NL8401189A - HYDROXYLATED DIPHENYLAZOMETHINE COMPOUNDS, THEIR PREPARATION AND THE THERAPEUTIC USE. - Google Patents
HYDROXYLATED DIPHENYLAZOMETHINE COMPOUNDS, THEIR PREPARATION AND THE THERAPEUTIC USE. Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
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- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
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Description
Λ + -1- 23832/Vk/mvlΛ + -1- 23832 / Vk / mvl
Korte aanduiding: Gehydroxyleerde difenylazomethineverbindingen, de bereiding hiervan en de therapeutische toepassing.Short designation: Hydroxylated diphenylazomethine compounds, their preparation and therapeutic use.
De onderhavige uitvinding heeft betrekking op gehydroxyleerde 5 difenylazomethineverbindingen, op de bereiding hiervan en de therapeutische toepassing.The present invention relates to hydroxylated diphenylazomethine compounds, their preparation and therapeutic use.
De verbindingen volgens de uitvinding komen overeen met formule 1, aangegeven op het formuleblad, waarbij n een geheel getal is van 1 tot 4, X^, en X^ elk onafhankelijk van elkaar een waterstofatoom, 10 een halogeenatoom, methoxyradikaal of een rechte of vertakte alkyl- radikaal met 1-4 koolstofatomen voorstellen, R het radikaal NH^, OH of OM is (waarbij M een alkalimetaal of aardalkalimetaal is) en Z een radikaal COOH, CGOalkyl, C0NH2, CONH alkyl, C0N(alkyl)2, CH20H, CHgOalkyl, Oalkyl, N02, NH2, NHalkyl of N(alkylis, waarbij de alkyl-15 groepen 1 tot 4 koolstofatomen hebben. De verbindingen die de voorkeur verdienen volgens de uitvinding zijn verbindingen overeenkomend met formule 3, vermeld op het formuleblad, waarbij de radikalen dezelfde betekenissen hebben als boven is aangegeven, meer in het bijzonder die verbindingen waarbij n gelijk is aan 2 of 3, X^ een halogeenatoom is 20 of de methylradikaal, X2 een halogeenatoom is of methylradikaal, R NH2, OH of ONa is en Z een groep CH20CH3, 0CH3, N(CH3)2 of NH2 is.The compounds of the invention correspond to formula 1, indicated on the formula sheet, where n is an integer from 1 to 4, X ^, and X ^ each independently a hydrogen atom, 10 a halogen atom, methoxy radical or a straight or branched alkyl radical of 1-4 carbon atoms, R is the radical NH ^, OH or OM (where M is an alkali or alkaline earth metal) and Z is a radical COOH, CGOalkyl, C0NH2, CONH alkyl, C0N (alkyl) 2, CH20H, CH8Oalkyl, Oalkyl, NO2, NH2, NHalkyl or N (alkylis, the alkyl groups having 1 to 4 carbon atoms. The preferred compounds of the invention are compounds corresponding to formula 3, listed on the formula sheet, wherein the radicals have the same meanings as indicated above, more particularly those compounds where n is 2 or 3, X ^ is a halogen atom or the methyl radical, X2 is a halogen atom or methyl radical, R is NH2, OH or ONa and Z is a group CH2OC H3, 0CH3, N (CH3) 2 or NH2.
Volgens de uitvinding kan men de verbindingen bereiden door als volgt te werk te gaan: men brengt een benzofenon met formule 2, vermeld op het formuleblad, in reactie met een verbinding met formule 25 H2N-(CH2)n-C0R, eventueel in de vorm van het zout, zoals het hydrochloride, bij een temperatuur van 20-80 °C in een oplosmiddel zoals methanol of ethanol.According to the invention, the compounds can be prepared by proceeding as follows: a benzophenone of formula 2, stated on the formula sheet, is reacted with a compound of formula 25 H2N- (CH2) n-COR, optionally in the form of the salt, such as the hydrochloride, at a temperature of 20-80 ° C in a solvent such as methanol or ethanol.
De benzofenonverbindingen waarvan wordt uitgegaan met formule 2, zijn nieuwe stoffen en worden bereid volgens werkwijzen die in de 30 literatuur zijn aangegeven.The benzophenone compounds starting from formula 2 are new substances and are prepared according to methods indicated in the literature.
