JP2924179B2 - Glycerol derivatives, devices and pharmaceutical compositions - Google Patents

Description

TECHNICAL FIELD The present invention relates to a compound represented by the following general formula [I].

In the formula, R ¹ and R ² are different from each other and are OY or -A- (CH ₂ ) _n-
E (where R ¹ and R ² are both OY, and R ¹ ,
Except when both R ² are -A- (CH ₂ ) n -E. ). n represents the integer of 0-4. E is pyrrolidino, piperidino,
Substituted or unsubstituted piperazino, morpholino, or substituted or unsubstituted guanidino, (R ³ and R ⁴ are the same or different and are hydrogen,
4 represents lower alkyl, hydroxy lower alkyl having 1 to 4 carbon atoms, or mono- or di-lower alkylaminoalkyl (2 to 8 carbon atoms). ).

A represents the following or

R and Y are the same or different and each represent a saturated or unsaturated aliphatic hydrocarbon group having 10 to 30 carbon atoms, or a saturated or unsaturated fatty acid residue having 10 to 30 carbon atoms.

Compound according to the present invention (hereinafter referred to as “the compound of the present invention”)
Is the so-called DDS (Drug Delivery System)
It is extremely useful as a raw material for device components as a pharmaceutical. The device refers to a substance having a function of transporting a substance having a physiological activity, such as a carrier.

BACKGROUND ART Devices comprising certain positively charged lipids (eg, cationic liposomes) are known to be useful for gene transfer into cells (see, for example,
No. 108391, W091 / 17424). It is also known that administration of a nucleic acid such as double-stranded RNA together with a device such as cationic liposome increases interferon inducer ability (US Pat. No. 5,049,386).
Since nucleic acids such as genes are negatively charged, it is presumed that they form complexes with cationic liposomes, which fuse with cell membranes, and that nucleic acids such as genes also enter cells.

As the cationic liposome, N- [1-
(2,3-dioleyloxy) propyl] -N, N, N-trimethylammonium chloride N- [1- (2,3-dioleylox)
y) propyl] -N, N, N-trimethylammonium chloride (hereinafter referred to as "DOTMA") and dioleoyl phosphatidylethanolamine
And Lipofectin (registered trademark, Bethesda Research Laborato, manufactured by Bethesda Research Laboratories).
ries Life Technologies Inc.) is well known.

However, DOTM, a component of lipofectin,
Since A has quaternary ammonium and has high hemolytic toxicity, it cannot be said to be suitable for use as a pharmaceutical.

A method has been devised to enhance the effect by applying a substance obtained by replacing lipofectin DOTMA with a cholesterol derivative (Third International Symposium on Catalytic RNAs)
and Targeted Gene Therapy for the Treatment of HIV
Infection, December 6-11, 1992).

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a device comprising a lipid having the same function as a cationic liposome and having low toxicity, and a component such as a lipid.

The present inventors have made intensive studies and found that the above-mentioned problems can be solved by using the compound of the present invention instead of DOTMA which is a component of lipofectin, and completed the present invention.

One of the points of the present invention lies in the structure itself of the compound represented by the general formula [I]. This compound of the present invention is a novel compound not described in any literature.

A structural feature of the compound of the present invention is that, when glycerol is used as a basic skeleton, one of the three hydroxyl groups of glycerol is substituted with a group represented by -A- (CH ₂ ) _n -E. It is in. Here, A, n, and E are the same as described above.

Another feature of the invention compounds, the -A- (CH _{2) n} A in -E is where there of, or below.

The compounds of the present invention do not include those in which the amine in the substituent E is quaternary ammonium. JP-A-4-108391
The publication discloses that liposomes, ie, lipids having quaternary ammonium as one of the constituent lipids of the device, are good, but such quaternary ammonium is not suitable for the purpose of the present invention.

Examples of the substituted piperazino related to E include 4-methylpiperazino, 4-ethylpiperazino, 4-n-propylpiperazino, 4-isopropylpiperazino, 4-n-butylpiperazino, 4-isobutylpiperazino, 4- (2- Examples thereof include (hydroxyethyl) piperazino, 4- (2-hydroxypropyl) piperazino, and 4- (3-hydroxypropyl) piperazino.

Examples of the substituted guanidino according to E include methylguanidino, ethylguanidino, n-propylguanidino, N, N
-Dimethylguanidino, N, N-diethylguanidino, N, N
-Di-n-propylguanidino, N, N'-dimethylguanidino, N, N'-diethylguanidino, N, N'-di-n-propylguanidino, N, N, N'-trimethylguanidino, N, N,
N′-triethylguanidino, N, N, N′-tri-n-propylguanidino, N, N, N ′, N′-tetramethylguanidino,
N, N, N ', N'-tetraethylguanidino, N, N, N', N'-tetra-n-propylguanidino and the like can be mentioned.

Examples of lower alkyl relating to R ³ and R ⁴ include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like.

Examples of the hydroxy lower alkyl related to R ³ and R ⁴ include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, and 3-hydroxypropyl.

Examples of the mono- or di-lower alkylaminoalkyl for R ³ and R ⁴ include methylaminomethyl, dimethylaminomethyl, 2- (methylamino) ethyl, 2-dimethylaminoethyl, 3- (methylamino) propyl, and 3-dimethyl Aminopropyl, ethylaminomethyl, diethylaminomethyl, 2- (ethylamino) ethyl, 2-diethylaminoethyl, 3- (ethylamino) propyl, 3-diethylaminopropyl, n-propylaminomethyl, di-
n-propylaminomethyl, 2- (n-propylamino) ethyl, 2- (di-n-propylamino) ethyl,
3- (n-propylamino) propyl, 3- (di-n-
Propylamino) propyl and the like.

In the general formula (I), R and Y are the same or different and each represent a saturated or unsaturated aliphatic hydrocarbon group having 10 to 30 carbon atoms, or a saturated or unsaturated fatty acid residue having 10 to 30 carbon atoms. However, unsaturated aliphatic hydrocarbons and unsaturated fatty acid residues having the same R and Y and having about 12 to 20 carbon atoms are preferable, and for example, when R and Y are an oleyl group, an oleoyl group or the like, more preferable. .

A is preferably a carbamate bond or an ester bond.

 The compounds of the present invention have extremely low toxicity.

The compound represented by the general formula [I] according to the present invention can be obtained, for example, by the following method.

(1) When R ¹ is OY and A is -OC (= O) -NH- (In the formula, B is, for example, imidazolyl, halogen, phenoxy, etc. Examples of the halogen are chlorine, bromine, iodine, etc. R, Y,
E and n are the same as described above. The compound [I] of the present invention can be obtained by reacting [II] and [II
And I] to react with each other.

The reaction between [II] and [III] is carried out by using 1 to 3 equivalents of [III] to 1 equivalent of [II], in the presence of a solvent at 0 ° C to 150 ° C.
C. for 1-20 hours. As the reaction solvent,
Examples include dimethylformamide, pyridine, toluene, benzene, ether, dioxane, tetrahydrofuran, chloroform and the like. Note that a base such as triethylamine may be added to promote the reaction.
Further, [III] in the above solvent, sodium hydride or n-
After conversion to a metal salt with butyllithium or the like, it may be reacted with [II].

(2) When R ¹ is OY and A is —NH—C (＝ O) —O— (In the formula, B, R, Y, E, and n are the same as described above.) The compound [I] of the present invention is obtained by converting [IV] and [IV] as in the above formula according to the reaction conditions of the above (1). V].

(3) When R ¹ is OY and A is —NH—C (＝ O) —O— (In the formula, R, Y, E, and n are the same as described above.) The compound [I] of the present invention can be obtained by converting [IV] and [III ′] as in the above formula according to the reaction conditions of the above (1). ] To react with each other.

(4) When R ¹ is OY and A is -OC (= O) -NH- (In the formula, R, Y, E, and n are the same as described above.) The compound [I] of the present invention can be obtained by converting [IV '] and [VII] as shown in the above formula according to the reaction conditions of the above (1). ] To react with each other.

(5) When R ¹ is OY and R ² is -A- (CH ₂ ) _n -E (Wherein A, E, and n are the same as those described above) by reacting the hydroxyl group of the compound represented by The compound [I] of the present invention can be synthesized by substituting with the substituent represented by Y. This synthesis method is preferable when R and Y are fatty acid residues.

<Raw materials (IV), (IV ′), (V), (VI), (VII),
Synthesis of [VIII]> (1) Synthesis of Raw Material [IV '] The raw material [IV'] can be synthesized, for example, according to the following reaction formula.

(In the formula, Tr represents a trityl group, Ts represents a tosyl group, and R and Y are the same as described above.) (2) Synthesis of raw material [IV] Raw material [IV] is synthesized by, for example, the following method. can do.

It can be synthesized from compound [IV '] by a conventional method such as, for example, azido conversion and then reduction.

(3) Synthesis of raw material [V] For example, raw material [V] in which B is imidazolyl can be synthesized by reacting compound [III '] with N, N'-carbonyldiimidazole in pyridine at room temperature. it can.

(4) Synthesis of Raw Material [VI] The raw material [VI] can be synthesized by reacting compound [IV] with diphosgene.

(5) Synthesis of Raw Material [VII] The raw material [VII] can be prepared by, for example, reacting compound [III] with diphosgene, or HOOC- (CH ₂ ) _n -E (wherein
n and E are the same as described above. ) To the compound represented by
After reacting PA (diphenylphosphoryl azide) at 0 to 150 ° C. in the presence of a tertiary amine such as triethylamine, the reaction is further carried out at 0 to 15 in the presence of a tertiary amine such as pyridine.
It can be easily synthesized by reacting at 0 ° C.

(6) Synthesis of Raw Material [VIII] When A is -OC (= O) -NH-, for example, it can be synthesized according to the following reaction formula.

(In the formula, Im represents an imidazolyl group.) When A is —NH—C (＝ O) —O—, it can be synthesized, for example, according to the following reaction formula.

(In the formula, Im represents an imidazolyl group, and E and n are the same as described above.) When A is -OC (= O)-, for example, it can be synthesized according to the following reaction formula. .

(Where DCC is dicyclohexylcarbodiimide, DMA
P represents 4-N, N-dimethylaminopyridine. E, n
Is the same as above. When A is -OC (= S) -NH-, for example, it can be synthesized according to the following reaction formula.

(In the formula, Im represents an imidazolyl group.) When A is -NH-C (= O)-, for example, it can be synthesized according to the following reaction formula.

(In the formula, DCC represents dicyclohexylcarbodiimide. E and n are the same as described above.) When A is —OSO ₂ —NH—, it can be synthesized, for example, according to the following reaction formula.

(Wherein, E, n are the same as defined above, and.) A is -O-P (= O) ( - CH 3) -O- ones can be synthesized according to, for example, the following reaction formula .

(In the formula, BT represents a 1-benzotriazolyl group.) Examples of the compound of the present invention include the following.

