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DE3151378A1 - Novel O-carbamoylglycero-2-phosphocholines and process for their preparation - Google Patents

Novel O-carbamoylglycero-2-phosphocholines and process for their preparation

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Publication number
DE3151378A1
DE3151378A1 DE19813151378 DE3151378A DE3151378A1 DE 3151378 A1 DE3151378 A1 DE 3151378A1 DE 19813151378 DE19813151378 DE 19813151378 DE 3151378 A DE3151378 A DE 3151378A DE 3151378 A1 DE3151378 A1 DE 3151378A1
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Prior art keywords
phosphocholine
glycero
hexadecyl
octadecyl
alycero
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DE19813151378
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German (de)
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Hans Dipl.-Chem. Dr. 5014 Kerpen Betzing
Hans-Heiner Dipl.-Chem. Dr. 5024 Pulheim Lautenschläger
Ottfried Dipl.-Chem. Dr. 5000 Köln Zierenberg
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A Natterman und Cie GmbH
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A Natterman und Cie GmbH
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Priority to DE19813151378 priority Critical patent/DE3151378A1/en
Priority to AT82106875T priority patent/ATE17007T1/en
Priority to DE8282106875T priority patent/DE3268024D1/en
Priority to EP82106875A priority patent/EP0072936B1/en
Priority to GR68948A priority patent/GR76280B/el
Priority to DK361282A priority patent/DK361282A/en
Publication of DE3151378A1 publication Critical patent/DE3151378A1/en
Priority to US06/621,131 priority patent/US4552869A/en
Priority to IE1855/82A priority patent/IE53402B1/en
Withdrawn legal-status Critical Current

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    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to novel O-carbamoylglycero-2-phosphocholines of the general formula I <IMAGE> and a process for their preparation and also their use as hydrolysis-resistant phospholipids in liposome technology.

Description

Beschreibungdescription

Die vorliegende Erfindung betrifft neue Carbamoyl-glycero-2-phosphocholine, Verfahren zu ihrer Herstellung, sowie ihre Anwendung als hydrolysenbestandige Phospholipide in der Liposomentechnik. Die erfindungsgemäßen Carbamvl-glycero-2-phoshocholine entsprechen der allgemeinen Formel I worin R1 und R2 einen geradkettigen gesättigten oder unsesättigten Kohlenwasserstoffrest mit 10-20 Kohlenstoffatomen bedeuten, die gleich oder verschieden sein können. Für R1 und R2 kommen insbesondere in Betracht: Hexadecyl, Octadecyl.The present invention relates to new carbamoyl-glycero-2-phosphocholines, processes for their production and their use as hydrolysis-resistant phospholipids in liposome technology. The carbamvl-glycero-2-phosphocholines according to the invention correspond to the general formula I. wherein R1 and R2 represent a straight-chain saturated or unsaturated hydrocarbon radical having 10-20 carbon atoms, which can be the same or different. Particularly suitable for R1 and R2 are: hexadecyl, octadecyl.

Verbindungen gemäß der Erfindung sind beispielsweise: 1-O-Decylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholin, 1b0-Hexadecyl-3-0-undecylcarbamoyl-qlycero-2-phosphocholin,.Compounds according to the invention are for example: 1-O-decylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholine, 1b0-hexadecyl-3-0-undecylcarbamoyl-qlycero-2-phosphocholine ,.