De uitvinding wordt nader toegelicht aan de hand van de volgende voorbeelden. De uitgevoerde analyses en de IR- en NMR-spektra bevestigden de struktuur van de verbindingen.The invention is further illustrated by the following examples. The analyzes performed and the IR and NMR spectra confirmed the structure of the compounds.
Voorbeeld IExample I
35 4-{[(4-chloorfenyl) (5-chloor 2-hydroxy 3-methoxyfényl)- methyleen]amino}butaanamide.4 - {[(4-chlorophenyl) (5-chloro-2-hydroxy-3-methoxyphenyl) -methylene] amino} butanamide.
Aan een suspensie van 0,37 g (2,69 mmol) gabamidehydro- 8401189 r t -2- 23832/Vk/mvl 3 3 chloride in 20 cm absolute ethanol werd 10, A cm toegevoegd van een ethanoloplossing van 0,27N natriumethylaat (2,8 mmol) en 0,8 g (2,69 mmol) V-5-dichloor 2-hydroxy 3-methoxybenzofenon.To a suspension of 0.37 g (2.69 mmol) of gabamide hydro- 8401189 rt -2-23832 / Vk / mvl 3 3 chloride in 20 cm absolute ethanol was added 10 A cm of an ethanol solution of 0.27N sodium ethylate (2 , 8 mmol) and 0.8 g (2.69 mmol) of V-5-dichloro 2-hydroxy 3-methoxybenzophenone.
Men verwarmde het mengsel tot koken onder terugvloeikoeling, 3 3 5 waarna 20 cm alcohol werd afgedestilleerd. Men voegde 200 cm absolute alcohol toe waarna men hetzelfde volume afdestilleerde.The mixture was heated to reflux, then 3 ml of alcohol was distilled off. 200 ml of absolute alcohol were added and the same volume was distilled off.
33
Na indampen tot droog werd 20 cm water aan het residu toegevoegd en geëxtraheerd met methyleenchloride. Het extract gaf na wassen met water en drogen over MgSO^ na indampen een residu dat werd 10 herkristalliseerd in absolute ethanol. Na wassen met petroleumether en drogen bij 100 °C gedurende 8 uren onder verlaagde druk, verkreeg men het produkt dat smolt bij 209-210 °C.After evaporation to dryness, 20 cm of water was added to the residue and extracted with methylene chloride. The extract, after washing with water and drying over MgSO4, after evaporation, gave a residue which was recrystallized in absolute ethanol. After washing with petroleum ether and drying at 100 ° C for 8 hours under reduced pressure, the product was melted at 209-210 ° C.
Voorbeeld IIExample II
4-{[(4-chloorfenyl) (5-chloor 2-hydroxy 3-methoxy-methylfenyl) 15 methyleen]amino}butaancarbonzuur en het natriumzout hiervan.4 - {[(4-chlorophenyl) (5-chloro 2-hydroxy 3-methoxy-methylphenyl) 15 methylene] amino} butanecarboxylic acid and its sodium salt.
1. In een kolf van 1 1 bracht men 5 g (1,61x10 mol) (4-chloorfenyl) (5-chloor 2-hydroxy 3-methoxymethylfenyl)methanon, —2 —2 300 ml methanol, 3,1 g (3x10 mol) γ-aminoboterzuur en 1,6 g (3x10 mol) natriummethylaat.1. 5 g (1.61x10 mol) (4-chlorophenyl) (5-chloro-2-hydroxy-3-methoxymethylphenyl) methanone, -2-2 300 ml methanol, 3.1 g (3x10) were placed in a 1 l flask. mol) γ-aminobutyric acid and 1.6 g (3x10 mol) of sodium methylate.
20 Men bracht het reactiemengsel op een temperatuur waarbij koken onder terugvloeikoeling plaatshad gedurende 8 uren, men dampte het in tot droog, nam het residu op in 1,8 1 gedestilleerd water, aangezuurd tot een pH van 4,5 door toevoeging van citroenzuur. Men extraheerde het extract twee keer met 400 ml dichloormethaan, voegde de organische 25 fasen samen, waste deze met 500 ml water, droogde ze over Na^SO^, waarna het mengsel werd afgefiltreerd en ingedampt tot droog.The reaction mixture was brought to a temperature at reflux for 8 hours, evaporated to dryness, the residue was taken up in 1.8 L of distilled water, acidified to a pH of 4.5 by addition of citric acid. The extract was extracted twice with 400 ml of dichloromethane, the organic phases were combined, washed with 500 ml of water, dried over Na 2 SO 4, then the mixture was filtered off and evaporated to dryness.
