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Publication numberWO1999009037 A1
Publication typeApplication
Application numberPCT/EP1998/005252
Publication dateFeb 25, 1999
Filing dateAug 18, 1998
Priority dateAug 18, 1997
Also published asEP1019417A1, EP1019417B1, US6344576, US6545169, US6828453, US7595411, US7939683, US8497388, US20030198663, US20050165245, US20100183705, US20120009246
Publication numberPCT/1998/5252, PCT/EP/1998/005252, PCT/EP/1998/05252, PCT/EP/98/005252, PCT/EP/98/05252, PCT/EP1998/005252, PCT/EP1998/05252, PCT/EP1998005252, PCT/EP199805252, PCT/EP98/005252, PCT/EP98/05252, PCT/EP98005252, PCT/EP9805252, WO 1999/009037 A1, WO 1999009037 A1, WO 1999009037A1, WO 9909037 A1, WO 9909037A1, WO-A1-1999009037, WO-A1-9909037, WO1999/009037A1, WO1999009037 A1, WO1999009037A1, WO9909037 A1, WO9909037A1
InventorsHans-Jörg EIBL
ApplicantMAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.
Export CitationBiBTeX, EndNote, RefMan
External Links: Patentscope, Espacenet
Phospholipid analogue compounds
WO 1999009037 A1
Abstract
The invention relates to novel phospholipid analogue compounds of general formula (I) wherein A represents (II), R1 and R2 being hydrogen, a saturated or an unsaturated acyl or alkyl radical independently of each other. Said radical can be optionally branched and/or substituted, the sum of the carbon atoms in acyl and alkyl being from 16 to 44 C-atoms. s represents a whole number from 0 to 8, c = and is a radical of a primary or secondary alcohol of formula RO-, R being a saturated or an unsaturated alkyl radical, mainly with a cis-double bond, of 12 to 30 carbon atoms, n represents a whole number from 2 to 8, and R3 represents the following:- a = and can be 1.2-dihydroxypropyl, b = and can be an alkyl with 1 to 3 C-atoms when z > 0 or c = and can be an alkyl with 1 to 3 C-atoms when n ¸ 2 and z = 0, m = and is 1 or 2, x = and represents a whole number from 0 to 8, y = and is 1 for z = 1 to 5 or = and is 1 to 4 for z = 1, and z = and represents a whole number from 0 to 5. The novel compounds are suitable as liposome components, solutizers and medicaments.
Claims(6)  translated from German
    Patentanspr├╝che Patentanspr├╝che
  1. Verbindung der allgemeinen Formel (I) Compound of general formula (I)
    A - PO, (CH 2 ) n - (CH 2 2)h CH, CH, - 0 H A - PO, (CH 2) n - (CH 2 2) h CH, CH, - 0 H
    Figure imgf000065_0002
    Figure imgf000065_0001
    worin A a = CH 2 - O - R, CH 2 - 0 - R, I wherein A a = CH 2 - O - R, CH 2 - 0 - R, I
    CH - 0 - R 2 oder CH - 0 - CH, - 0 - CH 2 - 0 - R 2 CH - 0 - R 2 or CH - 0 - CH, - 0 - CH 2 - 0 - R 2
    oder b = or b =
    CH 2 - 0 - R, CH 2 - 0 - R, CH 2 - 0 - CH 2 - 0 - R, CH 2 - 0 - R, CH 2 - 0 -
    (CH 2 ), oder CH - 0 - oder CH - O - R, \ . (CH 2), or CH - 0 - or CH - O - R, \. CH, - 0 (CH 2 ) S - H (CH 2 ) S - H CH, - 0 (CH 2) S - H (CH 2) S - H
    ist, wobei R, und R 2 unabhängig voneinander Wasserstoff, einen gesättigten oder ungesättigten Acyl- oder Alkylrest bedeuten, der gegebenenfalls verzweigt oder/und substituiert sein kann, und die Summe der Kohlenstoffatome in Acyl und Alkyl 1 6 bis 44 C-Atome beträgt, s eine ganze Zahl von 0 bis 8 darstellt, c = ein Rest eines primären oder sekundären Alkohols der Formel RO- ist, wobei R einen gesättigten oder ungesättigten Alkylrest vorwiegend mit cis-Doppelbindung, von 1 2 bis 30 Kohlenstoffatomen bedeutet, n eine ganze Zahl von 2 bis 8 darstellt, wherein R, and R 2 unabhängig of one another hydrogen, an acyl or alkyl radical ungesättigten gesättigten or, optionally branched and / or may be substituted, and the sum of the carbon atoms in acyl and alkyl is 1 to 6 44 carbon atoms beträgt, s represents an integer from 0 to 8, c = is a residue of primären or sekundären alcohol of the formula RO-, where R is a predominantly gesättigten or alkyl radical having ungesättigten cis-double bond of 1 2 to 30 carbon atoms, n is an integer from 2 to 8,
    R 3 a = 1 ,2-Dihydroxypropyl sein kann oder b = Alkyl mit 1 bis 3 C-Atomen sein kann, wenn z > 0 ist oder c = Alkyl mit 1 bis 3 C-Atomen sein kann, wenn n Γëá 2 und z = R 3 a = 1, may be 2-dihydroxypropyl or b = alkyl may be of 1 to 3 C atoms, if z> 0 or c = alkyl may be of 1 to 3 carbon atoms, when n Γëá 2 and z =
    0 ist, m = 1 oder 2 ist, x = eine ganze Zahl von 0 bis 8 darstellt, y = 1 f├╝rz = 1 bis 5 ist oder Is 0, m is 1 or 2, x = represents an integer from 0 to 8, y = 1 f├╝rz = 1 to 5 or
    = 1 bis 4 ist f├╝rz = 1 z = eine ganze Zahl von 0 bis 5 darstellt. = 1 to 4 is f├╝rz = 1 z = is an integer number from 0 to fifth
  2. 2. Verbindung nach Anspruch 1 mit m = 1 . 2. A compound according to claim 1 with m = 1st
    3. Verbindung nach Anspruch 2 mit m = 1 X = 0 y = 1 z = 1 . 3. A compound according to claim 2 with m = 1 X = 0 y = 1 z = 1st
    4. Verbindung nach Anspruch 2 mit m = 1 x = 0 4. A compound according to claim 2 with m = 1 x = 0
    V = 1 z = 2. V = 1 z =. 2
    5. Verbindung nach Anspruch 2 mit m = 1 x = 0 - ob - y = 1 z = 3. 5. A compound of Claim 2 where m = 1 x = 0 - OB - y = z = 1. 3
    6. Verbindung nach Anspruch 2 mit m = 1 x = 0 y = 1 z = 4. 6. A compound according to claim 2 with m = 1 x = 0 y = 1 z = 4th
    7. Verbindung nach Anspruch 2 mit m = 1 x = 1 - 3 z = 0. 7. A compound of Claim 2 where m = 1 x = 1-3 z = 0th
    8. Verbindung nach Anspruch 7 mit m = 1 x = 1 z = 0. 8. A compound according to claim 7 with m = 1 x = 1 z = 0th
    9. Verbindung nach einem der vorhergehenden Anspr├╝che mit n = 2 - 6. 9. A compound according to any one of the preceding Anspr├╝che with n = 2 - 6.
    1 0. Verbindung nach Anspruch 9 mit n = 2 - 4. 1 0. A compound of Claim 9 where n = 2-4.
    1 1 . 1. 1 Verbindung nach einem der vorhergehenden Anspr├╝che, worin R 3 einen CH 3 -Rest darstellt. A compound according to one of the preceding Anspr├╝che, wherein R 3 is a CH 3 radical.
    1 2. Verbindung nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß A eine Gruppe der Formel a darstellt. 1 2. A compound according to one of the preceding Ansprüche, characterized daß A represents a group of formula a.
  3. 3. Verbindung nach einem der Ansprüche 1 bis 1 1 , dadurch gekennzeichnet, daß A eine Gruppe der Formel a darstellt und einer von R, und R 2 H oder eine Alkylkette mit 1 - 3 C-Atomen ist. 3. A compound according to any one of Ansprüche 1 to 1 1, characterized in that daß A represents a group of formula a and one of R, and R 2 is H or an alkyl chain with 1-3 C-atoms.
  4. 4. Verbindung nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß A eine Gruppe der Formel a darstellt und n = 3 - 6. 4. A compound according to any one of the preceding Ansprüche, characterized daß A is a group of formula a and n = 3-6.
  5. 5. Verbindung nach Anspruch 1 4, dadurch gekennzeichnet, daß n = 3. 5. A compound according to claim 1 4, characterized in that n = daß third
    6. Verbindung nach Anspruch 14, dadurch gekennzeichnet, daß n = 4. 6. A compound according to claim 14, characterized in that n = daß 4th
    7. Verbindung nach einem der Ansprüche 1 bis 1 1 , dadurch gekennzeichnet, daß A eine Gruppe der Formel b darstellt. 7. A compound according to any one of Ansprüche 1 to 1 1, characterized in that daß A represents a group of formula b.
    8. Verbindung nach Anspruch 14 oder 1 5, dadurch gekennzeichnet, daß n = 2. 8. A compound according to claim 14 or 1 5, characterized in that n = daß second
    1 9. Verbindung nach einem der Ansprüche 1 bis 1 1 , dadurch gekennzeichnet, daß n = 3. 1 9. A compound according to any one of Ansprüche 1 to 1 1, characterized in that n = daß third
    20. Verbindung nach einem der Ansprüche 1 bis 1 1 , dadurch gekennzeichnet, daß n = 4. 20. A compound according to any one of Ansprüche 1 to 1 1, characterized in that n = daß 4th
    21 . 21st Verbindung nach einem der Ansprüche 1 bis 1 1 , dadurch gekennzeichnet, daß A eine Gruppe der Formel c darstellt. A compound according to any one of Ansprüche 1 to 1 1, characterized in that daß A represents a group of formula c.
    22. Verbindung nach Anspruch 21 , dadurch gekennzeichnet, daß n = 3. 22. A compound according to claim 21, characterized in that n = daß third
    23. Liposome, die Phospholipide oder/und Alkylphospholipide, gegebenenfalls Cholesterin und 1 bis 50 Mol-% einer Verbindung der allgemeinen Formel (I) von Anspruch 1 oder deren Salze enthalten, wobei das Cholesterin, die Phospholipide, die Alkylphospholipide und die Verbindung der Formel (I) zusammen 1 00 Mol-% ergeben. 23. Liposomes, phospholipids and / or alkylphospholipids, where appropriate cholesterol and 1 to 50 mol% of a compound of general formula (I) of claim 1 or salts thereof, wherein the cholesterol, the phospholipids, the alkylphospholipids and the compound of formula (I) together 1 00 mol% yield.
    24. Verwendung einer Verbindung der allgemeinen Formel (I) von Anspruch 1 als Gentransportvehikel. 24. Use of a compound of general formula (I) of claim 1 as a gene delivery vehicle.
    25. Verwendung einer Verbindung der allgemeinen Formel (I) von Anspruch 1 als L├╢sungsmittel f├╝r wasserunl├╢sliche Wirkstoffe. 25. Use of a compound of general formula (I) of claim 1 as L├╢sungsmittel f├╝r wasserunl├╢sliche active ingredients.
  6. 6. Verwendung nach Anspruch 25, dadurch gekennzeichnet, dass R 1 einen Erucasäurerest darstellt. 6. Use according to claim 25, characterized in that R 1 represents a Erucasäurerest.
Description  translated from German

Phospholipidanaloge Verbindungen Beschreibung Phospholipidanaloge compounds Description

Die Erfindung betrifft neue phospholipidanaloge Verbindungen, die als Liposomenbestandteile zum Transport von Arzneimitteln, als Lösungsvermittler für in Wasser schlecht lösliche Arzneimittel und auch als Wirkstoffe selbst gegen Erkrankungen wie Krebs und Leishmaniose eingesetzt werden können, diese neuen Verbindungen enthaltende Liposomen, Arzneimittelzusammensetzungen, welche diese Liposomen enthalten, und Verfahren zur Herstellung von Arzneimitteln. The invention relates to novel phospholipidanaloge compounds that can be used as liposome components for transporting drugs, as solubilizers for sparingly water soluble drugs as well as drugs themselves against diseases such as cancer and leishmaniasis, containing these novel compounds, liposomes, pharmaceutical compositions containing these liposomes and processes for the preparation of medicaments.

Insbesondere betrifft die Erfindung Phosphatidylverbindungen, die einen definierten hydrophilen Rest enthalten, sowie Liposomen, die eine verkürzte oder verlängerte Lebensdauer im Serum aufweisen und gezielt von bestimmten Zellen, beispielsweise Tumorzellen, aufgenommen werden können. In particular, the invention phosphatidyl compounds, which contain a defined hydrophilic group, as well as liposomes having a shortened or extended life in serum and may be taken up by certain cells, such as tumor cells specifically relates.

Herkömmliche Liposomen weisen im Serum eine Verweilzeit von bis zu 5 Stunden auf. Conventional liposomes have in the serum at a residence time of up to 5 hours. Insbesondere bei der Verwendung von Liposomen als Träger für pharmazeutische Wirkstoffe ist jedoch eine möglichst lange Verweilzeit von Liposomen im Blutkreislauf wünschenswert, insbesondere aber in Verbindung mit einer Aufnahme in ausgewählte Zielzellen. Particularly in the use of liposomes as carriers for pharmaceutical active ingredients, however, as long as possible residence time of liposomes in the blood stream is desirable, but in particular in combination with a receptacle in selected target cells.

Es wurden daraufhin die sogenannten "Stealth-Liposomen" entwickelt, die eine verlängerte Lebensdauer aufweisen. There were thus developed the so-called "stealth liposomes" which have a prolonged life. Diese "Stealth-Liposomen" sind auf der Basis von Phosphatidylverbindungen aufgebaut, die einen verlängerten Polyethylenglykolrest enthalten. This "stealth liposomes" are constructed on the basis of phosphatidyl compounds which contain an extended polyethylene glycol residue. Der Polyethylenglykolrest erwies sich für die angestrebte verlängerte Lebensdauer am wirksamsten bei Molekulargewichten zwischen 2000 und 3000. Ein wesentlicher Nachteil dieser "Stealth-Liposomen" bzw. der Phosphatidylverbindungen mit Polyethylenglykolrest liegt allerdings darin, dass es sich nicht um exakt definierte Verbindungen handelt, da die Polyethylenglykolreste unterschiedliche Kettenlängen aufweisen. The polyethylene glycol residue proved for the desired extended life most effective at molecular weights between 2000 and 3000. A major disadvantage of this "stealth liposomes" or phosphatidyl polyethylene glycol residue, however, lies in the fact that it is not at precisely defined compounds, since the polyethylene glycol residues have different chain lengths. Die sogenannten "Stealth- Liposomen" besitzen infolge des Phosphatrestes jedoch immer eine negative Oberflächenladung in der Liposomenmembran. The so-called "stealth liposomes" always possess due to the phosphate group, however, a negative surface charge in the liposome membrane. Aufgabe der eigenen älteren Patentanmeldung 1 96 22 224.9 war deshalb die Bereitstellung von Verbindungen, die die Lebensdauer von Liposomen erhöhen und eine exakt angebbare Zusammensetzung aufweisen, wobei ebenfalls Phosphatester und damit negative Ladungen verwendet wurden. Giving up their own prior patent application 1 96 22 224.9 was therefore to provide compounds that increase the life of liposomes and have an exactly assignable composition, also phosphate esters and thus negative charges were used.

Aufgabe der vorliegenden Erfindung ist es dagegen, Verbindungen bereitzustellen, welche diese negative Oberflächenladung vermeiden und die Oligoglycerin- oder Zuckerreste über ein Stickstoffatom in die Struktur einbinden. Object of the present invention, however, is to provide compounds which avoid these negative surface charge and integrate the oligoglycerol or sugar residues via a nitrogen atom in the structure. Durch die positive Ladung am Stickstoffrest wird die negative Ladung am Phosphat ausgeglichen oder sogar überkompensiert, wenn 2 Stickstoffatome im Molekül verwendet werden. By the positive charge on the nitrogen residue, the negative charge is balanced phosphate or even overcompensated when 2 nitrogen atoms are used in the molecule. Diese Aufgabe wird erfindungsgemäß gelöst durch eine Verbindung einer allgemeinen Formel I This object is achieved by a compound of general formula I

A - PO, :CH 2 ) n - (CH 2,)' > CH, - 0 H A - PO,: CH 2) n - (CH 2) '> CH, - 0 H

Figure imgf000004_0002
Figure imgf000004_0001

worin A a = CH, - O - R, CH 2 - O - R, tf wherein A a = CH - O - R, CH 2 - O - R, tf

CH - O - R, oder CH O - CH - O - R, or CH O -

I i I i

CH. CH. 0 CH 0 - R, 0 CH 0 - R,

CH 2 - O Ri CH 2 - O - R- CH, - O - \ ii (CH 2 ) S oder CH O - CH - O - R, i CH 2 - O Ri CH 2 - O - R CH, - O - \ ii (CH 2) S or CH O - CH - O - R, i

CH, - O - (CH 2' s H (CH 2' s H ist, wobei R, und R 2 unabhängig voneinander Wasserstoff, einen gesättigten oder ungesättigten Acyl- oder Alkylrest bedeuten, der gegebenenfalls verzweigt oder/und substituiert sein kann, wobei die Summe der Kohlenstoffatome in Acyl und Alkyl 1 6 bis 44 C-Atome beträgt, s eine ganze Zahl von 0 bis 8 darstellt, c = ein Rest eines primären oder sekundären Alkohols der Formel RO- ist, wobei R einen gesättigten oder ungesättigten Alkylrest vorwiegend mit cis-Doppelbindung von 1 2 bis 30 Kohlenstoffatomen bedeutet, n eine ganze Zahl von 2 bis 8 darstellt, R 3 a = 1 ,2-Dihydroxypropyl sein kann oder b = Alkyl mit 1 bis 3 C-Atomen sein kann, wenn z > 0 ist oder c = Alkyl mit 1 bis 3 C-Atomen sein kann, wenn n ≠ 2 und z = 0 ist, m = 1 oder 2 ist, x = eine ganze Zahl von 0 bis 8 darstellt, y = 1 für z = 1 bis 5 ist oder CH, - O - (CH 2 's H (CH 2' s H, where R, and R 2 are independently hydrogen, a saturated or unsaturated acyl or alkyl radical, optionally branched and / or can be substituted, the sum of the carbon atoms in acyl and alkyl is from 1 6 to 44 C-atoms, s represents an integer from 0 to 8, c = is a radical of a primary or secondary alcohol of formula RO- where R is mainly a saturated or unsaturated alkyl group means with cis-double bond of 1 2 to 30 carbon atoms, n is an integer from 2 to 8, R 3 a = 1, may be 2-dihydroxypropyl or b = alkyl may be of 1 to 3 C atoms, if z> is 0 or c = alkyl may be of 1 to 3 carbon atoms, when n ≠ = 2 and z is 0, m = 1 or 2, x = represents an integer from 0 to 8, y = 1 for z = 1 to 5 or

1 bis 4 ist für z = 1 z = eine ganze Zahl von 0 bis 5 darstellt. 1 to 4 for z = 1 z = is an integer number from 0 to fifth

Es sind Verbindungen bevorzugt, bei denen nicht gleichzeitig A = CH 2 - 0 - R, , CH - 0 - R 2 CH 2 - 0 - There are compounds preferred in which not at the same time A = CH 2 - 0 - R, CH - 0 - R 2 CH 2 - 0 -

m = 1 , n = 2, x = 0, z ≠ 0 ist und R 3 einen Alkylrest darstellt. m = 1, n = 2, x = 0, z ≠ 0 and R 3 represents an alkyl group.

Die in den hier beschriebenen Substanzen verwendeten Strukturelemente können beliebig variiert und maßgeschneidert der jeweiligen Verwendung angepasst werden. The structural elements used in the substances described herein can be arbitrarily varied and tailored adapted to the respective use.

