DE3131783A1 - 1-O-Alkyl-2-O-alkylcarbamoylglycero-3-phosphocholines, processes for their preparation and pharmaceutical preparations containing these compounds - Google Patents
1-O-Alkyl-2-O-alkylcarbamoylglycero-3-phosphocholines, processes for their preparation and pharmaceutical preparations containing these compoundsInfo
- Publication number
- DE3131783A1 DE3131783A1 DE19813131783 DE3131783A DE3131783A1 DE 3131783 A1 DE3131783 A1 DE 3131783A1 DE 19813131783 DE19813131783 DE 19813131783 DE 3131783 A DE3131783 A DE 3131783A DE 3131783 A1 DE3131783 A1 DE 3131783A1
- Authority
- DE
- Germany
- Prior art keywords
- glycero
- phosphocholine
- hexadecyl
- octadecyl
- alkyl
- 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.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 7
- -1 alkyl isocyanate Chemical class 0.000 claims description 6
- 239000012948 isocyanate Substances 0.000 claims description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002879 Lewis base Substances 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 150000007527 lewis bases Chemical class 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 2
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000004566 IR spectroscopy Methods 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VRVUKQWNRPNACD-UHFFFAOYSA-N 1-isocyanatopentane Chemical compound CCCCCN=C=O VRVUKQWNRPNACD-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- ANJPRQPHZGHVQB-UHFFFAOYSA-N hexyl isocyanate Chemical compound CCCCCCN=C=O ANJPRQPHZGHVQB-UHFFFAOYSA-N 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Titel:Title:
1-0-Alkyl-2-0-alkylcarbamoyl-glycero-3-phosphaChe Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate Beschreibung Die vorliegende Erfindung betrifft neue l-0-Alkyl-2-0-alkylcarbamoyl-glycero-3-phosphocholine, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Wirkstoff in Arzneimitteln, insbesondere zur Behandlung von Hochdruck und entzündlichen Erkrankungen.1-0-Alkyl-2-0-alkylcarbamoyl-glycero-3-phosphaChe process for their Manufacture and pharmaceutical preparations containing them Description The present Invention relates to new 1-0-alkyl-2-0-alkylcarbamoyl-glycero-3-phosphocholine, method for their production and their use as an active ingredient in pharmaceuticals, in particular for the treatment of hypertension and inflammatory diseases.
Die erfindungsgemäßen neuen 1-0-Alkyl-2-0-alkylcarbamoyl-glycero-3-phosphocholine entsprechen der allgemeinen Formel I worin R1 einen geradkettigen Kohlenwasserstoffrest mit 10-20 Kohlenstoffatomen bedeutet, während R2 einen geradkettigen oder verzweigten Kohlenwasserstoffrest mit 1 - 9 Kohlenstoffatomen darstellt.The new 1-0-alkyl-2-0-alkylcarbamoyl-glycero-3-phosphocholines according to the invention correspond to the general formula I. wherein R1 is a straight-chain hydrocarbon radical with 10-20 carbon atoms, while R2 represents a straight-chain or branched hydrocarbon radical with 1-9 carbon atoms.
Vrbindungen gemäß der Erfindung sind beispielsweise: 1-0-Hexadecyl-2-0-methylcarbomoyl-glycero-3-phosphocholin, 200vEthylearb2moyl^1-O-hexadecyl-glycero-3-phosphocholin, 1-0-Hexadecyl-2-0-propylcarbamoyl-glycero-3-phosphocholin, 1-0-Hexadecyl-2-0-isopropylcarbamoyl-glycero-3-phosphocholin, 2-0-butylcarbomoyl-1-0hexadecyl-glycero-3-phosphocholin, 1-0-Hexadecyl-2-0-pentylcarbamoyl-glycero-3-phosphocholin, 1-0-Hexadecyl-2-0-hexylcarbamoyl-glycero-3-phosphocholin, 2-0-Metylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, 2-0-Ethylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, 1-0-Octadecyl-2-0-propylcarbamoyl-glycero-3-phosphocholin, 2-0-Isopropylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, 2-0-Butylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, 1-0-Octadecyl-2-0-pentylcarbamoyl-glycero-3-phosphocholin, 2-0-Hexylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin.Compounds according to the invention are for example: 1-0-hexadecyl-2-0-methylcarbomoyl-glycero-3-phosphocholine, 200vEthylearb2moyl ^ 1-O-hexadecyl-glycero-3-phosphocholine, 1-0-hexadecyl-2-0-propylcarbamoyl-glycero-3-phosphocholine, 1-0-hexadecyl-2-0-isopropylcarbamoyl-glycero-3-phosphocholine, 2-0-butylcarbomoyl-1-0hexadecyl-glycero-3-phosphocholine, 1-0-hexadecyl-2-0-pentylcarbamoyl-glycero-3-phosphocholine, 1-0-hexadecyl-2-0-hexylcarbamoyl-glycero-3-phosphocholine, 2-0-methylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, 2-0-ethylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, 1-0-octadecyl-2-0-propylcarbamoyl-glycero-3-phosphocholine, 2-0-isopropylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, 2-0-butylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, 1-0-octadecyl-2-0-pentylcarbamoyl-glycero-3-phosphocholine, 2-0-hexylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine.
