DE2622622A1 - P-AMINOBENZOIC ACID BETA AMINO ALKYLESTER NICOTINATE - Google Patents
P-AMINOBENZOIC ACID BETA AMINO ALKYLESTER NICOTINATEInfo
- Publication number
- DE2622622A1 DE2622622A1 DE19762622622 DE2622622A DE2622622A1 DE 2622622 A1 DE2622622 A1 DE 2622622A1 DE 19762622622 DE19762622622 DE 19762622622 DE 2622622 A DE2622622 A DE 2622622A DE 2622622 A1 DE2622622 A1 DE 2622622A1
- Authority
- DE
- Germany
- Prior art keywords
- aminobenzoic acid
- general formula
- nicotinate
- ester
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
Description
Antistress AG , Rapperswil / SCHWEIZ Nicotinate der p-Arainobenzoesäure-ß-aminoalkylesterAntistress AG, Rapperswil / SWITZERLAND Nicotinates of the p-arenobenzoic acid ß-aminoalkyl ester
Die Erfindung betrifft Nicotinate der p-Aminobenzoesäure-ßaminoalkylester, Verfahren zu ihrer Herstellung, sowie die Herstellung pharmazeutischer Präparate, die neben den Nicotinaten der p-Aminobenzoesäure-ß-aminoalkylester pharmazeutisch verträgliches Trägermaterial enthalten.The invention relates to nicotinates of the p-aminobenzoic acid-ßaminoalkyl ester, Process for their production, as well as the production of pharmaceutical preparations, in addition to the nicotinates the p-aminobenzoic acid-ß-aminoalkyl ester pharmaceutical Contain compatible carrier material.
Aufgabe der Erfindung ist es, in ihrer pharmakodynamischen und pharmakokyne ti s.chen Wirksamkeit gegenüber Procain oder N-Nicotinoyl-p-aminobenzoesäure-diäthylaminoäthylester verbesserte Wirkstoffe herzustellen.The object of the invention is, in their pharmacodynamic and pharmakokyne ti s.chen effectiveness against procaine or N-nicotinoyl-p-aminobenzoic acid diethylaminoethyl ester improved Manufacture active ingredients.
609850/1048609850/1048
Gegenstand der Erfindung sind Nicotinate der p-Aminobenzoesäure-ß-aminoalkylester der allgemeinen Formel (i)The invention relates to nicotinates of the β-aminoalkyl p-aminobenzoate of the general formula (i)
COOHCOOH
in der R1, R2 und R-, unabhängig voneinander Wasserstoff, einen Methyl-, Äthyl-, Propyl- oder Isopropylrest bedeuten.in which R 1 , R 2 and R-, independently of one another, denote hydrogen, a methyl, ethyl, propyl or isopropyl radical.
Ein weiterer Gegenstand der Erfindung ist ein Verfahren zur Herstellung von Verbindungen der allgemeinen Formel (i), das dadurch gekennzeichnet ist, daß man p-Aminobenzoesäure-ßaminoalkylester der allgemeinen Formel (II)Another object of the invention is a process for the preparation of compounds of the general formula (i), the is characterized in that one p-aminobenzoic acid-ßaminoalkylester of the general formula (II)
in der R1, R2 und R^5 die genannte Bedeutung haben, mit Nicotinsäure in Wasser oder in einem organischen Lösungsmittel umsetzt. in which R 1 , R 2 and R ^ 5 have the meaning mentioned, reacted with nicotinic acid in water or in an organic solvent.
Es wurde überraschend gefunden, daß die Nicotinate der p-Aminobenzoesäure-ß-aminoalkylester gegenüber bereits bekannten Verbindungen dieses Typus wie Procain oder N-Nicotinoyl-p-aminobenzoesäure-diäthylaminoäthylester bzw. deren Hydrochloride, wesentlich vorteilhaftere pharmakodynamische und pharmakokynetische Eigenschaften aufweisen.It has surprisingly been found that the nicotinates of the p-aminobenzoic acid ß-aminoalkyl ester compared to already known compounds of this type such as procaine or N-nicotinoyl-p-aminobenzoic acid diethylaminoethyl ester or their hydrochlorides, much more advantageous pharmacodynamic and pharmacokynetic Have properties.
