CH561183A5 - - Google Patents
Info
- Publication number
- CH561183A5 CH561183A5 CH30674A CH30674A CH561183A5 CH 561183 A5 CH561183 A5 CH 561183A5 CH 30674 A CH30674 A CH 30674A CH 30674 A CH30674 A CH 30674A CH 561183 A5 CH561183 A5 CH 561183A5
- Authority
- CH
- Switzerland
- Prior art keywords
- product
- alpha
- pyridoxal
- ketoglutarate
- ethanol
- Prior art date
Links
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
- C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/347—Saturated compounds containing more than one carboxyl group containing keto groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
La présente invention a pour objet un procédé de préparation de l'alpha-cétoglutarate de pyridoxal.
La formule de l'alpha-cétoglutarate de pyridoxal est la sui
EMI1.1
Le procédé selon l'invention est caractérisé en ce qu'on fait réagir l'acide alpha-cétoglutarique avec la pyridoxal en solution dans un solvant, organique ou inorganique.
Le sel peut être utilisé comme tel, ou être dissous dans de l'eau et être neutralisé avec des bases organiques ou inorganiques, les sels doubles étant ensuite précipités.
Ci-après est décrit un exemple de réalisation de l'invention:
146.10 g (1 mol) d'acide alpha-cétoglutarique sont dissous dans 300 ml d'éthanol chaud et sont ajoutés à une solution, également chaude. de 167,10 g (I mol) de pyridoxal dans 550 ml d'éthanol. Le mélange est porté à ébullition et, si nécessaire, filtré à cette température, pour éliminer le solide qui pourrait être en suspension. La solution est gardée au réfrigérateur et on la filtre le lendemain. Les rendements varient entre 70% et 80%, bien que l'on puisse augmenter la précipitation par addition d'éther.
La purification du produit pour analyse est menée à bien par cristallisation dans de l'éthanol.
Analyse de l'alpha-cétoglutarate de pyridoxal:
pour C13H15NO8
Calculé: C 49.84 H 4,79 N 4,47
Trouvé: C 50,26 H 5,53 N 4,27
Le produit est un solide formé de cristaux de couleur blanche.
PF= 127-128 C (sans rectification). Il est soluble dans l'eau, les alcools à faible poids moléculaire (à chaud), et très peu dans les solvants à polarité faible ou nulle. Avec du chlorure ferrique, il donne une couleur rouge sang. Avec du sulfate de cuivre, il donne une couleur vert émeraude.
Bien que la réaction ait été menée à bien au sein de divers solvants. tant organiques qu'inorganiques, on a cité comme exemple celle qui a été effectuée dans l'éthanol, car ce solvant est l'un des meilleurs.
Le titulaire estime que le produit obtenu par cette méthode est nouveau et que, vu les applications spécifiques auxquelles il est destiné, il présente les avantages suivants: grande tolérance, puis
sante activité pharmacologique et solubilité facile dans l'eau.
Pharmacologie
La toxicité a été déterminée par injection intraveineuse du composé à des souris. La dose létale cinquante, calculée par la méthode de Litchfield et Wilcoxon, a donné le chiffre suivant: 18,6 mgisouris (930 mg/kg).
Ce chiffre montre une toxicité faible. Les animaux meurent en présentant des symptômes de coma acidoxique et la rapidité de l'injection est critique pour l'uniformité des résultats.
La toxicité chronique réalisée chez la souris, le rat et le lapin
pour une période de six mois montre une parfaite tolérance, meme à doses très élevées, du produit.
On a étudié l'activité anticonvulsivante face à la ss-éthyl-,B- méthyl glutarimide et on a constaté que le produit exerce une activité protectrice. Le résultat est significatif en analyse statistique.
Le produit agit aussi comme anticonvulsivant vis-à-vis de la thiosemicarbacide.
Les souris de vingt-cinq jours soumises pendant 60 jours à un traitement avec le produit ont pris du poids par rapport à des souris-témoins. Cette augmentation apparait sur la courbe pondérale à partir du 8' au 10' jour. La différence de poids entre les souris traitées par le produit et les souris-témoins est très significative.
