WO2004031199A2 - Lipidanaloge phosphorsäuretriester - Google Patents
Lipidanaloge phosphorsäuretriester Download PDFInfo
- Publication number
- WO2004031199A2 WO2004031199A2 PCT/EP2003/010870 EP0310870W WO2004031199A2 WO 2004031199 A2 WO2004031199 A2 WO 2004031199A2 EP 0310870 W EP0310870 W EP 0310870W WO 2004031199 A2 WO2004031199 A2 WO 2004031199A2
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- WO
- WIPO (PCT)
- Prior art keywords
- phospho
- glycero
- residue
- compound according
- compound
- Prior art date
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- -1 phosphoric acid triester Chemical class 0.000 title abstract description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 title abstract description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 title abstract description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 25
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 22
- 239000002502 liposome Substances 0.000 claims description 12
- 235000012000 cholesterol Nutrition 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- 229940106189 ceramide Drugs 0.000 claims description 3
- 150000001783 ceramides Chemical class 0.000 claims description 3
- 229960001231 choline Drugs 0.000 claims description 3
- 150000001982 diacylglycerols Chemical class 0.000 claims description 3
- 150000003333 secondary alcohols Chemical class 0.000 claims description 3
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 150000001985 dialkylglycerols Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 150000003138 primary alcohols Chemical class 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 2
- 101100240595 Mus musculus Nipal4 gene Proteins 0.000 claims 1
- 125000003473 lipid group Chemical group 0.000 abstract 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 235000011187 glycerol Nutrition 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 229940105990 diglycerin Drugs 0.000 description 6
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 6
- 150000005691 triesters Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000004437 phosphorous atom Chemical group 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 150000002632 lipids Chemical group 0.000 description 2
- 238000006140 methanolysis reaction Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- JWBOVDKFGDXGCR-QFIPXVFZSA-N (2s)-2-methoxy-3-octadecoxypropan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCOC[C@H](CO)OC JWBOVDKFGDXGCR-QFIPXVFZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- CRSOIYXNFFSUFD-UHFFFAOYSA-N 1,2,3-trihydroxypropylphosphonic acid Chemical compound OCC(O)C(O)P(O)(O)=O CRSOIYXNFFSUFD-UHFFFAOYSA-N 0.000 description 1
- HKJAWHYHRVVDHK-UHFFFAOYSA-N 15,16,17-trihydroxyhentriacontane-14,18-dione Chemical compound CCCCCCCCCCCCCC(=O)C(O)C(O)C(O)C(=O)CCCCCCCCCCCCC HKJAWHYHRVVDHK-UHFFFAOYSA-N 0.000 description 1
- LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 description 1
- UDIPIOHLDFSMLR-UHFFFAOYSA-N 2-phenylmethoxypropane-1,3-diol Chemical compound OCC(CO)OCC1=CC=CC=C1 UDIPIOHLDFSMLR-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- AGNTUZCMJBTHOG-UHFFFAOYSA-N 3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]propane-1,2-diol Chemical group OCC(O)COCC(O)COCC(O)CO AGNTUZCMJBTHOG-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- DRAWQKGUORNASA-XPWSMXQVSA-N [2-hydroxy-3-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)COC(=O)CCCCCCC\C=C\CCCCCCCC DRAWQKGUORNASA-XPWSMXQVSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 125000001549 ceramide group Chemical group 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 125000002966 glycerophosphoglycerophosphoglycerol group Chemical group 0.000 description 1
- 150000002321 glycerophosphoglycerophosphoglycerols Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 150000004668 long chain fatty acids Chemical group 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 229940042880 natural phospholipid Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- GWLJTAJEHRYMCA-UHFFFAOYSA-N phospholane Chemical compound C1CCPC1 GWLJTAJEHRYMCA-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000000075 primary alcohol group Chemical group 0.000 description 1
- 150000003152 propanolamines Chemical group 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
Definitions
- the present invention relates to new phosphoric acid triesters which contain apolar lipid structures.
- triesters can be used in particular as liposome components.
- the invention relates to a compound of the formula (I)
- R 1 represents a residue selected from cholesterol, diacylglycerols, dialkylglycerols, acylalkylglycerols, ceramides, primary or secondary alcohols with 1 2 to 24 carbon atoms or acylglycerobenzyl ethers
- R 2 represents a residue selected from ethanolamine, N-methylethanolamine, Propanolamine, choline, glycerol, oligoglycerols, glycoglycerols or serine, which may optionally contain protective groups
- R 3 represents a radical, selected from or or has the meaning R 2 .
- the compounds according to the invention are lipid-analogous phosphoric triesters, in particular phosphoric triesters with multiple hydroxyl groups per phosphorus atom, in particular at least two hydroxyl groups per phosphorus atom, more preferably at least three hydroxyl groups per phosphorus atom and even more preferably at least four hydroxyl groups per phosphorus atom.