Het verkregen zuur werd herkristalliseerd in 25 ml methanol. Het smeltpunt bedroeg 104-105 °C.The resulting acid was recrystallized in 25 ml of methanol. Melting point was 104-105 ° C.
_2 2. In een kolf van 500 ml bracht men 4,7 g (1,19x10 mol) 30 van het eerder verkregen zuur, 100 ml methanol en 9,7 ml natriummethylaat in oplossing (1,22N). Men dampte het reactiemengsel in bij 60 °C, voegde 200 ml pentaan toe en roerde het mengsel gedurende 10 minuten.2. In a 500 ml flask, 4.7 g (1.19x10 mol) of the previously obtained acid, 100 ml of methanol and 9.7 ml of sodium methylate were placed in solution (1.22N). The reaction mixture was evaporated at 60 ° C, 200 ml of pentane was added and the mixture was stirred for 10 minutes.
nn
Na filtratie, drogen aan de lucht en drogen in een exsiccator bij 1 8401189 °C in aanwezigheid van P„0C verkreeg men het natriumzout. Het smelt- c- o 35 punt bedroeg 136 °C.After filtration, air drying and drying in a desiccator at 18401189 ° C in the presence of P 2 OC, the sodium salt was obtained. The melting point was 136 ° C.
Voorbeeld IIIExample III
4-{[(4-chloorfenyl)(5-chloor 2-hydroxy 3-dimethylaminofenyl)-methyleen]amino}butaanamide.4 - {[(4-chlorophenyl) (5-chloro-2-hydroxy-3-dimethylaminophenyl) -methylene] amino} butanamide.
• I• I
* -3- 23832/Vk/mvl* -3- 23832 / Vk / mvl
In een kolf bracht men 2,35 g (0,017 mol) gabamidehydro-chloride, 500 ml ethanol, 17 ml van een molaire oplossing natrium-methylaat en 5,3 g (0,017 mol) (4-chloorfenyl)(5-chloor 2-hydroxy- 3-dimethylaminofenyl)methanon.2.35 g (0.017 mol) of gabamide hydrochloride, 500 ml of ethanol, 17 ml of a molar solution of sodium methylate and 5.3 g (0.017 mol) of (4-chlorophenyl) (5-chloro-2-) were placed in a flask hydroxy-3-dimethylaminophenyl) methanone.
5 Het reactiemengsel werd verwarmd tot terugvloeitemperatuur en ethanol werd afgedestilleerd.The reaction mixture was heated to reflux temperature and ethanol was distilled off.
Men verwarmde het mengsel tot droog, nam het residu op in water en chloroform, decanteerde de organische fase, droogde deze over magnesiumsulfaat en dampte het mengsel in.The mixture was heated to dryness, the residue was taken up in water and chloroform, the organic phase was decanted, dried over magnesium sulfate and the mixture was evaporated.
10 Het residu werd fijngewreven in pentaan, afgefiltreerd en herkristalliseerd in een mengsel van ethylacetaat/isopropylether.The residue was triturated in pentane, filtered and recrystallized from a mixture of ethyl acetate / isopropyl ether.
Het smeltpunt bedroeg 144,5-145 °C.The melting point was 144.5-145 ° C.
TABEL ATABLE A
verbinding met formule 1, vermeld op het formuleblad.compound of formula 1, stated on the formula sheet.