Über den Strukturparameter A können vorwiegend die apolaren Anteile der Moleküle variiert werden, zB über die Kettenlänge der Fettsäuren und der Alkylreste. About the structural parameters A, the apolar fractions of the molecules can be varied mainly, for example on the chain length of the fatty acids and of the alkyl groups. Eine Modifikation der polaren Anteile ist über die Phosphatgruppe, das Stickstoffatom und die damit verknüpften Oligoglycerine möglich. A modification of the polar components is possible via the phosphate group, the nitrogen atom and the associated oligoglycerins.

Die durch die allgemeine Formel I erfassten Verbindungen besitzen hervorragende biologische Eigenschaften und finden Verwendung als The compounds covered by general formula I possess excellent biological properties and are used as

1 ) Liposomenbestandteile zur gezielten Anreicherung von Wirkstoffen in Zielzellen, 1) liposome components for targeted enrichment of active compounds in target cells,

2) Lösungsvermittler für schwer intravenös applizierbare Substanzen, wie z. B. Taxol, 2) solution promoters for sparingly administered intravenously substances such. As Taxol,

3) Wirkstoffe gegen Krebs und Protozoenerkrankungen. 3) Anti-Cancer Agents and protozoan diseases.

Die Verbindungen, die in den verschiedenen Anwendungsbereichen besondere Bedeutung besitzen, werden nun im Detail beschrieben. The compounds which have special significance in the different application areas will now be described in detail. Dabei gibt es Überschneidungen, da disubstituierte Glycerine mit dem Strukturmerkmal A sowohl membranstabilisierende Eigenschaften (R, + R 2 > 20 C-Atome) wie auch membrandestabilisierende Eigenschaften (R, + R 2 < 20 C-Atome) besitzen können. There are no overlaps, as disubstituted glycerols with the structural feature A both membrane stabilizing properties (R, + R 2> 20 C atoms) as well as membrane destabilizing properties may have (R, + R 2 <20 carbon atoms). Insbesondere die Grenzbereiche zwischen Membran- und Mizellbildnern können hier von besonderem Interesse sein. In particular, the boundaries between membrane and Mizellbildnern may be of particular interest here.

Allen Strukturen gemeinsam ist die einfache Herstellung der neuartigen Moleküle, die durch Umsetzung von primären oder sekundären Aminen mit Epoxiden erfolgen kann. common to all structures is the ease of preparation of the novel molecules can be made by reacting primary or secondary amines with epoxides. So entsteht aus 1 ,2-Dipalmitoyl-sn-glycero-3- phospho-(N-methyl)-ethanolamin mit Benzylglycidol nach katalytischer Debenzylierung und Methylierung am Stickstoff ein Phospholipid mit lecithinartiger Struktur, das als Liposomenbestandteil verwendet wird. The result of 1, 2-dipalmitoyl-sn-glycero-3-phospho- (N-methyl) ethanolamine with Benzylglycidol after catalytic debenzylation and methylation on the nitrogen with a phospholipid lecithin-like structure, which is used as a liposome component.

Verbindungen mit nur einer langen Alkyl- oder Acylkette besitzen andere interessante Eigenschaften, wenn sie über primäre oder sekundäre Amine mit Epoxiden verknüpft werden, wie aus nachfolgender Beschreibung hervorgeht. Compounds having only one long alkyl or acyl chain possess other advantageous properties when they are attached via primary or secondary amines with epoxides, as is apparent from the following description. Es sind ausgezeichnete Lösungsvermittler für schlecht intravenös applizierbare Wirkstoffe und sogar direkte Wirkstoffe gegen Krebs und Leishmaniose. There are excellent solubilizers for poorly administered intravenously agents and even direct anticancer agents and leishmaniasis.

Der dieser Erfindung zugrundeliegende schrittweise Aufbau der hydrophilen Reste der Phosphatidylverbindungen der Formel I ermöglicht es, eine genau definierte Zusammensetzung der Verbindungen zu erhalten. The underlying this invention gradually build the hydrophilic residues of the phosphatidyl compounds of formula I makes it possible to obtain a well-defined composition of the compounds.

Es handelt sich also bei der erfindungsgemäßen Verbindung der Formel I nicht um ein Gemisch verschiedener Moleküle unbestimmter Zusammensetzung und Kettenlänge, sondern es kann gezielt eine gewünschte Struktur erhalten werden. It is therefore in the inventive compound of formula I is not a mixture of various molecules of indefinite composition and chain length, but it can be selectively obtain a desired structure. Dies bedeutet, falls das gewünschte Produkt ein N,N-Dimethyl-N-(2-hydroxypropyl-3, 1 -0,0-dihydroxypropyl)- ammoniumderivat ist mit y = 1 und z = 2 in der Formel I, dass die Verbindung chemisch definiert ist und keine Anteile mit y = 1 und z = 1 oder y = 1 und z = 3 usw. enthält. This means, if the desired product is a N, N-dimethyl-N- (2-hydroxypropyl-3, 1 -0,0-dihydroxypropyl) - ammonium derivative is with y = 1 and z = 2 in the formula I, the compound chemically defined and no play with y = 1 and z = 1 or y = 1 and z = 3, etc. contains. Bevorzugt werden Hydroxypropylderivate einer ganz bestimmten Kettenlänge verwendet, die im wesentlichen frei von anderen Kettenlängen sind. Hydroxypropyl derivatives are preferably a specific chain length used, which are free of other chain lengths substantially.

Erfindungsgemäß stellt die Verbindung der Formel I eine einheitliche Verbindung definierter Struktur dar. Bevorzugt ist die Verbindung hinsichtlich des Wertes von z größer als 99 % einheitlich. According to the invention, the compound of formula I a unitary compound of defined structure. Preferably the compound is in terms of the value of z is greater than 99% uniform. Es ist jedoch auch möglich, die Verbindung mit einer Einheitlichkeit von mehr als 99,9 % hinsichtlich des Wertes von z bereitzustellen. However, it is also possible to provide the connection with a consistency of more than 99.9% in terms of the value of z.

Bevorzugt handelt es sich bei der Verbindung um Hydroxypropylderivate am Stickstoff mit 1 bis 5 Hydroxypropyleinheiten, bevorzugt mit 1 bis 3 Hydroxypropyleinheiten. It is preferable that the compound is hydroxypropyl derivatives at the nitrogen by 1 to 5 Hydroxypropyleinheiten, preferably having 1 to 3 Hydroxypropyleinheiten. Es handelt sich dabei bevorzugt um 1 ,3-verknüpfte lineare Oligoglycerinreste, die über einen 2-Hydroxypropylrest mit dem Stickstoffatom verknüpft sind. This is preferably by 1, 3-linked linear Oligoglycerinreste, which are linked via a 2-hydroxypropyl radical with the nitrogen atom. Der Rest für A = c mit der Formel RO- leitet sich von einem primären oder sekundären Alkohol ab. The rest of A = c with the formula R-O- is derived from a primary or secondary alcohol. Wenn RO- von einem sekundären Alkohol stammt, sind solche Reste mit dem Sauerstoff am C 2 -, C 3 - oder C 4 -Atom bevorzugt. , C 3 - - When RO is derived from a secondary alcohol, such radicals with oxygen at C 2 or C 4 are preferred atom.

Die Reste R 1 und R 2 stellen erfindungsgemäß bevorzugt unabhängig voneinander Wasserstoff, einen gesättigten oder ungesättigten Acyl- oder Alkylrest dar, der gegebenenfalls verzweigt oder/und substituiert sein kann, wobei die Summe der Kohlenstoffatome in Acyl und Alkyl zwischen 1 6 und 44 liegt. The R 1 and R 2 according to the invention are preferably each independently hydrogen, a saturated or unsaturated acyl or alkyl radical, optionally branched and / or may be substituted, the sum of carbon atoms in acyl and alkyl from 1 to 6 and 44 lies.

Ein weiterer Gegenstand der Erfindung sind Liposomen, die Phospholipide oder/und Alkylphospholipide, gegebenenfalls Cholesterin und 1 bis 50 Mol- % einer Verbindung der allgemeinen Formel I beinhalten. Another object of the invention include liposomes, phospholipids or / and alkylphospholipids, optionally cholesterol and 1 to 50 mol% of a compound of the general formula I.

Die Phospholipide oder/und Alkylphospholipide können beispielsweise Diacylglycerophosphoverbindungen definierter Struktur sein. The phospholipids and / or alkyl may be for example Diacylglycerophosphoverbindungen defined structure. Allgemein können diese Bestandteile der Lipide als Verbindungen definierter Struktur eingesetzt werden. Generally these components of the lipids can be used as compounds defined structure.

Im Falle y > 1 stammt der Rest -CH 2 (CHOH) y -CH 2 -OH bevorzugt aus Zuckeralkoholen, die für y = 2, 3 Hydroxylgruppen, für y = 3, 4 Hydroxylgruppen und für y = 4, 5 Hydroxylgruppen aufweisen. In the case of y> 1 is the radical -CH 2 -OH preferably derived 2 (CHOH) y -CH from sugar alcohols which have for y = 2, 3 hydroxyl groups, for y = 3, 4 hydroxyl groups and for y = 4, 5, hydroxyl groups. Beispiele solcher Reste sind Mannitderivate für y = 4, Lyxitderivate für y = 3 und Threitderivate für y = 2. Examples of such radicals are mannitol for y = 4, y = 3 and for Lyxitderivate Threitderivate for y =. 2

Die erfindungsgemäßen Liposomen weisen eine deutlich veränderte Halbwertszeit in der Blutzirkulation auf. The liposomes of the invention have a significantly altered half-life in blood circulation. Die Liposomen mit m = 1 sind nach außen neutral und zeigen erhöhte Verweilzeiten im Blut, während die Liposomen mit m = 2 infolge der positiven Überschussladung in der Membran nur ganz kurz zirkulieren. The liposomes with m = 1 are neutral face outwards and increased residence times in the blood, while the liposomes circulate very briefly with m = 2 as a result of positive excess charge in the membrane. Ein weiterer Gegenstand der Erfindung ist eine pharmazeutische Zusammensetzung, die die oben beschriebenen Liposomen und in den Liposomen eingeschlossen einen oder mehrere pharmazeutische Wirkstoffe gegebenenfalls zusammen mit pharmazeutisch üblichen Verdünnungs-, Hilfs-, Träger- und Füllstoffen enthält. Another object of the invention is a pharmaceutical composition comprising the liposomes described above and in the liposomes including one or more pharmaceutical active substances optionally together with common pharmaceutical diluents, auxiliary substances, carriers and fillers.

Als Wirkstoffe können in der Regel alle Wirkstoffe verwendet werden, die sich mittels Liposomen überhaupt ins Plasma einbringen lassen. As active ingredients, all ingredients can be used in a rule, which can be via liposomes ever bring into the plasma. Bevorzugte Wirkstoffgruppen sind einerseits Cytostatika, insbesondere Anthracyclin- Antibiotika, wie etwa Doxorubicin, Epirubicin oder Daunomycin, wobei Doxorubicin besonders bevorzugt ist. Preferred groups of active ingredients are on the one hand cytostatic agents, especially anthracycline antibiotics such as doxorubicin, epirubicin or daunomycin, wherein doxorubicin is particularly preferred. Weitere bevorzugte Cytostatika sind Idarubicin, Hexadecylphosphocholin, 1 -Octadecyl-2-methyl-rac-glycero-3- phosphocholin, 5-Fluoruracil, cis-Platinkomplexe wie Carboplatin und Novantron sowie Mitomycine. Further preferred are cytostatics idarubicin, hexadecylphosphocholine, 1 -octadecyl-2-methyl-rac-glycero-3- phosphocholine, 5-fluorouracil, cis-platinum complexes such as carboplatin and Novantrone and mitomycins.

Weitere bevorzugte Wirkstoffgruppen sind immunmodulierende Substanzen wie etwa Cytokine, wobei unter diesen wiederum die Interferone und insbesondere das σ-lnterferon besonders bevorzugt sind, antimykotisch wirksame Substanzen (zB Amphotericin B) und Wirkstoffe gegen Protozoenerkrankungen (Malaria, Trypanosomen- und Leishmanien- Infektionen) . Further preferred groups of active ingredients are immune modulating substances such as cytokines, among which, in turn, the interferons, and in particular the σ-interferon are particularly preferred, antimycotically active substances (eg amphotericin B), and agents against protozoal diseases (malaria, trypanosome and leishmanial infections). Ebenfalls bevorzugt ist Taxol als Wirkstoff. Taxol is also preferred as an active ingredient.

Eine weitere bevorzugte Wirkstoffgruppe sind lytische Wirkstoffe, wie sie in der DE 41 32 345 A1 beschrieben sind. Another preferred group of active ingredients are lytic agents, as described in DE 41 32 345 A1. Bevorzugt sind Miltefosin, Edelfosin, llmofosin sowie SRI62-834. Preferably miltefosine edelfosine, llmofosin and SRI62-834 are. Insbesondere bevorzugt sind Alkylphosphocholine auch mit erweiterten Alkylketten, z. B. Erucylphosphocholin und Erucylphosphocholine mit erweitertem Phospho- Stickstoffabstand. Particularly preferred alkylphosphocholines are also available with extended alkyl chains, eg. B. erucylphosphocholine and Erucylphosphocholine extended phospho nitrogen distance.

Ein weiterer Gegenstand der vorliegenden Erfindung ist die Verwendung von erfindungsgemäßen Liposomen zur Herstellung eines Antitumormittels, wobei der Wirkstoff besonders bevorzugt Doxorubicin ist. Another object of the present invention is the use of liposomes according to the invention for the preparation of an antitumor agent, wherein the drug doxorubicin is particularly preferred. Noch ein weiterer Gegenstand der vorliegenden Erfindung ist die Verwendung der erfindungsgemäßen Liposomen zur Herstellung eines Mittels zur Beeinflussung der Zellproliferation, wobei der Wirkstoff ein Cytokin, besonders bevorzugt -lnterferon ist. Yet another object of the present invention is the use of the liposomes of the invention for the preparation of an agent for influencing cell proliferation, wherein the active ingredient is a cytokine, is particularly preferred -lnterferon.

Die erfindungsgemäßen Liposomen werden nach an sich bekannten Methoden hergestellt mit hierfür gängigen Vorrichtungen. The liposomes of the invention are prepared according to known methods with this popular devices. Typischerweise kann eine die verschiedenen Komponenten des Liposoms einschließlich 1 bis 50 Mol-% einer Verbindung der Formel I enthaltende Lösung in eine Lipidsuspension überführt werden, die dann unter hohem Druck durch Düsen oder durch Lochscheiben gepresst wird, wobei durch die Größe der Öffnungen in der Lochscheibe die Größe der erhaltenen Liposomen geregelt werden kann. Typically, a the various components of the liposome including 1 to 50 mol% of a compound of the formula are converted I-containing solution into a lipid suspension, which is then pressed under high pressure through nozzles or by means of perforated discs wherein the size of the openings in the perforated disc the size of the resulting liposomes can be controlled. Geeignete Maßnahmen zur Überführung einer Lipidsuspension in Liposomen sind dem Fachmann bekannt. Suitable measures for converting a lipid suspension into liposomes are known in the art. Bevorzugt werden 5 bis 55 Mol- % einer Verbindung der allgemeinen Formel I mit 35 bis 60 Mol-% Cholesterin und 40 bis 60 Mol-% Phospholipiden oder/und Alkylphospholipiden in eine Lipidsuspension überführt, die dann durch geeignete Maßnahmen auf an sich bekannte Weise in Liposomen umgewandelt wird. 5 to 55 mol% of a compound of the general formula I with 35 to 60 mol% cholesterol and 40 to 60 mol% phospholipids and / or Alkylphospholipiden preferably be converted into a lipid suspension, which is then in suitable measures in a known manner liposomes is converted. Solch bekannte Verfahren können auch zur Herstellung einer pharmazeutischen Zubereitung, die die erfindungsgemäßen Liposomen und einen oder mehrere pharmazeutische Wirkstoffe enthält, verwendet werden. Such known methods may also be used for producing a pharmaceutical preparation containing liposomes of the invention and one or more active pharmaceutical ingredients. Zum Einschluss wasserunlöslicher Wirkstoffe wird der Wirkstoff dabei zusammen mit den Lipidbestandteilen gelöst, während zum Einschluss wasserlöslicher Wirkstoffe der Lipidfilm mit einer wässrigen Lösung versetzt wird, die den wasserlöslichen Wirkstoff enthält. For inclusion of water-insoluble active substances, the active substance is thereby dissolved together with the lipid constituents, while for the inclusion of water-soluble active ingredients of the lipid film is added to an aqueous solution containing the water-soluble active ingredient.

Die Ausgangsphospholipide werden nach in der Literatur beschriebenen Verfahren hergestellt (DE 31 30 867 A1 ; Eibl et al., Chem. Phys. Lipids 28 ( 1 981 ), 1 -5, 41 ( 1 986), 53-63 und 47 ( 1 988), 47-53. Insbesondere kann hier auf Verfahren zurückgegriffen werden, die in der PCT/EP97/00749- Anmeldung vom 1 7.02.1 997 beschrieben worden sind. So können die erfindungsgemäßen Verbindungen der Formel I auf folgende Weise hergestellt werden: be prepared according to the Ausgangsphospholipide described in the literature (DE 31 30 867 A1,... Eibl et al, Chem Phys Lipids 28 (1981), 1 -5, 41 (1986), 53-63 and 47 (1 . 988), 47-53 in particular, here are resorted to methods that have been described in PCT / EP97 / 00749- registration from 1 7.02.1 997 Thus, the novel compounds of formula I can be prepared as follows.:

Beispiel (A = a; n = 2; m = 1 ; y = 1 ; z = 2) Example (A = a; n = 2; m = 1; y = 1 z = 2)

(Reaktion von 1 ,2-Diplamitoyl-sn-glycero-3-phospho-(N-methyl)-ethanolamin mit 1 ,2-lsopropyliden-glycero-glycidol) (Reaction of 1, 2-Diplamitoyl-sn-glycero-3-phospho- (N-methyl) ethanolamine with 1, 2-isopropylidene-glycero-glycidol)

CH, C0 - (CH 2 ) 14 - CH, J ' CH - 0 -C0 (CH 2 ) 14 CH- CH, C0 - (CH 2) 14 - CH, J 'CH - 0 -C0 (CH 2) 14 CH

CH, CH. CH, CH.

/ /

PO. PO. - CH 2 - CH 2 - - CH 2 - CH 2 -

) )

Figure imgf000011_0001

CH - 0 -CO (CH 2 ) U CH, f CH- CH. CH - 0 -CO (CH 2) U CH, CH CH f.

CH 0 - CO - (CH 2 ) 14 - CH 3 CH 0 - CO - (CH 2) 14 - CH 3

I CH, OH \ / CH. I CH, OH \ / CH. I ! I!

0 -P0 3 - CH 2 -CH 2 — NH -CH. 0 P0 3 - CH 2 CH 2 - NH CH. - - CH ~CH t 0 0 - - CH ~ CH t 0 0

CH, CH — CH, CH, CH - CH,

Entsprechende Umsetzungen können durchgeführt werden, die Verbindungen mit n = 3 - 10; Corresponding reactions can be carried out, the compounds with n = 3-10; m = 1; m = 1; y = 1; y = 1; z = 1 - 5. Ausgangsverbindungen für x = 2 und 3 sind Kephaline und N- Methylkephaline, deren Darstellung ausführlich beschrieben wurde. z = 1 - 5 starting compounds for x = 2 and 3 are cephalins and N- Methylkephaline whose depiction has been described in detail. Die Umsetzungen mit den entsprechenden Glycidolen, deren Herstellung in der deutschen Patentanmeldung "Phosphatidyloligoglycerine" 1 9622224 beschrieben ist, führt zu den gewünschten Produkten, wobei die Addition in einem 2-Phasensystem THF - Na 2 C0 3 /NaHC0 3 1 : 1 (0,5 M in H 2 O; pH 9 - 10) durchgeführt wird. The reactions with the corresponding glycidols, whose preparation is described in the German patent application "phosphatidyloligoglycerols" 1 9622224, leads to the desired products, with the addition in a 2-phase system THF - Na 2 C0 3 / NaHC0 3 1: 1 (0, 5 M in H 2 O; pH 9 - 10 is performed). Bei diesen pH-Werten wird jedoch keine Hydrolyse der Fettsäureester beobachtet. At these pH values but no hydrolysis of the fatty acid ester is observed.