3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dilaurylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dimyristylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dipalmitylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dioleylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dilinoleyl glycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
2-O-lauryl-1-O-myristylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1-O-oleyl-2-O-palmitylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1-O-linoleyl-2-O-oleylglycerol, 3-O- (dimethylaminomethyl) carbamoyl-1,2
-O-dioleylglycerol, 3-O- (3-dimethylaminopropyl) carbamoyl
-1,2-O-dioleylglycerol, 3-O- (4-dimethylaminobutyl) carbamoyl-
1,2-O-dioleylglycerol, 3-O- (2-diethylaminoethyl) carbamoyl-
1,2-O-dioleylglycerol, 3-O- (3-diethylaminopropyl) carbamoyl
-1,2-O-dioleylglycerol, 3-O- (2-di-n-propylaminoethyl) carba
Moyl-1,2-O-dioleylglycerol, 3-O- (2-diisopropylaminoethyl) carbamo
Yl-1,2-O-dioleylglycerol, 3-O- (2-di-n-butylaminoethyl) carbamo
Yl-1,2-O-dioleylglycerol, 3-O- (2-diisobutylaminoethyl) carbamoy
1,2-O-dioleylglycerol, 3-O- (2-di-sec-butylaminoethyl) carba
Moyl-1,2-O-dioleylglycerol, 3-O- [2- (N-ethyl-N-methylamino) ethyl
Carbamoyl-1,2-O-dioleylglycerol
3-O- (2-methylaminoethyl) carbamoyl-1,
2-O-dioleylglycerol, 3-O- (2-ethylaminoethyl) carbamoyl-1,
2-O-dioleylglycerol, 3-O- (2-n-propylaminoethyl) carbamoy
1,2-O-dioleylglycerol, 3-O- (2-n-butylaminoethyl) carbamoyl
-1,2-O-dioleylglycerol, 3-O- (2-aminoethyl) carbamoyl-1,2-O
-Dioleylglycerol, 3-O- [2- (N-methyl-N- (2-hydroxye
Tyl) amino) ethyl] carbamoyl-1,2-O-di
Rail glycerol, 3-O- [2- (N-ethyl-N- (2-hydroxy
Tyl) amino) ethyl] carbamoyl-1,2-O-di
Rail glycerol, 3-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] carbamoyl-1,2-O-dioleyl
Glycerol, 3-O- [2- (N (2-diethylamino) ethyl-N
-Methylamino) ethyl] carbamoyl-1,2-O-di
Oleyl glycerol, 3-O- [2- (4-methylpiperazino) ethyl] cal
Bamoyl-1,2-O-dioleylglycerol, 3-O- (2-morpholinoethyl) carbamoyl-1,2
-O-dioleylglycerol, 3-O- (2-piperidinoethyl) carbamoyl-1,2
-O-dioleylglycerol, 3-O- (2-pyrrolidinoethyl) carbamoyl-1,2
-O-dioleylglycerol, 3-O- (2-diethylaminoethyl) thiocarbamoy
1,2-O-dioleylglycerol, 3-O- (2-dimethylaminoethyl) thiocarbamoy
1,2-O-dioleylglycerol, 3-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] thiocarbamoyl-1,2-O-diole
Ilglycerol, 3-O- (2-pyrrolidinoethyl) thiocarbamoyl-
1,2-O-dioleylglycerol, 3-O- (2-dimethylaminoethyl) sulfamoyl
-1,2-O-dioleylglycerol, 3-O- (2-diethylaminoethyl) sulfamoyl
-1,2-O-dioleylglycerol, 3-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] sulfamoyl-1,2-O-dioleoyl
Luglycerol, 3-O- (2-pyrrolidinoethyl) sulfamoyl-1,
2-O-dioleylglycerol, 3-O- (N, N-dimethylaminoacetyl) -1,2-O-
Dioleyl glycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dilauryl glycerol, 3-O- (4-diethylaminobutanoyl) -1,2-O
-Dipalmityl glycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dioleylglycerol, 3-O- (4-diethylaminobutanoyl) -1,2-O
-Dioleylglycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dilinoleyl glycerol, 3-O- (4-dimethylaminobutanoyl) -1-O-
Oleyl-2-O-palmitylglycerol, 3-O- (4-dimethylaminobutanoyl) -1-O-
Linoleyl-2-O-oleylglycerol, 3-O- (3-dimethylaminopropionyl) -1,2-
O-dioleyl glycerol, 3-O- (5-dimethylaminopentanoyl) -1,2-
O-dioleyl glycerol, 3-O- (4-di-n-propylaminobutanoyl)-
1,2-O-dioleylglycerol, 3-O- (4-diisopropylaminobutanoyl) -1,
2-O-dioleylglycerol, 3-O- [4- (N-ethyl-N-methylamino) buta
Noyl] -1,2-O-dioleylglycerol, 3-O- [4-ethylaminobutanoyl) -1,2-O-
Dioleyl glycerol, 3-O- [4- (N-methyl-N- (2-hydroxy
Tyl) amino) butanoyl] -1,2-O-dioleig
Lycerol, 3-O- [4- (N, N-di- (2-hydroxyethyl)
Amino) butanoyl] -1,2-O-dioleylglycero
3-O- [4- (N- (2-diethylamino) ethyl-
N-methylamino) butanoyl] -1,2-O-dioleoyl
Luglycerol, 3-O- [4- (4-methylpiperazino) butanoyl]
-1,2-O-dioleylglycerol, 3-O- (4-morpholinobtanoyl) -1,2-O-di
Oleyl glycerol, 3-O- (4-pyrrolidinobutanoyl) -1,2-O-di
Oleyl glycerol, 3-O- (4-piperidinobutanoyl) -1,2-O-di
Oleyl glycerol, O- (2-diethylaminoethyl) -O '-(2,3-di
Railoxypropyl) methylphosphonate, O- (2-dimethylaminoethyl) -O '-(2,3-di
Railoxypropyl) methyl phosphonate, O- [2- (N, N-di- (2-hydroxyethyl) amido
No) Ethyl] -O '-(2,3-dioleyloxypropyl
M) methylphosphonate, O- (2-pyrrolidinoethyl) -O '-(2,3-diole
Ruoxypropyl) methylphosphonate, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dilauroylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dimyristoyl glycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dipalmitoyl glycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dioleoylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1,2-O-dilinolenylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-
1-O-oleoyl-2-O-palmitoyl glycerol
3-O- (2-dimethylaminoethyl) carbamoyl-
1-O-linolenyl-2-O-oleoylglycerol
3-O- (3-dimethylaminopropyl) carbamoyl
-1,2-O-dioleoylglycerol, 3-O- (2-diethylaminoethyl) carbamoyl-
1,2-O-dioleoylglycerol, 3-O- (2-di-n-propylaminoethyl) carba
Moyl-1,2-O-dioleoylglycerol, 3-O- (2-diisopropylaminoethyl) carbamo
Yl-1,2-O-dioleoylglycerol, 3-O- [2- (N-ethyl-N-methylamino) ethyl
Carbamoyl-1,2-O-dioleoylglycerol
3-O- (2-ethylaminoethyl) carbamoyl-1,
2-O-dioleoylglycerol, 3-O- [2- (N-methyl-N- (2-hydroxy
Tyl) amino) ethyl] carbamoyl-1,2-O-di
Reoyl glycerol, 3-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] carbamoyl-1,2-O-dioleoi
Luglycerol, 3-O- [2- (N- (2-diethylamino) ethyl-
N-methylamino) ethyl] carbamoyl-1,2-O-
Dioleoyl glycerol, 3-O- (2-piperidinoethyl) carbamoyl-1,2
-O-dioleoylglycerol, 3-O- (2-pyrrolidinoethyl) carbamoyl-1,2
-O-dioleoylglycerol, 3-O- (2-aminoethyl) carbamoyl-1,2-O
-Dioleoylglycerol, 3-O- (2-diethylaminoethyl) thiocarbamoy
1,2-O-dioleoylglycerol, 3-O- (2-dimethylaminoethyl) thiocarbamoy
1,2-O-dioleoylglycerol, 3-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] thiocarbamoyl-1,2-O-diole
Oil glycerol, 3-O- (2-pyrrolidinoethyl) thiocarbamoyl-
1,2-O-dioleoylglycerol, 3-O- (2-diethylaminoethyl) sulfamoyl
-1,2-O-dioleoylglycerol, 3-O- (2-dimethylaminoethyl) sulfamoyl
-1,2-O-dioleoylglycerol, 3-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] sulfamoyl-1,2-O-dioleo
Ilglycerol, 3-O- (2-pyrrolidinoethyl) sulfamoyl-1,
2-O-dioleoylglycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
Dilauroyl glycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dimyristoyl glycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dipalmitoyl glycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dioleoylglycerol, 3-O- (4-dimethylaminobutanoyl) -1,2-O
-Dilinolenylglycerol, 3-O- (4-dimethylaminobutanoyl) -1-O-
Oleoyl-2-O-palmitoylglycerol, 3-O- (4-dimethylaminobutanoyl) -1-O-
Linolenyl-2-O-oleoylglycerol, 3-O- (3-dimethylaminopropionyl) -1,2-
O-dioleoylglycerol, 3-O- (5-dimethylaminopentanoyl) -1,2-
O-dioleoylglycerol, 3-O- (4-diethylaminobutanoyl) -1,2-O
-Dioleoylglycerol, 3-O- (4-di-n-propylaminobutanoyl)-
1,2-O-dioleoylglycerol, 3-O- (4-diisopropylaminobutanoyl) -1,
2-O-dioleoylglycerol, 3-O- [4- (N-ethyl-N-methylamino) buta
Noyl] -1,2-O-dioleoylglycerol, 3-O- (4-ethylaminobutanoyl) -1,2-O-
Dioleoyl glycerol, 3-O- [4- (N-methyl-N- (2-hydroxy
Tyl) amino) butanoyl] -1,2-O-dioleoyl
Glycerol, 3-O- [4- (N, N-di- (2-hydroxyethyl)
Amino) butanoyl] -1,2-O-dioleoyl glyce
Roll, 3-O- [4- (N- (2-diethylamino) ethyl-
N-methylamino) butanoyl] -1,2-O-dioleo
Ilglycerol, 3-O- (4-pyrrolidinobutanoyl) -1,2-O-di
Oleoyl glycerol, O- (2-diethylaminoethyl) -O '-(2,3-di
Oleoyloxypropyl) methyl phosphonate, O- (2-dimethylaminoethyl) -O '-(2,3-di
Oleoyloxypropyl) methylphosphonate, O- [2- (N, N-di- (2-hydroxyethyl) amido
No) Ethyl] -O '-(2,3-dioleoyloxypropyl
M) methylphosphonate, O- (2-pyrrolidinoethyl-O '-(2,3-dioleoi)
Ruoxypropyl) methylphosphonate, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dilaurylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dimyristylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dipalmityl glycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dioleylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dilinoleyl glycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1-O-lauryl-3-O myristylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1-O-oleyl-3-O-palmitylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1-O-linoleyl-3-O-oleylglycerol, 2-O- (3-dimethylaminopropyl) carbamoyl
-1,3-O-dioleylglycerol, 2-O- (4-dimethylaminobutyl) carbamoyl-
1,3-O-dioleylglycerol, 2-O- (2-diethylaminoethyl) carbamoyl-
1,3-O-dioleylglycerol, 2-O- (2-di-n-propylaminoethyl) carba
Moyl-1,3-O-dioleylglycerol, 2-O- (2-diisopropylaminoethyl) carbamo
Yl-1,3-O-dioleylglycerol, 2-O- (2-di-n-butylaminoethyl) carbamo
Yl-1,3-O-dioleylglycerol, 2-O- (2-diisobutylaminoethyl) carbamoy
1,3-O-dioleylglycerol, 2-O- (2-di-sec-butylaminoethyl) carba
Moyl-1,3-O-dioleylglycerol, 2-O- [2- (N-ethyl-N-methyl) aminoethyl
Carbamoyl-1,3-O-dioleylglycerol
2-O- (2-methylaminoethyl) carbamoyl-1,
3-O-dioleylglycerol, 2-O- (2-ethylaminoethyl) carbamoyl-1,
3-O-dioleylglycerol, 2-O- (2-n-propylaminoethyl) carbamoy
1,3-O-dioleylglycerol, 2-O- (2-butylaminoethyl) carbamoyl-1,
3-O-dioleylglycerol, 2-O- (2-aminoethyl) carbamoyl-1,3-O
-Dioleylglycerol, 2-O- [2- (N-methyl-N- (2-hydroxye
Tyl) amino) ethyl] carbamoyl-1,3-O-di
Rail glycerol, 2-O- [2- (N-ethyl-N- (2-hydroxy
Tyl) amino) ethyl] carbamoyl-1,3-O-di
Rail glycerol, 2-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] carbamoyl-1,3-O-dioleyl
Glycerol, 2-O- [2- (N- (2-diethylamino) ethyl-
N-methylamino) ethyl] carbamoyl-1,3-O-
Dioleyl glycerol, 2-O- [2- (4-methylpiperazino) ethyl] cal
Bamoyl-1,3-O-dioleylglycerol, 2-O- (2-morpholinoethyl) carbamoyl-1,3
-O-dioleylglycerol, 2-O- (2-piperidinoethyl) carbamoyl-1,3
-O-dioleylglycerol, 2-O- (2-pyrrolidinoethyl) carbamoyl-1,3
-O-dioleylglycerol, 2-O- (2-dimethylaminoethyl) thiocarbamoy
1,3-O-dioleylglycerol, 2-O- (2-diethylaminoethyl) thiocarbamoy
1,3-O-dioleylglycerol, 2-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] thiocarbamoyl-1,3-O-diole
Ilglycerol, 2-O- (2-pyrrolidinoethyl) thiocarbamoyl-
1,3-O-dioleylglycerol, 2-O- (2-dimethylaminoethyl) sulfamoyl
-1,3-O-dioleylglycerol, 2-O- (2-diethylaminoethyl) sulfamoyl
-1,3-O-dioleylglycerol, 2-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] sulfamoyl-1,3-O-dioleoyl
Luglycerol, 2-O- (2-pyrrolidinoethyl) sulfamoyl-1,
3-O-dioleylglycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dilauryl glycerol, 2-O- (4-diethylaminobutanoyl) -1,3-O
Dipalmityl glycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dilinoleyl glycerol, 2-O- (4-dimethylaminobutanoyl) -1-O-
Oleyl-3-O-palmitylglycerol, 2-O- (4-dimethylaminobutanoyl) -1-O-
Linoleyl-3-O-oleylglycerol, 2-O- (3-dimethylaminopropionyl) -1,3-
O-dioleyl glycerol, 2-O- (5-dimethylaminopentanoyl) -1,3-
O-dioleyl glycerol, 2-O- (4-di-n-propylaminobutanoyl)-
1,3-O-dioleylglycerol, 2-O- (4-diisopropylaminobutanoyl) -1,
3-O-dioleylglycerol, 2-O- [4- (N-ethyl-N-methyl) aminobuta
Noyl] -1,3-O-dioleylglycerol, 2-O- (4-ethylaminobutanoyl) -1,3-O-
Dioleylglycerol, 2-O- [4- (N-methyl-N- (2-hydroxy
Tyl) amino) butanoyl] -1,3-O-dioleig
Lycerol, 2-O- [4- (N, N-di- (2-hydroxyethyl)
Amino) butanoyl] -1,3-O-dioleylglycero
2-O- [4- (N- (2-diethylamino) ethyl-
N-methylamino) butanoyl] -1,3-O-diole
Luglycerol, 2-O- [4- (4-methylpiperazino) butanoyl]
-1,3-O-dioleylglycerol, 2-O- (4-morpholinobtanoyl) -1,3-O-di
Oleyl glycerol, 2-O- (4-pyrrolidinobutanoyl) -1,3-O-di
Oleyl glycerol, 2-O- (4-piperidinobutanoyl) -1,3-O-di
Oleyl glycerol, O- (2-diethylaminoethyl) -O '-(1,3-di
Railoxypropyl) methylphosphonate, O- (2-dimethylaminoethyl) -O '-(1,3-di
Railoxypropan-2-yl) methylphosphone
G, O- [2- (N, N-di- (2-hydroxyethyl) amido
No) Ethyl] -O '-(1,3-dioleyloxypropane
-2-yl) methylphosphonate, O- (2-pyrrolidinoethyl) -O '-(1,3-dioleoyl)
Ruoxypropan-2-yl) methylphosphonate, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dilauroylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dimyristoyl glycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dipalmitoyl glycerol, 2-O- (2-diethylaminoethyl) carbamoyl-
1,3-O-dipalmitoyl glycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dioleoylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1,3-O-dilinolenylglycerol, 2-O- (2-dimethylaminoethyl) carbamoyl-
1-O-oleoyl-3-O-palmitoyl glycerol
2-O- (2-dimethylaminoethyl) carbamoyl-
1-O-linolenyl-3-O-oleoylglycerol
2-O- (dimethylaminomethyl) carbamoyl-1,3
-O-dioleoylglycerol, 2-O- (3-dimethylaminopropyl) carbamoyl