- the phosphoric acid triesters according to the invention contain a radical R 1 which contains an apolar lipid structure. Suitable structures for R 1 are in particular cholesterol residues, so that preferred phosphoric acid triesters are cholesteryl compounds.
- R 1 Another preferred radical for R 1 is diacylglycerol, the acyl groups each independently preferably containing 1 2 to 28, in particular 1 3 to 27 and more preferably 14 to 26 carbon atoms.
- the acyl radicals can be saturated or one or more, in particular two or three, unsaturated radicals.
- the acylglycerols which contain unsaturated fatty acid residues, such as residues of oleic acid, linoleic acid or linolenic acid, are particularly preferred.
- the radical R 1 can furthermore be a dialkylglycerol radical, the alkyl radicals therein, independently of one another, preferably having 1 to 28, in particular 1 2 to 26, more preferably 1 4 to 24 carbon atoms.
- the alkyl radicals in the dialkylglycerol radical can be saturated or mono- or polysaturated, in particular di- or trisaturated.
- the radicals (Z) -9-octadecenyl-, (ZZ) -9.1 are 2-octadecandienyl-, (ZZZ) -9. 1 2. 1 5- octadecantrienyl and lipophilic base body with a pharmaceutical effect, such as 1-octadecyl-2-methyl-sn-glycerol.
- R 1 can stand for a ceramide residue.
- Ceramides are the body's own lipophilic amides of the general formula (IV), which are found in particular in the brain substance and in the myelin of the CNS.
- R 4 is a long-chain fatty acid residue, in particular a fatty acid residue with 1 2 to 28 C atoms
- R 1 can furthermore be a radical of a primary or secondary alcohol having 1 2 to 24 carbon atoms, in particular 13 to 22 carbon atoms, it being possible for the alcohols to be saturated or mono- or polyunsaturated.
- R 1 can furthermore stand for an acylglycero-benzyl ether residue, such compounds being able to be used in particular as starting products for the synthesis of lysophospholipids.
- the radical R 1 can be present in enantiomerically pure form or as a racemic mixture.
- R 2 can stand for all residues as they occur in natural phospholipids and sphingomyelins.
- R 2 represents an ethanolamine residue, an N-methylethanol residue or a propanolamine residue, the residues optionally being provided with suitable protective groups, for example BOC.
- R 2 can furthermore stand for a choline residue.
- R 2 is preferably -CH 2 -CH 2 -N + (CH 3 ) 3 .
- R 2 can furthermore stand for a glycerol residue (-CH 2 -CH (OH) -CH 2 (OH)) as well as for an oligoglycerol residue, in particular a di- or triglycerol residue.
- Other suitable R 2 radicals are glycoglycerols and serine radicals. The glycerol and serine residues can optionally also be provided with suitable protective groups.
- R 3 represents a radical selected from C r C 8 alkyl or or can have one of the meanings given above for R 2 . If R 3 has one of the meanings given for R 2 , biologically highly active structures can be formed which are new cationic lipids are of great importance. Such cationic lipids can be used, for example, for gene transfection.
- R 3 can also only be of a temporary nature, i.e. take on the function of a protective group which will be replaced later.
- R 3 preferably represents methyl, ethyl, allyl or propyl.
- the compounds according to the invention are very stable between pH 3 and pH 8 and can be used in particular as liposome components.
- the invention further relates to a process for the preparation of a compound of the formula (I), which is characterized in that a compound of the formula (II) is esterified with a compound of the formula (III) HO-R 3 .
- the compounds are derived from phospholipids and arise, for example
- cholesterol derivatives can also be obtained
- connections can be made in different embodiments. They can also contain oligoglycerols, for example glyceroglycerol, diglyceroglycerol or triglyceroglycerol instead of glycerol.
- oligoglycerols for example glyceroglycerol, diglyceroglycerol or triglyceroglycerol instead of glycerol.
- cholesterol phospho-monoglycerol triglyceroglycerol has the following structural formula: 0
- the compounds according to the invention are particularly suitable for the production of liposomes or as liposome components. They give liposomes special properties, such as long circulation times in the blood, targeted accumulation in the liver or almost exclusive absorption in the spleen. With the aid of the phosphoric acid triesters according to the invention, liposomes with new properties can also be formed, which have a high serum stability, have long circulation times and are exclusively enriched in the spleen. Long circulation times are also particularly important because the structures are not enriched in the liver like known liposomes, but other targets, such as the spleen, or can be taken up by tumor cells. The compounds according to the invention can therefore also be used for the treatment of cancer.
- the invention further relates to a new synthetic route using the phosphoric triesters according to the invention as an intermediate.
