DE3131782A1 - Novel carbamoylglycero-3-phosphocholines and processes for their preparation - Google Patents
Novel carbamoylglycero-3-phosphocholines and processes for their preparationInfo
- Publication number
- DE3131782A1 DE3131782A1 DE19813131782 DE3131782A DE3131782A1 DE 3131782 A1 DE3131782 A1 DE 3131782A1 DE 19813131782 DE19813131782 DE 19813131782 DE 3131782 A DE3131782 A DE 3131782A DE 3131782 A1 DE3131782 A1 DE 3131782A1
- Authority
- DE
- Germany
- Prior art keywords
- glycero
- phosphocholine
- hexadecyl
- octadecyl
- phosphocholines
- 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- Withdrawn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
- 238000000034 method Methods 0.000 title claims abstract description 6
- 238000002360 preparation method Methods 0.000 title claims abstract description 5
- -1 alkyl isocyanate Chemical class 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 5
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 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
- 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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000007928 imidazolide derivatives Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 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
- 238000004809 thin layer chromatography Methods 0.000 description 2
- XFEWMFDVBLLXFE-UHFFFAOYSA-N 1-isocyanatodecane Chemical compound CCCCCCCCCCN=C=O XFEWMFDVBLLXFE-UHFFFAOYSA-N 0.000 description 1
- YIDSTEJLDQMWBR-UHFFFAOYSA-N 1-isocyanatododecane Chemical compound CCCCCCCCCCCCN=C=O YIDSTEJLDQMWBR-UHFFFAOYSA-N 0.000 description 1
- GFLXBRUGMACJLQ-UHFFFAOYSA-N 1-isocyanatohexadecane Chemical compound CCCCCCCCCCCCCCCCN=C=O GFLXBRUGMACJLQ-UHFFFAOYSA-N 0.000 description 1
- RWCDAKQLMGCVLI-UHFFFAOYSA-N 1-isocyanatoicosane Chemical compound CCCCCCCCCCCCCCCCCCCCN=C=O RWCDAKQLMGCVLI-UHFFFAOYSA-N 0.000 description 1
- HULTVDSPXGVYBQ-UHFFFAOYSA-N 1-isocyanatopentadecane Chemical compound CCCCCCCCCCCCCCCN=C=O HULTVDSPXGVYBQ-UHFFFAOYSA-N 0.000 description 1
- CSMJMAQKBKGDQX-UHFFFAOYSA-N 1-isocyanatotetradecane Chemical compound CCCCCCCCCCCCCCN=C=O CSMJMAQKBKGDQX-UHFFFAOYSA-N 0.000 description 1
- BAZBBHGFCBVAQU-UHFFFAOYSA-N 1-isocyanatotridecane Chemical compound CCCCCCCCCCCCCN=C=O BAZBBHGFCBVAQU-UHFFFAOYSA-N 0.000 description 1
- JXAYHHMVMJVFPQ-UHFFFAOYSA-N 1-isocyanatoundecane Chemical compound CCCCCCCCCCCN=C=O JXAYHHMVMJVFPQ-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
Landscapes
- 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)
Abstract
Description
Titel: Neu-e Carbamoyl-glycero-3-phosphocholine und Ver-Title: Neu-e Carbamoyl-glycero-3-phosphocholine and Ver
fahren zu ihrer Herstellung Beschreibung Die vorliegende Erfindung betrifft neue Calbamoyl-glycero-3-phosphocholine, Verfahren zu ihrer Herstellung, sowie ihre Anwendung als hydrolysenbeständiges Phospholipid in'der Liposomen-Technik. Die erfindungsgemäßen Carbamoyl-glycero-3-phosphocholine entsprechen der allgemeinen Formel I worin R1 und R2 einen geradkettigen Kohlenwasserstoffrest mit 10-20 Kohlenstoffatomen bedeuten, die gleichöder verschieden sein können. Für R1 und R2 kommen insbesondere in Betracht: Hexadecyl, Octadecyl Verbindungen gemäß der Erfindung sind beispielsweise: 2-0-Decylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholin, l-O-Hexadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholin 2-0-Dodecylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholinX 1-0-Hexadecyl-2-0-tetradecylcarbamoyl-glycero-3-phosphocholin1 2-0-Eicosylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholin, 2-0-Decylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholint 1-0-Octadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholin, 2-0-Dodecylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, 1-0-Octadecyl-2-0-teradecylcarbamoyl-glycero-3-phosphocholinX 2-0-Eicosylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, Besonders bevorzugt sind: 1-0-Hexadecyl-2-0-hexadecylcarbamoyl-glycero-3-phosphocholin, 1-0-Hexadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholin, 2-0-Hexadecylcarbamoyl-1 -0-octadecyl-glycero-3-phosphocholin 1-0-Octadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholin.proceed to their production Description The present invention relates to new calbamoyl-glycero-3-phosphocholines, processes for their production, and their use as hydrolysis-resistant phospholipid in liposome technology. The carbamoyl-glycero-3-phosphocholines according to the invention correspond to the general formula I. wherein R1 and R2 represent a straight-chain hydrocarbon radical with 10-20 carbon atoms, which can be identical or different. Particularly suitable for R1 and R2 are: Hexadecyl, octadecyl compounds according to the invention are, for example: 2-0-decylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholine, 10-hexadecyl-2-0-undecylcarbamoyl-glycero-3 -phosphocholine 2-0-dodecylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholineX 1-0-hexadecyl-2-0-tetradecylcarbamoyl-glycero-3-phosphocholin1 2-0-eicosylcarbamoyl-1-0-hexadecyl-glycero- 3-phosphocholine, 2-0-decylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, 1-0-octadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholine, 2-0-dodecylcarbamoyl-1-0-octadecyl -glycero-3-phosphocholine, 1-0-octadecyl-2-0-teradecylcarbamoyl-glycero-3-phosphocholineX 2-0-eicosylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, particularly preferred are: 1-0- Hexadecyl-2-0-hexadecylcarbamoyl-glycero-3-phosphocholine, 1-0-hexadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholine, 2-0-hexadecylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine 1 -0-Octadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholine.
Die erfindungsgemäßen Verbindungen weisen gegenüber den bisher in der Liposomentechnik verwendeten natürlichen oder synthetischen 1,2-Diacyl-glycero-3-phosphocholinen (z.B. DE-OS 27 12 031) deutliche Vorteile auf, da sie im Gegensatz zu diesen Phospholipiden gegen Phospholipase A2 beständig sind, und damit eine bessere Vermittlung des eingeschlossenen Wirkstoffes an den Wirkungsort ermöglichen.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) have clear advantages, as they are in contrast to these phospholipids are resistant to phospholipase A2, and thus better conveyance of the trapped Enable active ingredient to the place of action.
Die erfindungsgemäßen Substanzen werden nach an sich bekannten Verfahren durch Reaktion der Lysoverbindungen mit der allgemeinen Formel II, worin R1 die in der allgemeinen Formel I angegebene Bedeutung hat, mit Alkylisocyanaten der Formel III, worin R2 die in Formel I genannte Bedeutung hat, nach folgender Gleichung hergestellt: 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 0-1000C, vorzugsweise bei 40-60°C durchgeführt.The substances according to the invention are prepared according to processes known per se by reacting the lyso compounds with the general formula II, in which R1 has the meaning given in the general formula I, with alkyl isocyanates of the formula III, in which R2 has the meaning given in formula I, according to the following equation manufactured: The reaction is expediently carried out in organic aprotic solvents such as chloroform, acetone, dimethylformamide or mixtures thereof, optionally using a catalyst, in particular a Lewis base such as triethylamine, pyridine, 4-dimethylaminopyridine, dimethylformamide at temperatures between 0-1000C, preferably carried out at 40-60 ° C.
Die Alkylisocyanate können auch in Form ihrer Imidazolide mit der allgemeinen Formel IV wobei R2 die in Formel I angegebene Bedeutung hat, unter den oben genannten Bedingungen umgesetzt werden, da sich die Imidazolide wie freie Isocyanate verhalten (vgl. K.A. Staab u.The alkyl isocyanates can also be used in the form of their imidazolides with the general formula IV where R2 has the meaning given in formula I, can be reacted under the abovementioned conditions, since the imidazolides behave like free isocyanates (cf. KA Staab u.
W. Rohr, in: Neuere Methoden der präparativen organischen Chemie, S.79, Weinheim, 1967).W. Rohr, in: Newer Methods in Preparative Organic Chemistry, 79, Weinheim, 1967).