-1,3-O-dioleoylglycerol, 2-O- (2-diethylaminoethyl) carbamoyl-
1,3-O-dioleoylglycerol, 2-O- (2-di-n-propylaminoethyl) carba
Moyl-1,3-O-dioleoylglycerol, 2-O- (2-diisopropylaminoethyl) carbamo
Yl-1,3-O-dioleoylglycerol, 2-O- [2- (N-ethyl-N-methylamino) ethyl
Carbamoyl-1,3-O-dioleoylglycerol
2-O- [2- (N-methyl-NN-butylamino)
Ethyl] carbamoyl-1,3-O-dioleoyl glyce
Roll, 2-O- (2-ethylaminoethyl) carbamoyl-1,
3-O-dioleoylglycerol, 2-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] carbamoyl-1,3-O-dioleoi
Luglycerol, 2-O- [2- (N-methyl-N- (2-hydroxy
Tyl) amino) ethyl] carbamoyl-1,3-O-di
Reoyl glycerol, 2-O- [2- (N-ethyl-N- (2-hydroxy
Tyl) amino) ethyl] carbamoyl-1,3-O-di
Reoyl glycerol, 2-O- [2- (N- (2-diethylamino) ethyl-
N-methylamino) ethyl] carbamoyl-1,3-O-
Dioleoyl glycerol, 2-O- [2- (N, N, N ', N'-tetramethylguanidinium
No) Ethyl] carbamoyl-1,3-O-dioleoyl oil
Lycerol, 2-O- (2-morpholinoethyl) carbamoyl-1,3
-O-dioleoylglycerol, 2-O- (2-piperidinoethyl) carbamoyl-1,3
-O-dioleoylglycerol, 2-O- (2-pyrrolidinoethyl) carbamoyl-1,3
-O-dioleoylglycerol, 2-O- [2- (4-ethylpiperazino) ethyl] cal
Bamoyl-1,3-O-dioleoylglycerol, 2-O- [2- (4- (2-hydroxyethyl) pipera
Dino) ethyl] carbamoyl-1,3-O-dioleoyl
Glycerol, 2-O- (2-diethylaminoethyl) thiocarbamoy
1,3-O-dioleoylglycerol, 2-O- (2-dimethylaminoethyl) thiocarbamoy
1,3-O-dioleoylglycerol, 2-O- [2- (N, N-di- (2-hydroxyethyl)
Amino) ethyl] thiocarbamoyl-1,3-O-diole
Oil glycerol, 2-O- (2-pyrrolidinoethyl) thiocarbamoyl-
1,3-O-dioleoylglycerol, 2-O- (2-diethylaminoethyl) sulfamoyl
-1,3-O-dioleoylglycerol, 2-O- (2-dimethylaminoethyl) sulfamoyl
-1,3-O-dioleoylglycerol, 2-O- [2-N, N-di- (2-hydroxyethyl) a
Minoethyl] sulfamoyl-1,3-O-dioleoyl
Glycerol, 2-O- (2-pyrrolidinoethyl) sulfamoyl-1,
3-O-dioleoylglycerol, 2-O- (3-diethylaminopropionyl) -1,3-
O-dioleoylglycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dilauroyl glycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dimyristoyl glycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dipalmitoyl glycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dioleoylglycerol, 2-O- (4-dimethylaminobutanoyl) -1,3-O
-Dilinolenylglycerol, 2-O- (4-dimethylaminobutanoyl) -1-O-
Oleoyl-3-O-palmitoylglycerol, 2-O- (4-dimethylaminobutanoyl) -1-O-
Linolenyl-3-O-oleoylglycerol, 2-O- (3-dimethylaminopropionyl) -1,3-
O-dioleoylglycerol, 2-O- (5-dimethylaminopentanoyl) -1,3-
O-dioleoylglycerol, 2-O- (4-diethylaminobutanoyl) -1,3-O
-Dioleoylglycerol, 2-O- (4-di-n-propylaminobutanoyl)-
1,3-O-dioleoylglycerol, 2-O- (4-diisopropylaminobutanoyl) -1,
3-O-dioleoylglycerol, 2-O- [4- (N-ethyl-N-methylamino) buta
Noyl] -1,3-O-dioleoylglycerol, 2-O- [4- (ethyl) aminobutanoyl] -1,3-
O-dioleoylglycerol, 2-O- [4- (N-methyl-N- (2-hydroxy
Tyl) amino) butanoyl] -1,3-O-dioleoyl
Glycerol, 2-O- [4- (N, N-di- (2-hydroxyethyl)
Amino) butanoyl] -1,3-O-dioleoyl glyce
Roll, 2-O- [4- (N- (2-diethylamino) ethyl-
N-methylamino) butanoyl] -1,3-O-dioleo
Ilglycerol, 2-O- (4-pyrrolidinobutanoyl) -1,3-O-di
Oleoyl glycerol, O- (2-dimethylaminoethyl) -O '-(1,3-di
Oleoyloxypropan-2-yl) methylphosphone
G, O- (2-aminoethyl) -O '-(1,3-dioleoyl
Oxypropan-2-yl) methylphosphonate, O- (2-diethylaminoethyl) -O '-(1,3-di
Oleoyloxypropan-2-yl) methylphosphone
G, 2-dimethylaminoethyl N- (2,3-dilauryloxy)
(Cipropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dimyristyl)
Xypropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dioleyloxy)
(Cipropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dilinoleylio)
Xypropyl) carbamate, 2-dimethylaminoethyl N- (2-lauryloxy-
3-linoleyloxypropyl) carbamate, 2-dimethylaminoethyl N- (3-myristyloxy)
-2-oleyloxypropyl) carbamate, 3-dimethylaminopropyl N- (2,3-dioleoyl)
Xypropyl) carbamate, 4-dimethylaminobutyl N- (2,3-dioleyloxy)
(Cipropyl) carbamate, 2-diethylaminoethyl N- (2,3-dioleyloxy)
(Cipropyl) carbamate, 2-di-n-propylaminoethyl N- (2,3-diole)
Yloxypropyl) carbamate, 2-di-n-butylaminoethyl N- (2,3-diole
Ruoxypropyl) carbamate, 2-ethylmethylaminoethyl N- (2,3-dioleyl)
Oxypropyl) carbamate, 2- (N-ethyl-N-methylamino) ethyl N- (2,
3-dioleyloxypropyl) carbamate, 2-ethylaminobutyl N- (2,3-dioleyloxy)
Propyl) carbamate, 2-n-propylaminoethyl N- (2,3-dioleyl)
Oxypropyl) carbamate, 2- [N-methyl-N- (2-hydroxyethyl) amido
[No] ethyl N- (2,3-dioleyloxypropyl) ca
Rubamate, 2- [N-ethyl-N- (2-hydroxyethyl) amido
[No] ethyl N- (2,3-dioleyloxypropyl) ca
Rubamate, 2- [N, N-di- (2-hydroxyethyl) amino] d
Cyl N- (2,3-dioleyloxypropyl) carbame
2- [N- (2-diethylamino) ethyl-N-methyl
Amino] ethyl N- (2,3-dioleyloxypropyl
L) carbamate, 2- (4-methylpiperazino) ethyl N- (2,3-di
Railoxypropyl) carbamate, 2-morpholinoethyl N- (2,3-dioleyloxy)
Ropyl) carbamate, 2-piperidinoethyl N- (2,3-dioleyloxy)
Ropyl) carbamate, 2-pyrrolidinoethyl N- (2,3-dioleyloxy)
Ropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dioleyloxy)
Cypropyl) thiocarbamate, 2-diethylaminoethyl N- (2,3-dioleyloxy)
Cypropyl) thiocarbamate, 2- [N, N-di- (2-hydroxyethyl) amino]
Cyl N- (2,3-dioleyloxypropyl) thiocar
Bamate, 2-pyrrolidinoethyl N- (2,3-dioleyloxy
Ropyl) thiocarbamate, 2-dimethylaminoethyl N- (2,3-dioleyloxy)
Cypropyl) sulfamate, 2-diethylaminoethyl N- (2,3-dioleyloxy)
Cypropyl) sulfamate, 2- [N, N-di- (2-hydroxyethyl) amino]
Cyl N- (2,3-dioleyloxypropyl) sulfa
Mate, 2-pyrrolidinoethyl N- (2,3-dioleyloxy
Ropyl) sulfamate, N- (2,3-dioleyloxy) propyl-4-dimethyl
Aminobutyramide, N- (2,3-dioleyloxy) propyl-4-diethyl
Aminobutyramide, N- (2,3-dioleyloxy) propyl-4- [N, N-
Di- (2-hydroxyethyl) amino] butyramide, N- (2,3-dioleyloxy) propyl-4-pyrroli
Dinobutylamide, 2-dimethylaminoethyl N- (2,3-dilauroyl
Xypropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dimyristoyl)
Oxypropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dipalmitoyl
Oxypropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dioleoyloate)
Xypropyl) carbamate, 2-dimethylaminoethyl N- (2,3-dilinolenylo)
Xypropyl) carbamate, 2-dimethylaminoethyl N- (2-oleoyloxy)
-3-palmitoyloxypropyl) carbamate, 2-dimethylaminoethyl N- (2-linolenyloxy)
-3-oleoyloxypropyl) carbamate, 2-diethylaminoethyl N- (2,3-dioleoyloxy)
Xypropyl) carbamate, 3-dimethylaminopropyl N- (2,3-dioleoyl)
Oxypropyl) carbamate, 2-diisopropylaminoethyl N- (2,3-dioleo)
Yloxypropyl) carbamate, 2-di-n-propylaminoethyl N- (2,3-diole)
Oiloxypropyl) carbamate, 2- (N-ethyl-N-methylamino) ethyl N- (2,
3-dioleoyloxypropyl) carbamate, 2-ethylaminoethyl N- (2,3-dioleoyloxy)
Cypropyl) carbamate, 2- [N-methyl-N- (2-hydroxyethyl) amido
No] Ethyl N- (2,3-dioleoyloxypropyl)
Carbamate, 2- [N, N-di- (2-hydroxyethyl) amino] d
Cyl N- (2,3-dioleoyloxypropyl) carba
Mate, 2- [N- (2-diethylamino) ethyl-N-methyl
Amino] ethyl N- (2,3-dioleoyloxypropyl
L) carbamate, 2-piperidinoethyl N- (2,3-dioleoyloxy)
Propyl) carbamate, 2-pyrrolidinoethyl N- (2,3-dioleoyloxy)
Propyl) carbamate, 2-aminoethyl N- (2,3-dioleoyloxypro
Pill) carbamate, 2-dimethylaminoethyl N- (2,3-dioleoylo)
Xypropyl) thiocarbamate, 2-diethylaminoethyl N- (2,3-dioleoyloate)
Xypropyl) thiocarbamate, 2- [N, N-di- (2-hydroxyethyl) aminoethyl
] N- (2,3-dioleoyloxypropyl) thioca
Rubamate, 2-pyrrolidinoethyl N- (2,3-dioleoyloxy
Propyl) thiocarbamate, 2-dimethylaminoethyl N- (2,3-dioleoyloate)
Xypropyl) sulfamate, 2-diethylaminoethyl N- (2,3-dioleoyloate)
Xypropyl) sulfamate, 2- [N, N-di- (2-hydroxyethyl) aminoethyl
]] N- (2,3-dioleoyloxypropyl) sulf
Amate, 2-pyrrolidinoethyl N- (2,3-dioleoyloxy)
Propyl) sulfamate, N- (2,3-dioleoyloxy) propyl-4-dim
Tylaminobutyramide, N- (2,3-dioleoyloxy) propyl-4-die
N- (2,3-dioleoyloxy) propyl-4- [N, N
-Di- (2-hydroxyethyl) amino] butylamido
N- (2,3-dioleoyloxy) propyl-4-pyro
Lysinobutyramide, 2-dimethylaminoethyl N- (1,3-dilauryloxy
Cipropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dimyristylthio)
Xypropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dioleyloxy)
Cipropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dilinoleylio)
Xypropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1-lauryloxy-
3-linoleyloxypropan-2-yl) carbame
G, 2-dimethylaminoethyl N- (1-myristyloxy
-3-oleoyloxypropan-2-yl) carbame
2-dimethylaminoethyl N- (1-oleyloxy-
3-palmityloxypropan-2-yl) carbame
G, 3-dimethylaminopropyl N- (1,3-dioleio
Xipropan-2-yl) carbamate, 4-dimethylaminobutyl N- (1,3-dioleyloxy)
Cipropan-2-yl) carbamate, 2-diethylaminoethyl N- (1,3-dioleyloxy)
Cipropan-2-yl) carbamate, 2-di-n-propylaminoethyl N- (1,3-diole)
Yloxypropan-2-yl) carbamate, 2-di-n-butylaminoethyl N- (1,3-dioleoyl)
Ruoxypropan-2-yl) carbamate, 2- (N-ethyl-N-methylamino) ethyl N- (1,
3-dioleyloxypropan-2-yl) carbame
G, 2-methylaminoethyl N- (1,3-dioleyloxy
Propan-2-yl) carbamate, 2-ethylaminobutyl N- (1,3-dioleyloxy
Propan-2-yl) carbamate, 2-n-propylaminoethyl N- (1,3-dioleyl)
Oxypropan-2-yl) carbamate, 2-n-butylamino N- (1,3-dioleyloxy)
Lopan-2-yl) carbamate, 2- [N-methyl-N- (2-hydroxyethyl) amido
[No] ethyl N- (1,3-dioleyloxypropane-2)
-Yl) carbamate, 2- [N-ethyl-N- (2-hydroxyethyl) amido
[No] ethyl N- (1,3-dioleyloxypropane-2)
-Yl) carbamate, 2- [N, N-di- (2-hydroxyethyl) amino] e
Cyl N- (1,3-dioleyloxypropane-2-i
L) carbamate, 2- [N- (2-diethylamino] ethyl-N-methyl
Amino] ethyl N- (1,3-dioleyloxypropane
-2-yl) carbamate, 2- (4-methylpiperazino) ethyl N- (1,3-di
Railoxypropan-2-yl) carbamate, 2-piperidinoethyl N- (1,3-dioleyloxyprop)
Lopan-2-yl) carbamate, 2-pyrrolidinoethyl N- (1,3-dioleyloxy)
Lopan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dioleyloxy)
Cipropan-2-yl) thiocarbamate, 2-diethylaminoethyl N- (1,3-dioleyloxy)
Cipropan-2-yl) thiocarbamate, 2- [N, N-di- (2-hydroxyethyl) amino] e
Cyl N- (1,3-dioleyloxypropane-2-i
L) thiocarbamate, 2-pyrrolidinoethyl N- (1,3-dioleyloxyprop)
Lopan-2-yl) thiocarbamate, 2-dimethylaminoethyl N- (1,3-dioleyloxy)
Cipropan-2-yl) sulfamate, 2-diethylaminoethyl N- (1,3-dioleyloxy)
Cipropan-2-yl) sulfamate, 2- [N, N-di- (2-hydroxyethyl) amino] e
Cyl N- (1,3-dioleyloxypropane-2-i
Le) sulfamate, 2-pyrrolidinoethyl N- (1,3-dioleyloxy)
Lopan-2-yl) sulfamate, N- (4-dimethylaminobutanoyl) -1,3-diole
Yloxy-1-amino-propane, N- (4-diethylaminobutanoyl) -1,3-diole
Iloxy-1-amino-propane, N- [4- (N, N-di- (2-hydroxyethyl) amido
No) Butanoyl] -1,3-dioleyloxy-1-amido
No-propane, N-4-pyrrolidinobtanoyl-1,3-dioleyloxy
C-1-amino-propane, 2-dimethylaminoethyl N- (1,3-dilauroyl-
Xipropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dimyristoyl)
Oxypropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dipalmitoyl
Oxypropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dioleoyloxy)
Xypropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dilinolenylo)
Xypropan-2-yl) carbamate, 2-dimethylaminoethyl N- (1-oleoyloxy
-3-palmitoyloxypropan-2-yl) carba
Mate, 2-dimethylaminoethyl N- (1-linolenyloxy
-3-oleoyloxypropan-2-yl) carbame
2-diethylaminoethyl N- (1,3-dioleoyloate
Xipropan-2-yl) carbamate, 3-dimethylaminopropyl N- (1,3-dioleoyl)
Oxypropan-2-yl) carbamate, 2-diisopropylaminoethyl N- (1,3-dioleo)
Yloxypropan-2-yl) carbamate, 2-di-n-propylaminoethyl N- (1,3-diole)
Oiloxypropan-2-yl) carbamate, 2- (N-ethyl-N-methylamino) ethyl N- (1,
3-dioleoyloxypropan-2-yl) carbame
2-ethylaminoethyl N- (1,3-dioleoyloxy)
Cipropan-2-yl) carbamate, 2- [N-methyl-N- (2-hydroxyethyl) amido
No] ethyl N- (1,3-dioleoyloxypropane-
2-yl) carbamate, 2- [N, N-di- (2-hydroxyethyl) amino] e
Chill N- (1,3-dioleoyloxypropane-2-i
L) carbamate, 2- [N- (2-diethylamino) ethyl-N-methyl
Amino] ethyl N- (1,3-dioleoyloxypropa
N-2-yl) carbamate, 2-piperidinoethyl N- (1,3-dioleoyloxy)
Propan-2-yl) carbamate, 2-pyrrolidinoethyl N- (1,3-dioleoyloxy)
Propan-2-yl) carbamate, 2-aminoethyl N- (1,3-dioleoyloxypro
Pan-2-yl) carbamate, 2-dimethylaminoethyl N- (1,3-dioleoyloate)
Xipropan-2-yl) thiocarbamate, 2-diethylaminoethyl N- (1,3-dioleoylo)
Xypropan-2-yl) thiocarbamate, 2- [N, N-di- (2-hydroxyethyl) amino]
Chill N- (1,3-dioleoyloxypropane-2-i
Thiocarbamate, 2-pyrrolidinoethyl N- (1,3-dioleoyloxy)
Propan-2-yl) thiocarbamate, 2-dimethylaminoethyl N- (1,3-dioleoyloate)
Xypropan-2-yl) sulfamate, 2-diethylaminoethyl N- (1,3-dioleoylo)
Xypropan-2-yl) sulfamate, 2- [N, N-di- (2-hydroxyethyl) amino]
Chill N- (1,3-dioleoyloxypropane-2-i
Le) sulfamate, 2-pyrrolidinoethyl N- (1,3-dioleoyloxy)
Propan-2-yl) sulfamate, N- (2,3-dioleoyloxy) propyl-4-dim
Tylaminobutyramide, N- (2,3-dioleoyloxy) propyl-4-die
N- (2,3-dioleoyloxy) propyl-4- [N, N
-Di- (2-hydroxyethyl) amino] butylamido
N- (2,3-dioleoyloxy) propyl-4-pyro
Lysinobutyramide.