Zur Darstellung der Dioleoylverbindungen muss 1 ,2-Dioleyol-sn-glycero-3- phospho-(N-methyl)-ethanolamin hergestellt werden. To illustrate the need Dioleoylverbindungen 1, 2-Dioleyol-sn-glycero-3- (N-methyl) ethanolamine are prepared phosphorescent. Dies wird durch folgendes Reaktionsschema erreicht: This is achieved by the following equation:

CH 9 — 0 - CH ? C 6 H 5 i Channels 9 - 0 - CH C 6 H 5 i?

CH 0 - CH, CH 0 - CH,

C 6 H 5 C 6 H 5

Figure imgf000012_0001

CH, 0 - CH 2 - C 6 H 5 CH, 0 - CH 2 - C 6 H 5

CH 0 - CH, CH 0 - CH,

C 6 H 5 C 6 H 5

CH, CH,

\ \

0 - P 0 - CH, CH 9 i 0 - P 0 - CH, CH 9 i

OCH, N - BOC OCH, N - BOC

ti sche Hxdrogenolysε rung mi t Ol eoyl cl ori d tic Hxdrogenolysε tion wi th Ol eoyl cl ori d

Figure imgf000012_0002
CH 2 — 0 - CO - (CH 2 ) 7 - CH . CH 2 - 0 - CO - (CH 2) 7 - CH. CH - (CH 2 ) 7 - CH 3 CO - (CH 2 ) ? -CH = CH - (CH 2 ) 7 - CH3 CH - (CH 2) 7 - CH 3 CO - (CH 2) CH = CH - (CH 2) 7 - CH3

Figure imgf000013_0001
- 0-CH 2 - CH 2 - N + H 2 - CH 3 0 " - 0-CH 2 - CH 2 - N + H 2 - CH 3 0 "

Analog werden allgemein ungesättigte Verbindungen hergestellt. Are prepared analogously generally unsaturated compounds.

Entsprechend können Verbindungen mit n = 4 - 8 hergestellt werden, da die entsprechenden endständigen Alkanolamine käuflich erworben und in die N-BOC geschützten Verbindungen umgewandelt werden können. Accordingly, compounds with n = 4 - 8 are produced, since the corresponding terminal alkanolamines purchased and protected in the N-BOC compounds can be converted.

In der Folge werden Beispiele zur Synthese von Liposomenbestandteilen beschrieben, die die experimentelle Breite der vorliegenden Anmeldung belegen. As a result, examples of synthesizing liposomes components are described, which prove the experimental width of the present application. Es können, wie aus den Beispielen hervorgeht, beliebige Fettsäureester- und Alkyletherkombinationen hergestellt werden, die in Kettenlänge, Anzahl der cis-Doppelbindungen und Verzweigungsgrad variieren. It may, as is apparent from the examples, any fatty acid ester and Alkyletherkombinationen be produced which vary the number of cis double bonds, and degree of branching in chain length.

Die RF-Werte der Beispielsverbindungen 1 bis 279 wurden im System CHCI 3 /CH 3 OH (Eisessig/H 2 O: 100/60/20/5 Volumentanteile bestimmt. Sie liegen gruppenweise sehr dicht beisammen und zwar wie folgt: The RF values of the example compounds 1-279 3 OH (glacial acetic acid / H 2 O were in the system CHCI 3 / CH: 100/60/20/5 Volumentanteile determined you are in groups together very closely, as follows.:

RF Verbindung Nr.: RF connection No .:

0,10-0,15 129-135 0,15-0,20 117-128; 0,10-0,15 129-135 0,15-0,20 117-128; 167,172;209-216 167.172; 209-216

0,20-0,25 70-84; 0.20-0.25 70-84; 98-116; 98-116; 151-166; 151-166; 197-208 197-208

0,25-0,30 45-69; 0.25-0.30 45-69; 136-150; 136-150; 183-196; 183-196; 262-272 262-272

0,30-0,35 25-44; 0.30-0.35 25-44; 173-182; 173-182; 255-261; 255-261; 273-279 273-279

0,35-0,40 1-24 0,40-0,45 85-97 0,35-0,40 1-24 0,40-0,45 85-97

0,30-0,40 217-240 0.30-0.40 217-240

0,20-0,30 241-254 BEISPIELE 0.20-0.30 241-254 EXAMPLES

A) Herstellung von Erucoyl-propandiol-(1,3)-phopsho-N,N,N-trimethyl- propylammonium (Beispiel 176) A) Preparation of Erucoyl-propanediol (1,3) -phopsho-N, N, N-trimethyl-propylammonium (Example 176)

Erucoyl-propandiol-(1 ,3) Erucoyl-propanediol (1, 3)

Propandiol-(1,3), 153 g (MG 76,1; 2 Mol) wird in 1 I THF gelöst, mit 60 g Triethylamin (MG 101,2; 0,6 Mol) und 7,3 g 4-Dimethylaminopyridin (MG Propanediol- (1,3), 153 g (76.1 MG; 2 moles) is dissolved in 1 I of THF, 60 g triethylamine (MW 101.2; 0.6 mole) and 7.3 g of 4-dimethylaminopyridine ( MG

122,2; 122.2; 0,06 Mol) versetzt und in einem Wasserbad auf 20°C temperiert. 0.06 mol) was added and heated in a water bath to 20 ° C.

Unter stetem Rühren werden 178 g Erucoylchlorid (MG 35,0; 0,5 Mol) in With constant stirring to 178 g Erucoylchlorid (MG 35.0; 0.5 mol) in

500 ml THF langsam so zugetropft, daß die Temperatur 30°C im 500 ml of THF were added dropwise at a rate that the temperature of 30 ° C in

Re ktionsgemisch nicht übersteigt. Re ktionsgemisch does not exceed. Nach dem Eintropfen wird noch 30 Minuten auf 30°C erwärmt, mit 1,5 I Diisopropylether und 1,5 I 1N HCI versetzt. After the dropping is 30 minutes heated to 30 ° C, mixed with 1.5 l of diisopropyl ether and 1.5 l of 1N HCl. Nach gutem Schütteln und Phasenseparation wird die obere After shaking and phase separation, the upper

Etherphase nochmals mit 1 % NaCI-Lösung gewaschen und in Vakuum bei Ether phase washed again with 1% NaCl solution and in vacuum

45°C einrotiert. 45 ° C evaporated. Der Rückstand wird in 2 I Hexan aufgenommen und auf The residue is taken up in 2 I of hexane and

-20°C gekühlt. -20 ° C cooled. Die weißen Kristalle werden abgesaugt und im Vakuum getrocknet. The white crystals are filtered off and dried in a vacuum. Die Ausbeute an reinem Erucoyl-propandiol-(1,3) beträgt 123 g (MG 396,7; 62 %). The yield of pure Erucoyl-propanediol (1,3) is 123 g (MW 396.7; 62%). Die Substanz ist dünnschichtchromatographisch rein The substance is pure by TLC

(Rf-Wert 0,3 in Ether/Petnan/Essigsäure 200/200/2; Volumenanteile). (Rf 0.3 in ether / Petnan / acetic acid 200/200/2, v: v).

Mikroanalyse C 25 H 48 O 3 - Ber.: C, 75,70; Microanalysis C 25 H 48 O 3 - Calc .: C, 75.70; H, 12,20; H, 12.20; O, 12,10 - Gef.: C, 75,81; O, 12.10 - Gef .: C, 75.81; H, 12,16; H, 12.16; =, - =, -

Erucoyl-propandiol-d ,3)-phospho-N-methyl-propylammonium Erucoyl-propanediol d, 3) -phospho-N-methyl-propylammonium

Phophoroxychlorid, 24,2 g (MG 153,33; 0,16 Mol) in 15 ml THF wird in einem Eisbad auf 0°C gekühlt. Phophoroxychlorid, 24.2 g (MG 153.33; 0.16 mol) in 15 ml THF is cooled in an ice bath to 0 ° C. Man versetzt tropfenweise unter Rühren mit einer Lösung von Erucoyl-propandiol-(1,3), 60 g (MG 396,7; 0,15 Mol) und 17,2 g Triethylamin (MG 101,19; 0,17 Mol) in 250 ml THF, so daß die Temperatur im Reaktionsgemisch 15°C nicht übersteigt. Is added dropwise with stirring with a solution of Erucoyl-propanediol (1,3), 60 g (MW 396.7; 0.15 mol) and 17.2 g of triethylamine (MW 101.19; 0.17 mol) in 250 ml of THF, so that the temperature in the reaction mixture does not exceed 15 ° C. Nach dem Eintropfen der Lösung wird die Temperatur des Reaktionsgemisches auf 20°C gebracht und 30 Minuten weitergerührt. After dropping the solution, the temperature of the reaction mixture is brought to 20 ° C and further stirred for 30 minutes.

Die Umwandlung des gebildeten Erucoyl-propandiol-(1 ,3)- phosphorsäuredichlorids in das Zielprodukt erfolgt durch Umsetzung mit N- Methylpropanolamin über einen intermediären Sechsring. The conversion of the formed Erucoyl-propanediol (1, 3) - phosphorsäuredichlorids in the target product by reaction with N- methylpropanolamine via an intermediate six-membered ring. Dazu wird das Reaktionsgemisch unter Rühren mit einer Lösung von 16 g N-Methyl- propanolamin (MG 89,14; 0,18 Mol) und 35,4 g Triethylamin (MG 101, 19; 035 Mol) in 250 ml THF tropfenweise so versetzt, daß die Temperatur 35°C nicht übersteigt. For this, the reaction mixture is added with a solution of 16 g N-methyl propanolamine (MG 89.14; 0.18 mol) and 35.4 g of triethylamine (MG 101, 19; 035 mol) dropwise so in 250 ml of THF that the temperature does not exceed 35 ° C. Nach dem Eintropfen wird das Reaktionsgemisch noch 30 Minuten bei 25°C gehalten. After the dropping, the reaction mixture is kept at 25 ° C for 30 minutes. Das ausgefallene Triethylaminhydrochloird wird abfiltriert. The precipitated Triethylaminhydrochloird is filtered. Das Filtrat enthält das Zwischenprodukt (Rf 0,25 in CHCI 3 /Essigester 1:1; Volumenanteile), das durch Zusatz von 60 ml 2 N HCI unter Ringöffnung in Erucoyl-propandiol- ( 1 , 3) -phospho- N-methy l-propy I ammoni um (Rf 0,45 in CHCI 3 /CH 3 OH/Eisessig/H 2 0100/80/10/5, Volumenteile) umgewandelt wird. The filtrate containing the intermediate (Rf 0.25 in CHCI 3 / ethyl acetate 1: 1, v: v), obtained by adding 60 ml of 2N HCl, with ring opening in Erucoyl-propanediol (1, 3) -phospho- N-methy l -propy I Ammoni to (Rf 0.45 in CHCI 3 / CH 3 OH / acetic acid / H 2 0100/80/10/5, by volume) is converted. Die THF-Lösung des Produkts wird mit 200 ml 0,2 M Natriumphosphatlösung (pH ~ 8,0) versetzt und auf pH 6 - 7 gebracht. The THF solution of the product is mixed with 200 ml of 0.2 M sodium phosphate solution (pH ~ 8.0) and adjusted to pH 6 - 7 accommodated. Man fällt das Produkt durch Zugabe von 1 I Aceton aus und isoliert die Kristalle durch Absaugen bei 4°C. the product is precipitated by the addition of 1 l of acetone and the crystals isolated by suction at 4 ° C. Erucoyl-propandiol-(1 ,3)-phospho-N- methyl-propylammonium ist manchmal leicht verunreinigt. Erucoyl-propanediol (1, 3) -phospho-N- methyl-propylammonium is sometimes easily contaminated. Zur Reinigung kann eine Cromatographie an Kieselgel mit CHCI 3 /CH 3 OH/H 2 0 eingesetzt werden. For cleaning, a Cromatographie on silica gel with CHCI 3 / CH 3 OH / H 2 0 are used. Die Ausbeute an reinem Produkt - bezogen auf Erucoyl-propandiol- (1,3) - beträgt 65 g (MG 547,8; 79 %). The yield of pure product - based on Erucoyl-propanediol (1,3) - is 65 g (MW 547.8; 79%).

Mikroanalyse microanalysis

C 29 H 58 NO 6 P - Ber.: C, 63,59; C 29 H 58 NO 6 P - Calc .: C, 63.59; H, 10,67; H, 10.67; N, 2,56; N, 2.56; 0, 17,53; 0, 17.53; P, 5,66 - Gef.: C, 63,34; P, 5.66 - Gef .: C, 63.34; H, 10,49; H, 10.49; N, 2,49; N, 2.49; O, - ; O, -; P, 5,59 Erucoyl-propandiol-d ,3)-phospho-N,N,N-trimethyl-propylammonium P, 5.59 Erucoyl-propanediol d, 3) -phospho-N, N, N-trimethyl-propylammonium

Erucoyl-propandiol-(1,3)-phospho-N-methyl-propylammonium, 54,8 g (MG 547,8; 0,1 Mol) werdenmit 800 ml THF und 83 g K 2 C0 3 (0,6 Mol) in 800 ml H 2 0 versetzt. Erucoyl-propanediol (1,3) -phospho-N-methyl-propylammonium, 54.8 g (MW 547.8; 0.1 mole) werdenmit 800 ml THF and 83 g of K 2 C0 3 (0.6 mol) added in 800 ml H 2 0th Man erwärmt auf 50°C und erhält eine zweiphasige Lösung. It is heated to 50 ° C and is given a two-phase solution. Man tropft unter starkem Rühren 74,5 g Toiuolsulfonsäuremethylester (MG 186,23; 0,4 Mol) in 200 ml THF ein und kocht unter Rückfluß. with vigorous stirring is added dropwise 74.5 g Toiuolsulfonsäuremethylester (MW 186.23, 0.4 mol) in 200 ml of THF and boiled under reflux. Die Reaktion ist nach 60 Minuten beendet. The reaction is complete after 60 minutes. Erucoyl- propandiol-(1,3)-phospho-N,N,N-trimethyl-propylammonium als Produkt (Rf- Wert 0, 1 in CHCI 3 /CH 3 OH/Eisessig/H 2 0100/80/10/5, Volumenanteile) wird aus der THF-Phase mit 1,2 I Aceton ausgefällt, der Niederschlag in 300 ml CHCI 3 aufgenommen, filtriert und nochmals mit 1 ,2 I Aceton gefällt. Erucoyl- propanediol (1,3) -phospho-N, N, N-trimethyl-propylammonium as the product (Rf 0, 1 in CHCI 3 / CH 3 OH / acetic acid / H 2 0100/80/10/5, volume) is precipitated from the THF phase with 1.2 l of acetone, the precipitate in 300 ml CHCI 3 was added, filtered and again with 1, 2 l of acetone precipitated. Ist das Produkt nicht ganz rein, kann zur Aufreinigung eine Chromatographie an Kieselgel mit CHCI 3 /CH 3 OH/H 2 O eingesetzt werden. If the product is not completely pure, can 3 OH / H 2 O are used for purification, a chromatography on silica gel with CHCI 3 / CH. Die Ausbeute an reinem Produkt - bezogen auf die N-methyl-Verbindung - beträgt 49 g (MG 575, 8M 85 %). The yield of pure product - based on the N-methyl-compound - is 49 g (MG 575, 8M, 85%).

Mikroanalyse microanalysis

C 31 H 62 NO 6 P - Ber.: C, 64,66; C 31 H 62 NO 6 P - Calc .: C, 64.66; H, 10,85; H, 10.85; N, 2,43; N, 2.43; O, 16,67; O, 16.67; P, 5,38 - Gef.: C, 64,38; P, 5.38 - Gef .: C, 64.38; H, 10,81; H, 10.81; N, 2,39; N, 2.39; O, -; O, -; P, 5,27 P, 5.27

B) Herstellung von Erucoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N- (hydroxypropyl-dihydroxypropyl)-propylammonium (Beispiel 155) B) Preparation of Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (hydroxypropyl-dihydroxypropyl) -propylammonium (Example 155)

Zur Herstellung dieser Verbindung kann das Zwischenprodukt Erucoyl- propandiol-(1 ,3)-phospho-N-methyl-propylammoniumeingesetztwerden.Es wird in einer Reaktion zuerst mit einem Epoxyd umgesetzt und direkt weiter zum Endprodukt methyliert. To prepare this compound, the intermediate Erucoyl- can propanediol (1, 3) -phospho-N-methyl-propylammoniumeingesetztwerden.Es is first reacted in a reaction with an epoxy and further methylated directly to the final product. Erucoyl-propandiol-(1 ,3)-phospho-N-methyl-propylammonium, 54,8 g (MG 547,8; 0,1 Mol) werdenmit 800 ml THF un d83 g K 2 C0 3 (0,6 Mol) in 800 ml H 2 O versetzt, man erwärmt auf 50°C und erhält eine zweiphasige Lösung. Erucoyl-propanediol (1, 3) -phospho-N-methyl-propyl ammonium, 54.8 g (MW 547.8, 0.1 mol) werdenmit 800 ml THF un d83 g K 2 C0 3 (0.6 mol) added in 800 ml H 2 O, is heated to 50 ° C and is given a two-phase solution. Man tropft unter starkem Rühren eine Lösung aus 21 g 1,2- lsopropyliden-glycero-3,1-glycidol (MW 188,2; 0,11 Mol) in 200mlTHFein und erhöht die Temperatur auf 60°C. with vigorous stirring, a solution of 21 g of 1,2-isopropylidene-glycero-3,1-glycidol (188.2 MW; 0.11 mol) in 200mlTHFein and raises the temperature to 60 ° C. Das Reaktionsgemisch wird 2 Stunden unter leichtem Rückfluß gekocht und mit 37 g Tolüolsulfonsäuremethylester (MG 186,23; 0,2 Mol) in 100 ml THF versetzt. The reaction mixture is boiled for 2 hours under gentle reflux with 37 g Tolüolsulfonsäuremethylester (MW 186.23; 0.2 mol) in 100 ml THF. Nach 2 Stunden Kochen unter Rückfluß ist die Reaktion beendet. After 2 hours of refluxing the reaction is complete. Die THF-Phase wird bei 45°C weitgehend einrotiert und der Rückstand zur Entfernung der Isopropylidenschutzgruppe mit 300 ml 70 % Essigsäure auf 60 - 65°C erhitzt. The THF phase is largely evaporated at 45 ° C and the residue to remove the isopropylidene with 300 ml of 70% acetic acid at 60 - 65 ° C heated. Man versetzt das Reaktionsgemisch mit einem Gemisch aus 1 I CHCI 3 /II CH 3 OH/1 I 1 %ige NaCI-Lösung, schüttelt gut durch und entfernt das Lösungsmittel aus der unteren CHCI 3 -Phase im Vakuum. It added to the reaction mixture with a mixture of 1 I CHCI 3 / CH 3 OH II / 1 I 1% NaCl solution, shake thoroughly and the solvent is removed from the lower CHCI 3 phase in a vacuum. Der Rückstand wird in 400 ml CHCI 3 aufgenommen und mit 1 ,6 I Aceton gefällt. The residue is taken up in 400 ml CHCl 3 and precipitated with 1, 6 l of acetone. Zur Reinigung kann eine Chromatographie an Kieselgel mit CHCI 3 /CH 3 OH/H 2 0 eingesetzt werden. For purification, a chromatography on silica gel with CHCI 3 / CH 3 OH / H 2 0 are used. Man erhält 46 g Erucoyl-propandiol- (1 , 3)-phospho-N,N-dimethyl-N-(hydroxypropy 1-3,1 -dihydroxypropyl)- propylammonium (MG 709,94; 65 %). This gives 46 g Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (hydroxypropyl 1 to 3.1 -dihydroxypropyl) - propylammonium (MW 709.94; 65%).

Alle nachstehend aufgeführten Verbindungen können nach diesen allgemeinen Vorschriften zur Herstellung sowohl am Stickstoff hydroxylierter wie auch nicht hydroxylierter Verbindungen dargestellt werden. All compounds listed below can be prepared by these general rules for the production of hydroxylated both on nitrogen and non-hydroxylated compounds.