1O-Dodecylcarbamoyl-3aO-hexadecyl-lycero-2-phosphocholin, 1-O-Hexadecyl-3-O-tetradecalcarbamoyl-glycero-2-phosphocholin, 1-0-Hexadecyl-3-0-eicosylcarbamoyl-alycero-2-phosphocholin, 1-0- DecylcarbamOYl -3-O-octadecyl-alycero-2-phosphocholin, 1-0-Octadecyl-3-0-undecylcarbamoyl-alycero-2-phosphocholin, 1-0-Dodecylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholin, 1-0-Octadecyl-3-0-tetradecylcarbamoyl-glycero-2-phosphocholin, 1-0-Eicosylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholin, 1-0-Hexadecylcarbamoyl-3-0-oleyl-glycero-2-phosphochol in, 1-0-Hexadecylcarbamoyl-3-0-linolyl-glycero-2-phosphocholin, besonders bevorzugt sind: 1-0-Hexadecyl -3-0-hexadecyl carbamoyl -glycero-2-phosphochol in, 1-0-Hexadecyl-3-0-octadecylcarbamoyl-glycero-2-phosphocholin, 1-0-Hexadecylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholin, 1-0-Octadecyl-3-0-octadecylcarbamoyl-lycero-2-phosphocholin.1O-dodecylcarbamoyl-3aO-hexadecyl-lycero-2-phosphocholine, 1-O-hexadecyl-3-O-tetradecalcarbamoyl-glycero-2-phosphocholine, 1-0-hexadecyl-3-0-eicosylcarbamoyl-alycero-2-phosphocholine, 1-0- DecylcarbamOYl -3-O-octadecyl-alycero-2-phosphocholine, 1-0-octadecyl-3-0-undecylcarbamoyl-alycero-2-phosphocholine, 1-0-dodecylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholine, 1-0-octadecyl-3-0-tetradecylcarbamoyl-glycero-2-phosphocholine, 1-0-eicosylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholine, 1-0-hexadecylcarbamoyl-3-0-oleyl-glycero-2-phosphochol in, 1-0-hexadecylcarbamoyl-3-0-linolyl-glycero-2-phosphocholine, particularly preferred are: 1-0-hexadecyl -3-0-hexadecyl carbamoyl -glycero-2-phosphocholine in, 1-0-hexadecyl-3-0-octadecylcarbamoyl-glycero-2-phosphocholine, 1-0-hexadecylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholine, 1-0-octadecyl-3-0-octadecylcarbamoyl-lycero-2-phosphocholine.

Die erfindungsgemäßen Verbindungen weisen gegenüber den bisher in der Liposomentechnik verwendeten natürlichen oder synthetischen 1,2-Diacyl-glycero-3-phosphocholinen (z.B.The compounds according to the invention have compared to the previously in natural or synthetic 1,2-diacyl-glycero-3-phosphocholines used in liposome technology (e.g.

DE-OS 27 12 031) deutliche Vorteile auf, da-sie im Gegensatz zu diesen Phospholipiden genen PhospholipasenA1 und A2 beständig sind und damit eine bessere Vermittlung des eingeschlossenen Wirkstoffes an den Wirkungsort ermöglichen.DE-OS 27 12 031) has significant advantages because they are in contrast to these Phospholipids genes PhospholipasesA1 and A2 are resistant and therefore a better one Enable mediation of the included active ingredient to the place of action.

Die erfindungsgemäßen Substanzen werden durch Reaktion der Lysoverbindungen II, worin R1 die in Formel I genannte Bedeutung hat, mit Isocyanaten der Formel III, worin R2 die in Formel 1 angegebene Bedeutung hat, nach folgender Gleichung hergestellt: Die Reaktion wird zweckmäßig in organischen aprotischen Lösungsmitteln, wie z.B. Chloroform, Aceton, Dimethylformamid bzw. deren Mischungen, ggfs. unter Anwendung eines Katalysators, insbesondere einer Lewis-Base, wie z.B. Triethylamin, Pyridin, 4-Dimethylaminopyridin, Dimethylformamid, bei Temperaturen zwischen O° und 100°C, vorzugsweise bei 40 - 60°C, durchgeführt.The substances according to the invention are prepared by reacting the lyso compounds II, in which R1 has the meaning given in formula I, with isocyanates of the formula III, in which R2 has the meaning given in formula 1, according to the following equation: The reaction is expediently carried out in organic aprotic solvents such as chloroform, acetone, dimethylformamide or mixtures thereof, if necessary using a catalyst, in particular a Lewis base, such as triethylamine, pyridine, 4-dimethylaminopyridine, dimethylformamide, at temperatures between 0 ° and 100 ° C, preferably at 40-60 ° C.