In the compound of the present invention, for example, 3-O- (4-dimethylaminobutanoyl) -1,2-O-dioleylglycerol, 3-O- (2-dimethylaminoethyl) carbamoyl-1,2-O-dioxide Rail glycerol, 3-O-
(2-Diethylaminoethyl) carbamoyl-1,2-O
-Dioleylglycerol, 2-O- (2-diethylaminoethyl) carbamoyl-1,3-O-dioleoylglycerol and the like are preferred. Particularly, 3-O- (2-diethylaminoethyl) carbamoyl-1,2-O-dioleylglycerol is preferred.

Another aspect of the gist of the present invention resides in a device itself having a function as a DDS comprising the compound of the present invention represented by the general formula [I] and a phospholipid.

In general, liposomes, fat emulsions, and the like are devices having a function as a DDS containing lipid as a component.
A device having an action as a DDS according to the present invention (hereinafter, referred to as “device of the present invention”) is one of them.

The device of the present invention may be in any form of a lipid suspension, a liposome, or another form as long as it has a property capable of inducing a substance having a biological activity described below into cells.

Examples of the phospholipid constituting the device of the present invention include, for example, phosphatidylethanolamine (phosphatidylethanolamine).
thanolamine, phosphatidylcholine
choline) and the like.

In the device of the present invention, the composition ratio of the compound of the present invention to the phospholipid is suitably from 0.1: 9.9 to 9.9: 0.1 (the compound of the present invention: phospholipid (molar ratio)), and from 1: 9 to 9: 1 (molar ratio). Invention compound: phospholipid (molar ratio)) is preferable, and 1: 3 to 3: 1 (the present compound: phospholipid (molar ratio)) is more preferable.

The device of the present invention can be prepared, for example, by the following method.

The device of the present invention can be prepared by simply adding water and mixing the compound of the present invention and a phospholipid. In addition, the device of the present invention dissolves the compound of the present invention and phospholipid in chloroform, then sufficiently removes chloroform while blowing nitrogen gas, and then adds water and sufficiently agitates, followed by sonication for several minutes. It can also be prepared.

Another aspect of the present invention is a pharmaceutical composition containing the device of the present invention and a substance having a physiological activity.

As described above, even if a substance has a high physiological activity outside the cell, a substance that has insufficient entry into the cell can exert its activity sufficiently unless the dose is increased. Can not. For this reason, many useful drugs are not yet in practical use. This is not only a great industrial loss, but also unfavorable for maintaining the health of the people.

However, even in a compartment having insufficient physiological activity to enter cells, if administered to a living body together with the device of the present invention, the entry of a substance having biological activity into cells is improved, and the activity is sufficiently improved. Can be demonstrated. This will substantially revive useful drugs that have been abandoned.

Therefore, it can be said that the pharmaceutical composition according to the present invention (hereinafter, referred to as “the composition of the present invention”) is extremely useful in industrial and national health.

The device of the present invention can also be applied to a substance having sufficient physiological activity to enter cells. Even if the substance has sufficient physiological activity to enter the cells, administration into the living body together with the device of the present invention can further enhance the entry into the cells, so that the dose can be reduced, As a result, side effects are reduced.

Examples of the substance having a physiological activity applicable to the device of the present invention include, for example, a water-soluble anionic compound, an antitumor agent,
Examples include antiviral agents and antibiotics. Specifically, antisense nucleic acid that forms a double stranded RNA and duplex or triplex is a nucleic acid compound, such as heparan sulfate or dextran sulfate is acidic sugar, cytokines, cyclic AMP, ATP and IP _3, etc. Messengers, penicillins and cephalosporins, vitamins such as vitamin C and retinol, and other known drugs with acidic groups, interferons (α, β, γ), interleukins (IL-1, IL- 2), colony stimulating factor (CSF),
Tumor necrosis factor (TNF), levamisole, pestatin, retinoic acid, 5-fluorouracil (5-FU),
Examples include cytosine arabinoside (Ara-C), adenine arabinoside (Ara-A), cisplatin (CDDP), cyclophosphamide, azidothymidine (AZT), and the like.

Examples of the double-stranded RNA include the following.

(1) Homopolymer / homopolymer complex base modification polyinosinic acid / polycytidylic acid.

Polyinosinic acid / poly (5-bromocytidylic acid).

Polyinosinic acid / poly (2-thiocytidylic acid).

Poly (7-deazainosinic acid) / polycytidylic acid.

Poly (7-deazainosinic acid) poly (5-brocytidylic acid).

Sugar-modified poly (2'-azidoinosinic acid) / polycytidylic acid.

Phosphate-modified polyinosinic acid / poly (cytidine-5'-thiophosphoric acid).

(2) Homopolymer / copolymer composite Polyinosinic acid / poly (cytidylic acid, uridine acid).

Polyinosinic acid / poly (cytidylic acid, 4-thiouridine acid).

(3) Complex of synthetic nucleic acid and polycation Polyinosinic acid / polycytidylic acid / poly-L-lysine.

(4) Others Polyinosinic acid / poly (1-vinylcytidylic acid).

Antisense nucleic acids include natural nucleic acids and derivatives thereof, for example, methylphosphonat.
e), a nucleic acid having phosphorothioate, phosphorodithioate, or the like as an internal bond, and a derivative thereof.

The ratio of the device of the present invention and the substance having a physiological activity is
A weight ratio of 1: 0.1 to 1:10 (the device of the present invention: a substance having a physiological activity) is preferred.

The composition of the present invention can be prepared by adding a substance having a physiological activity to the device of the present invention and stirring appropriately. In addition, it can be prepared by adding a substance having a physiological activity in the process of manufacturing the device of the present invention.

The composition of the present invention is desirably administered in a dosage unit form, and is administered to animals including humans by intravenous administration, intraarterial administration,
It can be administered orally, intra-tissuely, topically (such as transdermally) or rectally. In particular, intravenous administration, intraarterial administration, and local administration are preferred. It is needless to say that the composition is administered in dosage forms suitable for these administration methods, for example, various injections, oral preparations, inhalants, eye drops, ointments, suppositories and the like.

For example, the pharmaceutical dose of the composition of the present invention may be a drug,
It is desirable to prepare in consideration of the dosage form, patient condition such as age and weight, administration route, the nature and extent of the disease, etc.
Usually, the amount of the active ingredient of the present invention for an adult is in the range of 0.1 mg to 10 g / day / human, preferably 1 mg / day.
The range of mg to 500 mg / day / human is common. In some cases, lower doses may be sufficient, and conversely, higher doses may be required. 1 to several times a day or 1
It can be administered at intervals of up to several days.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to examples and the like.

Reference Example 1 Synthesis of 1,2-O-dioleylglycerol (1) 4.6 g (50 mmol) of glycerol was dissolved in 50 ml of pyridine, 13.9 g (50 mmol) of trityl chloride was added, and the mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with ether. The organic layer was washed with water, dried over magnesium sulfate, concentrated, and then the residue was purified by column chromatography (silica gel / chloroform-methanol) to obtain 9.5 g (59%) of 1-O-tritylglycerol.

(2) 3.2-g (10 mmol) of 1-O-tritylglycerol
Was dissolved in 120 ml of xylene, 3.36 g (30 mmol) of potassium t-butoxide was added under an argon atmosphere, and the mixture was stirred for 5 minutes.
l) of 30 ml of xylene solution was added dropwise under reduced pressure (20-30 mmH
g) The mixture was stirred at room temperature for 30 minutes and at 50 ° C for 1 hour. The reaction mixture was poured into ice water, extracted with ether, washed with water, dried, and concentrated,
The residue was purified by column chromatography (silica gel / n-hexane-ethyl acetate) to obtain 6.10 g (73%) of 1,2-O-dioleyl-3-O-tritylglycerol.

(3) 6.10 g (7.3 mmol) of 1,2-O-dioleyl-3-O-tritylglycerol was reacted with 50 ml of a 5% trichloroacetic acid / methylene chloride (w / v) solution at room temperature for 1 hour, and the organic layer was separated. After washing with a saturated aqueous solution of sodium hydrogencarbonate and water, drying, concentration and purification by column chromatography (silica gel / chloroform) gave 3.75 g (87%) of the title compound.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz, CH
₃ × 2), 1.14-1.44 (44H, m, CH ₂ × 22), 1.48-1.68 (4
H, m, OCH ₂ CH ₂ × 2, 1.90−2.10 (8H, m, CH = CHCH ₂ ×
4), 3.38-3.78 (9H, m, OCH ₂ × 4 and OCH), 5.26-5.45
(4H, m, CH = CH × 2) MS (FAB): 593 (M + H) ⁺ Reference Example 2 Synthesis of 2,3-dioleyloxypropylamine (1) 1.00 g of 1,2-O-dioleylglycerol ( 1.7mmo
l), lithium azide 0.83 g (17 mmol), triphenylphosphine 0.89 g (3.4 mmol), carbon tetrabromide 1.13 g (3.4 mmo
10 ml of N, N-dimethylformamide was added to the mixture obtained in l) at a stretch, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, the solvent was distilled off, and water was added to the residue, followed by ether extraction. The ether layer was washed with water, dried and concentrated, and the residue was purified by column chromatography (silica gel / n-hexane-ethyl acetate), and 1.03 g (100%) of 2,3-dioleyloxypropyl azide as an oil was obtained. Obtained.