15 |-------- ding11*" n X1 X2 X3 Z R smeltpunt (°C) 1 3 5-C1 4-C1 H C00CH3 KH2 168-169 2 3 5-C1 4-C1 H C00CH3 OH 141-142 20 3 3 5-C1 4-C1 H C0NH2 NH2 143-144 4 3 5-Cl 4-C1 H C00H OH 235-236 5 3 5-Cl 4-C1 H CH2OCH3 NH2 107-108 6 3 5-Cl 4-C1 H CH20H NH2 158,5-159,5 7 3 5-Cl 4-C1 H CH20CH3 OH 104-105 8 3 5-Cl 4-C1 H CH20CH3 ONa 136' (ontleding) 9 3 5-Cl . 4-C1 H CONH ‘ OH 214-215 30 10 3 5-Cl 4-C1 H CONHC^ NH2 202-203 11 3 5-Cl 4-C1 H C0NHCH3 NH2 242-243 12' 3 5-Cl 4-C1 H 0CH3 OH 153-154 13 3 5-Cl 4-C1 H CONHC3H7 ONa 160-161 35 14 3 5-Cl 4—Cl H C0NHCH3 ONa > 250 (ontleding) 15 3 5-Cl 4-C1 H 0CH3 NH2 209-210 8401189 c, v -4- 23832/VK/mvl TABEL A (vervolg) ding1"" n X1 X2 X3 Z R smeltpunt (°C) 16 3 5-C1 4-C1 H N0o NH0 166-167 5 d d 17 3 ' 5-C1 4-Cl H N(CH3)2 0Na 153-158 18 3 5-C1 4-C1 H N(CH3)2 N&2 144,5-145 19 3 5-C1 4-C1 H N02 ONa 163-165 10 20 3 5-C1 4-C1 H NH2 ONa 257-259 21 3 5-C1 4-C1 H NH2 NH2 219-220 22 3 5-C1 4-C1 H CONHC^ OH .216-217 23 3 5-C1 4-C1 H CONHCH3 OH 218-219 15 24 3 5-C1 4-C1 Η N(CH3)2 OH 159-160 25 3 5-C1 4-C1 H . N02 OH 206-208 26 3 5-C1 4-C1 H 'NH2 OH 169-17015 | -------- thing11 * "n X1 X2 X3 ZR melting point (° C) 1 3 5-C1 4-C1 H C00CH3 KH2 168-169 2 3 5-C1 4-C1 H C00CH3 OH 141- 142 20 3 3 5-C1 4-C1 H C0NH2 NH2 143-144 4 3 5-Cl 4-C1 H C00H OH 235-236 5 3 5-Cl 4-C1 H CH2OCH3 NH2 107-108 6 3 5-Cl 4 -C1 H CH20H NH2 158.5-159.5 7 3 5-Cl 4-C1 H CH20CH3 OH 104-105 8 3 5-Cl 4-C1 H CH20CH3 ONa 136 '(decomposition) 9 3 5-Cl. 4- C1 H CONH 'OH 214-215 30 10 3 5-Cl 4-C1 H CONHC ^ NH2 202-203 11 3 5-Cl 4-C1 H C0NHCH3 NH2 242-243 12' 3 5-Cl 4-C1 H 0CH3 OH 153-154 13 3 5-Cl 4-C1 H CONHC3H7 ONa 160-161 35 14 3 5-Cl 4-Cl H C0NHCH3 ONa> 250 (decomposition) 15 3 5-Cl 4-C1 H 0CH3 NH2 209-210 8401189 c , v -4- 23832 / VK / mvl TABLE A (cont.) thing1 "" n X1 X2 X3 ZR melting point (° C) 16 3 5-C1 4-C1 H N0o NH0 166-167 5 dd 17 3 '5-C1 4-Cl HN (CH3) 2 0Na 153-158 18 3 5-C1 4-C1 HN (CH3) 2 N & 2 144.5-145 19 3 5-C1 4-C1 H N02 ONa 163-165 10 20 3 5- C1 4-C1 H NH2 ONa 257-259 21 3 5-C1 4-C1 H NH2 NH2 219-220 22 3 5-C1 4-C1 H CONHC ^ OH .216-217 23 3 5-C1 4-C1 H CONHCH3 OH 218-219 15 24 3 5-C 1 4-C1 Η N (CH3) 2 OH 159-160 25 3 5-C1 4-C1 H. NO2 OH 206-208 26 3 5-C1 4-C1 H 'NH2 OH 169-170
20 ™3EL I20 ™ 3EL I
Benzofenonverbindingen met formule 2.Benzophenone compounds of formula 2.