Sur des animaux endormis au pentobarbital, le produit agit pour les réveiller, écourtant le temps effectif cinquante d'une manière significative. La méthode employée pour établir la comparaison est celle de J.T. Litchfield, modifiée. Si l'on enregistre la pression artérielle d'un chat anesthésié, on observe une légère élévation de la pression quand on administre le produit par voie endoveineuse.
Grâce à des tests chimiques, le produit a montré les indications thérapeutiques suivantes:
Altérations du caractère, du langage et de la conduite. Difficulté d'apprentissage, de captation et retards scolaires. Fatigue psychophysique, neurasténie, névrose, les produits agissant, de façon générale, pour augmenter le rendement intellectuel.
Troubles psychomoteurs (retards locomoteurs, etc.). Anorexie psychogène. Maladies convulsives. Prophylaxie préanesthésique et guérison après anesthésie. Intoxications diverses avec atteinte du système nerveux central. Etats d'obnubilation, de stupeur et comas à étiologie variée (métaboliques, toxiques, traumatiques, méningoencéphaliques et comas dus à des accidents vasculaires).
Etats de vertiges. Nausées et vomissements. Alcoolisme aigu et chronique. Hépatites et cirrhoses.
REVENDICATION I
Procédé de préparation de I'alpha-cétoglutarate de pyridoxal
EMI1.2
caractérisé en ce qu'on fait réagir l'acide alpha-cétoglutarique avec la pyridoxal en solution dans un solvant organique ou inorganique.
SOUS-REVENDICATIONS
1. Procédé conformément à la revendication I, caractérisé en ce qu'on laisse refroidir ou qu'on concentre la solution pour faciliter la cristallisation du produit obtenu.
2. Procédé conformément à la revendication I ou la sousrevendication 1, caractérisé en ce qu'on précipite le produit formé par l'addition d'un précipitant adéquat.
3. Procédé conformément à la revendication I ou la sousrevendication 1, caractérisé en ce que le solvant est l'éthanol.
REVENDICATION Il
L'alpha-cétoglutarate de pyridoxal obtenue par le procédé conformément à la revendication I.
**ATTENTION** fin du champ DESC peut contenir debut de CLMS **.
The subject of the present invention is a process for preparing pyridoxal alpha-ketoglutarate.
The formula of pyridoxal alpha-ketoglutarate is the following
EMI1.1
The process according to the invention is characterized in that alpha-ketoglutaric acid is reacted with pyridoxal in solution in a solvent, organic or inorganic.
The salt can be used as such, or it can be dissolved in water and neutralized with organic or inorganic bases, the double salts then being precipitated.
An embodiment of the invention is described below:
146.10 g (1 mol) of alpha-ketoglutaric acid are dissolved in 300 ml of hot ethanol and are added to a solution, also hot. of 167.10 g (I mol) of pyridoxal in 550 ml of ethanol. The mixture is brought to a boil and, if necessary, filtered at this temperature, to remove any solid which may be in suspension. The solution is kept in the refrigerator and filtered the next day. The yields vary between 70% and 80%, although the precipitation can be increased by adding ether.
Purification of the product for analysis is carried out by crystallization from ethanol.
Analysis of pyridoxal alpha-ketoglutarate:
for C13H15NO8
Calculated: C 49.84 H 4.79 N 4.47
Found: C 50.26 H 5.53 N 4.27
The product is a solid formed from white crystals.
PF = 127-128 C (without rectification). It is soluble in water, low molecular weight alcohols (hot), and very little in low or no polarity solvents. With ferric chloride it gives a blood red color. With copper sulphate, it gives an emerald green color.
Although the reaction was carried out in various solvents. both organic and inorganic, the example which was carried out in ethanol was cited, since this solvent is one of the best.
The holder considers that the product obtained by this method is new and that, given the specific applications for which it is intended, it has the following advantages: high tolerance, then
healthy pharmacological activity and easy solubility in water.
Pharmacology
Toxicity was determined by intravenous injection of the compound into mice. The lethal dose fifty, calculated by the method of Litchfield and Wilcoxon, gave the following figure: 18.6 mg mouse (930 mg / kg).
This figure shows low toxicity. Animals die with symptoms of acidoxic coma and the speed of injection is critical for consistency of results.
Chronic toxicity achieved in mice, rats and rabbits
for a period of six months shows perfect tolerance, even at very high doses, of the product.