IR (neat, cm ^-1 ): 2920, 2850, 2100 (2) Lithium aluminum hydride 75 mg (2 mmo
l) was suspended in 30 ml of tetrahydrofuran, and 1.03 g of 2,3-dioleyloxypropyl azide (1.7 m
mol) was added dropwise, and the mixture was stirred for 30 minutes, and further stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was poured into ice water, extracted with ether, washed with water, dried and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to give the title compound 0.98 (98%) as a colorless oil.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz, CH
₃ × 2), 1.17 to 1.45 (44H, m, CH ₂ × 22), 1.48 to 1.70 (4
H, m, OCH ₂ CH ₂ × 2, 1.90−2.14 (8H, m, CH = CHCH ₂ ×
4), 2.64-2.91 (2H, m , NCH 2), 3.30-3.78 (9H, m, OCH 2
× 3 and OCH), 5.25-5.46 (4H, m, CH = CH × 2) MS (FAB): 592 (M + H) ⁺ Reference Example 3 Synthesis of 1,3-O-dioleylglycerol (1) 1.00 g of glycerol (11 mmol) and imidazole 2.9
6 g (43 mmol) were dissolved in pyridine and azeotropically distilled off, and the obtained residue was dissolved in 15 ml of N, N-dimethylformamide. Under ice cooling, 3.60 g (24 mmol) of t-butyldimethylsilyl chloride was added to this solution, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the solvent was distilled off, methylene chloride was added to the residue, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate. The washed material was then dried and concentrated to give 3.45 g (99%) of 1,3-O-di- (t-butyldimethylsilyl) glycerol.

(2) After dissolving 3.45 g (11 mmol) of 1,3-O-di- (t-butyldimethylsilyl) glycerol in dioxane, 3.03 g (12 mmol) of pyridium p-toluenesulfonate was added. 16.5 ml of dihydrofuran (22
mmol) was added slowly, and the mixture was stirred for 1 hour, returned to room temperature, and reacted overnight. After completion of the reaction, the solvent was distilled off, the residue was treated with methylene chloride and a saturated aqueous solution of sodium hydrogen carbonate, the methylene chloride layer was washed with water, dried and concentrated to give 1,3-O-di-.
4.25 g (100%) of (t-butyldimethylsilyl) -2-O-tetrahydrofuranylglycerol were obtained.

(3) 1,3-O-di (t-butyldimethylsilyl) -2
-O-tetrahydrofuranyl glycerol 4.25 g (11 mmo
30 ml of tetra-n-butylammonium fluoride (1 mol / 1 in THF) was added dropwise to a solution of l) in 30 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 2 hours. After the reaction, concentrate.
The resulting residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 1.70 g (96%) of 2-O-tetrahydrofuranylglycerol.

(4) 2-O-tetrahydrofuranyl glycerol 854m
g (5.3 mmol) was dissolved in 30 ml of xylene, and under an argon atmosphere, 1.78 g (15.9 mmol) of potassium t-butoxide was added.
After stirring for 5 minutes, oleyl-p-toluenesulfonate 6.
10 ml of a xylene solution of 71 g (15.9 mmol) was added dropwise, and the mixture was stirred under reduced pressure (20 to 30 mmHg) at room temperature for 30 minutes and at 50 ° C. for 1 hour. The reaction mixture was poured into ice water, extracted with ether, washed with water, dried and concentrated, and the residue was purified by column chromatography (silica gel / chloroform) to give 1,3-
628 mg (18%) of O-dioleyl-2-O-tetrahydrofuranylglycerol were obtained as a yellow oil.

(5) 628 mg (0.95 mmol) of 1,3-O-dioleyl-2-O-tetrahydrorafnylglycerol was dissolved in 30 ml of tetrahydrofuran, 5 ml of 10% diluted hydrochloric acid was added, and the mixture was stirred overnight. After completion of the reaction, water was added to the reaction solution, neutralized with a saturated aqueous solution of sodium hydrogen carbonate, and extracted with ether. Then, after drying and concentration, the residue was subjected to column chromatography (silica gel / n-hexane-ethyl acetate) to obtain 321 mg (57%) of the title compound as a colorless oil.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz, CH
₃ × 2), 1.14-1.26 (44H, m, CH ₂ × 22), 1.49-1.68 (4
H, m, OCH ₂ CH ₂ × 2,1.98-2.13 (8H, m, CH = CHCH ₂ ×
4), 3.37−3.56 (8H, m, OCH ₂ × 4), 3.95 (1H, brs, OC
H), 5.27-5.46 (4H, m, CH = CH × 2) MS (FAB): 593 (M + H) ⁺ Reference Example 4 Synthesis of 1,3-dioleyloxy-2-propylamine (1) 1,3 -O-dioleyl glycerol 150mg (0.25mm
ol) was dissolved in 5 ml of pyridine, 77 mg (0.40 mmol) of p-toluenesulfonyl chloride was added, and the mixture was heated to 60 ° C. and stirred for 2 days. After completion of the reaction, the solvent was distilled off, and water was added to the residue.
Extracted with ether. After that, it was dried, concentrated and 1,3-O-
150 mg (80%) of dioleyl-2-O- (p-toluenesulfonyl) glycerol were obtained as a yellow oil.

(2) The obtained 1,3-O-dioleyl-2-O- (p-
A mixture of 150 mg (80%) of toluenesulfonyl) glycerol, 30 mg (0.6 mmol) of lithium azide, and 5 ml of N, N-dimethylformamide was stirred at 100 ° C. for 2 hours. After cooling the reaction, the solvent was distilled off, and water was added, followed by ether extraction. Then, it was washed with water, dried and concentrated to give 125 mg (99%) of 1,3-dioleyloxy-2-propylazide as a pale brown oil.

(3) Lithium aluminum hydride 8mg (0.2mmo
l) was suspended in 3 ml of tetrahydrofuran, and 125 mg of 1,3-dioleyloxy-2-propylazide was added thereto under ice-cooling.
(0.2 mmol) was added dropwise, and the mixture was stirred at 0 ° C. for 2 hours. After completion of the reaction, the reaction mixture was poured into ice water, extracted with ether, washed with water,
After drying, it was concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 104 mg (89%) of the title compound as a colorless oil.

Reference Example 5 Synthesis of 1,2-O-dioleoylglycerol (1) 1 g (0.011 mol) of glycerin was dissolved in pyridine,
Azeotropic distillation. The obtained residue was dissolved in 30 ml of pyridine,
4.05 g of dimethoxytrityl chloride (0.012mo
l) was added and the mixture was stirred at room temperature overnight. After completion of the reaction, 5 ml of methanol was added and the mixture was stirred for 30 minutes, and the solvent was distilled off under reduced pressure. Then, methylene chloride was added to the residue, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate, and then dried and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol, 0.1% pyridine) to obtain 2.58 g (60.2%) of 1-O-dimethoxytritylglycerol.

(2) 290 mg (0.735 mmol) of the obtained 1-O-dimethoxytritylglycerol was dissolved in pyridine and azeotropically distilled off. mmol) and reacted at 50 ° C. for 6 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, methylene chloride was added to the residue, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate, and then dried and concentrated. The residue was subjected to column chromatography (silica gel / n-hexane-methylene chloride) to obtain 519 mg (76.5%) of 1-O-dimethoxytrityl-2,3-O-dioleoylglycerol.

¹ H-NMR (60 MHz, CDCl ₃ ) δ: 0.88 (6H, m), 1.27 (40
H, brs.), 1.50-1.70 (4H, m,), 1.90-2.10 (8H, m), 3.
10−3.30 (2H, m), 3.79 (6H, s), 4.20−4.40 (2H, m),
5.10-5.50 (5H, m), 6.70-7.40 (13H, m) (3) 1-O-dimethoxytrityl-2,3-O obtained
218 mg (0.236 mmol) of dioleoylglycerol in 5%
It was dissolved in formic acid-methylene chloride solution (10 ml) and reacted for 10 minutes. After completion of the reaction, the reaction solution was neutralized by adding a saturated aqueous solution of sodium hydrogen carbonate, and the organic layer was further washed with a saturated aqueous solution of sodium hydrogen carbonate, and then dried and concentrated. The residue was subjected to column chromatography (silica gel / n-hexane-methylene chloride-methanol) to give 100 mg (68.0%) of the title compound.
I got

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (40H, brs.), 1.50-1.70 (4H, m), 1.90-2.10 (8
H, m), 2.28−2.40 (4H, m), 3.72 (2H, d, J = 6Hz), 4.10
−4.40 (2H, m), 5.00−5.12 (1H, m), 5.30−5.40 (4H,
m) MS (FAB): 621 (M + H) ⁺ Reference Example 6 Synthesis of 1,3-O-dioleoylglycerol (1) 2-O- (t-butyldimethylsilyl) glycerol 2.75 g (0.013 mol) was added to pyridine. Dissolve in 60 ml, add 8.82 g (0.028 mol) of oleoyl chloride under ice cooling, and add
Reaction was performed at 15 ° C. for 15 hours. After completion of the reaction, the solvent was distilled off, and methylene chloride was added to the residue.
2-O- (t-butyldimethylsilyl) glycerol was obtained.

(2) The obtained 1,3-O-dioleoyl-2-O- (t
-Butyldimethylsilyl) glycerol in 0.1M tetra-
266 ml of n-butylammonium fluoride-tetrahydrofuran solution was added and reacted at room temperature for 30 minutes.After the reaction was completed, the solvent was distilled off under reduced pressure, and methylene chloride was added to the residue.
After washing with water, it was dried and concentrated. The residue was subjected to column chromatography (silica gel / ethyl acetate-n-hexane) to give 3.97 g (48.0%; of 2-Ot-butyldimethylsilylglycerol) of the title compound.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (40H, brs.), 1.50-1.70 (4H, m), 1.90-2.10 (8
H, m), 2.34 (4H, t, J = 8Hz), 4.10−4.22 (5H, m), 5.30
-5.40 (4H, m) MS (FAB): 621 (M + H) ⁺ Reference Example 7 Synthesis of 1,3-O-dioleoyl-2-O- (2-bromoethyl) carbamoylglycerol (1) 1,3-O- Dioleoyl glycerol 230mg (0.37
mmol) was dissolved in pyridine and azeotropically distilled off. The obtained residue was dissolved in pyridine (5 ml), N, N'-carbonyldiimidazole (120 mg, 0.740 mmol) was added, the mixture was stirred at room temperature for 3 hours, the solvent was concentrated under reduced pressure, and the residue was dissolved in methylene chloride. After washing with a 5% aqueous sodium dihydrogen phosphate solution, the mixture was dried and concentrated. The residue was dissolved in N, N-dimethylformamide (10 ml), 2-aminoethanol (45 mg, 0.737 mmol) was added, and the mixture was stirred at room temperature overnight. After completion of the reaction, the solvent was distilled off.
The residue was dissolved in methylene chloride, washed with a 5% aqueous solution of sodium dihydrogen phosphate, and dried and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to give 1,3-O-dioleoyl-2-O- (2-
Hydroxyethyl) carbamoylglycerol 204mg (7
9.5%).