verbinding I ^ ζ ζ Z Sm®è^unt 1 5-C1 4-C1 H C02CH3 114-115 25 2 5-C1 4-C1 H C0NH2 205-206 3 5-C1 4-C1 H C02H 198-199 4 5-C1 4-C1 H CH2OCH3 95-97 5 5-C1 4-C1 H CH2OH 102-103 30 6 5-C1 4-C1 H CONHC3H7 103-104 7 5-C1 4-C1 H C0NHCH3 169-170 8 5-C1 4-C1 H OCH3 142,5-143 9 5-C1 4-C1 H NO 112-112,5 35 10 5-C1 4-C1 H N+(CH3)2A"H 164-166 11 5-C1 4-C1 H NH2 94,5-95 8401189 -5- 23832/Vk/mvlcompound I ^ ζ ζ Z Sm®è ^ unt 1 5-C1 4-C1 H C02CH3 114-115 25 2 5-C1 4-C1 H C0NH2 205-206 3 5-C1 4-C1 H C02H 198-199 4 5 -C1 4-C1 H CH2OCH3 95-97 5 5-C1 4-C1 H CH2OH 102-103 30 6 5-C1 4-C1 H CONHC3H7 103-104 7 5-C1 4-C1 H C0NHCH3 169-170 8 5- C1 4-C1 H OCH3 142.5-143 9 5-C1 4-C1 H NO 112-112.5 35 10 5-C1 4-C1 H N + (CH3) 2A "H 164-166 11 5-C1 4- C1 H NH2 94.5-95 8401189 -5- 23832 / Vk / mvl
De antidepressieve activiteit van de verbindingen is aangetoond door het antagonisme ten aanzien van "head-twitches" (scheuten door het hoofd) veroorzaakt door L-5-hydroxytryptofaan toegediend aan muizen.The antidepressant activity of the compounds has been demonstrated by the antagonism to "head twitches" caused by L-5-hydroxytryptophan administered to mice.
5 De muizen (mannelijke CD1, Charles River, Frankrijk; lichaamsgewicht 18-22 g) kregen de te onderzoeken verbindingen toegediend in toenemende doseringen, of het oplosmiddel, gelijktijdig met L-5-HTP bij een dosering van 250 mg/kg door subcutane toediening.The mice (male CD1, Charles River, France; body weight 18-22 g) were administered the test compounds in increasing doses, or the solvent, simultaneously with L-5-HTP at a dose of 250 mg / kg by subcutaneous administration .
45 Minuten na deze injectie van 5-HTP werd het aantal "head-twitches" 10 geteld bij elke muis gedurende een minuut.45 minutes after this injection of 5-HTP, the number of "head twitches" was counted in each mouse for one minute.
Voor elke behandeling werd het gemiddeld aantal "head-twitches" geteld, evenals de procentuele variatie berekend ten aanzien van de ter vergelijking dienende proef.For each treatment, the average number of "head twitches" was counted, as was the percentage variation calculated from the comparative test.
Door uit te gaan van de curve van de effectieve dosering, 15 bepaalde men de DA-50 waarde (50% actieve dosering of dosering die 50% van het gemiddeld aantal "head-twitches" vermindert), door middel van de grafische methode van Miller en Tainter (1944).Using the curve of the effective dose, the DA-50 value (50% active dose or dose that reduces 50% of the average number of "head twitches") was determined by Miller's graphical method and Tainter (1944).
De DA-50 waarde van de verbindingen volgens de uitvinding varieerde van 40 tot 60 mg/kg bij intraperitoneale toediening.The DA-50 value of the compounds of the invention ranged from 40 to 60 mg / kg when administered intraperitoneally.
20 De anticonvulsieve activiteit van de verbindingen is aan getoond door het antagonisme ten aanzien van de sterfte veroorzaakt door bicuculline bij muizen.The anticonvulsant activity of the compounds has been demonstrated by the antagonism to the mortality caused by bicuculline in mice.
Bicuculline is een relatief selectief blokkeringsmiddel van GABA-energische post synaptische receptoren en de convulsieve 25 invloed hiervan en de lethale werking worden geantagoniseerd door de verbindingen die het gehalte van cerebrale GABA verhogen of een GABA-mimetische activiteit hebben.Bicucullin is a relatively selective blocking agent of GABA energetic post synaptic receptors and its convulsive influence and lethal activity are antagonized by the compounds that increase the content of cerebral GABA or have GABA mimetic activity.