Die Isocyanate können auch in Form ihrer Imidazolide 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 freie Isocyanate verhalten (verol. H.A.Staab und WORohrs in: Neuere Methoden der präparativen organischen Chemie, S. 79, Weinheim 1967).The isocyanates can also be used in the form of their imidazolides with the general formula IV in which R2 has the meaning given in formula I, can be used under the abovementioned conditions, since the imidazolides behave like free isocyanates (verol. HAStaab and WORohrs in: Newer methods of preparative organic chemistry, p. 79, Weinheim 1967).

als Ausgangsverbindungen II kommen in Frage: 1-O-Decyl-glycero-2-phosphocholin, 1-O-Undecyl-glycero-2-phosphocholin, 1-O-Dodecyl-glycero-2-phosphocholin, 1-O-Tridecyl-glycero-2-phosphocholin, 1-O-Tetradecyl-glycero-2-phosphocholin, 1-O-Pentadecyl-glycero-2-phosphocholin, 1-O-Hexadecyl-glycero-2-phosphocholin, 1-O-Heptadecyl-glycero-2-phosphocholin, 1-O-Octadecyl-glycero-2-phosphocholin, 1-O-Nonadecyl-glycero-2-phosphocholin, 1-O-Eicosyl-glycero-2-phosphocholin, 1-O-Oleyl-glycero-2-phosphocholin, 1-O-Linolyl-glycero-2-phosphocholin, wobei die Lysöverbindungen in der natürlichen sn-Form, in Form der Spiegelbildisomeren oder als Racemate eingesetzt werden können.starting compounds II are: 1-O-decyl-glycero-2-phosphocholine, 1-O-Undecyl-glycero-2-phosphocholine, 1-O-Dodecyl-glycero-2-phosphocholine, 1-O-Tridecyl-glycero-2-phosphocholine, 1-O-tetradecyl-glycero-2-phosphocholine, 1-O-pentadecyl-glycero-2-phosphocholine, 1-O-hexadecyl-glycero-2-phosphocholine, 1-O-heptadecyl-glycero-2-phosphocholine, 1-O-octadecyl-glycero-2-phosphocholine, 1-O-Nonadecyl-glycero-2-phosphocholine, 1-O-Eicosyl-glycero-2-phosphocholine, 1-O-oleyl-glycero-2-phosphocholine, 1-O-linolyl-glycero-2-phosphocholine, the lyso compounds in the natural sn form, in the form of the mirror image isomers or as racemates can be used.

Als Ausgangsverbindungen der Formel III kommen z.B. in Frage: Decylisocyanat, 9-Decenylisocyanat, Undecylisocyanat, Dodecylisocyanats Tridecylisocyanat, Tetradecylisocyanat, Pentadecylisocyanat, Hexadecylisocyanat, Eicosylisocyanat, Octadecylisocyanat, Nonadecylisocyanat.Possible starting compounds of the formula III are, for example: decyl isocyanate, 9-decenyl isocyanate, undecyl isocyanate, dodecyl isocyanate, tridecyl isocyanate, tetradecyl isocyanate, Pentadecyl isocyanate, hexadecyl isocyanate, eicosyl isocyanate, octadecyl isocyanate, nonadecyl isocyanate.

Die als Ausgangsverbindungen verwendeten O-Alkyl-glycero-2-phosphocholine II können durch milde alkalische Hydrolyse aus O-Acyl-O-alkyl-qlycero-2-phosphocholinen erhalten werden, die -sich aus den Glycerinderivaten der Formel V in der R1 die in Formel I angegebene Bedeutung hat und R4 einen geradkettiqen oder verzweigten Kohlenwasserstoffrest mit 1-6 Kohlenstoffatomen bedeutet, nach bekannten Phosphorviferungsverfahren, wie z.B. durch Umsetzen mit ß-Bromethylphosphorsäuredichlorid in Gegenwart einer Base und nachfolgendes Behandeln mit Trimethylamin herstellen lassen (verb. z.B.The O-alkyl-glycero-2-phosphocholine II used as starting compounds can be obtained by mild alkaline hydrolysis from O-acyl-O-alkyl-qlycero-2-phosphocholines, which are obtained from the glycerol derivatives of the formula V in which R1 has the meaning given in formula I and R4 denotes a straight-chain or branched hydrocarbon radical with 1-6 carbon atoms, can be prepared by known phosphorus processes, such as, for example, by reacting with β-bromoethylphosphoric acid dichloride in the presence of a base and subsequent treatment with trimethylamine (verb. e.g.

