DE2609147A1 - PROPIONIC ACID SALT BASED AMINO ACIDS - Google Patents

PROPIONIC ACID SALT BASED AMINO ACIDS

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Publication number
DE2609147A1
DE2609147A1 DE19762609147 DE2609147A DE2609147A1 DE 2609147 A1 DE2609147 A1 DE 2609147A1 DE 19762609147 DE19762609147 DE 19762609147 DE 2609147 A DE2609147 A DE 2609147A DE 2609147 A1 DE2609147 A1 DE 2609147A1
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DE
Germany
Prior art keywords
chlorophenoxy
propionate
amino acids
propionic acid
methyl
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
Application number
DE19762609147
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German (de)
Inventor
Giangiacomo Dr Massaroli
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Poli Industria Chimica SpA
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Poli Industria Chimica SpA
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Application filed by Poli Industria Chimica SpA filed Critical Poli Industria Chimica SpA
Publication of DE2609147A1 publication Critical patent/DE2609147A1/en
Pending legal-status Critical Current

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Classifications

    • 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
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
    • C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

2609H72609H7

M.M.

LW/XILW / XI

5. März 1976March 5th 1976

POLI Industrie Chimica S.p.A.
20141 Mailand, Piazza Agrippa 1POLI Industrie Chimica SpA
20141 Milan, Piazza Agrippa 1

Propionsäuresalze basischer AminosäurenPropionic acid salts of basic amino acids

Die Erfindung betrifft Salze der 2-p-Chlorphenoxy-2-methyl-propionsäure (I) mit basischen Aminosäuren der allgemeinen chemischen Formel RHN-(CH2)n~CH(NH3)-COOH (II). Vorzugsweise werden folgende basischen Aminosäuren verwendet: L-Lysin (in der Formel II: R=H, η = 4), L-Ornithin (in Formel II: R=H, η = 3) oder L-Arginin (in Formel II: R = H2N-C(NH)-, η = 3). Die Erfindung betrifft ausserdem ein Verfahren zur Herstellung dieser Salze, die die folgende allgemeine Formel haben:The invention relates to salts of 2-p-chlorophenoxy-2-methyl-propionic acid (I) with basic amino acids of the general chemical formula RHN- (CH 2 ) n ~ CH (NH 3 ) -COOH (II). The following basic amino acids are preferably used: L-lysine (in formula II: R = H, η = 4), L-ornithine (in formula II: R = H, η = 3) or L-arginine (in formula II: R = H 2 NC (NH) -, η = 3). The invention also relates to a process for the preparation of these salts, which have the following general formula:

o -. G _ COOH ♦ HHlMCSe)J-CB(IH9 )-000Ho -. G _ COOH ♦ HHlMCS e ) J-CB (IH 9 ) -000H

ι »ι »

Die Salze der Erfindung sind wertvolle therapeutische Wirkstoffe. Sie weisen insbesondere eine hohe hypolipaemische Aktivität auf.The salts of the invention are valuable therapeutic agents. In particular, they exhibit high levels of hypolipaemic Activity on.

609885/124 3609885/124 3

Wird beispielsweise Ratten oral 2-p-Chlorphenoxy-2-methylpropionat des L-Lysins verabreicht, so ist dessen Aktivität bezogen auf den Spiegel der 2-p-Chlorphenoxy-2-methylpropionsäure im Blut höher als der mit äquimolaren Mengen 2-p-Chlorphenoxy-2-methyl-propionsäureäthylester (CoIfibrate) erzielbare Spiegel.For example, rats use 2-p-chlorophenoxy-2-methylpropionate orally of L-lysine administered, its activity is based on the level of 2-p-chlorophenoxy-2-methylpropionic acid higher in the blood than that with equimolar amounts of ethyl 2-p-chlorophenoxy-2-methyl-propionate (CoIfibrate) achievable mirrors.