609850/1048609850/1048
Die erfindungsgemäßen p-Aminobenzoesäure-ß-aminoalkylester-Nicotinsäure-Additionsverbindungen haben gegenüber Procain oder N-Nicotinoyl-p-aminobenzoesäure-diäthylaminoäthylester in verstärktem Ausmaß die Fähigkeit, durch Zellmembranen, insbesondere durch die Membranen der Nervenzellen zu permeieren, und somit intensiver in den Zellstoffwechsel im Sinne einer allgemeinen Zellregeneration einzugreifen.The p-aminobenzoic acid-β-aminoalkyl ester-nicotinic acid addition compounds according to the invention have compared to procaine or N-nicotinoyl-p-aminobenzoic acid diethylaminoethyl ester to a greater extent the ability to permeate through cell membranes, in particular through the membranes of nerve cells, and thus to intervene more intensively in the cell metabolism in the sense of a general cell regeneration.
Die erfindungsgemäßen Verbindungen eignen sich insbesondere als Wirkstoffe in der Behandlung von Alterserkrankungen. Besonders hervorzuheben ist die starke Verbesserung der Lern- ■ fähigkeit und Gedächstnisleistung.The compounds according to the invention are particularly suitable as active ingredients in the treatment of diseases of the elderly. Particularly What should be emphasized is the strong improvement in learning ■ ability and memory performance.
Durch Umsetzen der p-Aminobenzoesäure-ß-aminoalkylester der allgemeinen Formel (II) mit Nicotinsäure in Wasser oder einem organischen Lösungsmittel werden die erfindungsgemäßen Nicotina te hergestellt. Durch Entfernen des Lösungsmittels, beispielsweise durch Abdestillieren oder durch Zugabe eines anderen Lösungsmittels, in dem die erfindungsgemäßen Verbindungen schwer löslich sind, erfolgt deren Isolierung. Geeignete Lösungsmittel sind beispielsweise: Wasser, niedere aliphatische Alkohole, Aceton, Diäthylketon, Methyläthylketon, Äther, Dioxan, Tetrahydrofuran, Chloroform und Trichloräthylen. Zur Isolierung der erfindungsgemäßen Nicotinate der allgemeinen Formel (i) durch Ausfällen sind beispielsweise folgende Lösung-smittel geeignet: Tetrachlorkohlenstoff, Petroläther und Benzin.By reacting the p-aminobenzoic acid-ß-aminoalkyl ester general formula (II) with nicotinic acid in water or an organic solvent are the nicotines according to the invention te manufactured. By removing the solvent, for example by distilling off or by adding a Another solvent in which the compounds according to the invention are sparingly soluble are isolated. Suitable Examples of solvents are: water, lower aliphatic Alcohols, acetone, diethyl ketone, methyl ethyl ketone, ether, dioxane, tetrahydrofuran, chloroform and trichlorethylene. To the Isolation of the nicotinates according to the invention of the general Formula (i) by precipitation are, for example, the following solvents suitable: carbon tetrachloride, petroleum ether and gasoline.
Die p-Aminobenzoesäure-ß-alkylaminoalkylester lassen sich in an sich bekannter Weise durch Verestern, von p-Aminobenzoesäure mit. ß-Aminoalkoholen oder durch Hydrieren der entsprechenden p-Nitrobenzoesäure-ß-aminoalky!ester herstellen.,The p-aminobenzoic acid-ß-alkylaminoalkyl esters can be in in a manner known per se, by esterification, of p-aminobenzoic acid with. ß-amino alcohols or by hydrogenating the corresponding Prepare p-nitrobenzoic acid-ß-aminoalkyl ester.,
-4--4-
.6 09850/1048.6 09850/1048
-it--it-
erfindungsgemäßen Verbindungen der allgemeinen Formel (I) können zu pharmazeutischen Präparaten verarbeitet werden, welche diese Verbindungen in Mischung mit einem für die enterale oder parenterale Applikation geeigneten Trägermaterial, wie beispielsweise Wasser, Gelatine, Milchzucker, Stärke, Magnesiumstearat, Talkum, Polyaklenglykole, Vaseline, Kieselsäure usw. oder in Kombination mit anderen therapeutisch wertvollen Wirkstoffen enthalten» Diese pharmazeutischen Präparate können in fester Form als Tabletten, Dragees, Suppositorien, Hart- oder Weichgelatinekapseln usw. oder in flüssiger Form als Lösungen, Suspensionen oder Emulsionen vorliegen. Diese Präparate können weitere Konservierungsmittel, Stabilisierungs-* Netz- oder Emulgiermittel enthalten.Compounds according to the invention of the general Formula (I) can be processed into pharmaceutical preparations, which these compounds in mixture with a Carrier material suitable for enteral or parenteral administration, such as water, gelatin, lactose, Starch, magnesium stearate, talc, polyalkene glycols, petrolatum, silica, etc. or in combination with others contain therapeutically valuable active ingredients »These pharmaceutical preparations can be in solid form as tablets, Dragees, suppositories, hard or soft gelatine capsules etc. or in liquid form as solutions, suspensions or Emulsions are present. These preparations can contain other preservatives, stabilizers * wetting agents or emulsifiers contain.