- a particular advantage of the synthetic route according to the invention is that the reaction procedure used in previous syntheses is avoided (a) and after (b) the important compound 1 .2-dioleyl-sn-glycero-3-phosphoglycerol or corresponding compounds are exposed under neutral conditions:
- Ri 1.2 - dioleoyl - sn - glycerin
- a major advantage of the new synthesis process is the ability to advance apolar intermediates as far as possible in the synthesis, so that polar structures are only introduced at the end of the process. This is explained below using an example. Cardiolipins and analogue compounds are complicated structures that are extremely difficult to access synthetically in kg quantities. With the help of our new synthesis strategy, however, this is easily possible. cardiolipin
- the starting product is 1.2-dipalmitoyl-sn-glycerol, which is converted to 1.2-dipalmitoyl-sn-glycero-3-phosphoric acid dichloride with phosphorus oxychloride in THF using triethylamine as the base:
- Module 1 (triethylamine in THF)
- Building block III can then be converted with building block I in the usual way to the direct precursor of cardiolipin, which is then by
- liposomes of the usual composition e.g.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Confectionery (AREA)
- Seasonings (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03750666A EP1556391B1 (de) | 2002-10-01 | 2003-10-01 | Lipidanaloge phosphors uretriester |
CA2500768A CA2500768C (en) | 2002-10-01 | 2003-10-01 | Lipid-analog phosphoric acid triester |
DE50307834T DE50307834D1 (de) | 2002-10-01 | 2003-10-01 | Lipidanaloge phosphors uretriester |
US10/529,889 US7592469B2 (en) | 2002-10-01 | 2003-10-01 | Lipid-analogous phosphoric acid triesters |
AU2003268895A AU2003268895A1 (en) | 2002-10-01 | 2003-10-01 | Lipid-analog phosphoric acid triester |
JP2004540761A JP4746319B2 (ja) | 2002-10-01 | 2003-10-01 | 脂質類似の燐酸トリエステル |
US12/552,799 US8273727B2 (en) | 2002-10-01 | 2009-09-02 | Lipid-analogous phosphoric triesters |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10245909A DE10245909A1 (de) | 2002-10-01 | 2002-10-01 | Lipidanaloge Phosphorsäuretriester |
DE10245909.6 | 2002-10-01 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10529889 A-371-Of-International | 2003-10-01 | ||
US12/552,799 Continuation US8273727B2 (en) | 2002-10-01 | 2009-09-02 | Lipid-analogous phosphoric triesters |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2004031199A2 true WO2004031199A2 (de) | 2004-04-15 |
WO2004031199A3 WO2004031199A3 (de) | 2004-09-02 |
Family
ID=32010077
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2003/010870 WO2004031199A2 (de) | 2002-10-01 | 2003-10-01 | Lipidanaloge phosphorsäuretriester |
Country Status (8)
Country | Link |
---|---|
US (2) | US7592469B2 (de) |
EP (1) | EP1556391B1 (de) |
JP (1) | JP4746319B2 (de) |
AT (1) | ATE368677T1 (de) |
AU (1) | AU2003268895A1 (de) |
CA (1) | CA2500768C (de) |
DE (2) | DE10245909A1 (de) |
WO (1) | WO2004031199A2 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007147644A3 (de) * | 2006-06-23 | 2008-11-06 | Max Planck Gesellschaft | Phosphorsäurediesteramide |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995001163A1 (fr) * | 1992-01-03 | 1995-01-12 | Corbiere Jerome | Nouvelles preparations pharmaceutiques a base de peptides pour la voie generale |
US5651981A (en) * | 1994-03-29 | 1997-07-29 | Northwestern University | Cationic phospholipids for transfection |
DE19622224A1 (de) * | 1996-02-16 | 1997-08-21 | Max Planck Gesellschaft | Phosphatidyloligoglycerine |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6271209B1 (en) | 1998-04-03 | 2001-08-07 | Valentis, Inc. | Cationic lipid formulation delivering nucleic acid to peritoneal tumors |
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2002
- 2002-10-01 DE DE10245909A patent/DE10245909A1/de not_active Withdrawn
-
2003
- 2003-10-01 AT AT03750666T patent/ATE368677T1/de not_active IP Right Cessation
- 2003-10-01 WO PCT/EP2003/010870 patent/WO2004031199A2/de active IP Right Grant
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007147644A3 (de) * | 2006-06-23 | 2008-11-06 | Max Planck Gesellschaft | Phosphorsäurediesteramide |
Also Published As
Publication number | Publication date |
---|---|
US7592469B2 (en) | 2009-09-22 |
CA2500768A1 (en) | 2004-04-15 |
US20060039963A1 (en) | 2006-02-23 |
US20100086583A1 (en) | 2010-04-08 |
ATE368677T1 (de) | 2007-08-15 |
US8273727B2 (en) | 2012-09-25 |
EP1556391B1 (de) | 2007-08-01 |
DE50307834D1 (de) | 2007-09-13 |
DE10245909A1 (de) | 2004-04-15 |
AU2003268895A1 (en) | 2004-04-23 |
JP4746319B2 (ja) | 2011-08-10 |
CA2500768C (en) | 2012-09-04 |
JP2006501287A (ja) | 2006-01-12 |
EP1556391A2 (de) | 2005-07-27 |
WO2004031199A3 (de) | 2004-09-02 |
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