Beispiele für zweikettiqe Glvcero-phospho-N,N-dimethyl-N- dihvdroxypropylalkvIammonium-Verbindunqen Examples of zweikettiqe Glvcero-phospho-N, N-dimethyl-N- dihvdroxypropylalkvIammonium-Verbindunqen

(A = a; n = 2-6; R 3 , CH 3 ; m = 1; χ = 0; y = 1; z = 1) (A = a; n = 2-6; R 3, CH 3; m = 1; χ = 0; y = 1 z = 1)

Formel formula

A - PO, ' (CH 2'n - CH 2 - O - H A - PO '(CH 2'n - CH 2 - O - H

Figure imgf000017_0001
1) 1 ,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 1) 1, 2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R„ R 2 = CO - (CH 2 ) 14 - CH 3 ) C 42 H 84 NO 10 P (794,10) (R "R 2 = CO - (CH 2) 14 - CH 3) C 42 H 84 NO 10 P (794.10)

2) 1,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 2) 2) 1,2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl- (n = 2)

(R„ R 2 = CO - (CH 2 ) 16 - CH 3 ) C 46 H g2 NO 10 P (850,20) (R "R 2 = CO - (CH 2) 16 - CH 3) C 46 H 10 NO g2 P (850.20)

3) 1 ,2-Dimyristoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 3) 1, 2-dimyristoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R,, R 2 = CO - (CH 2 ) 12 - CH 3 ) C 38 H 76 NO 10 P (737,99) (R ,, R 2 = CO - (CH 2) 12 - CH 3) C 38 H 76 NO 10 P (737.99)

4) 1,2-Dierucyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 2) 4) 1,2-Dierucyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl- (n = 2)

(R 1f R 2 = CO - (CH 2 ) - CH = CH - (CH 2 ) 7 - CH 3 ) C 54 H 104 NO 10 P (958,39) (R 1f R 2 = CO - (CH 2) - CH = CH - (CH 2) 7 - CH 3) C 54 H 104 NO 10 P (958.39)

5) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 2) 5) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl- (n = 2)

(RR 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 46 H 88 NO 10 P (846,17) (RR = 2 CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 46 H 88 NO 10 P (846.17)

6) 1-Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 6) 1-stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 17 - CH = CH - (CH 2 ) 7 -CH 3 ) C 46 H 90 NO 10 P (848,19) 7) 1 -Stearoyl-2-myristoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 17 - CH = CH - (CH 2) 7 CH 3) C 46 H 90 NO 10 P (848.19 ) 7) 1 -Stearoyl-2-myristoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 12 - CH 3 ) C 42 H 84 NO 10 P (794,10) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 12 - CH 3) C 42 H 84 NO 10 P (794.10)

8) 1 -Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 8) 1 -Stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 10 - CH 3 ) C 40 H 80 NO 10 P (766,04) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 10 - CH 3) C 40 H 80 NO 10 P (766.04)

1 -Lauroyl-2-stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) (R, = CO - (CH 2 ) 10 - CH 3 ; R 2 = CO - (CH 2 ) 16 - CH 3 ) C 40 H 80 N0 10 P (766,04) 1 -Lauroyl-2-stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2) (R, = CO - (CH 2) 10 - CH 3; R 2 = CO - (CH 2) 16 - CH 3) C 40 H 80 N0 10 P (766.04)

10) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 10) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R, = CO - (CH 2 ) - CH = CH -(CH 2 ) 7 - CH 3 ) (R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 50 H 96 N0 10 P (902,28) (R, = CO - (CH 2) - CH = CH - (CH 2) 7 - CH 3) (R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 50 H 96 N0 10 P (902.28)

11) 1-Oleoyl-2-erucyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 11) 1-oleoyl-2-erucyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

(R, = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) (R 2 = CO - (CH 2 ) - CH = CH - (CH 2 ) 7 - CH 3 ) (R, = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) (R 2 = CO - (CH 2) - CH = CH - (CH 2) 7 - CH 3)

C 50 H 96 NO 10 P (902,28) C 50 H 96 NO 10 P (902.28)

12) 1,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 3) (R 1f R 2 = Cl - (CH 2 ) 14 - CH 3 ) 12) 1,2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 3) (R 1f R 2 = Cl - (CH 2) 14 - CH 3)

C 43 H 86 NO 10 P (808,12) 13) 1 ,2-Dierucyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 3) C 43 H 86 NO 10 P (808.12) 13) 1, 2-Dierucyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl- (n = 3)

(R-, R 2 = CO - (CH 2 )„ - CH = CH - (CH 2 ) 7 - CH 3 ) C 55 H 106 NO 10 P (972,413) (R, R 2 = CO - (CH 2) "- CH = CH - (CH 2) 7 - CH 3) C 55 H 106 NO 10 P (972.413)

14) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 3) 14) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl- (n = 3)

(R„ R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 47 H 90 NO 10 P (860,20) (R "R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 47 H 90 NO 10 P (860.20)

15) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 3) 15) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 3)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 47 H 92 N0 10 P (862,21) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 47 H 92 N0 10 P (862.21 )

16) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 3) 16) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 3)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 10 - CH 3 ) C 41 H 82 NO 10 P (780,07) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 10 - CH 3) C 41 H 82 NO 10 P (780.07)

17) 1,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-butylammonium (n = 4) 17) 1,2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N-dihydroxypropyl-butylammonium (n = 4)

(R„ R 2 = CO - (CH 2 ) 14 - CH 3 ) C 44 H 88 NO 10 P (822,15) (R "R 2 = CO - (CH 2) 14 - CH 3) C 44 H 88 NO 10 P (822.15)

18) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- butylammonium (n = 4) 18) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-butylammonium dihydroxypropyl- (n = 4)

(R„ R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 48 H 92 N0 10 P (874,23) 19) 1 ,2-Dierucyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- butylammonium (n = 4) (R "R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 48 H 92 N0 10 P (874.23) 19) 1, 2-Dierucyl-sn-glycero -3-phospho-N, N-dimethyl-N-butylammonium dihydroxypropyl- (n = 4)

(R,, R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 56 H 108 NO 10 P (986,44) (R ,, R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 56 H 108 NO 10 P (986.44)

20) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-butylammonium (n = 4) 20) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-dihydroxypropyl-butylammonium (n = 4)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 48 H 94 NO 10 P (876,24) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 48 H 94 NO 10 P (876.24 )

21) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N~dimethyl-N- dihydroxypropyl-butylammonium (n = 4) 21) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N ~ dimethyl-N- dihydroxypropyl-butylammonium (n = 4)

(R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 10 - CH 3 ) C 42 H 84 NO 10 P (794,10) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 10 - CH 3) C 42 H 84 NO 10 P (794.10)

22) 1,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-hexylammonium (n = 6) 22) 1,2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N-hexylammonium dihydroxypropyl (n = 6)

(R„ R 2 = CO - (CH 2 ) 14 - CH 3 ) C 42 H 84 N0 10 P (794,10) (R "R 2 = CO - (CH 2) 14 - CH 3) C 42 H 84 N0 10 P (794.10)

23) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- hexylammonium (n = 6) 23) 1,2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N-hexylammonium dihydroxypropyl- (n = 6)

(RR 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 50 H 96 N0 10 P (902,28) (RR = 2 CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 50 H 96 N0 10 P (902.28)

24) 1,2-Dierucyl-sn-glycero-3-phospho-N,N-dimethyl-N-dihydroxypropyl- hexylammonium (n = 6) 24) 1,2-Dierucyl-sn-glycero-3-phospho-N, N-dimethyl-N-hexylammonium dihydroxypropyl- (n = 6)

(R 1f R 2 = CO - (CH 2 )„ - CH = CH - (CH 2 ) 7 - CH 3 ) C 58 H 1l2 NO l0 P (1014,49) Beispiele für zweikettiqe Glvcero-phospho-N,N-dimethyl-N-(2-hvdroxypropyl- 3,1 -0,0-dihvdroxypropyl)-alkylammonium-Verbindunqen (A = a; n = 2-6; R 3 , 0 3 ; m = 1 ; x = 0; y = 1 ; z = 2) (R 1f R 2 = CO - (CH 2) "- CH = CH - (CH 2) 7 - CH 3) C 58 H NO 1L2 l0 P (1014.49) Examples of zweikettiqe Glvcero-phospho-N, N- dimethyl-N- (2-hvdroxypropyl- -0.0 3.1-dihvdroxypropyl) -alkylammonium Verbindunqen (A = a; n = 2-6; R 3, 0 3; m = 1; x = 0; y = 1; z = 2)

Formel I formula I

A - PO, (CH 2 ) n - (CH 2'> CH 2 - 0 H A - PO, (CH 2) n - (CH 2 '> CH 2 - 0. H

Figure imgf000022_0001
Figure imgf000022_0002

25) 1 ,2-Dipalmitoyl-sn-glycero-3-phospho~N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-ethylammonium (n = 2) (R,; R 2 = CO - (CH 2 ) - CH 3 ) C 45 H 90 N0 12 P (868,18) 25) 1, 2-dipalmitoyl-sn-glycero-3-phospho ~ N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -ethylammonium (n = 2) (R ,; R 2 = CO - (CH 2) - CH 3) C 45 H 90 N0 12 P (868.18)

26) 1,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)ethylammonium (n = 2) (R„ R 2 = CO - (CH 2 ) 16 - CH 3 ) C 49 H 98 N0 12 P (924,28) 26) 1,2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) ethylammonium (n = 2) (R "R 2 = CO - (CH 2) 16 - CH 3) C 49 H 98 N0 12 P (924.28)

27) 1 ,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-ethylammonium (n = 2) (RR 2 = CO - (CH 2 ) - CH = CH - (CH 2 ) 7 - CH 3 ) C 57 H 110 N0 12 P (1032,47) 27) 1, 2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -ethylammonium (n = 2) (RR = 2 CO - (CH 2) - CH = CH - (CH 2) 7 - CH 3) C 57 H 110 N0 12 P (1032.47)

28) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3,1-0,0-dihydroxypropyl)-ethylammonium (n = 2) (R 1f R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 49 H 94 N0 12 P (920,25) 29) 1-Stearoyl-2-oleoyl-sn-glycero-3-phospho~N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-ethylammonium (n = 2) (R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) 28) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl from 3.1 to 0.0-dihydroxypropyl) -ethylammonium (n = 2) (R 1f R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 49 H 94 N0 12 P (920.25) 29) 1-stearoyl-2-oleoyl-sn-glycero-3 -phospho ~ N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -ethylammonium (n = 2) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3)

5 C 49 H 96 N0 12 P (922,27) 5 C 49 H 96 N0 12 P (922.27)

30) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-ethylammonium (n = 2) (R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 10 - CH 3 ) 30) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -ethylammonium (n = 2) (R , = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 10 - CH3)

10 C 43 H 86 N0 12 P (840,12) 10 C 43 H 86 N0 12 P (840.12)

31) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-ethylammonium 31) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -ethylammonium

(n = 2) 15 (R, = CO - (CH 2 ) ι CH = CH - (CH 2 ) 7 - CH 3 ; (n = 2) 15 (R, = CO - (CH 2) ι CH = CH - (CH 2) 7 - CH 3;

R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 53 H 102 NO 12 P (976,36) R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 53 H 102 NO 12 P (976.36)

32) 1-Oleoyl-2-erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- ° 20 hydroxypropyl-3,1-0,0-dihydroxypropyl)-ethylammonium (n = 2) 32) 1-oleoyl-2-erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-20 ° 3.1 to 0.0-dihydroxypropyl) -ethylammonium (n = 2)

(R, = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ; R 2 = CO - (CH 2 )„ - CH = CH - (CH 2 ) 7 - CH 3 ) C 53 H l02 NO 12 P (976,36) (R, = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3; R 2 = CO - (CH 2) "- CH = CH - (CH 2) 7 - CH 3) C 53 H l02 NO 12 P (976.36)

25 33) 1 ,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-propylammonium (n = 3) (R 1f R 2 = CO - (CH 2 ) 14 - CH 3 ) C 46 H 92 N0 12 P (882,20) 25 33) 1, 2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -propylammonium (n = 3) (R 1f R 2 = CO - (CH 2) 14 - CH 3) C 46 H 92 N0 12 P (882.20)

30 34) 1 ,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-propylammonium (n = 3) (R 1f R 2 = CO - (CH 2 ) 16 - CH 3 ) 30 34) 1, 2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -propylammonium (n = 3) (R 1f R 2 = CO - (CH 2) 16 - CH3)

C 50 H 10 oN0 12 P (938,31) C 50 H 10 on0 12 P (938.31)

35) 1 ,2-Dierucoyl-sn-giycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-propylammonium (n = 3) (R,, R 2 = CO - (CH 2 ) - CH = CH - (CH 2 ) 7 - CH 3 ) C 58 H 112 N0 12 P (1046,49) 35) 1, 2-sn-giycero-Dierucoyl-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -propylammonium (n = 3) (R ,, R 2 = CO - (CH 2) - CH = CH - (CH 2) 7 - CH 3) C 58 H 112 N0 12 P (1046.49)

36) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3,1-0,0-dihydroxypropyl)-propylammonium (n = 3) 36) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl from 3.1 to 0.0-dihydroxypropyl) -propylammonium (n = 3)

(R 1f R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 5 oH 96 N0 12 P (934,28) (R 1f R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 5 oH 96 N0 12 P (934.28)

37) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)propylammonium(n = 3) (R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 50 H 98 N0 12 P (936,29) 37) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) propylammonium (n = 3) (R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 50 H 98 N0 12 P (936.29)

38) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-propylammonium (n = 3) (R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 10 - CH 3 ) C 44 H 88 N0 12 P (854,15) 38) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -propylammonium (n = 3) (R , = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 10 - CH 3) C 44 H 88 N0 12 P (854.15)

39) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3,1-0,0-dihydroxypropyl)-butylammonium (n = 4) 39) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl from 3.1 to 0.0-dihydroxypropyl) -butylammonium (n = 4)

(RR 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 51 H 98 N0 12 P (948,30) 40) 1 ,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-butylammonium (n = 4) (R 1# R 2 = CO - (CH 2 ) - CH = CH - (CH 2 ) 7 - CH 3 ) C 59 H 114 N0 12 P (1060,52) (RR = 2 CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 51 H 98 N0 12 P (948.30) 40) 1, 2-Dierucoyl-sn-glycero-3 -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -butylammonium (n = 4) (R 1 # R 2 = CO - (CH 2) - CH = CH - (CH 2) 7 - CH 3) C 59 H 114 N0 12 P (1060.52)

41) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropy!)-butylammonium (n = 4) (R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 51 H 1O0 NO 12 P (950,32) 41) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropy) - butylammonium (n = 4) ( R, = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 51 H 12 NO 1o0 P (950.32)

42) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-butylammonium (n = 4) (R, = CO - (CH 2 ) 16 - CH 3 ; R 2 = CO - (CH 2 ) 10 - CH 3 ) C 45 H 90 NO 12 P (868,175) 42) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -butylammonium (n = 4) (R , = CO - (CH 2) 16 - CH 3; R 2 = CO - (CH 2) 10 - CH 3) C 45 H 90 NO 12 P (868.175)

43) 1 , 2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 1 ,3-0,0-dihydroxypropyl)-hexylammonium (n = 6) 43) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-1, 3 to 0.0-dihydroxypropyl) -hexylammonium (n = 6)

(R 2 , R 2 = CO - (CH 2 ) 7 - CH = CH - (CH 2 ) 7 - CH 3 ) C 53 H 102 NO 12 P (976,358) (R 2, R 2 = CO - (CH 2) 7 - CH = CH - (CH 2) 7 - CH 3) C 53 H 102 NO 12 P (976.358)

44) 1 ,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3,1-0,0-dihydroxypropyl)-hexylammonium (n = 6) (R„ R 2 = CO - (CH 2 )„ - CH = CH - (CH 2 ) 7 - CH 3 ) C 61 H 118 N0 12 P (1088,57) 44) 1, 2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3.1 to 0.0-dihydroxypropyl) -hexylammonium (n = 6) (R "R 2 = CO - (CH 2) "- CH = CH - (CH 2) 7 - CH 3) C 61 H 118 N0 12 P (1088.57)

Beispiele für zweikettiqe Glvcero-phospho-N,N-dimethyl-N-(2-hvdroxypropyl- 3,1 -0,0-2-hvdroxypropyl-3, 1 -O,0-dihydroxypropyl)-alkylammonium- Verbindungen Examples of zweikettiqe Glvcero-phospho-N, N-dimethyl-N- (2-hvdroxypropyl- 3.1 -0,0-2-hvdroxypropyl-3, 1 O, 0-dihydroxypropyl) alkylammonium compounds

(A = a; n - 2-8; R 3 , CH 3 ; m 1; x = 0; y = 1; z = 3) (A = a; n - 2-8; R 3, CH 3; m is 1; x = 0; y = 1 z = 3)

Formel I formula I

A - PO- (CH 2'x CH 2 CH, - 0 - H A - PO (CH 2'x CH 2 CH, - 0 - H

Figure imgf000026_0002
Figure imgf000026_0001

45) 1,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3, 1-0, 0-2-hydroxypropy 1-3,1 -dihydroxypropy I)- ethylammonium (n = 2) 45) 1,2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1-0, 0-2 hydroxypropyl-1 to 3.1 -dihydroxypropy I) - ethylammonium (n = 2)

(im weiterenTextwirdN-(2-hydroxypropyl-3,1-0,0-2-hydroxypropyl- 3,1-dihydroxypropyl) abgekürzt als N-(HP r HP 2 -diHP 3 ) C 48 H 96 N0 14 P (942,25) (in weiterenTextwirdN- (2-hydroxypropyl-3,1-0,0-2-hydroxypropyl 3,1-dihydroxypropyl) abbreviated as N- (HP 2 HP r -diHP 3) C 48 H 96 N0 14 P (942, 25)

46) 1,2-Distearoyl-sn-glycero-3-phospho-N,Nd ; methyl-N-(HP 1 HP 2 -diHP 3 )- ethylammonium (n = 2) 46) 1,2-distearoyl-sn-glycero-3-phospho-N, Nd; methyl-N- (1 HP 2 HP -diHP 3) - ethylammonium (n = 2)

C 52 H 104 NO l4 P (998,36) C 52 H 104 NO l4 P (998.36)

47) 1,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- ethylammonium (n = 2) C 60 H 116 NO 14 P (1106,54) 47) 1,2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - ethylammonium (n = 2) C 60 H 116 NO 14 P (1106, 54)

48) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- ethylammonium ( n = 2) 48) 1,2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - ethylammonium (n = 2)

C 52 H 100 N0 14 P (994,33) 49) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N(HP r HP 2 - diHP 3 )-ethylammonium (n = 2) C 52 H 102 N0 14 P (996,35) C 52 H 100 N 0 14 P (994.33) 49) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N (HP HP r 2 - 3 DIHP) -ethylammonium (n = 2) C 52 H 102 N 0 14 P (996.35)

50) 1 -StearoyI-2-lauroyI-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - diHP 3 )-ethylammonium (n = 2) C 46 H 92 N0 14 P (914,20) 50) 1 -StearoyI-2-lauroyI-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 DIHP) -ethylammonium (n = 2) C 46 H 92 N0 14 P ( 914.20)

51 ) 1 -Palmitoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - diHP 3 )-ethylammonium (n = 2) 51) 1-palmitoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 DIHP) -ethylammonium (n = 2)

C 44 H 88 N0 14 P (886, 1 5) C 44 H 88 N0 14 P (886, 1 5)

52) l ^-Dipalmitoyl-sn-glycero-S-phospho-N^-dimethyl-N-JHP T -HP^ diHP 3 )-propylammonium (n = 3) C 49 H 98 N0 14 P (956,28) 52) l ^ -Dipalmitoyl-sn-glycero-S-phospho-N ^ -dimethyl-N-T JHP -HP ^ DIHP 3) -propylammonium (n = 3) C 49 H 98 N0 14 P (956.28)

53) 1 ,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- propylammonium (n = 3) 53) 1, 2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - propylammonium (n = 3)