The anticonvulsant activity against ss-ethyl-, B-methyl glutarimide was studied and it was found that the product exerts a protective activity. The result is significant in statistical analysis.
The product also acts as an anticonvulsant against thiosemicarbacid.
Twenty-five day old mice treated for 60 days with the product gained weight compared to control mice. This increase appears on the weight curve from the 8 'to the 10' day. The difference in weight between the mice treated with the product and the control mice is very significant.
In animals asleep with pentobarbital, the product acts to wake them up, shortening the effective time to fifty significantly. The method used to establish the comparison is that of J.T. Litchfield, modified. If the blood pressure of an anesthetized cat is recorded, a slight increase in pressure is observed when the product is administered endovenously.
Through chemical tests, the product has shown the following therapeutic indications:
Alterations in character, language and behavior. Difficulty in learning, capturing and school delays. Psychophysical fatigue, neurastenia, neurosis, products acting, in general, to increase intellectual performance.
Psychomotor disorders (locomotor delays, etc.). Psychogenic anorexia. Convulsive illnesses. Pre-anesthetic prophylaxis and healing after anesthesia. Various intoxications with damage to the central nervous system. Obnubilation, stupor and coma states of various etiology (metabolic, toxic, traumatic, meningoencephalic and comas due to vascular accidents).
States of dizziness. Nausea and vomiting. Acute and chronic alcoholism. Hepatitis and cirrhosis.
CLAIM I
Process for preparing pyridoxal alpha-ketoglutarate
EMI1.2
characterized in that alpha-ketoglutaric acid is reacted with pyridoxal in solution in an organic or inorganic solvent.
SUB-CLAIMS
1. Process according to claim I, characterized in that the solution is left to cool or that it is concentrated to facilitate crystallization of the product obtained.
2. Method according to claim I or subclaim 1, characterized in that the product formed is precipitated by the addition of a suitable precipitant.
3. Method according to claim I or subclaim 1, characterized in that the solvent is ethanol.
CLAIM It
Pyridoxal alpha-ketoglutarate obtained by the process according to claim I.
** ATTENTION ** end of DESC field can contain start of CLMS **.
Claims (1)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BE790118D BE790118A (en) | 1972-10-09 | PYRIDOXAL AND PYRIDOXAMINE ALPHA-CETOGLUTARATE DERIVATIVES, | |
CH30674A CH561183A5 (en) | 1972-10-09 | 1972-10-09 | |
GB4712172A GB1346014A (en) | 1972-10-09 | 1972-10-12 | Derivatives of alpha-ketoglutaric acid and their preparation |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH30674A CH561183A5 (en) | 1972-10-09 | 1972-10-09 | |
GB4712172 | 1972-10-12 | ||
BE790118 | 1972-10-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
CH561183A5 true CH561183A5 (en) | 1975-04-30 |
Family
ID=27159418
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH30674A CH561183A5 (en) | 1972-10-09 | 1972-10-09 |
Country Status (3)
Country | Link |
---|---|
BE (1) | BE790118A (en) |
CH (1) | CH561183A5 (en) |
GB (1) | GB1346014A (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6043259A (en) * | 1998-07-09 | 2000-03-28 | Medicure Inc. | Treatment of cardiovascular and related pathologies |
US6339085B1 (en) | 1999-03-08 | 2002-01-15 | The University Of Manitoba | Therapeutics for cardiovascular and related diseases |
US6417204B1 (en) | 2000-07-07 | 2002-07-09 | Medicure International Inc. | Pyridoxine AMD pyridoxal analogues: cardiovascular therapeutics |
US6489345B1 (en) | 1999-07-13 | 2002-12-03 | Medicure, Inc. | Treatment of diabetes and related pathologies |
US6548519B1 (en) | 2001-07-06 | 2003-04-15 | Medicure International Inc. | Pyridoxine and pyridoxal analogues: novel uses |