T. Muramatsu et al., Chemistry and Physics of Lipids, 29, 121-127 (1981)).T. Muramatsu et al., Chemistry and Physics of Lipids, 29, 121-127 (1981)).

Die ClXycerinderivate V sind ihrerseits aus 2,3-Epoxypropylethern durch Umsetzung mit den entsprechenden Säuren R4COoH analog dem von U. Zeidler, Fette, Seifen, Anstrichmittel, 83, (2), 57 (1981) für Esteralkohole beschriebenen Verfahren zugänzlich. 2,3-Epoxyether erhält man aus Epichlorhydrinen und den entsprechenden Alkoholen R1OH am besten durch Phasen-Transferkatalyse nach literaturbekannten Verfahren. Andererseits lassen sich die Glycerinderivate V durch Isomerisieruna aus den entsprechenden 2-O-Acvl-plycerinethern VI z.B. durch einfaches Erwärmen gewinnen. Die Synthese der 2-O-Acyl-glycerinether wird von K. Mangold, Angew. Chemie 91, 550-560 (1979) beschrieben.The ClXycerin derivatives V are in turn accessible from 2,3-epoxypropyl ethers by reaction with the corresponding acids R4COoH analogous to the process described by U. Zeidler, Fette, Seifen, Anstrichmittel, 83, (2), 57 (1981) for ester alcohols. 2,3-Epoxy ether is best obtained from epichlorohydrins and the corresponding alcohols R1OH by phase transfer catalysis according to processes known from the literature. On the other hand, the glycerol derivatives V can be isomerized from the corresponding 2-O-Acvl-plycerol ethers VI eg win by simply heating. The synthesis of the 2-O-acyl glycerol ethers is described by K. Mangold, Angew. Chemie 91, 550-560 (1979).

Die Lysoverbindungen II können auch aus 1-0-Alkyl-3-0-benzylglycerinen synthetisiert werden, indem man diese in Form der einzelnen Enantiomeren oder des Racemats durch Umsetzen mit ß-Bromethylphosphorsäuredichlorid in Gegenwart einer Base und nachfolgendes Behandeln mit Trimethylamin in die 1-0-Alkyl-3-O-benzyl-glycero-2-phosphocholin überführt-, die ihrerseits durch Hydrieren in Gegenwart eines Katalysators, wie z.B.The lyso compounds II can also be prepared from 1-0-alkyl-3-0-benzylglycerols can be synthesized by converting them in the form of the individual enantiomers or the Racemats by reacting with ß-Bromoethylphosphorsäuredichlorid in the presence of a Base and subsequent treatment with trimethylamine to form the 1-0-alkyl-3-O-benzyl-glycero-2-phosphocholine transferred- which in turn by hydrogenation in the presence of a catalyst such as e.g.

Palladium/Aktivkohle, die Verbindungen II erqeben.Palladium / activated carbon, the compounds II erqeben.

Die Herstellung der erfindungsoemäßen Verbindunoen wird durch die folgenden Beispiele näher erläutert. Da sich die.Verbindungen der Formel I aufgrund ihrer wachsartigen Konsistenz nicht durch Schmelzpunkte charakterisieren lassen, sind die Jeweiligen IR-Daten sowie die RF-Werte der Substanzen aus Formel B angegeben. Die IR-Spektren wurden mit dem Gerät Perkin-Elmer 257 aufgenommen, wobei die Substanzen als Chloroformlösungen vermessen wurden.The production of the connections according to the invention is carried out by the the following examples are explained in more detail. Since die.Verbindungen of the formula I due to their waxy consistency cannot be characterized by melting points, the respective IR data and the RF values of the substances from formula B are given. The IR spectra were recorded with the Perkin-Elmer 257 device, with the substances as chloroform solutions were measured.