C 53 H l 06 NO 14 P ( 101 2,39) C 53 H 06 NO 14 l P (101 2.39)

54) 1 ,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- propylammonium (n = 3) 54) 1, 2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - propylammonium (n = 3)

C 6l H ll 8 N0 14 P ( 1 1 20,57) C 6l H ll 8 N0 14 P (1 1 20.57)

55) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- propylammonium (n = 3) C 53 H 102 NO 14 P ( 1008,36) 55) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - propylammonium (n = 3) C 53 H 102 NO 14 P (1008, 36)

56) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP l -HP 2 - diHP 3 )-propylammonium (n = 3) 56) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (l HP -HP 2 - 3 DIHP) -propylammonium (n = 3)

C 53 H 104 NO 14 P ( 1 01 0,37) 57) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - diHP 3 )-propylammonium (n = 3) C 47 H 94 N0 14 P (928,23) C 53 H 104 NO 14 P (1 01 0.37) 57) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 DIHP) - propylammonium (n = 3) C 47 H 94 N0 14 P (928.23)

58) 1 -Palmitoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP HP 2 - diHP 3 )-propylammonium (n = 3) C 45 H 90 NO 14 P (900,17) 58) 1-palmitoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP - DIHP 3) -propylammonium (n = 3) C 45 H 90 NO 14 P (900 , 17)

59) 1 ,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - diHP 3 )-butylammonium (n = 4) 59) 1, 2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 DIHP) -butylammonium (n = 4)

C 5O H 100 NO 14 P (970,31) C 5O H 100 NO 14 P (970.31)

60) 1,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- butylammonium (n = 4) C 54 H 108 NO l4 P (1026,41) 60) 1,2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - butylammonium (n = 4) C 54 H 108 NO l4 P (1026, 41)

61 ) 1 ,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP HP 2 -diHP 3 )- butylammonium (n = 4) 61) 1, 2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP -diHP 3) - butylammonium (n = 4)

C 62 H l20 N0 14 P (1134,60) C 62 H 14 N0 l20 P (1134.60)

62) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- butylammonium (n = 4) 62) 1,2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - butylammonium (n = 4)

C 54 H 104 NO 14 P (1022,38) C 54 H 104 NO 14 P (1022.38)

63) 1 ,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP 1 -HP 2 - diHP 3 )-hexylammonium (n = 6) C 52 H 104 NO 14 P (998,36) 63) 1, 2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 1 -HP 2 - 3 DIHP) -hexylammonium (n = 6) C 52 H 104 NO 14 P (998 , 36)

64) 1,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- hexylammonium (n = 6) 64) 1,2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - hexylammonium (n = 6)

C 56 H 112 NOP 14 P (1054,47) 65) 1,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- hexylammonium (n = 6) C 64 H 124 NO l4 P (1162,65) C 56 H 14 P 112 NOP (1054.47) 65) 1,2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - hexylammonium (n = 6) C 64 H 124 NO l4 P (1162.65)

66) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- hexylammonium (n = 6) C 56 H 108 N0 14 P (1050,44) 66) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - hexylammonium (n = 6) C 56 H 14 N0 108 P (1050, 44)

67) 1,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- octylammonium (n = 8) 67) 1,2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - octylammonium (n = 8)

C 58 H 116 N0 14 P (1082,52) C 58 H 116 N0 14 P (1082.52)

68) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- octylammonium (n = 8) C 58 H 112 N0 14 P (1078,49) 68) 1,2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - octylammonium (n = 8) C 58 H 14 N0 112 P (1078, 49)

69) 1,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP HP 2 -diHP 3 )- octylammonium (n = 8) C 66 H 128 N0 14 P (1190,70) 69) 1,2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP -diHP 3) - octylammonium (n = 8) C 66 H 128 N 0 14 P (1190.70 )

Beispiele für zweikettiqe Glvcero-phospho-N,N-dimethyl-N-(2-hvdroxypropyl- Examples of zweikettiqe Glvcero-phospho-N, N-dimethyl-N- (2-hvdroxypropyl-

3, 1 -0,0-2-hvdroχypropyl-3, 1 -0,0-2-hvdroχypropyl-3, 1 -0,0-dihvdroxypropyl)- alkylammonium-Verbindunqen 3, 1 -0,0-2-hvdroχypropyl-3, 1--0,0-2 hvdroχypropyl-3, 1 -0,0-dihvdroxypropyl) - alkylammonium Verbindunqen

(A = a; n = 2, 3; R 3 , 0 3 ; m = 1; x = 0; y = 1; z = 4) (A = a; n = 2, 3; R 3, 0 3; m = 1; x = 0; y = 1 z = 4)

Formel I formula I

A - PO, (CH 2 ) n - (CH 2h CH, CH, - 0 - H A - PO, (CH 2) n - (CH 2h CH, CH, - 0 - H

Figure imgf000029_0001
Figure imgf000029_0002
70) 1 ,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3, 1 -0,0-2-hydroxypropyl-3, 1 -0,0-hydroxypropyl-3, 1 - dihydroxypropyD-ethylammonium (n = 2) 70) 1, 2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1-hydroxypropyl-3 -0,0-2, 1-hydroxypropyl -0.0 -3, 1 - dihydroxypropyD-ethylammonium (n = 2)

(im weiteren Text wird N[2-hydroxypropyl-3, 1 -0,0-2-hydroxypropyl- 3,1-0,0-dihydroxypropyl-3,1-0,0-dihydroxypropyl] abgekürzt als N- (In further text is N [1-hydroxypropyl -0,0-2 3.1 to 0.0 3.1 to 0.0-dihydroxypropyl-dihydroxypropyl-2-hydroxypropyl-3] abbreviated as N-

(HP r HP 2 -HP 3 -diHP 4 ) angegeben. (HP HP r 2 -HP 3 -diHP 4). C 51 H 102 N0 16 P (1016,33) C 51 H 102 N0 16 P (1016.33)

71 ) 1 ,2-Distearoyl-sn~glycero-3-phospho-N,N-dimethyl-N-(HP 1 -HP 2 -HP 3 - diHP 4 )-ethylammonium (n = 2) 71) 1, 2-distearoyl-sn ~ glycero-3-phospho-N, N-dimethyl-N- (HP 1 -HP 2 -HP 3 - 4 DIHP) -ethylammonium (n = 2)

C 55 H 110 N0 16 P (1072,44) C 55 H 110 N0 16 P (1072.44)

72) 1,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -HP 3 - diHP 4 )-ethylammonium (n = 2) C 63 H 122 N0 16 P (1180,62) 72) 1,2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -HP 3 - 4 DIHP) -ethylammonium (n = 2) C 63 H 122 N 0 16 P (1180.62)

73) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -HP 3 - diHP 4 )-ethylammonium (n = 2) 73) 1,2-dioleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -HP 3 - 4 DIHP) -ethylammonium (n = 2)

C 55 H 106 N0 16 P (1068,41) C 55 H 106 N0 16 P (1068.41)

74) 1-Stearoyl-2-oleoyI-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - HP 3 -diHP 4 )-ethylammonium (n = 2) 74) 1-Stearoyl-2-oleoyI-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 HP -diHP 4) -ethylammonium (n = 2)

C 55 H 108 NO 16 P (1070,42) C 55 H 108 NO 16 P (1070.42)

75) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP l -HP 2 - HP 3 -diHP 4 )-ethylammonium (n = 2) C 49 H 98 N0 16 P (988,28) 75) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (l HP -HP 2 - 3 HP -diHP 4) -ethylammonium (n = 2) C 49 H 98 N0 16 P (988.28)

76) 1-Palmitoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - HP 3 -diHP 4 )-ethylammonium (n = 2) 76) 1-palmitoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 HP -diHP 4) -ethylammonium (n = 2)

C 47 H 94 N0 16 P (960,23) 77) 1,2-Dipalmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -HP 3 - diHP 4 )-propylammonium (n = 3) C 52 H 104 NO l6 P (1030,36) C 47 H 94 N0 16 P (960.23) 77) 1,2-dipalmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -HP 3 - 4 DIHP) -propylammonium (n = 3) C 52 H 104 NO L6 P (1030.36)

78) 1 ,2-Distearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -HP 3 - diHP 4 )-propylammonium (n = 3) C 56 H ll2 N0 16 P (1086,47) 78) 1, 2-distearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -HP 3 - 4 DIHP) -propylammonium (n = 3) C 56 H 16 P ll2 N0 (1086.47)

79) 1,2-Dierucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -HP 3 - diHP 4 )-propylammonium (n = 3) 79) 1,2-Dierucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -HP 3 - 4 DIHP) -propylammonium (n = 3)

80) 1,2-Dioieoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP l -HP 2 -HP 3 - diHP 4 )-propylammonium (n = 3) 80) 1,2-Dioieoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (l HP -HP 2 -HP 3 - 4 DIHP) -propylammonium (n = 3)

C 56 H 108 NO 16 P (1082,43) C 56 H 108 NO 16 P (1082.43)

81) 1-Stearoyl-2-lauroyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP HP 2 - HP 3 -diHP 4 )-propylammonium (n = 3) 81) 1-stearoyl-2-lauroyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP - HP 3 -diHP 4) -propylammonium (n = 3)

C 5O H 100 NO 16 P (1002,31) C 5O H 100 NO 16 P (1002.31)

82) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - HP 3 -diHP 4 )-propylammonium (n = 3) C 56 H 110 N0 16 P (1084,45) 82) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 HP -diHP 4) -propylammonium (n = 3) C 56 H 110 N 0 16 P (1084.45)

83) 1-Arachinoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP HP 2 - HP 3 -diHP 4 )-propylammonium (n = 3) 83) 1-Arachinoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP - HP 3 -diHP 4) -propylammonium (n = 3)

C 58 H ll4 N0 16 P (1112,50) C 58 H 16 N0 ll4 P (1112.50)

84) 1-Behenoyl-2-oleoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 - HP 3 -diHP 4 )-propylammonium (n = 3) C 60 H ll8 NO 16 P (1140,56) Beispiele für zweikettiqe Glvcero-phospho-Verbindunqen, die nicht am 84) 1-Behenoyl-2-oleoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP HP r 2 - 3 HP -diHP 4) -propylammonium (n = 3) C 60 H LL8 NO 16 P (1140.56) Examples of zweikettiqe Glvcero-phospho-Verbindunqen who do not take

Stickstoff hydroxyliert sind Nitrogen are hydroxylated

(A = a; n = 2-6; m = 1 ; x = 1 ; z = 0) (A = a; n = 2-6; m = 1; x = 1; z = 0)

Formel I formula I

Figure imgf000032_0001

85) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N,N-trimethyl-propylammonium C 45 H 86 N0 8 P (800,15) 85) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium C 45 H 86 N0 8 P (800.15)

86) 1 ,2-Dioleoyl-sn-glycero-3-phospho-N,N,N-trimethyl-butylammonium C 46 H 88 N0 8 P (814,17) 86) 1, 2-dioleoyl-sn-glycero-3-phospho-N, N, N-trimethyl-butylammonium C 46 H 88 N0 8 P (814.17)

87) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N,N-trimethyl-pentylammonium C 47 H 90 NO P (828,20) 87) 1,2-dioleoyl-sn-glycero-3-phospho-N, N, N-trimethyl-pentylammonium C 47 H 90 NO P (828.20)

88) 1,2-Dioleoyl-sn-glycero-3-phospho-N,N,N-trimethyl-hexylammonium C 48 H 92 N0 8 P (842,23) 88) 1,2-dioleoyl-sn-glycero-3-phospho-N, N, N-trimethyl-hexylammonium C 48 H 92 N0 8 P (842.23)

89) 1-Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N,N-trimethyl propylammonium 89) 1-stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N, N-trimethyl propylammonium

C 45 H 88 N0 8 P (802,16) C 45 H 88 N0 8 P (802.16)

90) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N,N,N-trimethyl butylammonium C 46 H 90 N0 8 P (816,19) 91) 1-Palmitoyl-2-lauroyl-sn-glycero-3-phospho-N,N,N-trimethyl propylammonium C 37 H 74 N0 8 P (691,97) 90) 1 -Stearoyl-2-oleoyl-sn-glycero-3-phospho-N, N, N-trimethyl butylammonium C 46 H 90 N0 8 P (816.19) 91) 1-palmitoyl-2-lauroyl-sn glycero-3-phospho-N, N, N-trimethyl propylammonium C 37 H 74 N0 8 P (691.97)

92) 1 -Oleoyl-2-lauroyl-sn-glycero-3-phospho-N,N,N-trimethyl propylammonium C 39 H 76 N0 8 P (718,00) 92) 1 -Oleoyl-2-lauroyl-sn-glycero-3-phospho-N, N, N-trimethyl propylammonium C 39 H 76 N0 8 P (718.00)

93) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N,N,N-trimethyl propylammonium 93) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N, N, N-trimethyl propylammonium

C 49 H 94 N0 8 P (856,26) C 49 H 94 N0 8 P (856.26)

94) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N,N,N-trimethyl butylammonium C 50 H 96 N0 8 P (870,28) 94) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N, N, N-trimethyl butylammonium C 50 H 96 N0 8 P (870.28)

95) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N,N,N-trimethyl hexylammonium 95) 1-Erucoyl-2-oleoyl-sn-glycero-3-phospho-N, N, N-trimethyl hexylammonium

C 52 H 100 NO 8 P (898,34) C 52 H 100 NO 8 P (898.34)

96) 1 -NervonoyI-2-lauroyl-sn-glycero-3-phospho-N,N,N-trimethyl propylammonium 96) 1 -NervonoyI-2-lauroyl-sn-glycero-3-phospho-N, N, N-trimethyl propylammonium

C 45 H 88 N0 8 P (802,16) C 45 H 88 N0 8 P (802.16)

97) 1-Nervonoyl-2-oleoyl-sn-glycero-3-phospho-N,N,N-trimethyl propylammonium C 51 H 98 N0 8 P (884,31) 2) Lösunqsvermittler 97) 1-Nervonoyl-2-oleoyl-sn-glycero-3-phospho-N, N, N-trimethyl propylammonium C 51 H 98 N0 8 P (884.31) 2) Lösunqsvermittler

Es hat sich gezeigt, dass bestimmte Substanzen aus den hier vorgestellten Verbindungen insbesondere diejenigen, welche ethanollöslich sind, ausgezeichnete Lösungsvermittler für in Wasser schwerlösliche Substanzen sind. It has been shown that certain substances from the compounds presented here in particular those which are ethanollöslich, excellent solubilizers for slightly water-soluble substances. So kann man beispielsweise Taxol auf einfache Weise in eine intravenös applizierbare Form bringen. So you can for example bring Taxol easily in a intravenously administrable form. Ebenso erwiesen sich zB Taxoter, Cyclosporin, Cholesterin und deren Derivate, Steroide, Cortison und Analoga, Erucylphosphocholin (Auflösung der gelartigen Strukturen) als gut lösbar. Likewise, as taxotere, cyclosporine, cholesterol and derivatives thereof, steroids, cortisone and analogues, erucylphosphocholine (dissolution of the gel-like structures) have proved easy to solve.

Insbesondere haben sich hier Substanzen bewährt, die zwischen Phosphat und Ammonium einen Abstand von 3 C-Atomen besitzen (n = 3 in der allgemeinen Formel I), zB die Substanzen aus den Beispielen 1 4, 85, 1 1 1 , 1 39, 1 44, 1 76. Hervorragend geeignet für diese Zwecke ist eine einfache Su bstanz, 1 - Erucoyl-propandiol-( 1 , 3) -phospho-N , N , N-trimethyl- propylammonium ( 1 76) . Especially here substances 85 1 1 1 1 39 1 have proved that between phosphate and ammonium a distance of 3 carbon atoms have (n = 3 in the general formula I), for example, the substances of Examples 1 4,,,, 44, 1 76. Excellent for this purpose a simple Su is bstanz, 1 - Erucoyl-propanediol (1, 3) -phospho-N, N, N-trimethyl-propylammonium (1 76). Diese Substanz kann einfach in hohen Ausbeuten im Tonnenmaßstab hergestellt werden. This substance can be easily produced in high yields by the ton.

Bevorzugt handelt es sich bei den Lösungsvermittlern um einkettige Verbindungen, dh dass bei A = a einer von R, und R 2 Wasserstoff oder ein Alkyl mit 1 bis 3 C-Atomen darstellt. It is preferable that in the solubilisers are single-chain compounds, ie that when A = a one of R, and R 2 represents hydrogen or an alkyl having 1 to 3 carbon atoms.

Taxol zur intravenösen Anwendung Taxol for intravenous use

Man stelle eine Lösung von 0,3 g Taxol und 1 ,75 g Substanz Nr. 1 76 in 7,95 g absolutem Ethanol her. Prepare a solution of 0.3 g taxol and 1, 75 g of substance No. 1 76 absolute in 7.95 g of ethanol is prepared. Die Lösung wird steril filtriert und bis zur Verwendung bei 4 °C aufbewahrt. The solution is sterile filtered and stored until use at 4 ° C.

Für eine intravenöse Gase wird die Stammlösung 1 : 10 oder 1 : 1 00 mit physiologischer Kochsalzlösung verdünnt. 10 or 1: For intravenous gases, the stock solution is 1 1 00 diluted with saline. Beispiele für einkettiqe Glvcero-phospho-N,N-dimethyl-N-dihvdroxypropyl- alkylammonium-Verbindunqen Examples of einkettiqe Glvcero-phospho-N, N-dimethyl-N-alkylammonium dihvdroxypropyl- Verbindunqen

(A = a; n = 2-6; R 3 , CH 3 ; m = 1, x = 0, y = 1, z = 1) (A = a; n = 2-6; R 3, CH 3; m = 1, x = 0, y = 1, z = 1)

A - PO. A - PO. |CH 2 ) n - (CH 2') CH, CH 2 - 0 H | CH 2) n - (CH 2 ') CH, CH 2 - 0. H

Figure imgf000035_0002
Figure imgf000035_0001

98) 1 -Palmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) C 26 H 54 N0 9 P (555,69) 98) 1-palmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2) C 26 H 54 N0 9 P (555.69)

99) 1-Stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) 99) 1-Stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2)

C 28 H 58 N0 9 P (583,74) C 28 H 58 N 0 9 P (583.74)

100) 1-Arachinoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = z) C 30 H 62 N0 9 P (611,79) 100) 1-Arachinoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = z) C 30 H 62 N0 9 P (611.79)

101) 1 -Behenyol-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP) ethylammonium (n = 2) 101) 1 -Behenyol-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) ethylammonium (n = 2)

C 32 H 66 N0 9 P (639,85) C 32 H 66 N 0 9 P (639.85)

102) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP) ethylammonium (n = 2) 102) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) ethylammonium (n = 2)

C 32 H 64 N0 9 P (637,83) C 32 H 64 N 0 9 P (637.83)

103) 1-Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) C 34 H 68 N0 9 P (665,88) 104) 1-0-Hexadecyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) 103) 1-Nervonoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2) C 34 H 68 N0 9 P (665.88) 104) 1-0- hexadecyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2)

105) 1-0-Octadecyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) 105) 1-0-octadecyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2)

C 28 H 60 NO 8 P (569,76) C 28 H 60 NO 8 P (569.76)

106) 1-0-Eicosanyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) C 30 H 64 N0 8 P (597,81) 106) 1-0-eicosanyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2) C 30 H 64 N0 8 P (597.81)

107) 1-0-Behenyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- ethylammonium (n = 2) 107) 1-0-Behenyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - ethylammonium (n = 2)

C 32 H 68 N0 8 P (625,86) C 32 H 68 N0 8 P (625.86)

108) 1 -Palmitoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- propylammonium (n = 3) 108) 1-palmitoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - propylammonium (n = 3)

C 27 H 56 N0 9 P (569,71) C 27 H 56 N 0 9 P (569.71)

109) 1-Stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- propylammonium (n = 3) C 29 H 60 NO 9 P (597,77) 109) 1-Stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - propylammonium (n = 3) C 29 H 60 NO 9 P (597.77)

110) 1-Behenoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- propylammonium (n = 3) 110) 1-Behenoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - propylammonium (n = 3)

C 33 H 68 N0 9 P (653,87) C 33 H 68 N 0 9 P (653.87)

111) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- propylammonium (n = 3) C 33 H 66 N0 9 P (651,86) 112) 1-Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- propylammonium (n = 3) C 35 H 70 NO 9 P (679,91) 111) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - propylammonium (n = 3) C 33 H 66 N0 9 P (651.86) 112) 1-Nervonoyl- sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - propylammonium (n = 3) C 35 H 70 NO 9 P (679.91)

113) 1-Stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- butylammonium (n = 4) C 30 H 62 N0 9 P (611,79) 113) 1-Stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - butylammonium (n = 4) C 30 H 62 N0 9 P (611.79)

114) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- butylammonium (n = 4) 114) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - butylammonium (n = 4)

C 34 H 68 N0 9 P (665,88) C 34 H 68 N 0 9 P (665.88)

115) 1-Stearoyl-sn-glycero-3-phosρho-N,N-dimethyl-N-(diHP)- hexylammonium (n = 6) C 32 H 66 N0 9 P (639,85) 115) 1-Stearoyl-sn-glycero-3-phosρho-N, N-dimethyl-N- (DIHP) - hexylammonium (n = 6) C 32 H 66 N0 9 P (639.85)

116) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(diHP)- hexylammonium (n = 6) C 36 H 72 N0 9 P (693,94) 116) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (DIHP) - hexylammonium (n = 6) C 36 H 72 N0 9 P (693.94)

Beispiele für einkettiqe Gl vcero-phospho-N,N-dimethyl-N-(2-hvdroxypropyl- 3,1 -0,0-dihvdroxypropyl)-alkylammonium-Verbindunqen (A = 0; n = 2-6; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 2) Examples of Gl einkettiqe vcero-phospho-N, N-dimethyl-N- (2-hvdroxypropyl- -0.0 3.1-dihvdroxypropyl) -alkylammonium Verbindunqen (A = 0; n = 2-6; R 3, CH 3; m = 1; x = 0; y = 1 z = 2)

Formel I formula I

A - PO- (CH 2'n - (CH 2'x CH 7 - 0 - H A - PO (CH 2'n - (CH CH 2'x 7 - 0 - H

Figure imgf000037_0001
Figure imgf000037_0002
117) 1-Stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )- ethylammonium (n = 2) C 31 H 64 NO P (657,82) 117) 1-Stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (1 HP -diHP 2) - ethylammonium (n = 2) C 31 H 64 NO P (657.82)

118) 1-Arachinoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- ethylammonium (n = 2) C 33 H 68 NO P (685,87) 118) 1-Arachinoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - ethylammonium (n = 2) C 33 H 68 NO P (685.87)

119) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- ethylammonium (n = 2) 119) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - ethylammonium (n = 2)

C 35 H 70 NO P (711,91) C 35 H 70 NO P (711.91)

120) 1-Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP l -diHP 2 )- ethylammonium (n = 2) C 37 H 74 NO„P (739,96) 120) 1-Nervonoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (l HP -diHP 2) - ethylammonium (n = 2) C 37 H 74 NO "P (739.96)

121) 1-0-Octadecyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- ethylammonium (n = 2) 121) 1-0-octadecyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - ethylammonium (n = 2)

C 31 H 66 NO 10 P (643,83) C 31 H 66 NO 10 P (643.83)

122) 1-0-Behenyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- ethylammonium (n = 2) 122) 1-0-Behenyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - ethylammonium (n = 2)

C 35 H 74 NO P (699,94) C 35 H 74 NO P (699.94)

123) 1 -Stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )- propylammonium (n = 3) 123) 1 -Stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (1 HP -diHP 2) - propylammonium (n = 3)

Figure imgf000038_0001

124) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP l -diHP 2 )- propylammonium (n = 3) 124) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (l HP -diHP 2) - propylammonium (n = 3)

C 36 H 72 NO„P (725,94) 125) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP l -diHP 2 )- butylammonium (n = 4) C 37 H 74 NO P (739,98) C 36 H 72 NO "P (725.94) 125) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (l HP -diHP 2) - butylammonium (n = 4) 37 C H 74 NO P (739.98)

126) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- hexylammonium (n = 6) C 39 H 78 NO P (768,04) 126) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - hexylammonium (n = 6) C 39 H 78 NO P (768.04)

127) 1-Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- propylammonium (n = 3) 127) 1-Nervonoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - propylammonium (n = 3)

C 38 H 76 NO P (754,01) C 38 H 76 NO P (754.01)

128) 1 -Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )- butylammonium (n = 4) 128) 1 -Nervonoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) - butylammonium (n = 4)

Figure imgf000039_0001

Beispiele füreinkettigeGlvcero-phospho-N,N-dimethyl-N-(2-hvdroxypropyl- Examples füreinkettigeGlvcero-phospho-N, N-dimethyl-N- (2-hvdroxypropyl-

3, 10-0,0-2-hvdroxypropyl-3, 1 -O,0-dihvdroxypropyl)-alkylammonium- 3, 10-0,0-2-hvdroxypropyl-3, 1-O, 0-dihvdroxypropyl) -alkylammonium

Verbindungen compounds

(A = a; n = 2-6; R 3 , CH 3 ; n = 1; x = 0; y = 1; z = 3) (A = a; n = 2-6; R 3, CH 3; n = 1; x = 0; y = 1 z = 3)

Formel I formula I

A - PO, - H A - PO, - H

Figure imgf000039_0002
129) 1 -Stearoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- ethylammonium (n = 2) C 34 H 70 NO 13 P (731,90) 129) 1 -Stearoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - ethylammonium (n = 2) C 34 H 70 NO 13 P (731.90)

130) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- ethylammonium (n = 2) C 38 H 76 N0 13 P (785,99) 130) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - ethylammonium (n = 2) C 38 H 76 N0 13 P (785.99)

131) 1-Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- ethylammonium (n = 2) 131) 1-Nervonoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - ethylammonium (n = 2)

C 4O H 80 NO 13 P (814,04) C 4O H 80 NO 13 P (814.04)

132) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- propylammonium (n = 3) C 39 H 78 N0 13 P (800,01) 132) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - propylammonium (n = 3) C 39 H 78 N0 13 P (800.01)

133) 1 -Nervonoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- propylammonium (n = 3) 133) 1 -Nervonoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - propylammonium (n = 3)

C 41 H 82 N0 13 P (828,07) C 41 H 82 N0 13 P (828.07)

134) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- butylammonium (n = 4) 134) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - butylammonium (n = 4)

C 40 H 80 NO 13 P (814,04) C 40 H 80 NO 13 P (814.04)

135) 1-Erucoyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- hexyiammonium (n = 6) C 42 H 84 N0 13 P (842,09) Beispiele für einkettige Glvcero-phospho-Verbindungen, die nicht am 135) 1-Erucoyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - hexyiammonium (n = 6) C 42 H 84 N0 13 P (842.09) Examples of single-chain Glvcero-phospho-compounds which are not on

Stickstoff hydroxyliert sind Nitrogen are hydroxylated

(A = a; n = 3; R 3 , CH 3 ; m = 1 ; x = 1 ; z = 0) (A = a; n = 3; R 3, CH 3; m = 1; x = 1; z = 0)

Formel I formula I

A - PO, H A - PO, H

Figure imgf000041_0001
Figure imgf000041_0002

1 36) 1 -PaImitoyl-sn-glycero-3-phospho-N,N,N-trimethyl-propylammonium (n = 3) C 25 H 52 N0 7 P (509,66) 1 36) 1 -PaImitoyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3) C 25 H 52 N0 7 P (509.66)

1 37) 1 -Stearoyl-sn-glycero-3-phospho-N,N,N-trimethyl-propylammonium (n = 3) C 27 H 56 N0 7 P (537,71 ) 1 37) 1 -Stearoyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3) C 27 H 56 N0 7 P (537.71)

1 38) 1 -Behenoyl-sn-glycero-3-phospho-N,N,N-trimethyl-propylammonium (n = 3) C 31 H 64 N0 7 P (593,82) 1 38) 1 -Behenoyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3) C 31 H 64 N0 7 P (593.82)

1 39) 1 -Erucoyl-sn-glycero-3-phospho-N,N,N-trimethyl-propylammonium (n = 3) 1 39) 1 -Erucoyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3)

C 31 H 62 N0 7 P (591 ,81 ) C 31 H 62 N0 7 P (591, 81)

1 40) 1 -Nervonoyl-sn-glycero-3-phospho-N,N,N-trimethyl-propylammonium (n = 3) C 33 H 66 N0 7 P (61 9,86) Beispiele für 6c,6t/-Alkandiol-phospho-N,N-dimethyl-N-dihvdroxypropyl- alkylammonium- Verbindungen 1 40) 1 -Nervonoyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3) C 33 H 66 N0 7 P (61 9.86) Examples of 6c, 6T / alkanediol -phospho-N, N-dimethyl-N-alkylammonium compounds dihvdroxypropyl-

(A = b; n = 2-4; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 1) (A = B; n = 2-4; R 3, CH 3; m = 1; x = 0; y = 1 z = 1)

Formel I formula I

A - PO. A - PO. (CH 2 ) n - H (CH 2) n - H

Figure imgf000042_0001

141) 1 -Stearoyl-ethylenglykol-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 2) C 27 H 56 N0 8 P (553,71) 141) 1 -Stearoyl-ethylene glycol-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl- (n = 2) C 27 H 56 N0 8 P (553.71)

142) 1-Behenoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 142) 1-Behenoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

C 32 H 66 N0 8 P (623,85) C 32 H 66 N0 8 P (623.85)

143) 1 -Stearoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 2) 143) 1 -Stearoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium (n = 2)

C 28 H 58 N0 8 P (567,74) C 28 H 58 N0 8 P (567.74)

144) 1-Erucoyl-propandiol-(1,3)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium (n = 2) 144) 1-Erucoyl-propanediol (1,3) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium (n = 2)

C 32 H 64 N0 8 P (621,83) C 32 H 64 N0 8 P (621.83)

145) 1-Erucoyl-propandiol-(1,3)-phospho-N,N-dimethyl-N-dihydroxypropyl- propylammonium (n = 3) 145) 1-Erucoyl-propanediol (1,3) -phospho-N, N-dimethyl-N-propylammonium dihydroxypropyl- (n = 3)

C 33 H 66 N0 8 P (635,86) 146) 1 -Erucoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-dihydroxypropyl- butylammonium (n = 4) C 34 H 68 N0 8 P (649,88) C 33 H 66 N0 8 P (635.86) 146) 1 -Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N-butylammonium dihydroxypropyl- (n = 4) C 34 H 68 N0 8 P (649.88)

Beispiele für Alkandiol-(1 ,2)-phospho-N,N-dimethyl-N-dihvdroxypropyl- alkylammonium-Verbindunqen Examples of Alkandiol- (1, 2) -phospho-N, N-dimethyl-N-alkylammonium dihvdroxypropyl- Verbindunqen

(A = b; n = 2-4; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 1) (A = B; n = 2-4; R 3, CH 3; m = 1; x = 0; y = 1 z = 1)

Formel I formula I

A - P0 3 - ICH 2'n (CH 2'x CH- - 0 - H A - 3 P0 - I 2'n (CH 2'x CH - 0 - H

Figure imgf000043_0001
Figure imgf000043_0002

147) 2-Erucoyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium C 32 H 64 N0 8 P (621,33) 147) 2-Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium C 32 H 64 N0 8 P (621.33)

148) 1 -Erucoyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium 148) 1 -Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium

C 32 H 64 N0 8 P (621,33) C 32 H 64 N0 8 P (621.33)

149) 2-Erucoyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- propylammonium 149) 2-Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl propylammonium

C 33 H 66 N0 8 P (635,86) C 33 H 66 N0 8 P (635.86)

150) 1-Erucoyl-propandiol-(1,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- butylammonium C 34 H 68 N0 8 P (649,88) Beispiele für 6 ,α/-Alkandiol-phospho-N,N-dimethyl-N-(2-hvdroxypropyl)-3, 1 150) 1-Erucoyl-propanediol (1,2) -phospho-N, N-dimethyl-N-dihydroxypropyl butylammonium C 34 H 68 N0 8 P (649.88) Examples 6, α / alkane-phospho- N, N-dimethyl-N- (2-hvdroxypropyl) -3, 1

0,0-dihvdroxypropyl)-alkylammonium-Verbindunqen (A = b; n = 2 - 4; R 3 , CH 3 ; m = 1, x = 0; y = 1; z 2) 0,0-dihvdroxypropyl) -alkylammonium Verbindunqen (A = b; n = 2-4; R 3, CH 3; m = 1, x = 0; y = 1; Z 2)

Formel formula

A - (CH 2,)'> CH, CH 2 - 0 H A - (CH 2) '> CH, CH 2 - 0. H

Figure imgf000044_0002
Figure imgf000044_0001

151) 1-Stearoyl-ethylenglykol-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3,1-0,0-dihydroxypropyl)-ethylammonium 151) 1-stearoyl-ethylene glycol-phospho-N, N-dimethyl-N- (2-hydroxypropyl from 3.1 to 0.0-dihydroxypropyl) -ethylammonium

C 30 H 62 NO 10 P (627,79) C 30 H 62 NO 10 P (627.79)

152) 1-Behenoyl-propandiol-(1,3)-phospho-N,N-dimethyl-N-(2- hydroxypropyl-3, 1 -O,0-dihydroxypropyl)-ethylammonium C 35 H 72 N0 10 P (697,93) 152) 1-Behenoyl-propanediol (1,3) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -ethylammonium C 35 H 72 N0 10 P (697 , 93)

153) 1-Stearoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-(2- hydroxypropyl)-3, 1 -0,0-dihydroxypropyl-ethylammonium C 31 H 64 N0 10 P (641,82) 153) 1-stearoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (2-hydroxypropyl) -3, 1 -0,0-dihydroxypropyl-ethylammonium C 31 H 64 N0 10 P (641 , 82)

154) 1 -Erucoyl-propandiol-( 1 ,3)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-ethylammonium 154) 1 -Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -ethylammonium

C 35 H 70 NO 10 P (695,91) C 35 H 70 NO 10 P (695.91)

155) 1-Erucoyl-propandiol-(1,3)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium C 36 H 72 N0 10 P (709,94) 1 56) 1-Erucoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-butylammonium C 37 H 74 N0 10 P (723,96) 155) 1-Erucoyl-propanediol (1,3) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium C 36 H 72 N0 10 P (709 , 94) 56 1) 1-Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -butylammonium C 37 H 74 N0 10 P (723.96)

1 57) 1 -Erucoyl-butandiol-( 1 ,4)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium C 37 H 74 N0 10 P (723,96) 1 57) 1 -Erucoyl-butanediol (1, 4) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium C 37 H 74 N0 10 P ( 723.96)

1 58) 1 -Erucoyl-hexandiol-(1 ,6)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium 1 58) 1--Erucoyl hexanediol- (1, 6) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium

C 39 H 78 N0 10 P (752,02) C 39 H 78 N0 10 P (752.02)

1 59) 1 -Erucoyl-octandiol-(1 ,8)-phospho-N,N-dimethyl-N-(2-hydroxypropyl)- 3, 1 -O,0-dihydroxypropyl)-propylammonium C 41 H 82 NO 10 P (780,07) 1 59) 1--Erucoyl octanediol- (1, 8) -phospho-N, N-dimethyl-N- (2-hydroxypropyl) - 3, 1 is -O, 0-dihydroxypropyl) -propylammonium C 41 H 82 NO 10 P (780.07)

Beispiele für Alkandiol-(1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl-3, 1 - Examples of Alkandiol- (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 -

O,0-dihvdroxypropyl)-alkylammonium- Verbindungen O, 0-dihvdroxypropyl) -alkylammonium compounds

(A = b; n = 2 - 4; R 3 , CH 3 ; m = 1 ; x = 0; y = 1 ; z = 2) (A = B; n = 2-4; R 3, CH 3; m = 1; x = 0; y = 1 z = 2)

Formel I formula I

A - P0 3 (CH 2 n (CH 2h CH, - 0 H A - P0 3 (CH 2 N (CH 2 H CH, - 0 H

Figure imgf000045_0001
Figure imgf000045_0002

1 60) 2-Erucoyl-propandiol-( 1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-ethylammonium 1 60) 2-Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -ethylammonium

C 35 H 70 NO 10 P (695,91 ) 61 ) 1 -Erucoyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-ethylammonium (C 35 H 70 N0 10 P (695,91 ) C 35 H 70 NO 10 P (695.91) 61) 1 -Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl ) -ethylammonium (C 35 H 70 N0 10 P (695.91)

62) 2-Erucoyl-propandiol-( 1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium C 36 H 72 NO 10 P (709,94) 62) 2-Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium C 36 H 72 NO 10 P (709 , 94)

63) 1 -Erucoyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-butylammonium 63) 1 -Erucoyl-propanediol (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -butylammonium

C 37 H 74 NO 10 P (723,96) C 37 H 74 NO 10 P (723.96)

64) 1 -Erucoyl-butandiol-( 1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium C 37 H 74 NO 10 P (723,96) 64) 1 -Erucoyl-butanediol (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium C 37 H 74 NO 10 P (723 , 96)

65) 1 -Erucoyl-hexandiol-(1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium 65) 1--Erucoyl hexanediol- (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium

C 39 H 78 NO 10 P (752,02) C 39 H 78 NO 10 P (752.02)

66) 1 -Erucoyl-octandiol-(1 ,2)-phospho-N,N-dimethyl-N-(2-hydroxypropyl- 3, 1 -O,0-dihydroxypropyl)-propylammonium C 41 H 82 NO l 0 P (780,07) 66) 1--Erucoyl octanediol- (1, 2) -phospho-N, N-dimethyl-N- (2-hydroxypropyl-3, 1 O, 0-dihydroxypropyl) -propylammonium C 41 H 82 NO l 0 P ( 780.07)

Beispiele für α,C(/-Alkandiol-N,N-dimethyl-N-(2-hvdroxypropyl-3, 1 -0,0-2- hvdroxypropyl-3,1-0,0-dihvdroxypropyi)-alkylammonium- Verbindungen (Abkürzurg: HP = 2-Hydroxypropyl diHP = Dihydroxypropyl) (A = b; n = 2 - 6; R, CH 3 ; m = 1; x = 0; y = 1; z = 3) Examples of α, C (/ - alkanediol-N, N-dimethyl-N- (2-hvdroxypropyl-3, 1-hvdroxypropyl -0,0-2- 3.1 to 0.0-dihvdroxypropyi) alkylammonium compounds ( Abkürzurg: HP = 2-hydroxypropyl DIHP = dihydroxypropyl) (A = b; n = 2-6; R, CH 3; m = 1; x = 0; y = 1 z = 3)

Formel I formula I

A - PO. A - PO. [CH 2'n - CH, - 0 - H [CH 2'n - CH, - 0 - H

Figure imgf000047_0001

167) 1-Oleoyl-ethylenglykol-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- ethylammonium 167) 1-oleoyl-ethylene glycol-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) - ethylammonium

C 34 H 68 N0 12 P (713,88) C 34 H 68 N0 12 P (713.88)

168) 1-Erucoyl-propandiol-(1,3)-phospho-N,N-dimethyI-N-(HP r HP 2 -diHP 3 )- ethylammonium C 38 H 76 N0 12 P (769,99) 168) 1-Erucoyl-propanediol (1,3) -phospho-N, N-dimethyI-N- (HP HP r 2 -diHP 3) - ethylammonium C 38 H 76 N0 12 P (769.99)

169) 1-Oleoyl-propandiol-(1 ,3)-ρhospho-N,N-dimethyl-N-(HP HP 2 -diHP 3 )- propylammonium 169) 1-oleoyl-propanediol (1, 3) -ρhospho-N, N-dimethyl-N- (2 HP HP -diHP 3) - propylammonium

C 35 H 70 N0 12 P (727,91) C 35 H 70 N0 12 P (727.91)

170) 1-Erucoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- propylammonium C 39 H 78 N0 12 P (784,01) 170) 1-Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (HP HP r 2 -diHP 3) - propylammonium C 39 H 78 N0 12 P (784.01)