Als Ausgangsverbindungen II kommen z.B. in Frage: 1-0-Decyl-glycero-3-phosphocholin 1-0-Undecyl-glycero-3-phosphocholin, 1 -0-Dodecyl- glycero- 3-phosphocholin1 1-0-Tridecyl-glycero-3-phosphocholin, l-0-Tetradecyl-glycero-3-phosphocholin, 1-0-Pentadecyl-glycero-3-phosphocholin, 1 -0-Hexadecyl-glycero-3-phosphocholin1 1 -0-Heptadecyl-glycero-3-phosphocholini 1-0-Octadecyl-glycero-3-phosphocholin, 1-0-Nonadecyl-glycero-3-phosphocholin 1-0-Eicosyl-glycero-3-phosphocholin wobei die Lysoverbindungen in der natürlichen sn-Form, in Form der Spiegelbildisomeren oder als Racemate eingesetzt werden können.Possible starting compounds II are, for example: 1-0-decyl-glycero-3-phosphocholine 1-0-undecyl-glycero-3-phosphocholine, 1 -0-dodecyl-glycero-3-phosphocholine1 1-0-tridecyl-glycero-3-phosphocholine, l-0-tetradecyl-glycero-3-phosphocholine, 1-0-pentadecyl-glycero-3-phosphocholine, 1 -0-hexadecyl-glycero-3-phosphocholin1 1 -0-heptadecyl-glycero-3-phosphocholini 1-0-octadecyl-glycero-3-phosphocholine, 1-0-nonadecyl-glycero-3-phosphocholine, 1-0-eicosyl-glycero-3-phosphocholine 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-glycero-3-phosphocholine--der allgemeinen Formel II sind entweder durch Organextraktion [z.B. M. Blank et al., Biochemical and Biophysical Research Cömmunications 90 (4), 1194ff,'(1979)0 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. Ober die Herstellung der 2-0-Acyl-1-0-alkyl-glycero-3-phosphocholine wird in einem Obersichtsartikel berichtet (H.K. Mangold, Angew. Chemie 91, 550-560, 1979).The 1-0-alkyl-glycero-3-phosphocholine used as starting compounds - the general formula II are either by organ extraction [e.g. M. Blank et al., Biochemical and Biophysical Research Communications 90 (4), 1194ff, '(1979) 0 accessible or can be prepared by 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. About the production of 2-0-acyl-1-0-alkyl-glycero-3-phosphocholines is reported in a review article (H.K. Mangold, Angew. Chemie 91, 550-560, 1979).
Als Ausgangsverbindungen der Formel III kommen z.B. in Frage: Decylisocyanat, Undecylisocyanat, Dodecylisocyanat, Tridecylisocyanat, Tetradecylisocyanat, Pentadecylisocyanat, Hexadecyisocyanat, Eicosylisocyanat.Possible starting compounds of the formula III are, for example: decyl isocyanate, Undecyl isocyanate, dodecyl isocyanate, tridecyl isocyanate, tetradecyl isocyanate, pentadecyl isocyanate, Hexadecyisocyanate, eicosyl isocyanate.
Die Herstellung der erfindungsgemäßen Verbindungen wird durch die folgenden Beispiele näher erläutert. Wegen der wachsartigen Konsistenz der Verbindungen wurden die IR-Daten und die Rf-Werte zur Charakterisierung herangezogen.The preparation of the compounds according to the invention is carried out by the following examples are explained in more detail. Because of the waxy consistency of the joints the IR data and the Rf values were used for characterization.
Die IR-Spektren wurden mit dem Gerät Perkin-Elmer 257 aufgenommen, wobei die Substanzen als Chloroformlösungen vermessen wurden.The IR spectra were recorded with the Perkin-Elmer 257 device, whereby the substances were measured as chloroform solutions.