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (40H, brs.), 1.50-1.80 (4H, m), 1.90-2.10 (8
H, m), 2.34 (4H, t, J = 8Hz), 3.28-3.40 (2H, m), 3.64
−3.80 (2H, m), 4.20−4.40 (4H, m), 5.06−5.20 (2H, m
m), 5.30-5.50 (4H, m) MS (FAB): 690 (M-OH) ⁺ (2) 1,3-O-dioleoyl-2-O- (2
-Hydroxyethyl) carbamoylglycerol 160mg
(0.226 mmol), 150 mg (0.452 mmol) of carbon tetrabromide and 120 mg (0.458 mmol) of triphenylphosphine were added to a mixture of N,
10 ml of N-dimethylformamide was added all at once, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was distilled off, the residue was dissolved in methylene chloride, washed with water, and concentrated by drying. The residue was subjected to column chromatography (silica gel / ethyl acetate-n
-Hexane) to give 91 mg (52.2%) of the title compound.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.86 (6H, t, J = 6 Hz),
1.28 (40H, brs.), 1.50-1.70 (4H, m), 1.90-2.10 (8
H, m), 2.31 (4H, t, J = 8Hz), 3.40-3.52 (2H, m), 3.52
−3.70 (2H, m), 4.20−4.44 (4H, m), 5.06−5.20 (2H, m
m), 5.25-5.40 (4H, m) MS (FAB): 770 (M) ⁺ Example 1 Synthesis of 3-O- (2-dimethylaminoethyl) carbamoyl-1,2-O-dioleylglycerol 1, 2.00 g (3.4 mmol) of 2-O-dioleylglycerol
N, N'-carbonyldiimidazole in 25 ml of pyridine solution
After adding 0.66 g (4.1 mmol) and stirring at room temperature for 5 hours, the solvent was concentrated under reduced pressure, and the residue was dissolved in methylene chloride.
After washing with an aqueous solution of sodium dihydrogen phosphate, the solution was dried and concentrated. The residue was dissolved in N, N-dimethylformamide 20 ml,
595 mg (6.8 mmol) of N, N-dimethylethyldiamine was added, and the mixture was stirred overnight. After completion of the reaction, the solvent was distilled off, water was added to the residue, methylene chloride was extracted, washed with water, dried and concentrated. The residue was subjected to column chromatography (silica gel /
Chloroform-methanol) to give the title compound of the present invention.
2.18 g (91%) were obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 7 Hz, CH
₃ × 2), 1.16-1.44 (44H, m, CH ₂ × 22), 1.47-1.68 (4
H, m, OCH ₂ CH ₂ × 2,1.84-2.12 (8H, m, CH = CHCH ₂ ×
4), 2.20 (6H, s , N (CH 3) 2), 2.39 (2H, t, J = 6Hz, NCH 2),
3.18−3.31 (2H, m, CONHC H ₂ ), 3.36−3.64 (7H, m, OCH ₂
× 3 and OCH), 4.03-4.26 (2H, m, CH ₂ OCO), 5.22 (1H, b
rs, NHCO), 5.28-5.43 (4H, m, CH = CH × 2) MS (FAB): 707 (M + H) ⁺ Example 2 3-O- (2-methylaminoethyl) carbamoyl-1,2-O -Synthesis of dioleylglycerol The title compound of the present invention was obtained in the same manner as in Example 1 except that N-methylethylenediamine was used instead of N, N-dimethylethylenediamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.50-1.60 (4H, m), 1.90-2.10 (8H,
m), 2.43 (3H, s), 2.71 (2H, t, J = 6 Hz, 3.28 (2H, q, J = 6
Hz), 3.40-3.70 (7H, m), 4.05-4.26 (2H, m), 5.14 (1
H, brs), 5.30-5.44 (4H, m) MS (FAB): 693 (M + H) ⁺ Example 3 3-O- (2-aminoethyl) carbamoyl-
Synthesis of 1,2-O-dioleylglycerol Using a compound obtained in the same manner as in Example 1 except that N-tritylethylenediamine was used instead of N, N-dimethylethylenediamine, the compound obtained in 5% trichloroacetic acid / methylene chloride was used. After that, the title compound of the present invention was obtained by the same purification method.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.50-1.60 (4H, m), 1.90-2.10 (8H,
m), 3.10-3.20 (2H, m), 3.40-3.70 (9H, m), 4.04-4.
26 (2H, m), 5.30-5.45 (4H, m), 6.20 (1 H, brs) MS (FAB): 679 (M + H) ⁺ Example 4 3-O- (2-diethylaminoethyl) carbamoyl-1,2 Synthesis of —O-dioleylglycerol The title compound of the present invention was obtained in the same manner as in Example 1 except that N, N-dimethylethylenediamine was used instead of N, N-dimethylethylenediamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.87 (6H, t, J = 6 Hz),
1.01 (6H, t, J = 6Hz), 1.27 (44H, brs), 1.46-1.62 (4
H, m), 1.90−2.10 (8H, m), 2.48−2.62 (6H, m), 3.18−
3.30 (2H, m), 3.38-3.66 (7H, m), 4.04-4.24 (2H, m
m), 5.24-5.44 (5H, m) MS (FAB): 735 (M + H) ⁺ Example 5 Synthesis of 3-O- (4-dimethylaminobutyl) carbamoyl-1,2-O-dioleylglycerol N, Using 4-dimethylaminobutylamine instead of N-dimethylethylenediamine, the title compound of the present invention was obtained in the same manner as in Example 1.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.46-1.70 (8H, m), 1.90-2.10 (8H,
m), 2.39 (6H, s), 2.44-2.56 (2H, m), 3.10-3.24 (2
H, m), 3.36-3.70 (7H, m), 4.00-4.24 (2H, m), 5.18-
5.42 (5H, m) MS (FAB): 736 (M + H) ⁺ Example 6 Synthesis of 3-O- (2-dimethylaminoethyl) thiocarbamoyl-1,2-O-dioleylglycerol In Example 1, N, The title compound of the present invention was obtained in the same manner as in Example 1, except that N, N'-thiocarbonyldiimidazole was used instead of N'-carbonyldiimidazole.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.50-1.60 (4H, m), 1.90-2.10 (8H,
m), 2.21 (6H, d, J = 4 Hz), 2.36−2.54 (2H, m), 3.30−
3.80 (9H, m), 4.40-4.70 (2H, m), 5.26-5.45 (4H, m) MS (FAB): 723 (M + H) ⁺ Example 7 3-O- (4-dimethylaminobutanoyl)-
Synthesis of 1,2-O-dioleyl glycerol 120 mg (0.20 mmol) of 1,2-O-dioleyl glycerol was combined with 6 ml of methylene chloride-N, N-dimethylformamide (1: 2).
168mg of 4-dimethylaminobutyric acid / hydrochloride (1mm
ol), 206 mg (1 mmol) of N, N'-dicyclohexylcarbodiimide (DCC) and 25 mg (0.2 mmol) of 4-dimethylaminopyridine were added, and the mixture was reacted at room temperature overnight. After the precipitated urea was removed by filtration with a glass filter, the filtrate was concentrated to dryness under reduced pressure, subjected to a liquid separation treatment with methylene chloride-saturated sodium hydrogen carbonate solution, and the methylene chloride layer was dried over sodium sulfate.
Thereafter, the solvent was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 123 mg (87%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.20-1.40 (44H, m), 1.45-1.60 (4H, m), 1.70-1.90
(2H, m), 1.90-2.10 (8H, m), 2.22 (6H, s), 2.30 (2H, m
t, J = 8Hz), 2.36 (2H, t, J = 8Hz), 3.38-3.85 (7H, m),
4.04-4.30 (2H, m), 5.30-5.45 (4H, m) MS (FAB): 706 (M + H) ⁺ Example 8 3-O- (N, N-dimethylaminoacetyl) -1,
Synthesis of 2-O-dioleylglycerol N, N-dimethylglycine 572 mg (5.547 mmol) was suspended in a mixed solvent of N, N-dimethylformamide 22 ml and methylene chloride 11 ml, and N, N′-dicyclohexylcarbodiimide (DC
C) 1736 mg (8.414 mmol) was added, and the mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was dissolved in 12 ml of a pyridine solution of 327 mg (0.551 mmol) of 1,2-O-dioleylglycerol, and N, N'-dicyclohexylcarbodiimide (DC
C) 80 mg (0.388 mmol) was added and reacted at 50 ° C. overnight.
After completion of the reaction, the solvent was distilled off, the residue was dissolved in methylene chloride, washed with a saturated aqueous solution of sodium hydrogen carbonate, and dried.
Concentrated. The residue was subjected to column chromatography (silica gel / ethyl acetate-n-hexane) to obtain 251 mg (67.2%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.36 (6H, s), 3.23 (2H, s), 3.40-3.70 (7H, m),
4.00-4.20 (2H, m), 5.20-5.40 (4H, m) MS (FAB): 678 (M + H) ⁺ Example 9 3-O- (4-diethylaminobutanoyl)-
Synthesis of 1,2-O-dioleylglycerol (1) 300 mg (0.51 mm) of 1,2-O-dioleylglycerol
ol) was dissolved in 5 ml of anhydrous pyridine, and 188 mg (1.01 mmol) of 4-bromobutyryl chloride was added under ice cooling. After the temperature was raised to room temperature, the reaction was performed at 50 ° C. for 1 hour. After the solvent was distilled off, the mixture was separated with a methylene chloride-saturated sodium hydrogen carbonate solution, dried over sodium sulfate, and the solvent was distilled off under reduced pressure and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to give the bromo compound 15
9 mg (42%) were obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.27 (44H, brs), 1.50-1.70 (4H, m), 1.90-2.20 (10
H, m), 2.53 (2H, t, J = 8Hz), 3.40-3.70 (9H, m), 4.05
-4.30 (2H, m), 5.25-5.45 (4H, m) (2) Dissolve 130 mg (0.18 mmol) of the above bromo compound in 6 ml of N, N-dimethylformamide-isopropyl alcohol-chloroform (1: 1: 1). , Diethylamine 1 ml, N, N-diisopropylethylamine 70 mg (0.54 mmol)
After heating at 20 ° C. for 20 hours, the reaction was further carried out at 80 ° C. for 6 hours. After evaporating the solvent under reduced pressure, the residue was separated with methylene chloride-water, the methylene chloride layer was dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to give the title compound 63.
mg (50%) was obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.04 (6H, t, J = 6Hz), 1.27 (44H, brs), 1.50-1.70 (4
H, m), 1.80 (2H, m), 1.90-2.10 (8H, m), 2.37 (2H, t, J
= 6Hz), 2.44-2.70 (6H, m), 3.40-3.70 (7H, m), 4.05
-4.30 (2H, m), 5.30-5.45 (4H, m) MS (FAB): 734 (M + H) ⁺ Example 10 N- (2,3-dioleyloxy) propyl-4
-Synthesis of dimethylaminobutyramide 2,3-dioleyloxypropylamine 100mg (0.17mm
ol) in 3 ml of anhydrous N, N-dimethylformamide,
-Dimethylaminobutyric acid / hydrochloride 71 mg (0.42 mmol), N, N '
-Dicyclohexylcarbodiimide (DCC) 105 mg (0.51
mmol), 4.1 mg of 4-dimethylaminopyridine (0.034 mmo
l) was added and reacted at room temperature overnight. After the reaction, Example 6
Post-treatment was conducted in the same manner as in the above to give 115 mg (96%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.20-1.40 (44H, m), 1.50-1.60 (4H, m), 1.70-1.90
(2H, m), 1.90-2.10 (8H, m), 2.23 (6H, s), 2.24 (2H,
t, J = 8Hz), 2.34 (2H, t, J = 8Hz), 3.20-3.60 (9H, m),
5.30-5.42 (4H, m) MS (FAB): 705 (M + H) ⁺ Example 11 Synthesis of 3-O- (2-dimethylaminoethyl) sulfamoyl-1,2-O-dioleylglycerol 1,2-O -Dioleyl glycerol 150 mg (0.25 mmol)
Was dissolved in 4 ml of methylene chloride-pyridine (2: 1), and (2-
Dimethylaminoethyl) sulfamoyl chloride 150m
g (0.75 mmol) in 1 ml of methylene chloride solution,
The reaction was performed for 2 hours. After the reaction, the solvent was distilled off under reduced pressure, liquid separation was performed with methylene chloride-saturated sodium hydrogen carbonate solution, the methylene chloride layer was dried over sodium sulfate, and then distilled off under reduced pressure.
The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to give the title compound (34 mg).
(18%).