171) 1 -Erucoyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )- butylammonium C 40 H 80 NO 12 P (798,04) 172) 1-Erucoyl-propandiol-(1,3)-phospho-N,N-dimethyl-N-(HP r HP 2 _diHP 3 )- hexylammonium C 42 H 84 N0 12 P (826,10) 171) 1 -Erucoyl-propanediol (1, 3) -phospho-N, N-dimethyl-N- (HP HP r 2 -diHP 3) - butylammonium C 40 H 80 NO 12 P (798.04) 172) 1 -Erucoyl-propanediol (1,3) -phospho-N, N-dimethyl-N- (HP HP r 2 _diHP 3) - hexylammonium C 42 H 84 N0 12 P (826.10)

Beispiele für Alkandiol-phospho-Verbindungen, die nicht am Stickstoff hvdroxyliert sind Examples of alkanediol-phospho-compounds which are not on the nitrogen hvdroxyliert

(A = b; n = 2 - 6; R, CH 3 ; m = 1 ; x = 1 ; z = 0) (A = B; n = 2-6; R, CH 3; m = 1; x = 1; z = 0)

Formel I formula I

Figure imgf000048_0001

173) 1 -Erucoyl-ethylenglykol-phospho-N,N,N-trimethyl-propylammonium 173) 1 -Erucoyl-ethylene glycol-phospho-N, N, N-trimethyl-propylammonium

C 3O H 60 NO 6 P (561,78) C 3O H 60 NO 6 P (561.78)

174) 1 -Arachinoyl-propandiol-( 1 ,3)-phospho-N,N,N-trimethyl- propylammonium C 29 H 69 N0 6 P (549,77) 174) 1 -Arachinoyl-propanediol (1, 3) -phospho-N, N, N-trimethyl propyl ammonium C29 69 N0 6 P (549.77)

175) 1-Stearoyl-propandiol-(1,3)-phospho-N,N,N-trimethyl- propylammonium 175) 1-stearoyl-propanediol (1,3) -phospho-N, N, N-trimethyl-propylammonium

C 27 H 56 N0 6 P (521,71) C 27 H 56 N 0 6 P (521.71)

176) 1 -Erucoyl-propandiol-(1 ,3)-phospho-N,N,N-trimethyl-propylammonium C 31 H 62 N0 6 P (575,81) 176) 1 -Erucoyl-propanediol (1, 3) -phospho-N, N, N-trimethyl-propyl ammonium C 31 H 62 N 0 6 P (575.81)

177) 1-Erucoyl-propandiol-(1,3)-phospho-N,N,N-trimethyl-butylammonium C 32 H 64 N0 6 P (589,83) 1 78) 1 -Erucoyl-propandiol-( 1 ,3)-phospho-N,N,N-trimethyl-pentylammonium C 33 H 66 N0 6 (603,86) 177) 1-Erucoyl-propanediol (1,3) -phospho-N, N, N-trimethyl-butyl ammonium C 32 H 64 N 0 6 P (589.83) 1 78) 1 -Erucoyl-propanediol (1, 3 ) -phospho-N, N, N-trimethyl-pentylammonium C 33 H 66 N0 6 (603.86)

1 79) 1 -Erucoyl-propandiol-( 1 ,2)-phospho-N,N,N-trimethyl-propylammonium C 31 H 62 N0 6 P (575,81 ) 1 79) 1 -Erucoyl-propanediol (1, 2) -phospho-N, N, N-trimethyl-propyl ammonium C 31 H 62 N 0 6 P (575.81)

1 80) 2-Erucoyl-propandiol-(1 ,2)-phospho-N,N,N-trimethyl-propylammonium C 31 H 62 N0 6 P (575,81 ) 1 80) 2-Erucoyl-propanediol (1, 2) -phospho-N, N, N-trimethyl-propylammonium C 31 H 62 N0 6 P (575.81)

1 81 ) 1 -Erucoyl-propandiol-( 1 ,2)-phospho-N,N,N-trimethyl-butylammonium C 32 H 64 N0 6 P (589,83) 1 81) 1 -Erucoyl-propanediol (1, 2) -phospho-N, N, N-trimethyl-butylammonium C 32 H 64 N0 6 P (589.83)

1 82) 1 -Erucoyl-propandiol-( 1 ,2)-phospho-N,N,N-trimethyl-hexylammonium C 34 H 68 N0 6 P (61 7,92) 1 82) 1 -Erucoyl-propanediol (1, 2) -phospho-N, N, N-trimethyl-hexylammonium C 34 H 68 N0 6 P (61 7.92)

3) Wirkstoffe 3) active ingredients

In früheren Untersuchungen wurde festgestellt, dass Alkylphosphocholine nur dann antitumorale Wirksamkeit besitzen, wenn der Phosphat- Ammoniumabstand zwei C-Atome beträgt, also Phosphocholin (n = 2 in der allgemeinen Formel I) entspricht. In previous studies it was found that alkylphosphocholines only possess antitumor activity when the phosphate ammonium distance is two carbon atoms, so phosphocholine (n = 2 in the general formula I). Verbindungen mit dem Abstand n > 2 waren unwirksam. Links with the distance n> 2 were ineffective. Bei diesen früheren Untersuchungen wurden die Wirkstoffe oral appliziert. In these previous studies, the active compounds were administered orally.

Überraschenderweise haben wir nun festgestellt, dass Erucylphospho- Verbindungen mit Phosphat-Ammoniumabständen > 2 exzellente, den Alkylphosphocholinen sogar überlegene Antitumorwirksamkeit besitzen, wenn diese Substanzen intravenös angewendet werden, wie folgender Vergleich zeigt: Erucylphosphocholin (n = 2 in allgemeiner Formel I) Surprisingly, we have now found that Erucylphospho- compounds with phosphate ammonium intervals have> 2 excellent, the alkylphosphocholines even superior antitumor activity when these substances are administered intravenously, as the following comparison shows: erucylphosphocholine (n = 2 in the general formula I)

Die Substanz bildet in Wasser gelartige Strukturen und ist deshalb in höheren Konzentrationen intravenös nur schwer anwendbar. The substance forms in water gel structures and is therefore intravenously difficult to apply in higher concentrations. Eurcylphosphocholin besitzt im Tiermodell Methylnitrosoharnstoff- induziertes Mammakarzinom nur eine geringe Langzeitwirkung. Eurcylphosphocholin has in animal models Methylnitrosoharnstoff- induced breast cancer, only a small long-term effect. Bereits 7 Tage nach Absetzen der Therapie wird wiederTumorwachstum beobachtet. Already 7 days after discontinuation of therapy again tumor growth is observed.

Erucyl-phospho-N,N,N-trimethyl-propylammonium (n = 3) Erucyl-phospho-N, N, N-trimethyl-propylammonium (n = 3)

Die Substanz ist in Wasser leicht löslich, bildet keine Gele und kann problemlos intravenös verabreicht werden. The substance is easily soluble in water, does not form gels and can be safely administered intravenously. Sie kann deshalb uach als You can therefore uach as

Lösungsvermittler Verwendung finden. find solubilizers. Insbesondere auffällig und eindrucksvoll ist aber ihre Langzeitwirkung in obigem Tiermodell. Particularly striking and impressive but their long-term activity in this animal model. Selbst 4 Even 4

Wochen nach Absetzen der Therapie ist kein neues Tumorwachstum zu beobachten. Weeks after discontinuation of therapy is observed no new tumor growth.

Beispiele für Alkyl-phospho-N,N-dimethyl-N-dihvdroxypropyl alkylammonium-Verbindungen Examples of alkyl-phospho-N, N-dimethyl-N-dihvdroxypropyl alkylammonium compounds

(A = c; n = 2 - 6; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 1) (A = c; n = 2-6; R 3, CH 3; m = 1; x = 0; y = 1 z = 1)

Formel formula

A - PO. A - PO. (CH 2'n (CH 2'x CH, - 0 H (CH 2'n (CH 2'x CH, - 0 H

Figure imgf000050_0002
Figure imgf000050_0001

183) Hexadecyl-phospho-N,N-dimethyl-N-dihydroxypropyl-ethylammonium 183) hexadecyl-phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammonium

C 23 H 50 N0 6 P (467,62) C23 50 N0 6 P (467.62)

184) Octadecyl-phospho-N,N-dimethyl-N-dihydroxypropyl-ethylammonium C 25 H 54 N0 6 P (495,68) 185) Erucyl-phospho-N,N-dimethyl-N-dihydroxypropyl-ethylammonium C 29 H 60 NO 6 P (549,77) 184) octadecyl-phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammonium C 25 H 54 N0 6 P (495.68) 185) erucyl-phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammonium C 29 H 60 NO 6 P (549.77)

186) Erucyl-phospho-N,N-dimethyl-N-dihydroxypropyl-propylammonium C 30 H 62 N0 6 P (563,80) 186) erucyl-phospho-N, N-dimethyl-N-dihydroxypropyl-propylammonium C 30 H 62 N0 6 P (563.80)

187) Erucyl-phospho-N,N-dimethyl-N-dihydroxypropyl-butylammonium C 31 H 64 N0 6 P (577,82) 187) erucyl-phospho-N, N-dimethyl-N-dihydroxypropyl-butylammonium C 31 H 64 N0 6 P (577.82)

188) Erucyl-phospho-N,N-dimethyl-N-dihydroxypropyl-hexylammonium C 33 H 68 N0 6 P (605,88) 188) erucyl-phospho-N, N-dimethyl-N-dihydroxypropyl-hexylammonium C 33 H 68 N0 6 P (605.88)

189) Oleyl-phospho-N,N-dimethyl-N-dihydroxypropyl-ethylammonium C 25 H 52 N0 6 P (493,66) 189) Oleyl-phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammonium C 25 H 52 N0 6 P (493.66)

190) Oleyl-phospho-N,N-dimethyl-N-dihydroxypropyl-propylammonium C 26 H 54 N0 6 P (507,69) 190) Oleyl-phospho-N, N-dimethyl-N-dihydroxypropyl-propylammonium C 26 H 54 N0 6 P (507.69)

191) Oleyl-phospho-N,N-dimethyl-N-dihydroxypropyl-butylammonium C 27 H 56 N0 6 P (521,21) 191) Oleyl-phospho-N, N-dimethyl-N-dihydroxypropyl-butylammonium C 27 H 56 N0 6 P (521.21)

192) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium 192) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl-

C 27 H 56 N0 6 P (521,21) C 27 H 56 N 0 6 P (521.21)

193) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-dihydroxypropyl- propylammonium C 28 H 58 N0 6 P (535,74) 193) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N-propylammonium dihydroxypropyl C 28 H 58 N0 6 P (535.74)

194) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-dihydroxypropyl butylammonium C 29 H 60 NO 6 P (549,77) 195) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-dihydroxypropyl- pentylammonium 194) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N-butylammonium dihydroxypropyl C 29 H 60 NO 6 P (549.77) 195) (Z-11) -Eicosenyl-phospho-N, N- dimethyl-N-pentylammonium dihydroxypropyl-

C 30 H 62 N0 6 P (563,80) C 30 H 62 N 0 6 P (563.80)

196) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-dihydroxypropyl- hexylammonium 196) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N-hexylammonium dihydroxypropyl-

C 31 H 64 N0 6 P (577,82) C 31 H 64 N 0 6 P (577.82)

Beispiele für Alkyl-phospho-N,N-dimethyl-N-(2-hvdroxypropyl-1 ,2- dihydroxypropyD-alkylammonium (A = c; n = 2 - 6; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 2) Examples of alkyl-phospho-N, N-dimethyl-N- (2-hvdroxypropyl-1, 2- dihydroxypropyD-alkylammonium (A = c; n = 2-6; R 3, CH 3; m = 1; x = 0 y = 1 z = 2)

Formel I formula I

A - PO, (CH 2,)h CH. A - PO, (CH 2) h CH. CH, - OH CH, - OH

Figure imgf000052_0002
Figure imgf000052_0001

197) Hexadecyl-phospho-N,N-dimethyl-N-(HP r diHP 2 )-ethylammonium C 26 H 56 N0 8 P (541,70) 197) hexadecyl-phospho-N, N-dimethyl-N- (HP DIHP r 2) -ethylammonium C 26 H 56 N0 8 P (541.70)

198) Octadecyl-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )-ethylammonium 198) octadecyl-phospho-N, N-dimethyl-N- (1 HP -diHP 2) -ethylammonium

'28 H 60 NO 8 P (569,76) '28 H 60 NO 8 P (569.76)

199) Erucyl-phospho-N,N-dimethyl-N-(HP r diHP 2 )-ethylammonium 199) erucyl-phospho-N, N-dimethyl-N- (HP DIHP r 2) -ethylammonium

C 32 H 66 N0 8 P (623,85) C 32 H 66 N0 8 P (623.85)

200) Erucyl-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )-propylammonium C 33 H 68 N0 8 P (637,87) 201 ) Erucyl-phospho-N,N-dimethyl-N-(HP r diHP 2 )-butylammonium C 34 H 70 NO 8 P (651,90) 200) erucyl-phospho-N, N-dimethyl-N- (1 HP -diHP 2) -propylammonium C 33 H 68 N0 8 P (637.87) 201) erucyl-phospho-N, N-dimethyl-N- ( HP r DIHP 2) -butylammonium C 34 H 70 NO 8 P (651.90)

202) Erucyl-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )-hexylammonium C 36 H 74 N0 8 P (679,95) 202) erucyl-phospho-N, N-dimethyl-N- (1 HP -diHP 2) -hexylammonium C 36 H 74 N0 8 P (679.95)

203) Oleyl-phospho-N,N-dimethyl-N-(HP r diHP 2 )-ethylammonium C 28 H 58 N0 8 P (567,74) 203) Oleyl-phospho-N, N-dimethyl-N- (HP DIHP r 2) -ethylammonium C 28 H 58 N0 8 P (567.74)

204) Oleyl-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )-propylammonium C 29 H 60 NO 8 P (581,77) 204) Oleyl-phospho-N, N-dimethyl-N- (1 HP -diHP 2) -propylammonium C 29 H 60 NO 8 P (581.77)

205) Oleyl-phospho-N,N-dimethyl-N-(HP r diHP 2 )-butylammonium C 30 H 62 NO 8 P (595,79) 205) Oleyl-phospho-N, N-dimethyl-N- (HP DIHP r 2) -butylammonium C 30 H 62 NO 8 P (595.79)

206) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-(HP r diHP 2 )-ethylammonium C 30 H 62 NO 8 P (595,79) 206) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N- (HP DIHP r 2) -ethylammonium C 30 H 62 NO 8 P (595.79)

207) (Z-11)-Eicosenyl-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )- propylammonium 207) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N- (1 HP -diHP 2) - propylammonium

C 30 H 64 NO 8 P (609,82) C 30 H 64 NO 8 P (609.82)

208) (Z-11 )-Eicosenyl-phospho-N,N-dimethyl-N-(HP 1 -diHP 2 )-butylammonium C 32 H 66 N0 8 P (623,85) 208) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N- (1 HP -diHP 2) -butylammonium C 32 H 66 N0 8 P (623.85)

Beispiele für Alkyl-phospho-N,N-dimethyl-N-(2-hvdroxypropyl-3, 1-0,0- hydroxypropyl-3, 1-0,0-1 ,2-dihvdroxypropyl)-alkylammonium-Verbindungen (A = c; n = 2 - 4; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 3) Examples of alkyl-phospho-N, N-dimethyl-N- (2-hvdroxypropyl-3, 1-0,0- hydroxypropyl-3, 1-0,0-1, 2-dihvdroxypropyl) alkylammonium compounds (A = c; n = 2-4; R 3, CH 3; m = 1; x = 0; y = 1 z = 3)

Formel I formula I

H H

Figure imgf000054_0001

209) Hexadecyl-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )-ethylammonium C 29 H 62 N0 10 P (615,78) 209) hexadecyl-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) -ethylammonium C 29 H 62 N0 10 P (615.78)

210) Octadecyl-phospho-N,N-dimethyl-N-(HP r HP 2 -diHP 3 )-ethylammonium C 31 H 66 N0 10 P (643,83) 210) octadecyl-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) -ethylammonium C 31 H 66 N0 10 P (643.83)

211) Oleol-phospho-N,N-dimethyl-N-(HP HP 2 -diHP 3 )-ethylammonium C 31 H 64 N0 l0 P (641,82) 211) Oleol-phospho-N, N-dimethyl-N- (HP 2 HP -diHP 3) -ethylammonium C 31 H 64 N0 l0 P (641.82)

212) (Z-11)-Eicosenyl-phospho-N,N-dimethyl-N-(HP l -HP 2 -diHP 3 )- ethylammonium 212) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N- (l HP -HP 2 -diHP 3) - ethylammonium

C 33 H 68 NO 10 P (669,87) C 33 H 68 NO 10 P (669.87)

213) (Z-11)-Eicosenyl-phospho-N,N-dimethyl-N-(HP 1 -HP 2 -diHP 3 )- propylammonium C 34 H 70 NO 10 P (683,90) 213) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N- (HP 1 -HP 2 -diHP 3) - propylammonium C 34 H 70 NO 10 P (683.90)

214) (Z-11)-Eicosenyl-phospho-N,N-dimethyl-N-(HP l -HP 2 -diHP 3 )- butylammonium 214) (Z-11) -Eicosenyl-phospho-N, N-dimethyl-N- (l HP -HP 2 -diHP 3) - butylammonium

C 35 H 72 N0 10 P (697,93) 21 5) Erucyl-phospho-N, N-dimethyl-N-(HP 1 -HP 2 -diHP 3 )-ethylammonium C 35 H 72 N0 10 P (697,93) C 35 H 72 N0 10 P (697.93) 21 5) erucyl-phospho-N, N-dimethyl-N- (HP 1 -HP 2 -diHP 3) -ethylammonium C 35 H 72 N0 10 P (697.93 )

21 6) Erucyl-phospho-N, N-dimethyl-N-(HP r HP 2 -diHP 3 )-propylammonium C 36 H 74 N0 10 P (71 1 ,95) 21 6) erucyl-phospho-N, N-dimethyl-N- (HP 2 HP r -diHP 3) -propylammonium C 36 H 74 N0 10 P (71 1, 95)

Beispiele für Alkylphospho-Verbindungen, die am Stickstoff keine Dihydroxyalkylreste tragen Examples of Alkylphospho compounds at the nitrogen no Dihydroxyalkylreste

(A = a; n = 3-6; R 3 , CH 3 ; m = 1 , x = 1 -3; z = 0) (A = a; n = 3-6; R 3, CH 3; m = 1, x = 1 -3; z = 0)

A - PO, [CH- - CH, - 0 - H A - PO, [CH - CH, - 0 - H

Figure imgf000055_0001

21 7) Eurcyl-phospho-N,N,N-trimethyl-propylammonium C 28 H 58 N0 4 P (503,74) 21 7) Eurcyl-phospho-N, N, N-trimethyl-propylammonium C 28 H 58 N0 4 P (503.74)

21 8) Erucyl-phospho-N,N-dimethyl-N-ethyl-propylammonium C 29 H 60 NO 4 P (51 7,77) 21 8) erucyl-phospho-N, N-dimethyl-N-ethyl-propylammonium C 29 H 60 NO 4 P (51 7.77)

21 9) Erucyl-phospho-N,N-dimethyl-N-propyl-propylammonium C 30 H 62 N0 4 P (531 ,80) 21 9) erucyl-phospho-N, N-dimethyl-N-propyl-propylammonium C 30 H 62 N0 4 P (531, 80)

220) Erucyl-phospho-N,N-dimethyl-N-allyl-propylammonium 220) erucyl-phospho-N, N-dimethyl-N-allyl-propylammonium

C 30 H 60 NO 4 P (529,78) C 30 H 60 NO 4 P (529.78)

Rf-Werte der Substanzen 21 7-240 im beschriebenen System: Rf 0,30-0,40 221 ) (Z)- 1 0-Docosenyl-2-phospho-N,N,N-trimethyl-propylammonium C 28 H 58 N0 4 P (503,74) Rf values of the substances 21 7-240 in the system described: Rf 0.30-0.40 221) (Z) - 1 0-docosenyl-2-phospho-N, N, N-trimethyl-propylammonium C 28 H 58 N0 4 P (503.74)