Die erfindungsgemäßen Verbindungen zeigen eine sehr starke anti-Bypertensive Wirkung sowie eine günstige Beeinflussung rheumatischer und asthmatischer Krankheiten. Die genannten Verbindungen können daher bzw. darüber hinaus zur Behandlung des Hochdruks, verschiedener rheumatischer und asthmatischer Beschwerden und einiger atherosklerotischer Krankheitsbilder am menschen genutzt werden0 Die erfindungsgemäßen Substanzen werden durch Reaktion der Lysoverbindungen II, worin R1 die in Formel I genannte Bedeutung hat, mit Alkylisocyanaten der Formel III, worin R2 die in Formel 1 angegebene Bedeutung hat, nach folgender Gleichung hergestellt. The compounds according to the invention show a very strong anti-byypertensive effect and a favorable influence on rheumatic and asthmatic diseases. The compounds mentioned can therefore or in addition be used for the treatment of high pressure, various rheumatic and asthmatic complaints and some atherosclerotic diseases in humans Formula III, in which R2 has the meaning given in formula 1, prepared according to the following equation.
Die Reaktion wird zweckmäßig in organischen aprotischen Lösungsmitteln wie z.B. Chloroform, Aceton, Dimethylformamid bzw. deren Mischungen, gegebenenfalls unter Anwendung eines Katalysators, insbesondere einer Lewis-Base wie z.B. Triäthylamin, Pyridin, 4-Dimethylaminopyridin, Dimethylformamid bei Temperaturen zwischen 0-100°C, vorzugsweise bei 40-600C durchgeführt.The reaction is conveniently carried out in organic aprotic solvents such as chloroform, acetone, dimethylformamide or their mixtures, if appropriate using a catalyst, in particular a Lewis base such as triethylamine, Pyridine, 4-dimethylaminopyridine, dimethylformamide at temperatures between 0-100 ° C, preferably carried out at 40-600C.
Die Alkylisocyanate können auch in Form ihrer Imidd£blide mit der allgemeinen Formel IV worin R2 die in Formel I angegebene Bedeutung hat, unter den obengenannten Bedingungen eingesetzt werden, da sich die Imidazolide wie freieIsocyanate verhalten (vgl. H.A. Staab u.W.Rohr in: Neuere Methoden der präparativen organischen Chemie, S.79, Weinheim 1967).The alkyl isocyanates can also be used in the form of their imides having the general formula IV where R2 has the meaning given in formula I, can be used under the abovementioned conditions, since the imidazolides behave like free isocyanates (cf. HA Staab and W Rohr in: Newer methods of preparative organic chemistry, p.79, Weinheim 1967).
Als Ausgangsverbindungen 11 kommen z.B. in Frage: 1-0-Decyl-glycero-3-phosphocholin, 1-0-Undecyl-glycero-3-phosphocholin, 1-0-Dodecyl-glycero-3-phosphocholin, 1 -0-Tridecyl-glycero-3-phosphocholin 1-0-Tetradecyl-glycero-3-phosphocholin, 1 -0-Pentadecyl-glycero-3-phosphocholin< 1-0-Hexadecyl-glycero-3-phosphocholin, 1-0-Heptadecyl-glycero-3-phosphocholin 1-0-Octadecyl-glycero-3-phosphocolin, 1-0-Nonadecyl-glycero-3-phosphocholin, l-0-Eicosyl-glycero-3-phosphocholinl wobei die Lysoverbindungen in der natürlichen sn-Form, in Form der Spiegelbildisomeren oder als Racemate eingesetzt werden können.Possible starting compounds 11 are, for example: 1-0-decyl-glycero-3-phosphocholine, 1-0-undecyl-glycero-3-phosphocholine, 1-0-dodecyl-glycero-3-phosphocholine, 1-0-tridecyl-glycero-3-phosphocholine 1-0-tetradecyl-glycero-3-phosphocholine, 1-0-pentadecyl-glycero-3-phosphocholine < 1-0-hexadecyl-glycero-3-phosphocholine, 1-0-heptadecyl-glycero-3-phosphocholine, 1-0-octadecyl-glycero-3-phosphocoline, 1-0-nonadecyl-glycero-3-phosphocholine, l-0-eicosyl-glycero-3-phosphocholine1 where the lyso compounds in the natural sn form, in the form of the mirror image isomers or can be used as racemates.