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.20-1.40 (44H, m), 1.45-1.65 (4H, m), 1.90-2.10
(8H, m), 2.24 (6H, s), 2.48 (2H, t, J = 6Hz), 3.18 (2
H, t, J = 6Hz), 3.40-3.60 (6H, m), 3.60-3.75 (1H,
m), 4.08-4.30 (2H, m), 5.30-5.40 (4H, m) MS (FAB): 743 (M + H) ⁺ Example 12 2-dimethylaminoethyl N- (2,3-dioleyloxypropyl) Synthesis of carbamate 45 mg (0.5 mmol) of 2-dimethylaminoethanol was dissolved in 2 ml of pyridine, and N, N′-carbonyldiimidazole 9
7 mg (0.6 mmol) was added, and the mixture was stirred for 4 hours. 2,
355 mg (0.6 mmol) of 3-dioleyloxypropylamine
Was added dropwise, followed by stirring overnight. After completion of the reaction, the solvent is distilled off.
The residue was dissolved in methylene chloride, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried, and concentrated. The residue was purified by column chromatography (silica gel / methylene chloride-methanol) to obtain 383 mg (100%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.87 (6H, t, J = 6 Hz, CH
₃ × 2), 1.12-1.44 (44H, m, CH ₂ × 22), 1.46-1.64 (4
H, m, OCH ₂ CH ₂ × 2,1.88−2.12 (8H, m, CH = CHCH ₂ ×
4), 2.37 (6H, s, N (CH ₃ ) ₂ ), 2.54 (2H, t, J = 6Hz, NC
_{H 2), 3.32-3.64 (9H,} m, OCH 2 × 3, OCH and NHCH 2), 4.16
(2H, t, J = 6Hz, COOCH ₂ ), 5.17 (1H, brs, NHCO), 5.26-
5.46 (4H, m, CH = CH × 2) MS (FAB): 707 (M + H) ⁺ Example 13 Synthesis of 2-O- (2-dimethylaminoethyl) carbamoyl-1,3-O-dioleylglycerol 1 , 3-O-dioleylglycerol 150mg (0.253mmo
l) N, N'-carbonyldiimidazole 82 mg (0.51 mmol) was added to 2 ml of the pyridine solution of l), and the mixture was stirred at room temperature for 5 hours.
The solvent was concentrated under reduced pressure, and the residue was dissolved in methylene chloride.
After washing with a 5% aqueous solution of sodium dihydrogen phosphate, the solution was dried and concentrated. The residue was dissolved in 1.6 ml of N, N-dimethylformamide, and 45 mg (0.51 mmol) of N, N-dimethylethylenediamine
Was added and stirred overnight. After completion of the reaction, the solvent was distilled off, water was added to the residue, methylene chloride was extracted, washed with water, dried and concentrated. The residue was subjected to column chromatography (silica gel / chloroform-methanol) to obtain 179 mg (100%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.50-1.65 (4H, m), 1.90-2.10 (8H,
m), 2.20 (6H, s,), 2.39 (2H, t, J = 6 Hz), 3.20-3.30
(2H, m), 3.34-3.55 (4H, m), 3.55-3.70 (4H, d, J = 4H
z), 4.99 (1H, t, J = 4 Hz), 5.25-5.46 (5H, m) MS (FAB): 707 (M + H) ⁺ Example 14 2-dimethylaminoethyl N- (1,3-dioleyloxy) Synthesis of propan-2-yl) carbamate The title compound of the present invention was obtained in the same manner as in Example 12 using 1,3-dioleyloxy-2-propylamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (44H, brs), 1.50-1.60 (4H, m), 1.90-2.10 (8H,
m), 2.28 (6H, s), 2.54 (2H, t, J = 6 Hz), 3.40-3.55 (8
H, m), 3.80-3.90 (1H, m), 4.15 (2H, t, J = 6Hz), 5.10.
-5.20 (1H, m), 5.20-5.45 (4H, m) MS (FAB): 707 (M + H) ⁺ Example 15 3-O- (2-dimethylaminoethyl) carbamoyl-1,2-O-diole Synthesis of Oil Glycerol Using 1,2-O-dioleoylglycerol, the title compound of the present invention was obtained in the same manner as in Example 1.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.22 (6H, s), 2.24-2.40 (4H, m), 2.41 (2H, t, J =
6Hz), 3.20-3.30 (2H, m), 4.10-4.15 (4H, m), 5.20-
5.30 (2H, m), 5.30-5.45 (4H, m) MS (FAB): 735 (M + H) ⁺ Example 16 2-O- (2-dimethylaminoethyl) carbamoyl-1,3-O-dioleoyl Example 1 Synthesis of Glycerol Using 1,3-O-dioleoylglycerol, Example 1
The title compound of the present invention was obtained in the same manner as in 3.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.26 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.22 (6H, s), 2.32 (4H, t, J = 8Hz), 2.42 (2H, t, J
= 6Hz), 3.20-3.30 (2H, m), 4.12-4.25 (4H, m), 5.15
(1H, t, J = 6Hz), 5.20-5.45 (5H, m) MS (FAB): 735 (M + H) ⁺ Example 17 2-dimethylaminoethyl N- (2,3-dioleoyloxypropyl) carbamate Synthesis of 2-dimethylaminoethanol 500 mg (5.61 mmol) was dissolved in anhydrous pyridine 30 ml, N, N, -carbonyldiimidazole (1.91 g, 11.8 mmol) was added, and the mixture was reacted at room temperature for 5 hours. After completion of the reaction, 1.97 mg (2.16 mmol) of 3-amino-1,2-propanediol was added to the reaction solution, and the mixture was reacted at room temperature overnight. Then, pyridine was distilled off under reduced pressure, and the carbamate compound as a crude product was dissolved again in anhydrous pyridine. After adding 5.22 g (17.4 mmol) of oleoyl chloride under ice-cooling, the mixture was reacted at 50 ° C. for 14 hours. Then, pyridine was distilled off under reduced pressure, the residue was dissolved in methylene chloride, washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over sodium methylene chloride and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 250 mg (16%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.25 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.28 (6H, s), 2.30 (4H, t, J = 8Hz), 2.57 (2H, t, J
= 6Hz), 3.30-3.50 (2H, m), 4.06-4.30 (4H, m), 5.04
-5.15 (2H, m), 5.25-5.40 (4H, m) MS (FAB): 735 (M + H) ⁺ Example 18 2-dimethylaminoethyl N- (1,3-dioleoyloxypropan-2-yl) ) Synthesis of carbamate In Example 17, 372 mg of the title compound was used in the same manner as in Example 17 except that 3-amino-1,2-propanediol was used instead of 3-amino-1,2-propanediol.
(2.2 mmol) was obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.87 (6H, t, J = 7 Hz),
1.20-1.40 (40H, m), 1.50-1.70 (4H, m), 1.90-2.10
(8H, m), 2.30 (6H, s), 2.32 (4H, t, J = 8Hz), 2.59 (2
H, t, J = 6Hz), 4.00-4.25 (7H, m), 5.10-5.20 (1H,
m), 5.30-5.45 (4H, m) MS (FAB): 735 (M + H) ⁺ Example 19 Synthesis of 2-O- (2-piperidinoethyl) carbamoyl-1,3-O-dioleoylglycerol 1,3 The title compound of the present invention was obtained in the same manner as in Example 13 using -O-dioleoylglycerol and 1- (2-aminoethyl) piperidine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (40H, brs), 1.44-1.54 (2H, m), 1.54-1.76 (8H,
m), 1.90−2.10 (8H, m), 2.32 (4H, t, J = 8Hz), 2.39−
2.56 (6H, m), 3.20-3.40 (2H, m), 4.12-4.40 (4H,
m), 5.08-5.24 (1H, m), 5.24-5.52 (5H, m) MS (FAB): 773 (M + H) ⁺ Example 20 2-O- (2-diethylaminoethyl) carbamoyl-1,3-O -Synthesis of dioleoyl glycerol The title compound of the present invention was obtained in the same manner as in Example 13 using 1,3-O-dioleoyl glycerol and N, N-diethylethylenediamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.02 (6H, t, 6Hz), 1.28 (40H, brs), 1.50-1.70 (4H,
m), 1.90−2.10 (8H, m), 2.32 (4H, t, J = 8Hz), 2.44−
2.66 (6H, m), 3.16-3.32 (2H, m), 4.22-4.38 (4H, m
m), 5.08-5.22 (1H, m), 5.26-5.52 (5H, m) MS (FAB): 763 (M + H) ⁺ Example 21 2-O- (2-diisopropylaminoethyl)
Synthesis of carbamoyl-1,3-O-dioleoylglycerol Using 1,3-O-dioleoylglycerol and N, N-diisopropylethylenediamine, the title compound of the present invention was obtained in the same manner as in Example 13.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.00 (12H, t, 6Hz), 1.27 (40H, brs), 1.50-1.70 (4H,
m), 1.90−2.10 (8H, m), 2.30 (4H, t, J = 8Hz), 2.48−
2.64 (2H, m), 2.88−3.20 (4H, m), 4.10−4.32 (4H, m
m), 5.06-5.28 (2H, m), 5.30-5.42 (4H, m) MS (FAB): 791 (M + H) ⁺ Example 22 2-O- (2-pyrrolidinoethyl) carbamoyl-1,3- Synthesis of O-dioleoylglycerol The title compound of the present invention was obtained in the same manner as in Example 13 using 1,3-O-dioleoylglycerol and 1- (2-aminoethyl) pyrrolidine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.27 (40H, brs), 1.50-1.70 (4H, m), 1.74-1.88 (4H,
m), 1.90−2.10 (8H, m), 2.30 (4H, t, J = 8Hz), 2.44−
2.70 (6H, m), 3.20-3.40 (2H, m), 4.20-4.42 (4H,
m), 5.08-5.22 (1H, m), 5.24-5.46 (5H, m) MS (FAB): 761 (M + H) ⁺ Example 23 2-O- (2-morpholinoethyl) carbamoyl-1,3-O -Synthesis of dioleoylglycerol The title compound of the present invention was obtained in the same manner as in Example 13 using 1,3-O-dioleoylglycerol and 4- (2-aminoethyl) morpholine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.27 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.31 (4H, t, J = 8 Hz), 2.40-2.54 (6H, m), 3.20-
3.40 (2H, m), 3.70 (4H, t, J = 6Hz), 4.12-4.38 (4H, m
m), 5.08-5.20 (2H, m), 5.20-5.46 (4H, m) MS (FAB): 777 (M + H) ⁺ Example 24 2-O- (3-diethylaminopropyl) carbamoyl-1,3-O -Synthesis of dioleoylglycerol The title compound of the present invention was obtained in the same manner as in Example 13 using 1,3-O-dioleoylglycerol and 3-diethylaminopropylamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.03 (6H, t, 6Hz), 1.28 (40H, brs), 1.50-1.70 (4H,
m), 1.90−2.10 (8H, m), 2.30 (4H, t, J = 8Hz), 2.46−
2.58 (6H, m), 3.20-3.32 (2H, m), 4.10-4.34 (4H, m
m), 5.10-5.20 (1H, m), 5.30-5.42 (4H, m), 6.18-6.
30 (1H, brs) MS (FAB): 777 (M + H) ⁺ Example 25 2-O- [2- (N-methyl-N- (2-hydroxyethyl) amino) ethyl] carbamoyl-1,3-
Synthesis of O-dioleoylglycerol 173 mg (0.224 mmol) of 1,3-O-dioleoyl-2-O- (2-bromoethyl) carbamoylglycerol was dissolved in 10 ml of chloroform, and 543 mg (7.228 mmol) of 2- (methylamino) ethanol was dissolved. ) And diisopropylethylamine
27 mg (0.209 mmol) was added, and the mixture was refluxed at 80 ° C. overnight. After completion of the reaction, the reaction solution was washed with a 5% aqueous solution of sodium dihydrogen phosphate, dried and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 128 mg (74.3%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.86 (6H, t, J = 6 Hz),
1.27 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.26-2.38 (7H, m), 2.50-2.70 (4H, m), 3.20-3.
40 (2H, m), 3.61 (4H, t, J = 6Hz), 4.20-4.44 (4H, m),
5.06-5.20 (2H, m), 5.30-5.45 (4H, m) MS (FAB): 765 (M + H) ⁺ Example 26 2-O- [2- (N-ethyl-N- (2-hydroxyethyl) Amino) ethyl] carbamoyl-1,3-
Synthesis of O-dioleoylglycerol The title compound of the present invention was obtained in the same manner as in Example 25 using 2- (ethylamino) ethanol.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.03 (3H, t, 6Hz), 1.28 (40H, brs), 1.50-1.70 (4H,
m), 1.90−2.10 (8H, m), 2.32 (4H, t, J = 8Hz), 2.54−
2.68 (6H, m), 3.20-3.30 (2H, m), 3.56 (2H, t, J = 6H
z), 4.12-4.34 (4H, m), 5.06-5.20 (2H, m), 5.30-5.
44 (4H, m) MS (FAB): 779 (M + H) ⁺ Example 27 2-O- [2- (N, N-di- (2-hydroxyethyl) amino) ethyl] carbamoyl-1,3-O -Synthesis of dioleoyl glycerol The title compound of the present invention was obtained in the same manner as in Example 25 using diethanolamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.28 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.32 (4H, t, J = 8 Hz), 2.60-2.70 (6H, m), 3.20-
3.30 (2H, m), 3.60 (4H, t, J = 6Hz), 4.12-4.40 (4H, m
m), 5.08-5.20 (1H, m), 5.30-5.42 (4H, m), 5.60-5.
70 (1H, brs) MS (FAB): 795 (M + H) ⁺ Example 28 2-O- [2- (N-methyl-NN-butylamino) ethyl] carbamoyl-1,3-O-diole Synthesis of oil glycerol The title compound of the present invention was obtained in the same manner as in Example 25 using N-methylbutylamine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.82-0.96 (9H, m),
1.10-1.50 (42H, m), 1.50-1.75 (6H, m), 1.90-2.10
(8H, m), 2.19 (3H, s), 2.26-2.40 (6H, m), 2.46 (2H,
m), 3.20-3.30 (2H, m), 4.10-4.30 (4H, m), 5.08-5.
20 (1H, m), 5.25-5.40 (4H, m) MS (FAB): 777 (M + H) ⁺ Example 29 2-O- [2- (4- (2-hydroxyethyl) piperazino) ethyl] carbamoyl- Synthesis of 1,3-O-dioleoylglycerol The title compound of the present invention was obtained in the same manner as in Example 25 using 1- (2-hydroxyethyl) piperazine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (3H, t, J = 6 Hz),
1.28 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.32 (4H, t, J = 8 Hz), 2.40-2.60 (12H, m), 3.18-
3.32 (2H, m), 3.62 (2H, t, J = 6Hz), 4.12-4.32 (4H, m
m), 5.08-5.24 (2H, m), 5.30-5.40 (4H, m) MS (FAB): 820 (M + H) ⁺ Example 30 2-O- [2- (N, N, N ', N') Synthesis of [tetramethylguanidino) ethyl] carbamoyl-1,3-O-dioleoylglycerol Example 2 using N, N, N ′, N′-tetramethylguanidine
In the same manner as in 5, the title compound of the present invention was obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (3H, t, J = 6 Hz),
1.27 (40H, brs), 1.50-1.70 (4H, m), 1.90-2.10 (8H,
m), 2.30 (4H, t, J = 8 Hz), 2.96 (3H, s), 3.10 (3H, s),
3.35−3.40 (2H, m), 3.60−3.70 (2H, m), 4.04−4.34
(4H, m), 4.98-5.08 (1H, m), 5.30-5.40 (4H, m), 6.3
0-6.40 (1H, m) MS (FAB): 805 (M + H) ⁺ Example 31 2-O- [2- (N- (2-diethylamino)
Ethyl-N-methylamino) ethyl] carbamoyl-1,
Synthesis of 3-O-dioleoylglycerol Using N, N-diethyl-N′-methylethylenediamine, the title compound of the present invention was obtained in the same manner as in Example 25.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.04 (6H, t, J = 6Hz), 1.26 (40H, brs), 1.50-1.70 (4
H, m), 1.90−2.10 (8H, m), 2.26−2.36 (7H, m), 2.44−
2.64 (10H, m), 3.15-3.25 (2H, m), 4.16-4.26 (4H,
m), 5.08-5.18 (1H, m), 5.30-5.40 (4H, m), 6.46-6.
60 (1H, brs) MS (FAB): 820 (M + H) ⁺ Example 32 Synthesis of 2-O- [2- (4-ethylpiperazino) ethyl] carbamoyl-1,3-O-dioleoylglycerol 1-ethyl The title compound of the present invention was obtained in the same manner as in Example 25 using piperazine.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.10 (3H, t, J = 6Hz), 1.26 (40H, brs), 1.50-1.70 (4
H, m), 1.90-2.10 (8H, m), 2.32 (4H, t, J = 8Hz), 2.38
−2.60 (12H, m), 3.22−3.34 (2H, m), 4.12−4.34 (4H,
m), 5.10-5.30 (2H, m), 5.30-5.42 (4H, m) MS (FAB): 802 (M + H) ⁺ Example 33 2-O- [2- (N-ethyl-N-methylamino) Synthesis of ethyl] carbamoyl-1,3-O-dioleoylglycerol 131 mg (0.170 mmol) of 1,3-O-dioleoyl-2-O- (2-bromoethyl) carbamoylglycerol was dissolved in 3 ml of chloroform, and N-ethyl was dissolved. Methylamine 470mg
(7.951 mmol) was added thereto, and the tube was sealed at 80 ° C. overnight. After completion of the reaction, the reaction solution was washed with a 5% aqueous solution of sodium dihydrogen phosphate, dried and concentrated. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 104 mg (81.5%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.04 (3H, t, 6Hz), 1.26 (40H, brs), 1.50-1.70 (4H,
m), 1.90−2.10 (8H, m), 2.20 (3H, s), 2.32 (4H, t, J =
8Hz), 2.38−2.52 (4H, m), 3.20−3.30 (2H, m), 4.12−
4.32 (4H, m), 5.10-5.20 (1H, m), 5.25-5.42 (5H, m) MS (FAB): 749 (M + H) ⁺ Example 34 2-O- (2-diethylaminoethyl) carbamoyl-1 Synthesis of 1,3-O-dipalmitoylglycerol Using 1,3-O-dipalmitoylglycerol and N, N-diethylethylenediamine, the title compound of the present invention was obtained in the same manner as in Example 13.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.87 (6H, t, J = 6 Hz),
1.00 (6H, t, J = 6Hz), 1.25 (48H, brs), 1.50-1.70 (4
H, m), 2.30 (4H, t, J = 8Hz), 2.46-2.60 (6H, m), 3.10
−3.30 (2H, m), 4.12−4.32 (4H, m), 5.10−5.20 (1H,
m), 5.20-5.35 (1H, m) MS (FAB): 711 (M + H) ⁺ Example 35 Synthesis of 2-diethylaminoethyl N- (1,3-dioleoyloxypropan-2-yl) carbamate 2- After dissolving 470 mg (4 mmol) of diethylaminoethanol in methylene chloride and adding 633 mg (8 mmol) of pyridine, 690 mg (4.4 mmol) of phenyl chloroformate was added under ice cooling.
l) was added and reacted at room temperature for 2 hours. After the reaction,
The solvent was distilled off under reduced pressure, and the mixture was separated with ethyl acetate-1% sodium hydrogen carbonate solution. The ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure to obtain 705 mg (74%) of a crude carbonate. This crude carbonate is dissolved in anhydrous pyridine,
134 mg (1.47 mmol) of -amino-1,3-propanediol was added and reacted at 80 ° C overnight. Further, 973 mg (3.2 mmol) of oleoyl chloride was added and reacted at room temperature for 24 hours. After completion of the reaction, the solvent was concentrated under reduced pressure, separated with methylene chloride-saturated sodium hydrogen carbonate solution, and dried over sodium sulfate. Then, the solvent was concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 250 mg (22%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.87 (6H, t, J = 6 Hz),
1.04 (6H, t, 6Hz), 1.28 (40H, brs), 1.50-1.70 (4H,
m), 1.90−2.10 (8H, m), 2.30 (4H, t, J = 8Hz), 2.50−
2.70 (6H, m), 4.00-4.30 (7H, m), 5.05-5.20 (1H,
m), 5.25-5.45 (4H, m) MS (FAB): 763 (M + H) ⁺ Example 36 2-O- (3-diethylaminopropionyl)
Synthesis of 1,3-O-dioleoylglycerol 1,3-dioleoylglycerol 172 mg (0.277 mmol)
Was dissolved in a mixed solvent of 3 ml of N, N-dimethylformamide and 6 ml of methylene chloride, and 101 mg (0.556 mmol) of N, N-diethyl-β-alanine (hydrochloride) and 114 mg (0.553 mmol) of N, N-dicyclohexylcarbodiimide were added. 7 mg (0.057 mmol) of 4-dimethylaminopyridine was added, and the mixture was stirred at room temperature overnight. After completion of the reaction, the reaction solution was filtered, the filtrate was concentrated under reduced pressure, methylene chloride was added to the residue, and the mixture was washed with water. After washing and concentration, the washed product was subjected to column chromatography (silica gel / methylene chloride-methanol) to obtain 129 mg (62%) of the title compound of the present invention.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
1.20-1.40 (46H, m), 1.50-1.70 (4H, m), 1.90-2.10
(8H, m), 2.32 (4H, t, J = 8Hz), 2.76-2.84 (6H, m), 3.
04−3.14 (2H, m), 4.08−4.42 (4H, m), 5.18−5.30 (1
H, m) .5.30-5.44 (4H, m) MS (FAB): 748 (M + H) ⁺ Example 37 O- (2-dimethylaminoethyl), O '-(1,3
Synthesis of -dioleoyloxypropyl) methylphosphonate After drying azeotropically with 310 mg (0.50 mmol) of 1,3-dioleoylglycerol in pyridine, 0.11M methyl-bis-O, O- (1-
Benzotriazolyl) phosphonate in dioxane 9.
1 ml (1 mmol) was added and reacted at room temperature for 3 hours. After completion of the reaction, 446 mg of 2-dimethylaminoethanol (5 mg
mmol) and 411 mg (5 mmol) of 1-methylimidazole were added, and further reacted at room temperature overnight. Then, after liquid separation with a methylene chloride-5% sodium dihydrogen phosphate solution, the methylene chloride layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel / methylene chloride-methanol) to give 272 mg (59 mg) of the title compound.
%).