222) (Z)-10-Docosenyl-2-phospho-N,N-dimethyl-N-ethyl-propylammonium C 29 H 60 N0 4 P (51 7,77) 222) (Z) -10 docosenyl-2-phospho-N, N-dimethyl-N-ethyl-propylammonium C 29 H 60 N0 4 P (51 7.77)

223) Erucyl-phospho-N,N,N-trimethyl-butylammonium C 29 H 60 NO 4 P (51 7,77) 223) erucyl-phospho-N, N, N-trimethyl-butylammonium C 29 H 60 NO 4 P (51 7.77)

224) Erucyl-phospho-N,N-dimethyl-N-ethyl-butylammonium C 30 H 62 N0 4 P (531 ,80) 224) erucyl-phospho-N, N-dimethyl-N-ethyl-butylammonium C 30 H 62 N0 4 P (531, 80)

225) Erucyl-phospho-N,N-dimethyl-N-propyl-butylammonium C 31 H 64 N0 4 P (545,82) 225) erucyl-phospho-N, N-dimethyl-N-propyl-butylammonium C 31 H 64 N0 4 P (545.82)

226) (Z)- 1 0-Docosenyl-2-phospho-N,N,N-trimethyl-butylammonium C 29 H 60 N0 4 P (51 7,77) 226) (Z) - 1 0-docosenyl-2-phospho-N, N, N-trimethyl-butylammonium C 29 H 60 N0 4 P (51 7.77)

227) (Z)-1 1 -Eicosenyl-phospho-N,N,N-trimethyl-propylammonium C 26 H 54 N0 4 P (475,69) 227) (Z) -1 1 -Eicosenyl-phospho-N, N, N-trimethyl-propylammonium C 26 H 54 N0 4 P (475.69)

228) (Z)-1 1 -Eicosenyl-phospho-N,N-dimethyl-N-ethyl-propylammonium C 27 H 56 N0 4 P (489,72) 228) (Z) -1 1 -Eicosenyl-phospho-N, N-dimethyl-N-ethyl-propylammonium C 27 H 56 N0 4 P (489.72)

229) (Z)-1 1 -Eicosenyl-phospho-N,N-diethyl-N-methyl-propylammonium C 28 H 58 N0 4 P (503,74) 229) (Z) -1 1 -Eicosenyl-phospho-N, N-diethyl-N-methyl-propylammonium C 28 H 58 N0 4 P (503.74)

230) (Z)-1 1 -Eicosenyl-phospho-N,N-dimethyl-N-propyl-propylammonium C 28 H 58 N0 4 P (503,74) 230) (Z) -1 1 -Eicosenyl-phospho-N, N-dimethyl-N-propyl-propylammonium C 28 H 58 N0 4 P (503.74)

231 ) (Z)- 1 1 -Eicosenyl-phospho-N,N,N-trimethyl-butylammonium C 27 H 56 N0 4 P (489,72) 232) (Z)- 1 1 -Eicosenyl-phospho-N,N-dimethyl-N-ethyl-butylammonium C 28 H 58 N0 4 P (503,74) 231) (Z) - 1 1 -Eicosenyl-phospho-N, N, N-trimethyl-butylammonium C 27 H 56 N0 4 P (489.72) 232) (Z) - 1 1 -Eicosenyl-phospho-N, N -dimethyl-N-ethyl-butylammonium C 28 H 58 N0 4 P (503.74)

233) (Z)-1 1 -Eicosenyl-phospho-N,N-dimethyl-N-propyl-butylammonium C 29 H 60 N0 4 P (51 7,77) 233) (Z) -1 1 -Eicosenyl-phospho-N, N-dimethyl-N-propyl-butylammonium C 29 H 60 N0 4 P (51 7.77)

234) (Z)-1 1 -Eicosenyl-phospho-N,N-dimethyl-N-alkyl-butylammonium C 29 H 58 N0 4 P (575,75) 234) (Z) -1 1 -Eicosenyl-phospho-N, N-dimethyl-N-alkyl-butylammonium C 29 H 58 N0 4 P (575.75)

235) Oleyl-phospho-N,N,N-trimethyl-propylammonium C 24 H 50 N0 4 P (447,64) 235) Oleyl-phospho-N, N, N-trimethyl-propylammonium C 24 H 50 N0 4 P (447.64)

236) Oleyl-phospho-N,N-dimethyl-N-ethyl-propylammonium C 25 H 52 N0 4 P (461 ,66) 236) Oleyl-phospho-N, N-dimethyl-N-ethyl-propylammonium C 25 H 52 N0 4 P (461, 66)

237) Oleyl-phospho-N,N-dimethyl-N-propylen-propylammonium C 26 H 54 N0 4 P (475,69) 237) Oleyl-phospho-N, N-dimethyl-n-propylene-propylammonium C 26 H 54 N0 4 P (475.69)

238) Oleyl-phospho-N,N,N-trimethyl-butylammonium C 25 H 52 N0 4 P (461 ,66) 238) Oleyl-phospho-N, N, N-trimethyl-butylammonium C 25 H 52 N0 4 P (461, 66)

239) Oleyl-phospho-N,N-dimethyl-N-ethyl-butylammonium C 26 H 54 N0 4 P (475,69) 239) Oleyl-phospho-N, N-dimethyl-N-ethyl-butylammonium C 26 H 54 N0 4 P (475.69)

240) Oleyl-phospho-N,N-dimethyl-N-propyl-butylammonium C 27 H 56 N0 4 P (489,72) Wirkstoffe, die auf alkylierten (Ether)-Lvsolecithinen aufgebaut und am 240) Oleyl-phospho-N, N-dimethyl-N-propyl-butylammonium C 27 H 56 N0 4 P (489.72) agents based on alkylated (ether) and at -Lvsolecithinen

Stickstoff hvdroxyliert sind Nitrogen hvdroxyliert

(A = a; n = 2 - 4; R 3 , CH 3 ; m = 1 ; x = 0; y = 1 ; z = 1 , 2) (A = a; n = 2-4; R 3, CH 3; m = 1; x = 0; y = 1 z = 1, 2)

Formel I formula I

Figure imgf000058_0001

241 ) 1 -0-Octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N- dihydroxypropyl-ethylammoniu (n = 2) 241) 1 -0-octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammoniu (n = 2)

C 29 H 62 N0 8 P (583,78) C 29 H 62 N0 8 P (583.78)

242) 3-0-Octadecyl-2-0-methyl-sn-glycero- 1 -phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 242) 3-0-octadecyl-2-0-methyl-sn-glycero-1 -phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

C 29 H 62 N0 8 P (583,78) C 29 H 62 N0 8 P (583.78)

243) 1 -0-Octadecyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) C 32 H 68 N0 8 P (625,86) 243) 1 -0-octadecyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2) C 32 H 68 N0 8 P (625, 86)

244) 3-0-Octadecyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) 244) 3-0-octadecyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2)

C 32 H 68 N0 8 P (625,86) C 32 H 68 N0 8 P (625.86)

245) 1 -0-Octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N- dihydroxypropyl-propylammonium (n = 3) C 30 H 64 NO 8 P (597,81 ) 246) 1 -0-Octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N- dihydroxypropyl-butylammonium (n = 4) C 31 H 66 N0 8 P (61 1 ,84) 245) 1 -0-octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N-dihydroxypropyl-propylammonium (n = 3) C 30 H 64 NO 8 P (597.81) 246) 1 -0-octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N-dihydroxypropyl-butylammonium (n = 4) C 31 H 66 N0 8 P (61 1, 84 )

247) 1 -0- Erucyl-2~0-methyl-sn-g lycero-3-phospho-N, N-dimethyl-N- dihydroxypropyl-ethylammonium (n = 2) C 33 H 68 N0 8 P (637,87) 247) 1 -0- erucyl 2 ~ 0-methyl-sn-3-phospho-g lycero-N, N-dimethyl-N-ethylammonium dihydroxypropyl (n = 2) C 33 H 68 N0 8 P (637.87 )

248) 1 -0-Erucyl-2-0-methyl-sn-g lycero-3-phospho-N, N-dimethyl-N- dihydroxypropyl-propylammonium (n = 3) 248) 1 -0-erucyl-2-0-methyl-sn-3-phospho-g lycero-N, N-dimethyl-N-dihydroxypropyl-propylammonium (n = 3)

C 34 H 70 NO 8 P (651 ,90) C 34 H 70 NO 8 P (651, 90)

249) 1 -0-Octadecyl-2-0-methyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )-ethylammonium (n = 2) C 32 H 68 N0 10 P (657,86) 249) 1 -0-octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) -ethylammonium (n = 2) C 32 H 68 N0 10 P (657.86)

250) 1 -0-Octadecyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N-dimethyl-N- (HP r diHP 2 )-ethylammonium (n = 2) 250) 1 -0-octadecyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) -ethylammonium (n = 2)

C 35 H 74 N0 10 P (699,94) C 35 H 74 N0 10 P (699.94)

251 ) 1 -0-Octadecyl-2-0-methyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )-propylammonium (n = 3) 251) 1 -0-octadecyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) -propylammonium (n = 3)

C 33 H 70 N0 10 P (671 ,89) C 33 H 70 N0 10 P (671, 89)

252) 1 -0-Octadecyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N-dimethyl-N- (HP 1 -diHP 2 )-propylammonium (n = 3) C 36 H 76 N0 10 P (71 3,97) 252) 1 -0-octadecyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N-dimethyl-N- (1 HP -diHP 2) -propylammonium (n = 3) C 36 H 76 N0 10 P (71 3.97)

253) 1 -0-Octadecyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N-dimethyl-N- (HP diHP 2 )-butylammonium (n = 4) 253) 1 -0-octadecyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP 2) -butylammonium (n = 4)

C 37 H 78 NO 10 P (727,99) 254) 1-0-Erucyl-2-0-methyl-sn-glycero-3-phospho-N,N-dimethyl-N-(HP r diHP 2 )-butylammonium (n = 4) C 38 H 78 NO 10 P (739,01) C 37 H 78 NO 10 P (727.99) 254) 1-0-erucyl-2-0-methyl-sn-glycero-3-phospho-N, N-dimethyl-N- (HP DIHP r 2) -butylammonium (n = 4) C 38 H 78 NO 10 P (739.01)

Wirkstoffe, die auf alkylierten (Ether)-Lvsolecithinen aufgebaut sind und am Active ingredients which are based on alkylated (ether) and at -Lvsolecithinen

Stickstoff nicht hydroxyliert sind Nitrogen are not hydroxylated

(A = a; n = 3, 4; R 3 , CH 3 ; m = 1 ; x = 1 ; z = 0) (A = a; n = 3, 4; R 3, CH 3; m = 1; x = 1; z = 0)

Formel I formula I

A - PO, H A - PO, H

Figure imgf000060_0001

255) 1-0-Erucyl-2-0-methyl-sn-glycero-3-phospho-N,N,N-trimethyl- propylammonium (n = 3) 255) 1-0-erucyl-2-0-methyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3)

C 32 H 66 N0 6 P (591,85) C 32 H 66 N 0 6 P (591.85)

256) 1 -0-Erucyl-3-0-methyl-sn-glycero-2-phopsho-N,N,N-trimethyl- propylammonium (n = 3) 256) 1 -0-erucyl-3-0-methyl-sn-glycero-2-phopsho-N, N, N-trimethyl-propylammonium (n = 3)

C 32 H 66 N0 6 P (591,85) C 32 H 66 N 0 6 P (591.85)

257) 1-0-(Z)-11-Eicosenyl-2-0-methyl-sn-glycero-3-phospho-N,N,N- trimethyl-propylammonium (n = 3) C 30 H 62 NO 6 P (563,80) 257) 1-0- (Z) -11-eicosenyl-2-0-methyl-sn-glycero-3-phospho-N, N, N- trimethyl-propylammonium (n = 3) C 30 H 62 NO 6 P ( 563.80)

258) 1-0-(Z)-11-Eicosenyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N,N- trimethyl-propylammonium (n = 3) 258) 1-0- (Z) -11-eicosenyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N, N- trimethyl-propylammonium (n = 3)

C 33 H 68 N0 6 P (605,88) 259) 1-0-OleyI-2-0-tert.butyl-sn-glycero-3-phospho-N,N,N-trimethyl- propylammonium (n = 3) C 31 H 64 N0 6 P (577,82) C 33 H 68 N0 6 P (605.88) 259) 1-0-OleyI-2-0-tert-butyl-sn-glycero-3-phospho-N, N, N-trimethyl-propylammonium (n = 3) C 31 H 64 N 0 6 P (577.82)

260) 1-0-(Z)-11-Eicosenyl-2-0-tert.butyl-sn-glycero-3-phospho-N,N,N- butylammonium (n = 4) C 34 H 70 NO 6 P (619,90) 260) 1-0- (Z) -11-eicosenyl-2-0-tert-butyl-sn-glycero-3-phospho-N, N, N-butylammonium (n = 4) C 34 H 70 NO 6 P ( 619,90)

261) 1-0-Oleyi-2-0-tert.butyl-sn-glycero-3-phospho-N,N,N-trimethyl- butylammonium (n = 4) 261) 1-0-Oleyi-2-0-tert-butyl-sn-glycero-3-phospho-N, N, N-trimethyl-butylammonium (n = 4)

C 32 H 66 N0 6 P (591,85) C 32 H 66 N 0 6 P (591.85)

Wirkstoffe, die auf Alkandiolpbospho-Verbindungen aufgebaut und am Active ingredients which built on Alkandiolpbospho compounds and the

Stickstoff hydroxyliert sind Nitrogen are hydroxylated

(A = b; n = 2, 3; R 3 , CH 3 ; m = 1; x = 0; y = 1; z = 1) (A = b; n = 2, 3; R 3, CH 3; m = 1; x = 0; y = 1 z = 1)

Formel I formula I

A (CH 2 2)h CH, CH, - OH A (CH 2 2) h CH, CH, - OH

Figure imgf000061_0002
Figure imgf000061_0001

262) 1-0-Erucyl-ethylenglykol-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium 262) 1-0-erucyl-ethylene glycol-phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl-

C 31 H 64 N0 7 P (593,82) C 31 H 64 N0 7 P (593.82)

263) 1 -0-Erucyl-propandiol-(1 ,3)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium C 32 H 66 N0 7 P (607,85) 264) 1 -0-Erucyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium C 32 H 66 N0 7 P (607,85) 263) 1 -0-erucyl propanediol (1, 3) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium C 32 H 66 N0 7 P (607.85) 264) 1 -0-erucyl-propanediol - (1, 2) -phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl C 32 H 66 N0 7 P (607.85)

265) 2-0-Erucyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium C 32 H 66 N0 7 P (607,85) 265) 2-0-erucyl propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium C 32 H 66 N0 7 P (607.85)

266) 1-0-(Z)-11-Eicosenyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium 266) 1-0- (Z) -11-eicosenyl propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammonium

C 30 H 62 NO 7 P (579,49) C 30 H 62 NO 7 P (579.49)

267) 2-0-(Z)-11-Eicosenyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium C 30 H 62 NO 7 P (579,49) 267) 2-0- (Z) -11-eicosenyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-ethylammonium dihydroxypropyl C 30 H 62 NO 7 P (579.49)

268) 1-0-Oleyl-propandiol-(1,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium 268) 1-0-oleyl-propanediol (1,2) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium

C 28 H 58 N0 7 P (551,74) C 28 H 58 N0 7 P (551.74)

269) 2-0-Oleyl-propandiol-(1,2)-phospho-N,N-dimethyl-N-dihydroxypropyl- ethylammonium 269) 2-0-oleyl-propanediol (1,2) -phospho-N, N-dimethyl-N-dihydroxypropyl ethylammonium

C 28 H 58 N0 7 P (551,74) C 28 H 58 N0 7 P (551.74)

270) 2-0-Octadecyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N- dihydroxypropyl-ethylammonium C 28 H 60 NO 7 P (553,76) 270) 2-0-octadecyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl-ethylammonium C 28 H 60 NO 7 P (553.76)

271) 1-0-0ctadecyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N- dihydroxypropyl-propylammonium 271) 1-0-0ctadecyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl-propylammonium

C 29 H 62 N0 7 P (626,24) 272) 2-0-0ctadecyl-propandiol-(1 ,2)-phospho-N,N-dimethyl-N- dihydroxypropyl-propylammonium C 29 H 62 N0 7 P (626,24) C 29 H 62 N0 7 P (626.24) 272) 2-0-0ctadecyl-propanediol (1, 2) -phospho-N, N-dimethyl-N-dihydroxypropyl-propylammonium C 29 H 62 N0 7 P (626 , 24)

Wirkstoffe, die auf Alkandiolphospho-Verbindunqen aufgebaut und am Agents that built on Alkandiolphospho-Verbindunqen and on

Stickstoff nicht hydroxyliert sind Nitrogen are not hydroxylated

(A = b; n = 3; R 3 , CH 3 ; m = 1 ; x = 1 ; z = 0) (A = b; n = 3; R 3, CH 3; m = 1; x = 1; z = 0)

Formel I formula I

A - PO- - H A - PO - H

Figure imgf000063_0001

273) 1-0-Erucyl-propandiol-(1 ,2)-phospho-N,N,N-trimethyl- propylammonium 273) 1-0-erucyl propanediol (1, 2) -phospho-N, N, N-trimethyl-propylammonium

C 31 H 64 N0 5 P (562,82) C 31 H 64 N0 5 P (562.82)

274) 1-0-Erucyl-propandiol-(1 ,2)-phospho-N,N,N-trimethyl- propylammonium C 31 H 64 N0 5 P (562,82) 274) 1-0-erucyl propanediol (1, 2) -phospho-N, N, N-trimethyl propyl ammonium C 31 H 64 N0 5 P (562.82)

275) 1-0-(Z)-11-Eicosenyl-propandiol-(1,3)-phospho-N,N,N-trimethyl- propylammonium 275) 1-0- (Z) -11-eicosenyl propanediol (1,3) -phospho-N, N, N-trimethyl-propylammonium

C 29 H 60 N0 5 P (533,77) C 29 H 60 N0 5 P (533.77)

276) 1 -0-Oleyl-propandiol-(1 ,2)-phospho-N,N,N-trimethyl-propylammonium C 27 H 56 N0 5 P (505,72) 277) 2-0-0 leyl-propandiol-(1,2)-phospho-N,N,N-trimethyl-propylammonium C 27 H 56 N0 5 P (505,72) 276) 1 -0-oleyl-propanediol (1, 2) -phospho-N, N, N-trimethyl-propyl ammonium C 27 H 56 N0 5 P (505.72) 277) 2-0-0 leyl-propanediol (1,2) -phospho-N, N, N-trimethyl-propylammonium C 27 H 56 N0 5 P (505.72)

278) 1-0-0ctadecyl-propandiol-(1 ,2)-phospho-N,N,N-propylammonium C 27 H 58 N0 5 P (507,73) 278) 1-0-0ctadecyl-propanediol (1, 2) -phospho-N, N, N-propyl ammonium C27 58 N0 5 P (507.73)

279) 2-0-Octadecyl-propandiol-(1 ,2)-phospho-N,N, N-trimethyl- propylammonium 279) 2-0-octadecyl-propanediol (1, 2) -phospho-N, N, N-trimethyl-propylammonium

C 27 H 58 N0 5 P (507,73) C 27 H 58 N0 5 P (507.73)

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Referenced by
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WO2000008031A1 *Aug 6, 1999Feb 17, 2000MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.Novel phospholipids with unsaturated alkyl and acyl chains
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EP1578754A2 *Oct 29, 2003Sep 28, 2005MakScientific CorporationAntiprotozoal ring-substituted phospholipids
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US8097752Oct 29, 2003Jan 17, 2012Makscientific, LlcAntiprotozoal ring-substituted phospholipids
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Classifications
International ClassificationC07F9/09, A61K48/00, C12N15/87, C12N15/09, A61K9/127, A61K47/24, C07F9/10
Cooperative ClassificationA61K9/0019, A61K9/1271, A61K48/00, C07F9/10, C07F9/091, A61K47/24, C12N15/87, A61K9/1272
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