Hyperlipaemisch nach Tensho et al. (J. Pharm. Soc. Jap. 1972, Ji2_, 879) ernährte männliche Wistar-Ratten werden an fünf aufeinanderfolgenden Tagen mit 2-p-Chlorphenoxy-2-methylpropionat von Lysin mit Tagesdosen von 400 mg/kg behandelt. Dadurch wird eine Verringerung der Cholesterinwerte, Triglyceridwerte und Lipidwerte insgesamt im Serum erzielt, die grosser als die mit der äquimolaren Menge, das sind 270 mg/kg, Colfibrate erzielbar sind.Hyperlipaemic according to Tensho et al. (J. Pharm. Soc. Jap. 1972, Ji2_, 879) are fed male Wistar rats for five consecutive days with 2-p-chlorophenoxy-2-methylpropionate treated of lysine at daily doses of 400 mg / kg. This will reduce cholesterol levels, Triglyceride values and total lipid values achieved in the serum that are greater than those with the equimolar amount, that is 270 mg / kg, colfibrates are achievable.

Selbst mit der gewichtsmässig gleichen Dosis von 270 mg/kg 2-p-Chlorphenoxy-2-methylpropionat von Lysin werden Veränderungen der genannten Blutspiegelwerte erzielt, die zumindest gleich, zum Teil grosser als die mit 270 mg/kg Colfibrate erzielbaren Werte sind.Even with the same weight dose of 270 mg / kg 2-p-chlorophenoxy-2-methylpropionate from lysine results in changes in the blood levels mentioned at least the same, in some cases larger than the 270 mg / kg Colfibrates are achievable values.

Die gegenüber dem Colfibrate höhere Aktivität des 2-p-Chlorphenoxy-2-methyl-propionats des Lysins ist wahrscheinlich auf die Fähigkeit des L-Lysins zurückzuführen, ebenfalls die Cholesterinwerte, Triglyceridwerte und Lipidwerte, zumindest in ihrer Summe, im Serum positiv zu beeinflussen. Zumindest lassen dies in dieser Richtung durchgeführte Versuche vermuten.The higher activity of 2-p-chlorophenoxy-2-methyl-propionate compared to colfibrate of lysine is probably due to the ability of L-lysine to also the cholesterol levels, triglyceride levels and To positively influence lipid values, at least in their sum, in the serum. At least let this go in that direction suspect performed experiments.

In der nachstehenden Tabelle sind die Versuchsergebnisse im einzelnen dargestellt. Die angegebenen Zahlen sind prozentuale Veränderungen gegenüber der Kontrollgruppe.The test results are shown in detail in the table below. The figures given are percentages Changes compared to the control group.

609885/124 3609885/124 3

_3- 2609U7_3-2609U7

Lysin-2-p-chlor-Lysine-2-p-chlorine-

Coleet·- MgLy- Llpld rm otrid Coleet · - MgLy- Llpld rm otrid

270 me/k« -33,68 -61,34 -23.17270 me / k «-33.68 -61.34 -23.17

phenoxy-2-methyl-phenoxy-2-methyl-

propionat *°° "*/** -41 »32 -59,5« -43,09 propionate * °° "* / ** -41" 32 -59.5 "-43.09

Clefilwate 270 awk« -21,36 -56,17 -18,70Clefilwate 270 awk "-21.36 -56.17 -18.70

Die Substanzen der Erfindung werden durch Umsetzen äquimolarer Mengen der Säure der Formel I und einer Aminosäure der Formel II in wässrigen alkoholischen Lösungen hergestellt. Dabei hat ein Abweichen vom äquimolaren Einsatzverhältnis keine negativen Auswirkungen auf die erhaltenen Produkte erkennen lassen. Die Umsetzung erfolgt vorzugsweise in der Wärme. Die auf diese Weise erhaltenen Salze der Erfindung scheiden sich in praktisch vollkommen reiner Form kristallin ab.The substances of the invention are prepared by reacting equimolar amounts of the acid of the formula I and an amino acid of the formula II in aqueous alcoholic solutions . A deviation from the equimolar usage ratio did not reveal any negative effects on the products obtained. The reaction is preferably carried out in the heat. The salts of the invention obtained in this way separate in crystalline form in practically completely pure form.