Die als Ausgangsverbindungen eingesetzten 1-0-Alkyl-3-phosphocholine II sind entweder durch Organextraktion [z.B. M. Blank et al., Biochemical and Biophysical Research Communications 90 (4), 1194ff (1979)] zugänglich oder lassen sich nach den üblichen Verfahren, z.B. durch enzymatische Spaltung (Phospholipase A2) oder milde alkalische Hydrolyse aus den entsprechenden 2-0-Acyl-1-0-alkyl-glycero-3-phosphocholinen synthetisieren.The 1-0-alkyl-3-phosphocholines used as starting compounds II are either by organ extraction [e.g. M. Blank et al., Biochemical and Biophysical Research Communications 90 (4), 1194ff (1979)] accessible or can be obtained from the usual methods, e.g. by enzymatic cleavage (phospholipase A2) or mild alkaline hydrolysis from the corresponding 2-0-acyl-1-0-alkyl-glycero-3-phosphocholines synthesize.
Ober die Herstellung der 2-0-Acyl-1-0-alkyl-glycero-3-phosphocholine wird in einem Obersichtsartikel berichtet [H.K.Mangold Angew. Chem. 91, 550-560 (1979)].About the production of 2-0-acyl-1-0-alkyl-glycero-3-phosphocholines is reported in a review article [H.K. Mangold Angew. Chem. 91, 550-560 (1979)].
Als Ausgangsverbindungen III kommen z.B. in Frage: Methylisocyanat, Ethylisocyanat, Propylisocyanat, Isopropylisocyanat Butylisocyanat, Pentylisocyanat, Hexylisocyanat.Possible starting compounds III include: methyl isocyanate, Ethyl isocyanate, propyl isocyanate, isopropyl isocyanate, butyl isocyanate, pentyl isocyanate, Hexyl isocyanate.
Die vorliegende Erfindung betrifft ebenfalls pharmazeutische Präparate, welche Verbindungen der Formel I enthalten. Bei den erfindungsgemäßen pharmazeutischen Präparaten hande-lt es sich um solche zur enteralen, wie oralen oder rektalen sowie parenteralen Verabreichung, welche die pharmakologischen Wirkstoffe allein oder zusammen mit einet üblichen, pharmazeutisch anwendbauen Trägermaterial enthalten.The present invention also relates to pharmaceutical preparations, which compounds of formula I contain. In the pharmaceutical according to the invention Preparations are concerned with those for enteral, such as oral or rectal as well parenteral administration, which the pharmacologically active ingredients alone or together with a conventional, pharmaceutically applicable carrier material.
\Torteilhafterweise- liegt die pharmazeutische Zubereitung des Wirkstoffes in Form von Einzeldosen vor, die auf die gewünschte Verabreichung abgestimmt sind, wie z.B. Tabletten, DragEes, Kapseln Suppositorien, Granulate, Lösungen, Emulsionen oder Suspensionen.The pharmaceutical preparation of the active ingredient is a disadvantage in the form of single doses that are tailored to the desired administration, such as tablets, DragEes, capsules, suppositories, granulates, solutions, emulsions or suspensions.
Die Dosierung der Verbindungen liegt üblicherweise zwischen 1-50 mg pro Dosis, vorzugsweise zwischen 5-158 mg je Dosis, und kann ein- oder mehrmals, bevorzugt zwei- bis dreimal tägsich, verabreicht werden0 Die Herstellung der erfindungsgemäßen Verbindungen wird durch die folgenden Beispiele näher erläutert. Da sich die Verbindungen der Formel 1 aufgrund ihrer wachsartigen Konsistenz nicht durch Schmelzpunkte charakterisieren lassen, sind die jeweiligen IR-Daten sowie die Rf-Werte der Substanzen aus Formel I im vergleich zur entsprechenden Lysoverbindung in einer Tabelle usammengefaßt. Die Herstellung von Verbindungen der Formel I wird durch eine allgemeine Vorschrift erläutert, die der Tazelle 1 vorangestellt ist. Die einzelnen Beispiele mit genauen Angaben über Edukte, eingesetzte Mengen und Produktausbeuten sind der Tabelle 1 zu entnehmen.The dosage of the compounds is usually between 1-50 mg per dose, preferably between 5-158 mg per dose, and can be used one or more times, preferably two to three times a day, are administered0 The preparation of the invention Compounds are illustrated in more detail by the following examples. Since the connections of formula 1 due to their waxy consistency cannot be characterized by melting points are the respective IR data and the Rf values of the substances from the formula I summarized in a table in comparison with the corresponding lyso compound. The preparation of compounds of the formula I is carried out by a general rule explained, which precedes the Tazelle 1. The individual examples with exact Information on starting materials, amounts used and product yields are given in Table 1 refer to.
