | AU3966385A (en) |
DK (1) | DK107385A (en) |
ES (1) | ES541079A0 (en) |
FI (1) | FI850923L (en) |
FR (1) | FR2560871B1 (en) |
GR (1) | GR850593B (en) |
HU (1) | HUT37391A (en) |
IL (1) | IL74513A0 (en) |
NO (1) | NO850920L (en) |
PT (1) | PT80082B (en) |
ZA (1) | ZA851772B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
-
1984
- 1984-03-09 FR FR8403686A patent/FR2560871B1/en not_active Expired
-
1985
- 1985-02-26 EP EP85400352A patent/EP0160582A1/en not_active Withdrawn
- 1985-03-06 IL IL74513A patent/IL74513A0/en unknown
- 1985-03-08 AU AU39663/85A patent/AU3966385A/en not_active Abandoned
- 1985-03-08 JP JP60047318A patent/JPS60204751A/en active Pending
- 1985-03-08 HU HU85876A patent/HUT37391A/en unknown
- 1985-03-08 NO NO850920A patent/NO850920L/en unknown
- 1985-03-08 ZA ZA851772A patent/ZA851772B/en unknown
- 1985-03-08 PT PT80082A patent/PT80082B/en unknown
- 1985-03-08 GR GR850593A patent/GR850593B/el unknown
- 1985-03-08 FI FI850923A patent/FI850923L/en not_active Application Discontinuation
- 1985-03-08 ES ES541079A patent/ES541079A0/en active Granted
- 1985-03-08 DK DK107385A patent/DK107385A/en not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
FR2560871B1 (en) | 1986-10-10 |
PT80082B (en) | 1987-02-23 |
EP0160582A1 (en) | 1985-11-06 |
JPS60204751A (en) | 1985-10-16 |
FI850923A0 (en) | 1985-03-08 |
DK107385D0 (en) | 1985-03-08 |
IL74513A0 (en) | 1985-06-30 |
FI850923L (en) | 1985-09-10 |
AU3966385A (en) | 1985-09-12 |
HUT37391A (en) | 1985-12-28 |
GR850593B (en) | 1985-07-08 |
ES8602620A1 (en) | 1985-12-01 |
ZA851772B (en) | 1985-10-30 |
PT80082A (en) | 1985-04-01 |
DK107385A (en) | 1985-09-10 |
FR2560871A1 (en) | 1985-09-13 |
ES541079A0 (en) | 1985-12-01 |
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