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.86 (6H, t, J = 6 Hz),
1.25 (40H, brs), 1.54 (3H, d, J = 20Hz), 1.50-1.70 (4
H, m), 2.32 (4H, t, J = 8Hz), 2.35 (6H, s), 2.68 (2H, t,
J = 6Hz), 4.05-4.25 (4H, m), 4.25-4.35 (2H, m), 4.7
0-4.90 (1H, m), 5.25-5.40 (4H, m) MS (FAB): 770 (M + H) ⁺ Example 38 O- (2-aminoethyl) -O '-(1,3-dioleoyl) Synthesis of oxypropyl) methylphosphonate A compound obtained in the same manner as in Example 37 using t-butyl N- (2-hydroxyethyl) carbamate instead of 2-dimethylaminoethanol was converted to trifluoroacetic acid / methylene chloride (1: The title compound was obtained by treating with 2).

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.88 (6H, t, J = 6 Hz),
2.25 (40H, brs), 1.50-1.90 (7H, m), 1.90-2.10 (8H,
m), 2.34 (4H, t, J = 8 Hz), 3.30-3.40 (2H, s), 4.10-
4.50 (6H, m), 4.75-4.90 (1H, m), 5.30-5.40 (4H, m) MS (FAB): 742 (M + H) ⁺ Example 39 O- (2-diethylaminoethyl) -O '-( 1,
Synthesis of 3-dioleoyloxypropyl) methylphosphonate Using 2-diethylaminoethanol, 166 mg (70.7%) of the title compound of the present invention was obtained in the same manner as in Example 37.

¹ H-NMR (200 MHz, CDCl ₃ ) δ: 0.87 (6H, t, J = 6 Hz),
1.01 (6H, t, J = 6Hz), 1.26 (40H, brs), 1.48-1.70 (7
H, m), 1.90-2.10 (8H, m), 2.32 (4H, t, J = 8Hz), 2.57
(4H, q, J = 6Hz), 2.80 (2H, t, J = 6Hz), 3.90−4.40 (6
H, m), 4.70-4.90 (1H, m), 5.30-5.42 (4H, m) MS (FAB): 798 (M + H) ⁺ Example 40 5 mg of the compound of the present invention according to Example 4 and 5 mg of yolk phosphatidylethanolamine Was dissolved in 200 μl of chloroform in a vial, and nitrogen gas was blown on the solution to remove the chloroform, thereby forming a thin film on the wall surface of the vial.
This was further allowed to stand under reduced pressure overnight, and then 2 ml of sterile distilled water was added thereto and stirred with a vortex mixer to peel off the thin film.
The inside of the vial is replaced with nitrogen gas, and then sealed.
After standing for a while, the device of the present invention was prepared by sonication for 10 minutes using a bath sonicator.

Example 41 Using the compound of the present invention according to Example 7, a device of the present invention was prepared in the same manner as in Example 40.

Example 42 Using the compound of the present invention according to Example 20, a device of the present invention was prepared in the same manner as in Example 40.

Example 43 A device of the present invention was prepared in the same manner as in Example 40, except that egg yolk phosphatidylcholine was used instead of egg yolk phosphatidylethanolamine.

Example 44 A device of the present invention was prepared in the same manner as in Example 43, using the compound of the present invention according to Example 7.

Example 45 A device of the present invention was prepared in the same manner as in Example 43, using the compound of the present invention according to Example 20.

Example 46 Composition for Injection 60 μl of the device of the present invention according to Example 40 was added to saline 0.1.
9 ml was added thereto, and mismatched double-stranded RNA [polyinosinic acid and cytidylic acid copolymer in which one 4-thiouridylic acid was replaced by cytidylic acid for every 20 cytidylic acids was added thereto. A drug that is a heavy-chain RNA and whose molecular size distribution is controlled to about 50 to 10,000 in terms of the number of bases (hereinafter referred to as “the present test drug”)] 100 μg / ml
Was added and stirred to prepare an injectable composition.

Example 47 Injectable composition Injectable compositions were prepared in the same manner as in Example 46 for the devices of the present invention according to Examples 41 to 45.

Example 48 Composition for injection Using 10 mM phosphate buffer instead of saline,
A composition for injection was prepared in the same manner as in Example 46.

Test Example 1 Hemolysis Action 0.1 ml of an aqueous suspension of the compound of the present invention was added to 0.9 ml of a rat erythrocyte suspension washed with an isotonic solution, followed by incubation at 37 ° C with shaking for 45 minutes. After centrifugation at 3000 rpm for 2 minutes, the absorbance of the supernatant was measured at a wavelength of 540 nm. 0.1
The absorbance when 0 ml of isotonic solution was added was 0% (no hemolysis), and the absorbance when 0.1 ml of 0.1% Triton X-100 was added was 1%.
The degree of hemolysis by the device of the present invention was calculated as 00% (complete hemolysis). Table 1 shows the results. The erythrocyte suspension was prepared so that the absorbance at 540 nm when the erythrocyte suspension was completely lysed was 1.2.

As is clear from Table 1, the device of the present invention has approximately 1/10 the effect of hemolyzing red blood cells by 30% as compared with a commercially available lipid device. Therefore, it was suggested that the device of the present invention is a device having extremely low toxicity.

Test Example 2 Growth inhibitory effect on HeLaS3 cells (in vitro) HeLaS3 cells were seeded at a density of 10 ⁴ cells / well (96-well plate) (90 μl), and on the next day each well contained various concentrations of lipid containing the test drug at various concentrations. 30 μg / ml Lipofectin® or 30 μg / ml lipid device of the present invention at 10 μg
1 was added. After culturing for 72 hours after addition, 5 mg / ml MT
T (3- (4,5-Dimethylthiazol-2-yl) -2,5-Diph
(enyl Tetrazolium Bromide) solution was added to each well in an amount of 10 μl, and after 2 to 4 hours, the reaction was stopped by adding a mixed solution of isopropanol / 0.04N hydrochloric acid. After suspending each well, the absorbance at 540 nm was measured with a plate reader (manufactured by Corona), and the growth inhibition rate (%) of HeLaS3 cells was calculated. The calculation was based on the following equation. The cell growth inhibition rate of the test drug alone without lipofectin or the device of the present invention was used as a control.

Table 2 shows the results.

As is clear from Table 2, the growth inhibitory effect when the device of the present invention is used is the same as that when using the existing lipid device Lipofectin (registered trademark), or 3 to 20 times.
Was twice as expensive.

In addition, 3β [N- (N ', N'-dimethylaminoethane)-
carbamoyl] -cholesterol (DC-chol) and a yolk phosphatidylethanolamine (1: 1) lipid device in the literature [Biochemical and Biophysical Research]
Communication, 280-285, Vol. 179, No. 1 (1991)], and the inhibition of the proliferation of the HeLaS3 cells with the device of the present invention (Examples 40 and 43) was examined.
When the test drug of 0.1 μg / ml and the lipid concentration of 30 μg / ml were applied, the device of the present invention showed an approximately 6-fold higher cell growth inhibitory effect than the DC-chol lipid device.

──────────────────────────────────────────────────続 き Continued on front page (51) Int.Cl. ⁶ Identification code FI C07D 207/08 C07D 207/08 211/08 211/08 241/04 241/04 265/30 265/30

Claims (10)

(57) [Claims] 1. A compound represented by the following general formula [I]. Wherein R ¹ and R ² are different from each other and are OY or -A- (CH ₂ ) n-
E (where R ¹ and R ² are both OY, and R ¹ ,
Except when both R ² are -A- (CH ₂ ) n -E. ). n represents the integer of 0-4. E is pyrrolidino, piperidino,
Substituted or unsubstituted piperazino, morpholino, or substituted or unsubstituted guanidino, (R ³ and R ⁴ are the same or different and are hydrogen,
4 represents lower alkyl, hydroxy lower alkyl having 1 to 4 carbon atoms, or mono- or di-lower alkylaminoalkyl (2 to 8 carbon atoms). ). A represents the following or R and Y are the same or different and each represent a saturated or unsaturated aliphatic hydrocarbon group having 10 to 30 carbon atoms, or a saturated or unsaturated fatty acid residue having 10 to 30 carbon atoms. 2. A compound represented by the following general formula [I ']. In the formula, R ¹¹ and R ²¹ are the same or different and represent oleyl or oleoyl. D represents -NH-. R ³⁰ and R ⁴⁰ are the same or different and represent methyl or ethyl. (3) 3-0- (2-dimethylaminoethyl) carbamoyl-1,2-0-dioleylglycerol,
0- (2-diethylaminoethyl) carbamoyl-1,2
3. The composition of claim 2, wherein said glycerol is selected from the group consisting of -0-dioleylglycerol and 2-0- (2-diethylaminoethyl) carbamoyl-1,3-0-dioleoylglycerol.
A compound as described. 4. A device for DDS, comprising the compound represented by the general formula [I] according to claim 1 and a phospholipid as essential components. 5. A device for DDS, comprising the compound represented by the general formula [I '] according to claim 2 and a phospholipid as essential components. 6. A compound represented by the general formula [I ′] according to claim 2,
3-0- (2-dimethylaminoethyl) carbamoyl-
1,2-0-dioleylglycerol, 3-0- (2-diethylaminoethyl) carbamoyl-1,2-0-dioleylglycerol, and 2-0- (2-diethylaminoethyl) carbamoyl-1,3-0 -A device for DDS, comprising a compound selected from the group consisting of dioleoylglycerol and a phospholipid as essential components. 7. The DD according to claim 4, wherein the phospholipid is phosphatidylethanolamine or phosphatidylcholine.
Device for S. 8. The DD according to claim 5, wherein the phospholipid is phosphatidylethanolamine or phosphatidylcholine.
Device for S. 9. The DD according to claim 6, wherein the phospholipid is phosphatidylethanolamine or phosphatidylcholine.
Device for S. 10. A pharmaceutical composition comprising the device for DDS according to claim 4 and an antitumor agent, an antiviral agent or an antibiotic.