Die IR-Spektren wurden mit dem Gerät Perkin-Elmer 257 aufgenommen, wobei die Substanzen als Chioroformlösungen vermessen wurden.The IR spectra were recorded with the Perkin-Elmer 257 device, whereby the substances were measured as chloroform solutions.
Dünnschichtchromatographie: DC-Pertigplatten Kieselgel 60F-254, Fa. Merck Art. 5719 Laufmittel: Chloroform/Methanol/Wasser = 65/25/5 (V/V/V) Darstellung von 1-0-Alkyl-2-0-alkylcarbamoyl-glycero-3-phosphocholinen der allgemeinen Formel 1.Thin layer chromatography: TLC ready-to-use plates silica gel 60F-254, Fa. Merck Art. 5719 Mobile phase: chloroform / methanol / water = 65/25/5 (V / V / V) representation of 1-0-alkyl-2-0-alkylcarbamoyl-glycero-3-phosphocholines of the general formula 1.
Eine Mischung aus 1-0-Alkyl-glycero-3-phosphocholin, Alkylisocyanat, Chloroform und Dimethylformamid (DMF) wird bei 40-600C gerührt, bis eine klare Lösung entstanden ist und das Lysophospholipid dünnschichtchromatographisch nicht mehr nachweisbar ist. Die Lösungsmittel und überschüssiges Alkylisocyanat werden im Vakuum entfernt und der Rückstand durch präparative Dickschichtchromatographie oder Säulenchromatographie (Kieselgel/Chloroform/Methanol/Wasser) gereinigt.A mixture of 1-0-alkyl-glycero-3-phosphocholine, alkyl isocyanate, Chloroform and dimethylformamide (DMF) is stirred at 40-600C until a clear solution has arisen and the lysophospholipid is no longer according to thin-layer chromatography is demonstrable. The solvents and excess alkyl isocyanate are in vacuo removed and the residue by preparative thick layer chromatography or column chromatography (Silica gel / chloroform / methanol / water).
Tabelle 1 Beispiele, Ausgangskomponenten, Ausbeuten und IR-Daten betr.
Herstellung der 1-0-Alkyl-2-0-alkylcarbomoyl-glycero-3-Phosphocholine der allgemeinen
Formel I
Claims (1)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813131783 DE3131783A1 (en) | 1981-08-12 | 1981-08-12 | 1-O-Alkyl-2-O-alkylcarbamoylglycero-3-phosphocholines, processes for their preparation and pharmaceutical preparations containing these compounds |
| AT82106875T ATE17007T1 (en) | 1981-08-12 | 1982-07-30 | NEW O-ALKYL-O-CARBAMOYL-GLYCERO-PHOSPHOCHOLINES AND PROCESS FOR THEIR PRODUCTION. |
| DE8282106875T DE3268024D1 (en) | 1981-08-12 | 1982-07-30 | 0-alkyl-0-carbamoyl-glycero-phospho-cholines and process for their preparation |
| EP82106875A EP0072936B1 (en) | 1981-08-12 | 1982-07-30 | 0-alkyl-0-carbamoyl-glycero-phospho-cholines and process for their preparation |
| GR68948A GR76280B (en) | 1981-08-12 | 1982-08-03 | |
| JP57138636A JPS5839690A (en) | 1981-08-12 | 1982-08-11 | Novel o-alkyl-o-carbamoylglycerophosphocholine and manufacture |
| DK361282A DK361282A (en) | 1981-08-12 | 1982-08-11 | PROCEDURE FOR THE PREPARATION OF O-ALKYL-O-CARBAMOYL GLYCEROPHOSPHOCHOLINES |
| US06/621,131 US4552869A (en) | 1981-08-12 | 1984-06-15 | O-Alkyl-O-carbamoylglycerophosphocholines and the use for treating hypertension |
| IE1855/82A IE53402B1 (en) | 1981-08-12 | 1988-07-30 | New o-alkyl-o-carbamoylglycerophosphocholines and processes for their preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813131783 DE3131783A1 (en) | 1981-08-12 | 1981-08-12 | 1-O-Alkyl-2-O-alkylcarbamoylglycero-3-phosphocholines, processes for their preparation and pharmaceutical preparations containing these compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3131783A1 true DE3131783A1 (en) | 1983-03-24 |
Family
ID=6139109
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19813131783 Withdrawn DE3131783A1 (en) | 1981-08-12 | 1981-08-12 | 1-O-Alkyl-2-O-alkylcarbamoylglycero-3-phosphocholines, processes for their preparation and pharmaceutical preparations containing these compounds |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS5839690A (en) |
| DE (1) | DE3131783A1 (en) |
-
1981
- 1981-08-12 DE DE19813131783 patent/DE3131783A1/en not_active Withdrawn
-
1982
- 1982-08-11 JP JP57138636A patent/JPS5839690A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5839690A (en) | 1983-03-08 |
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