US6586414B2 (en) | 2000-03-28 | 2003-07-01 | Medicure International Inc. | Treatment of cerebrovascular disease |
US6605612B2 (en) | 2000-02-29 | 2003-08-12 | Medicure International Inc. | Cardioprotective phosohonates and malonates |
US6677356B1 (en) | 1999-08-24 | 2004-01-13 | Medicure International Inc. | Treatment of cardiovascular and related pathologies |
US6897228B2 (en) | 2000-07-07 | 2005-05-24 | Medicure International Inc. | Pyridoxine and pyridoxal analogues: new uses |
US7812037B2 (en) | 2004-10-28 | 2010-10-12 | Medicure International, Inc. | Dual antiplatelet/anticoagulant pyridoxine analogs |
-
0
- BE BE790118D patent/BE790118A/en unknown
-
1972
- 1972-10-09 CH CH30674A patent/CH561183A5/fr not_active IP Right Cessation
- 1972-10-12 GB GB4712172A patent/GB1346014A/en not_active Expired
Cited By (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6043259A (en) * | 1998-07-09 | 2000-03-28 | Medicure Inc. | Treatment of cardiovascular and related pathologies |
US6339085B1 (en) | 1999-03-08 | 2002-01-15 | The University Of Manitoba | Therapeutics for cardiovascular and related diseases |
US7230009B2 (en) | 1999-03-08 | 2007-06-12 | Medicure, Inc. | Pyridoxal analogues and methods of treatment |
US6890943B2 (en) | 1999-03-08 | 2005-05-10 | Medicure Inc. | Pyridoxal analogues and methods of treatment |
US6489345B1 (en) | 1999-07-13 | 2002-12-03 | Medicure, Inc. | Treatment of diabetes and related pathologies |
US7148233B2 (en) | 1999-08-24 | 2006-12-12 | Merrill Lynch Capital Canada Inc. | Treatment of cardiovascular and related pathologies |
US6677356B1 (en) | 1999-08-24 | 2004-01-13 | Medicure International Inc. | Treatment of cardiovascular and related pathologies |
US7144892B2 (en) | 1999-08-24 | 2006-12-05 | Merrill Lynch Capital Canada Inc. | Treatment of cardiovascular and related pathologies |
US7125889B2 (en) | 1999-08-24 | 2006-10-24 | Medicure International Inc. | Treating of cardiovascular and related pathologies |
US7132430B2 (en) | 1999-08-24 | 2006-11-07 | Medicure International Inc. | Treatment of cardiovascular and related pathologies |
US7115626B2 (en) | 1999-08-24 | 2006-10-03 | Medicure International Inc. | Treatment of cardiovascular and related pathologies |
US7115625B2 (en) | 1999-08-24 | 2006-10-03 | Medicure International Inc. | Treatment of cardiovascular and related pathologies |
US6605612B2 (en) | 2000-02-29 | 2003-08-12 | Medicure International Inc. | Cardioprotective phosohonates and malonates |
US6667315B2 (en) | 2000-02-29 | 2003-12-23 | Medicure International Inc. | Cardioprotective phosphonates and malonates |
US6780997B2 (en) | 2000-02-29 | 2004-08-24 | Medicure International Inc. | Cardioprotective phosphonates and malonates |
US6867215B2 (en) | 2000-02-29 | 2005-03-15 | Medicure International Inc. | Cardioprotective phosphonates and malonates |
US7105673B2 (en) | 2000-02-29 | 2006-09-12 | Medicure International Inc. | Cardioprotective phosphonates and malonates |
US6586414B2 (en) | 2000-03-28 | 2003-07-01 | Medicure International Inc. | Treatment of cerebrovascular disease |
US6861439B2 (en) | 2000-03-28 | 2005-03-01 | Medicure International, Inc. | Treatment of cerebrovascular disease |
US6897228B2 (en) | 2000-07-07 | 2005-05-24 | Medicure International Inc. | Pyridoxine and pyridoxal analogues: new uses |
US6417204B1 (en) | 2000-07-07 | 2002-07-09 | Medicure International Inc. | Pyridoxine AMD pyridoxal analogues: cardiovascular therapeutics |
US6548519B1 (en) | 2001-07-06 | 2003-04-15 | Medicure International Inc. | Pyridoxine and pyridoxal analogues: novel uses |
US7812037B2 (en) | 2004-10-28 | 2010-10-12 | Medicure International, Inc. | Dual antiplatelet/anticoagulant pyridoxine analogs |
Also Published As
Publication number | Publication date |
---|---|
GB1346014A (en) | 1974-02-06 |
BE790118A (en) | 1973-02-01 |
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Legal Events
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