In den folgenden Beispielen bedeuten Teile Gewichtsteile.In the following examples, parts mean parts by weight.
4,8 Teile p-Aminobenzoesäure-diäthylaminoäthylester und 2,5 Teile Nicotinsäure werden in 10 Teilen Aceton gelöst und die Lösung filtriert. Nach dem Abdestillieren des Acetons unter vermindertem Druck verbleibt als Rückstand das p-Aminobenzoesäure-diäthylaminoäthylester-Nicotinat, das in der Kälte glasigamorph erstarrt und in Wasser und den meisten organischen Lösungsmitteln gut löslich ist.4.8 parts of diethylaminoethyl p-aminobenzoate and 2.5 parts of nicotinic acid are dissolved in 10 parts of acetone and the solution is filtered. After the acetone has been distilled off The residue under reduced pressure is the p-aminobenzoic acid diethylaminoethyl ester nicotinate, which in the cold it solidifies in a glass-amorphous manner and is readily soluble in water and most organic solvents.
6,3 Teile p-Aminobenzoesäure-dimethyiaminoäthylester und j5,6 Teile Nicotinsäure werden in J50 Teilen Methanol gelöst, filtriert und mit 100 Teilen Tetrachlorkohlenstoff versetzt,6.3 parts of p-aminobenzoic acid dimethyiaminoethyl ester and 5.6 parts of nicotinic acid are dissolved in 50 parts of methanol, filtered and mixed with 100 parts of carbon tetrachloride,
-5--5-
609850/1048609850/1048
Aus der Lösung kristallisiert das Nicotinat des p-Aminobenzoesäure-ß-dimethylaminoäthylesters aus. Die Kristalle werden abgesaugt und mit Tetrachlorkohlenstoff ausgewaschen. Fp.: Io4 - lo6°C.The nicotinate of p-aminobenzoic acid-ß-dimethylaminoethyl ester crystallizes out of the solution the end. The crystals are suctioned off and washed out with carbon tetrachloride. M.p .: Io4 - lo6 ° C.
2,2 Teile p-Aminobenzoesäure-dimethylaminoisopropylester und 1,2 Teile Nicotinsäure werden in Io Teilen Isopropanol gelöst, filtriert und das Isopropanol anschließend unter vermindertem Druck abdestilliert. Nach dem Abdestillieren bleibt das p-Aminobenzoesäure-dimethylaminoisopropylester-Nicotinat als in der Kälte glasig-amorph erstarrende, in Wasser und den meisten organischen Lösungsmitteln gut lösliche Verbindung zurück.2.2 parts of dimethylaminoisopropyl p-aminobenzoate and 1.2 parts of nicotinic acid are added to io parts of isopropanol dissolved, filtered and the isopropanol then under reduced Distilled pressure. After distilling off, the p-aminobenzoic acid dimethylaminoisopropyl ester nicotinate remains as Compound that solidifies glassy-amorphous in the cold and is readily soluble in water and most organic solvents return.
609850/1048609850/1048
Claims (7)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH680175 | 1975-05-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2622622A1 true DE2622622A1 (en) | 1976-12-09 |
Family
ID=4315232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19762622622 Pending DE2622622A1 (en) | 1975-05-26 | 1976-05-20 | P-AMINOBENZOIC ACID BETA AMINO ALKYLESTER NICOTINATE |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS51148012A (en) |
| DE (1) | DE2622622A1 (en) |
| FR (1) | FR2312250A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5162344A (en) * | 1987-05-04 | 1992-11-10 | Robert Koch | Procaine double salt complexes |
-
1976
- 1976-05-20 DE DE19762622622 patent/DE2622622A1/en active Pending
- 1976-05-25 JP JP6053776A patent/JPS51148012A/en active Pending
- 1976-05-26 FR FR7615919A patent/FR2312250A1/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5162344A (en) * | 1987-05-04 | 1992-11-10 | Robert Koch | Procaine double salt complexes |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2312250A1 (en) | 1976-12-24 |
| JPS51148012A (en) | 1976-12-18 |
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