BUnnschlchtchromatographie: Kieselgel 60 F-254, Fa. Merck, Art. 5719 Laufmittel: Chloroform/Methanol/Wasser = 65/25/4 (v/v/v) Beispiel 1 1-0-Hexadecyl-3-0-hexadecylcarbamoyl-glycero-2-phosphocholin.Thin-layer chromatography: silica gel 60 F-254, Merck, Art. 5719 Mobile phase: chloroform / methanol / water = 65/25/4 (v / v / v) example 1 1-0-hexadecyl-3-0-hexadecylcarbamoyl-glycero-2-phosphocholine.

Eine Mischung aus 50 ma 1-0-Hexadecyl-glycero-2-phosphocholin, 107 mg Hexadecylisocyanat, 5 ml Chloroform und 0,1 ml Dimethylformamid wird bei 60°C gerührt (48 Stunden). Das überschüssige Al-kylisocyanat wird durch Zugabe von wenia Wasser hydrolysiert und die Mischung im Vakuum weitgehend einneenot, Der Rückstand wird durch präparative Dünnschichtchromatocrphie (Kieselgel//Chloroform/Methanol/Wasser ) gereinigt.A mixture of 50 ma 1-0-hexadecyl-glycero-2-phosphocholine, 107 mg of hexadecyl isocyanate, 5 ml of chloroform and 0.1 ml of dimethylformamide are heated to 60.degree stirred (48 hours). The excess alkyl isocyanate is by adding wenia Water hydrolyzed and the mixture largely einneenot in vacuo, the residue is determined by preparative thin-layer chromatography (silica gel // chloroform / methanol / water ) cleaned.

Ausbeute: 52 mg Wachs Rf = 0,5 IR: gamma;(c=o) o) = 1712 cm 1 Analoa dieser Vorschrift werden hergestellt: Beispiel 2 1-0-Hexadecyl -3-0-octadecyl carbamoyl -glycero-2-phosphochol in aus 50 mg 1-0-Hexadecyl-glycero-2-phosphochol in 120 mg Octadecylisocyanat in 5 ml Chloroform und 0,1 ml Dimethylformamid Ausbeute: 61 mg, Rf = 0,5, #(c=o) = 1715 cm -1 Beispiel 3 1-0-Hexadecyl carbamoyl -3-0-octadecyl-glycero-2-phosphochol in aus 50 mg 1-O-Octadecyl-glycero-2-phosphocholin 100 mg Hexadecylisocyanat in 5 ml Chloroform und 0,1 l Dimethylformamid.Yield: 52 mg wax Rf = 0.5 IR: gamma; (c = o) o) = 1712 cm -1 Analoa according to this specification are prepared: Example 2 1-0-Hexadecyl -3-0-octadecyl carbamoyl -glycero-2-phosphochol in from 50 mg 1-0-hexadecyl-glycero-2-phosphochol in 120 mg Octadecyl isocyanate in 5 ml of chloroform and 0.1 ml of dimethylformamide Yield: 61 mg, Rf = 0.5, # (c = o) = 1715 cm -1 Example 3 1-0-Hexadecyl carbamoyl -3-0-octadecyl-glycero-2-phosphochol in from 50 mg 1-O-octadecyl-glycero-2-phosphocholine 100 mg hexadecyl isocyanate in 5 ml of chloroform and 0.1 l of dimethylformamide.