Men heeft de 50% actieve dosering (DA-50), welke dosering 50% van de dieren beschermt tegen de werking van 30 bicuculline, bepaald bij de te onderzoeken stoffen.The 50% active dose (DA-50), which dose protects 50% of the animals against the action of bicuculline, has been determined in the substances to be tested.
De DA-50 waarde van de verbindingen volgens de uitvinding varieerde van 10 tot 100 mg/kg bij intraperitoneale toediening.The DA-50 value of the compounds of the invention ranged from 10 to 100 mg / kg when administered intraperitoneally.
De verbindingen volgens de uitvinding zijn actief als antidepressieve en anticonvulsieve middelen en hebben zelfs anti-35 ulcere, anxxolytische, analgetische en anti-inflammatoire eigenschappen. Ze zijn geschikt als geneesmiddel voor mensen en dieren, door de behandeling van diverse ziekten in het centrale zenuwstelsel, bijvoor- 8401189 J Λ.The compounds of the invention are active as antidepressant and anticonvulsant agents and even have anti-ulcer, anxolytic, analgesic and anti-inflammatory properties. They are suitable as medicines for humans and animals by treating various diseases in the central nervous system, eg 8401189 J Λ.
-6- 23832/Vk/mvl beeld voor de behandeling van depressies, psychosen, bepaalde neurologische ziekten zoals epilepsie, spasticiteit en diskynesie.-6- 23832 / Vk / mvl image for the treatment of depression, psychoses, certain neurological diseases such as epilepsy, spasticity and discynesia.
Zodoende heeft de uitvinding betrekking op alle farmaceutische samenstellingen die de verbindingen met formule 1 als 5 actieve stof bevatten, samen met de hiertoe geschikte hulpstoffen • voor de toediening, met name voor orale toediening (tabletten, dragees, gelules, capsules, cachets, drinkbare oplossingen of suspensies) of parenterale toediening.Thus, the invention relates to all pharmaceutical compositions containing the compounds of formula 1 as active substance, together with the suitable auxiliaries for administration • in particular for oral administration (tablets, dragees, capsules, capsules, cachets, drinkable solutions or suspensions) or parenteral administration.
De dagelijkse dosering kan variëren van 100 tot 3000 mg.The daily dosage can range from 100 to 3000 mg.
XX
Λ 84011898401189
Claims (6)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8306082A FR2544309B1 (en) | 1983-04-14 | 1983-04-14 | HYDROXYLATED DIPHENYLAZOMETHINES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
| FR8306082 | 1983-04-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NL8401189A true NL8401189A (en) | 1984-11-01 |
Family
ID=9287836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8401189A NL8401189A (en) | 1983-04-14 | 1984-04-13 | HYDROXYLATED DIPHENYLAZOMETHINE COMPOUNDS, THEIR PREPARATION AND THE THERAPEUTIC USE. |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS59199665A (en) |
| AU (1) | AU2682584A (en) |
| BE (1) | BE899423A (en) |
| DE (1) | DE3414051A1 (en) |
| DK (1) | DK191684A (en) |
| ES (1) | ES531605A0 (en) |
| FI (1) | FI841484A (en) |
| FR (1) | FR2544309B1 (en) |
| GB (1) | GB2138000A (en) |
| GR (1) | GR79857B (en) |
| HU (1) | HUT34153A (en) |
| IL (1) | IL71540A0 (en) |
| IT (1) | IT1176042B (en) |
| LU (1) | LU85311A1 (en) |
| NL (1) | NL8401189A (en) |
| NO (1) | NO841486L (en) |
| NZ (1) | NZ207840A (en) |
| PT (1) | PT78429B (en) |
| SE (1) | SE8402082L (en) |