DUnnschichtchromatographie: DC-Fertigplatten Kieselgel 60F-254, Fa. Merck, Art. 5719 Laufmittel: Chloroform/Methanol/Wasser = 65/25/5 (V/V/V) Beispiel 1 1-0-Hexadecyl-2-0-hexadecylcarbamoyl-glycero-3-phosphocholin Eine Mischung aus 50 mg 1-0-Hexadecyl-glycero-3-phosphocholin, 107 mg Hexadecylisocyanat, 5 ml Chloroform und 0,1 ml Dimethylformamid wird bei 600C gerührt (48 Stunden). Das überschüssige Alkylisocyanat wird durch Zugabe von wenig Wasser hydrolysiert und die Mischung im Vakuum weitgehend eingeengt. Der Rückstand wird durch präparative Dünnschichtchromatographie (Kieselgel/ Chloroform/Methanol/Wasser = 65/25/5) gereinigt.Thin-layer chromatography: TLC prefabricated silica gel plates 60F-254, Fa. Merck, Art. 5719 Mobile phase: chloroform / methanol / water = 65/25/5 (V / V / V) example 1 1-0-hexadecyl-2-0-hexadecylcarbamoyl-glycero-3-phosphocholine A mixture of 50 mg 1-0-hexadecyl-glycero-3-phosphocholine, 107 mg hexadecyl isocyanate, 5 ml chloroform and 0.1 ml of dimethylformamide is stirred at 60 ° C. (48 hours). The excess Alkyl isocyanate is hydrolyzed by adding a little water and the mixture largely concentrated in vacuo. The residue is analyzed by preparative thin layer chromatography (Silica gel / chloroform / methanol / water = 65/25/5).
Ausbeute: 45 mg Wachs Rf = 0,5 , IR: 1710 cm 1 (t)c"o) Analog werden hergestellt: 2. 1-0-Hexadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholint 3. 2-0-Hexadecylcarbamoyl- 1 -0-octadecyl-glycero-3-phosphocholin1 4. 1-0-Octadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholin, 5. 2-0-Decylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholint 6. 1-0-Hexadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholin 7. 2-0-Dodecylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholin1 8. 1-0-Hexadecyl-2-0-tetradecylcarbamoyl-glycero-3-phosphocholin 9. 2-0-Eicosylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholinf 10. 2-0-Decylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholin, 11. 1-0-Octadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholinX 12. 2-0-Dodecylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholint 13. 1-0-Octadecyl-2-0-tetradecylcarbamoyl-glycero-3-phosphocholin, 14. 2-0-Eicosylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholinbYield: 45 mg wax Rf = 0.5, IR: 1710 cm 1 (t) c "o) Analogue are produced: 2. 1-0-hexadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholine 3. 2-0-Hexadecylcarbamoyl- 1-0-octadecyl-glycero-3-phosphocholine1 4. 1-0-Octadecyl-2-0-octadecylcarbamoyl-glycero-3-phosphocholine, 5. 2-0-decylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholine 6. 1-0-hexadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholine 7. 2-0-dodecylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholine1 8. 1-0-hexadecyl-2-0-tetradecylcarbamoyl-glycero-3-phosphocholine 9.2-0-Eicosylcarbamoyl-1-0-hexadecyl-glycero-3-phosphocholine 10. 2-0-Decylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine, 11. 1-0-Octadecyl-2-0-undecylcarbamoyl-glycero-3-phosphocholine X 12. 2-0-Dodecylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine 13. 1-0-octadecyl-2-0-tetradecylcarbamoyl-glycero-3-phosphocholine, 14. 2-0-eicosylcarbamoyl-1-0-octadecyl-glycero-3-phosphocholine b
Claims (1)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813131782 DE3131782A1 (en) | 1981-08-12 | 1981-08-12 | Novel carbamoylglycero-3-phosphocholines and processes 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 | |
| ZA825684A ZA825684B (en) | 1981-08-12 | 1982-08-05 | New o-alkyl-o-carbamoylglycerophospho-cholines and process for their preparation |
| 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 |
|---|---|---|---|
| DE19813131782 DE3131782A1 (en) | 1981-08-12 | 1981-08-12 | Novel carbamoylglycero-3-phosphocholines and processes for their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3131782A1 true DE3131782A1 (en) | 1983-02-24 |
Family
ID=6139108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19813131782 Withdrawn DE3131782A1 (en) | 1981-08-12 | 1981-08-12 | Novel carbamoylglycero-3-phosphocholines and processes for their preparation |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE3131782A1 (en) |
| ZA (1) | ZA825684B (en) |
-
1981
- 1981-08-12 DE DE19813131782 patent/DE3131782A1/en not_active Withdrawn
-
1982
- 1982-08-05 ZA ZA825684A patent/ZA825684B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA825684B (en) | 1983-06-29 |
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