Die Erfindung ist im folgenden anhand eines Beispiels näher erläutert.The invention is explained in more detail below using an example.

Beispielexample

Eine angewärmte Lösung von 153 g(0,71 mol) 2-p-Chlorphenoxy-2-methyl-propionsäure in 800 ml Äthanol wird mit einer Lösung von 104 g (o,71 mol) L-Lysin in 400 ml Wasser versetzt. Nach dem Abscheiden der Kristalle wird filtriert, mit einem Äthanol-Wasser-Gemisch (2 :1) gewaschen und dann getrocknet. Es werden 230 g, entsprechend einer Ausbeute von 89,4 %, eines Produktes erhalten, dessen Schmelzpunkt bei 212 bis 214 0C und dessen acidimetrischer Titer (Ha1O4) 99,2 % beträgt.A warmed solution of 153 g (0.71 mol) of 2-p-chlorophenoxy-2-methyl-propionic acid in 800 ml of ethanol is mixed with a solution of 104 g (0.71 mol) of L-lysine in 400 ml of water. After the crystals have separated out, it is filtered, washed with an ethanol-water mixture (2: 1) and then dried. 230 g, corresponding to a yield of 89.4%, of a product are obtained whose melting point is 212 to 214 ° C. and whose acidimetric titer (Ha 1 O 4 ) is 99.2 %.

609885/1243609885/1243

_4_ 2609H7_ 4 _ 2609H7

In gleicher Weise werden das 2-p-Chlorphenoxy-2-methylpropicnat des Arginins (F3 199 - 200 0C) und das 2-p-ChIorphenoxy-2-methyl-propionat des Ornithins erhalten. Letzteres schmilzt unter Zersetzung bei 185 bis 186 0C.Similarly, the 2-p-chlorophenoxy-2-methylpropicnat be of arginine (F 3199-200 0 C) and 2-p-ChIorphenoxy-2-methyl-propionate of ornithine obtained. The latter melts with decomposition at 185 to 186 0 C.

Die se erhaltenen Substanzen werden in gebräuchlichen pharmazeutischen Ärzneimittelrezepturen und galenischen Formen eingesetzt, beispielsweise als Kapseln, Tabletten oder Dragees. Je nach der gewünschten Aktivität beträgt die Einheitsdosierung vorzugsweise etwa 200 bis 600 mg.The substances obtained are used in common pharmaceutical Medicinal product formulations and galenic forms are used, for example as capsules, tablets or dragees. The unit dosage is preferably about 200 to 600 mg, depending on the activity desired.

Die klinischen Versuche haben gezeigt, dass Behandlungen mit Tagesdosen von 600 bis 3000 mg bei Patienten mit Lipidstoffwechselkrankiieiten zu ausgezeichneten Erfolgen führen.The clinical trials have shown that treatments with daily doses of 600 to 3000 mg in patients with lipid metabolism disorders lead to excellent results.

609885/1243609885/1243

Claims (6)