| ZA (1) | ZA842798B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1212000B (en) * | 1987-12-24 | 1989-11-08 | Sigma Tau Ind Farmaceuti | PHENYLBENZYLIDEN-DERIVATIVES OF ACID 3) AMINOPROPANSULPHONIC WITH ANTI-CONVULSIVE ACTIVITY AND THEIR PHARMACEUTICAL COMPOSITIONS FOR THE THERAPEUTIC TREATMENT OF EPILEPSY |
| FR2788691B1 (en) | 1999-01-21 | 2002-06-14 | Oreal | COMPOSITIONS FOR OXIDATION DYEING OF KERATINIC FIBERS COMPRISING A CATIONIC COUPLER, NOVEL CATIONIC COUPLERS, THEIR USE FOR OXIDATION DYEING, AND DYEING METHODS |
| FR2788768B1 (en) | 1999-01-21 | 2001-02-16 | Oreal | NEW CATIONIC 2-ACYLAMINOPHENOLS, THEIR USE AS COUPLER FOR OXIDATION DYEING, COMPOSITIONS COMPRISING THEM, AND DYEING METHODS |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2319338A1 (en) * | 1975-08-01 | 1977-02-25 | Synthelabo | NEW A-PHENYL BENZYLIDENIC DERIVATIVES OF AMINO ACIDS, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM |
| FR2430936A1 (en) * | 1978-07-13 | 1980-02-08 | Synthelabo | Alpha-phenyl 2-hydroxy-benzylidene amino-alkanoic acid derivs. - and novel di:phenyl-ketone intermediates, useful as anticonvulsants for treating epilepsy |
| FR2516509B1 (en) * | 1981-11-18 | 1985-07-26 | Synthelabo | BENZYLIDENIC DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
-
1983
- 1983-04-14 FR FR8306082A patent/FR2544309B1/en not_active Expired
-
1984
- 1984-04-13 FI FI841484A patent/FI841484A/en not_active Application Discontinuation
- 1984-04-13 GR GR74421A patent/GR79857B/el unknown
- 1984-04-13 ES ES531605A patent/ES531605A0/en active Granted
- 1984-04-13 NO NO841486A patent/NO841486L/en unknown
- 1984-04-13 NL NL8401189A patent/NL8401189A/en not_active Application Discontinuation
- 1984-04-13 BE BE0/212765A patent/BE899423A/en not_active IP Right Cessation
- 1984-04-13 GB GB08409686A patent/GB2138000A/en not_active Withdrawn
- 1984-04-13 DE DE19843414051 patent/DE3414051A1/en not_active Withdrawn
- 1984-04-13 AU AU26825/84A patent/AU2682584A/en not_active Abandoned
- 1984-04-13 SE SE8402082A patent/SE8402082L/en not_active Application Discontinuation
- 1984-04-13 ZA ZA842798A patent/ZA842798B/en unknown
- 1984-04-13 HU HU841456A patent/HUT34153A/en unknown
- 1984-04-13 JP JP59075679A patent/JPS59199665A/en active Pending
- 1984-04-13 PT PT78429A patent/PT78429B/en unknown
- 1984-04-13 DK DK191684A patent/DK191684A/en not_active Application Discontinuation
- 1984-04-13 IL IL71540A patent/IL71540A0/en unknown
- 1984-04-13 IT IT20528/84A patent/IT1176042B/en active
- 1984-04-13 LU LU85311A patent/LU85311A1/en unknown
- 1984-04-13 NZ NZ207840A patent/NZ207840A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GR79857B (en) | 1984-10-31 |
| PT78429A (en) | 1984-05-01 |
| PT78429B (en) | 1986-08-22 |
| ES8502677A1 (en) | 1985-01-16 |
| DE3414051A1 (en) | 1984-10-18 |
| FR2544309B1 (en) | 1986-01-10 |
| ZA842798B (en) | 1984-11-28 |
| AU2682584A (en) | 1984-10-18 |
| DK191684D0 (en) | 1984-04-13 |
| GB2138000A (en) | 1984-10-17 |
| FR2544309A1 (en) | 1984-10-19 |
| JPS59199665A (en) | 1984-11-12 |
| ES531605A0 (en) | 1985-01-16 |
| SE8402082D0 (en) | 1984-04-13 |
| IT8420528A0 (en) | 1984-04-13 |
| NZ207840A (en) | 1986-02-21 |
| HUT34153A (en) | 1985-02-28 |
| FI841484A0 (en) | 1984-04-13 |
| NO841486L (en) | 1984-10-15 |
| IT1176042B (en) | 1987-08-12 |
| IL71540A0 (en) | 1984-07-31 |
| DK191684A (en) | 1984-10-15 |
| BE899423A (en) | 1984-10-15 |
| FI841484A (en) | 1984-10-15 |
| LU85311A1 (en) | 1985-11-27 |
| SE8402082L (en) | 1984-10-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A85 | Still pending on 85-01-01 | ||
| BV | The patent application has lapsed |