Ausbeute: 48 mg, Rf = 0,51, r (c=o)=1710 com 1 Beispiel 4 1-O-Octadecyl-3-O-octadecylcarbamoyl-glycero-2-phosphocholin aus 50 mg 1-O-Octadecyl-glycero-2-phosphocholin 120 mg Octadecylisocyanat in 5 ml Chloroform und 0,1 ml Dimethylformamid Analog den Beispielen 1-4 werden hergestellt: 1-O-Decylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholin 1°O-Hexadecyl°3-0-undecylcarbamoyl-glycero-2-phosphocholin, 1¢0-Dodecylcarbamoyl-3-0-hexadecyl-alycero-2-phosphocholin, 1-O-Hexadecyl-3-O-tetradecylcarbamoyl-glycero-2-phosphocholin, 1-O-Eicosylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholin, 1-O-Decylcarbamoyl-3-O-octadecyl-glycero-2-phosphocholin, 1-O-Octadecyl-3-O-undecylcarbamoyl-glycero-2-phosphocholin, 2°0°Dodecylcarbamoyl-3~0-octadecyl-alycero-2-phosDhocholin, 1-O-Octadecyl-3-O-tetradecylcarbamoyl-glycero-2-phosphocholin, 1-O-Eicosylcarbamoyl-3-O-octadecyl-glycero-2-phosphocholin, 1-O-Hexadecylcarbamoyl-3-O-oleyl-glycero-2-phosphocholin, 1-O-Hexadecylcarbamoyl-2-O-linolyl-glycero-2-phosphocholin,Yield: 48 mg, Rf = 0.51, r (c = o) = 1710 com 1 Example 4 1-O-Octadecyl-3-O-octadecylcarbamoyl-glycero-2-phosphocholine from 50 mg 1-O-octadecyl-glycero-2-phosphocholine 120 mg octadecyl isocyanate in 5 ml Chloroform and 0.1 ml dimethylformamide Analogous to Examples 1-4 are produced: 1-O-decylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholine 1 ° O-hexadecyl ° 3-0-undecylcarbamoyl-glycero-2-phosphocholine, 1 [0-dodecylcarbamoyl-3-0-hexadecyl-alycero-2-phosphocholine, 1-O-hexadecyl-3-O-tetradecylcarbamoyl-glycero-2-phosphocholine, 1-O-eicosylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholine, 1-O-decylcarbamoyl-3-O-octadecyl-glycero-2-phosphocholine, 1-O-Octadecyl-3-O-undecylcarbamoyl-glycero-2-phosphocholine, 2 ° 0 ° Dodecylcarbamoyl-3 ~ 0-octadecyl-alycero-2-phosphocholine, 1-O-octadecyl-3-O-tetradecylcarbamoyl-glycero-2-phosphocholine, 1-O-eicosylcarbamoyl-3-O-octadecyl-glycero-2-phosphocholine, 1-O-hexadecylcarbamoyl-3-O-oleyl-glycero-2-phosphocholine, 1-O-hexadecylcarbamoyl-2-O-linolyl-glycero-2-phosphocholine,

Claims (19)