PatentansprücheClaims 1. 2-p-Chlorphenoxy-2-methyl-propionat, gekennzeichnet durch ../ die Formel1. 2-p-chlorophenoxy-2-methyl-propionate, characterized by ../ the formula οι -V //-(«-ooch.οι -V // - («- ooch. wobei R ein Wasserstoffatom oder ein Rest der Formel H2N-C(NH)- ist und η eine ganze Zahl von 3 oder 4 ist.where R is a hydrogen atom or a radical of the formula H 2 NC (NH) - and η is an integer of 3 or 4. 2. Propionat nach Anspruch 1, dadurch gekennzeichnet, dass es L-Lysin-2-p-chlorphenoxy-2-methyl-propionat ist.2. Propionate according to claim 1, characterized in that it is L-lysine-2-p-chlorophenoxy-2-methyl-propionate. 3. Propionat nach Anspruch 1, dadurch gekennzeichnet, dass es L-Arginin-2-p-chlorphenoxy-2-methyl-propionat ist.3. Propionate according to claim 1, characterized in that it is L-arginine-2-p-chlorophenoxy-2-methyl-propionate. 4. Propionat nach Anspruch 1, dadurch gekennzeichnet, dass es L-Ornithin-2-p-chlorphenoxy-2-methylpropionat ist.4. Propionate according to claim 1, characterized in that it is L-ornithine-2-p-chlorophenoxy-2-methylpropionate. 5. Verfahren zur Herstellung der Propionate nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass man äquimolare Mengen der beiden Komponenten des Salzes in einer wässrigen alkoholischen Lösung umsetzt.5. Process for the preparation of the propionates according to one of claims 1 to 4, characterized in that one converts equimolar amounts of the two components of the salt in an aqueous alcoholic solution. 6. Arzneimittel, bestehend in der Einheitsdosis aus 200 bis 600 mg mindestens einer der Verbindungen nach einem der Ansprüche 1 bis 4 und gebräuchlichen Hilfs- und bzw. oder Trägerstoffen.6. Medicaments, consisting in the unit dose of 200 to 600 mg of at least one of the compounds according to any one of claims 1 to 4 and customary auxiliaries and / or carriers. 609885/12609885/12
DE19762609147 1975-07-02 1976-03-05 PROPIONIC ACID SALT BASED AMINO ACIDS Pending DE2609147A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IT25037/75A IT1049540B (en) 1975-07-02 1975-07-02 LIPOLIPEMIZING COMPOUNDS

Publications (1)

Publication Number Publication Date
DE2609147A1 true DE2609147A1 (en) 1977-02-03

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ID=11215496

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DE19762609147 Pending DE2609147A1 (en) 1975-07-02 1976-03-05 PROPIONIC ACID SALT BASED AMINO ACIDS

Country Status (7)

Country Link
JP (1) JPS527934A (en)
BE (1) BE840651A (en)
DE (1) DE2609147A1 (en)
FR (1) FR2315917A1 (en)
GB (1) GB1494299A (en)
IT (1) IT1049540B (en)
MX (1) MX3314E (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0502007A1 (en) * 1989-11-22 1992-09-09 BARBUL, Adrian Arginine nicotinate for reducing blood cholesterol

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2475546A1 (en) * 1980-02-11 1981-08-14 Pierre Moreau Moroxydine clofibrate and chlorobenzoyl-phenoxy-isobutyrate - with anti-atherosclerotic and antithrombotic activity
CH651032A5 (en) * 1980-02-11 1985-08-30 Moreau Pierre D MOROXYDIN PHENOXYISOBUTYRATES AND MEDICAMENTS CONTAINING THEM.
FR2497666B2 (en) * 1981-01-14 1987-10-16 Moreau Pierre MEDICINES CONTAINING PHENOXYISOBUTYRIC ACID AND MOROXYDINE
IT1303253B1 (en) * 1998-10-27 2000-11-06 Fatro Spa AMMONIUM SALTS OF PHENOXYSIOBUTYRIC ACID AND RELATED PHARMACEUTICAL FORMULATIONS.

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0502007A1 (en) * 1989-11-22 1992-09-09 BARBUL, Adrian Arginine nicotinate for reducing blood cholesterol
EP0502007A4 (en) * 1989-11-22 1992-11-19 Adrian Barbul Method for reducing blood cholesterol using arginine

Also Published As

Publication number Publication date
GB1494299A (en) 1977-12-07
BE840651A (en) 1976-08-02
FR2315917A1 (en) 1977-01-28
JPS527934A (en) 1977-01-21
IT1049540B (en) 1981-02-10
MX3314E (en) 1980-08-17

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