Patentansprüche (1.) Carbamoyl-glycero-2-phosphocholine der allgemeinen Formel I worin R1 und R2 einen geradkettigen gesättigten oder unter sättlgten Kohlenwasserstoffrest mit 10-20 Kohlenstoffatomen bedeuten, wobei ß1 und R2 gleich oder verschieden sein können.Claims (1.) Carbamoyl-glycero-2-phosphocholine of the general formula I. where R1 and R2 are a straight-chain saturated or saturated hydrocarbon radical with 10-20 carbon atoms, where β1 and R2 can be the same or different. 2. Carbamoyl-glycero-2-phosphochline der allgemeinen Formel I, worin R1 und R2 einen aeradkettiqen nesättioten oder unter sättigten Kohlenwasserstoffrest mit 16-18 Kohlenstoffatomen bedeuten wobei R1 und R2 gleich oder verschieden sein können.2. Carbamoyl-glycero-2-phosphochlins of the general formula I, in which R1 and R2 an aeradkettiqen nesättioten or below saturated hydrocarbon radical with 16-18 carbon atoms mean where R1 and R2 are identical or different can. 3. 1-O-Decylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholin. 3. 1-O-decylcarbamoyl-3-O-hexadecyl-glycero-2-phosphocholine. 4, 1-0-Hexadecyl-3-0-undecylcarbamoyl-glycero-2-phosphocholin.4, 1-0-hexadecyl-3-0-undecylcarbamoyl-glycero-2-phosphocholine. 5. 1-0-Dodecylcarbamoyl-3-0-hexadecyl-alycero-2-phosphocholin. 5. 1-0-dodecylcarbamoyl-3-0-hexadecyl-alycero-2-phosphocholine. 6. 1-0-Hexadecyl-3-0-tetradecwylcarbamoyl-alycero-2-phosphocholin. 6. 1-0-hexadecyl-3-0-tetradecylcarbamoyl-alycero-2-phosphocholine. 7. 1-0-Hexadecyl-3-0-hexadecylcarbamoyl-elycero-2-phosphocholin. 7. 1-0-hexadecyl-3-0-hexadecylcarbamoyl-elycero-2-phosphocholine. 8. 1-0-Hexadecyl-3-0-octadecylcarbamoyl-alycero-2-phosphocholin. 8. 1-0-hexadecyl-3-0-octadecylcarbamoyl-alycero-2-phosphocholine. 9. 1-0-Hexadecyl-3-0-eicosylcarbamo,yl-glycero-2-phosphocholin. 9. 1-0-hexadecyl-3-0-eicosylcarbamo, yl-glycero-2-phosphocholine. 10. 1-O-Decylcarbamoyl-3-O-octadecyl-glycero-2-phosphocholin.10. 1-0-Decylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholine. 11. 1-0-Octadecyl-3-0-undecylcarbamoyl-glycero-2-phosphocholin.11. 1-0-Octadecyl-3-0-undecylcarbamoyl-glycero-2-phosphocholine. 12. 1-0-Dodecylcarbamoyl-3-0-octadecyl-qlycero-2-phosphocholin.12. 1-0-dodecylcarbamoyl-3-0-octadecyl-glycero-2-phosphocholine. 13. 1-O-Octadecyl-3-O-tetradecylcarbamoyl-glycero-2-phosphocholin.13. 1-0-Octadecyl-3-0-tetradecylcarbamoyl-glycero-2-phosphocholine. 14. 1-0-Hexadecyl carbamoyl -3-0-octadecyl-lycero-2-phosphocholin.14. 1-0-Hexadecyl carbamoyl -3-0-octadecyl-lycero-2-phosphocholine. 15. 1-0-Octadecyl-3-0-octadecylcarbamoyl-alycero-2-phosphocholin.15. 1-0-Octadecyl-3-0-octadecylcarbamoyl-alycero-2-phosphocholine. 16. 1-0-Eicosylcarbamoyl-3-0-octadecyl-alycero-2-phosphocholin.16. 1-0-Eicosylcarbamoyl-3-0-octadecyl-alycero-2-phosphocholine. 17. 1-0-Hexadecylcarbamoyl-3-0-ole,yl-alycero-2-phosphocholin.17. 1-0-Hexadecylcarbamoyl-3-0-ols, yl-alycero-2-phosphocholine. 18. 1-0-Hexadecylcarbamoyl-3-0-linolyl-alycero-2-phosphocholin.18. 1-0-Hexadecylcarbamoyl-3-0-linolyl-alycero-2-phosphocholine. 19. Verfahren zur Herstellung von Verbindungen der Formel I gemäß den Ansprüchen 1-18, dadurch gekennzeichnet, daß man die Lysoverbindung der allgemeinen Formel II in der R1 die in Formel I angegebene Bedeutung besitzt, in einem aprotischen organischen Lösungsmittel, gqfs. unter Zusatz einer Lewis-Base als Katalysator, mit dem entsprechenden Alkylisocyanat oder dessen Imidazolid umsetzt.19. A process for the preparation of compounds of the formula I according to claims 1-18, characterized in that the lyso compound of the general formula II in which R1 has the meaning given in formula I, in an aprotic organic solvent, if necessary. with the addition of a Lewis base as a catalyst, with the corresponding alkyl isocyanate or its imidazolide.
DE19813151378 1981-08-12 1981-12-24 Novel O-carbamoylglycero-2-phosphocholines and process for their preparation Withdrawn DE3151378A1 (en)

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DE19813151378 DE3151378A1 (en) 1981-12-24 1981-12-24 Novel O-carbamoylglycero-2-phosphocholines and process for their preparation
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
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

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