JPH11510489A - 新規アミド基本カチオン性脂質 - Google Patents
新規アミド基本カチオン性脂質Info
- Publication number
- JPH11510489A JPH11510489A JP9506945A JP50694597A JPH11510489A JP H11510489 A JPH11510489 A JP H11510489A JP 9506945 A JP9506945 A JP 9506945A JP 50694597 A JP50694597 A JP 50694597A JP H11510489 A JPH11510489 A JP H11510489A
- Authority
- JP
- Japan
- Prior art keywords
- moiety
- carbon atoms
- lipid
- alkyl
- construction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001408 amides Chemical class 0.000 title claims abstract description 26
- -1 cationic lipid Chemical class 0.000 title claims description 103
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 105
- 150000002632 lipids Chemical class 0.000 claims abstract description 103
- 239000000203 mixture Substances 0.000 claims abstract description 57
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 31
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 31
- 229920002521 macromolecule Polymers 0.000 claims abstract description 29
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 230000014509 gene expression Effects 0.000 claims abstract description 10
- 150000001450 anions Chemical class 0.000 claims abstract description 9
- 229920000447 polyanionic polymer Polymers 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 230000002452 interceptive effect Effects 0.000 claims abstract 2
- 108091034117 Oligonucleotide Proteins 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 108020004414 DNA Proteins 0.000 claims description 24
- 150000001412 amines Chemical class 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 150000003973 alkyl amines Chemical group 0.000 claims description 11
- 229960003104 ornithine Drugs 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 8
- 125000000539 amino acid group Chemical group 0.000 claims description 7
- 150000001413 amino acids Chemical class 0.000 claims description 7
- 230000000295 complement effect Effects 0.000 claims description 7
- 239000013604 expression vector Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 5
- 150000004982 aromatic amines Chemical class 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 4
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- 150000001409 amidines Chemical group 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 150000002081 enamines Chemical group 0.000 claims description 3
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- AHLPHDHHMVZTML-BYPYZUCNSA-N ornithyl group Chemical class N[C@@H](CCCN)C(=O)O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 229940063673 spermidine Drugs 0.000 claims description 2
- 238000010276 construction Methods 0.000 claims 16
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims 2
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 claims 1
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 1
- 125000002091 cationic group Chemical group 0.000 abstract description 33
- 239000003925 fat Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 115
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 101
- 150000001875 compounds Chemical class 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 42
- 230000015572 biosynthetic process Effects 0.000 description 36
- 238000003786 synthesis reaction Methods 0.000 description 32
- 238000000746 purification Methods 0.000 description 30
- 239000002585 base Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- 238000001890 transfection Methods 0.000 description 28
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 26
- 239000002502 liposome Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 22
- 150000002148 esters Chemical class 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 239000002777 nucleoside Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 17
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical group C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 16
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 16
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 230000032258 transport Effects 0.000 description 13
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 12
- 238000010511 deprotection reaction Methods 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
- HKUFIYBZNQSHQS-UHFFFAOYSA-N n-octadecyloctadecan-1-amine Chemical compound CCCCCCCCCCCCCCCCCCNCCCCCCCCCCCCCCCCCC HKUFIYBZNQSHQS-UHFFFAOYSA-N 0.000 description 11
- 150000003833 nucleoside derivatives Chemical class 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 10
- 125000003835 nucleoside group Chemical group 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 150000007523 nucleic acids Chemical class 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 210000000170 cell membrane Anatomy 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 229960002989 glutamic acid Drugs 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 7
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000003834 intracellular effect Effects 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 239000012124 Opti-MEM Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 229940104302 cytosine Drugs 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
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- 229910052786 argon Inorganic materials 0.000 description 5
- 229960001230 asparagine Drugs 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- DJGACOXTAHQLTD-UHFFFAOYSA-N 2-amino-n-(2-amino-2-oxoethyl)acetamide Chemical compound NCC(=O)NCC(N)=O DJGACOXTAHQLTD-UHFFFAOYSA-N 0.000 description 4
- FKIRRWIIVPMGEK-UHFFFAOYSA-N 2-amino-n-[2-oxo-2-(pentatriacontan-18-ylamino)ethyl]acetamide Chemical compound CCCCCCCCCCCCCCCCCC(NC(=O)CNC(=O)CN)CCCCCCCCCCCCCCCCC FKIRRWIIVPMGEK-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 101150055766 cat gene Proteins 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- DMCJFWXGXUEHFD-UHFFFAOYSA-N diheptadecyl ketone Natural products CCCCCCCCCCCCCCCCCC(=O)CCCCCCCCCCCCCCCCC DMCJFWXGXUEHFD-UHFFFAOYSA-N 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- JHCLUTILJRJUHZ-UHFFFAOYSA-N pentatriacontan-18-amine Chemical compound CCCCCCCCCCCCCCCCCC(N)CCCCCCCCCCCCCCCCC JHCLUTILJRJUHZ-UHFFFAOYSA-N 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
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- 230000010474 transient expression Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000006163 transport media Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical group C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/10—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Nanotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50580295A | 1995-07-21 | 1995-07-21 | |
| US08/505,802 | 1995-07-21 | ||
| PCT/US1996/012087 WO1997003939A1 (en) | 1995-07-21 | 1996-07-22 | Novel amide-based cationic lipids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH11510489A true JPH11510489A (ja) | 1999-09-14 |
| JPH11510489A5 JPH11510489A5 (cg-RX-API-DMAC7.html) | 2004-09-16 |
Family
ID=24011908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9506945A Withdrawn JPH11510489A (ja) | 1995-07-21 | 1996-07-22 | 新規アミド基本カチオン性脂質 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6020526A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0869937A4 (cg-RX-API-DMAC7.html) |
| JP (1) | JPH11510489A (cg-RX-API-DMAC7.html) |
| AU (1) | AU707947B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2227373A1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ313839A (cg-RX-API-DMAC7.html) |
| WO (1) | WO1997003939A1 (cg-RX-API-DMAC7.html) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003519199A (ja) * | 1999-12-30 | 2003-06-17 | ノバルティス アクチエンゲゼルシャフト | 遺伝子治療のための新規なコロイド合成ベクター |
| JP2014001237A (ja) * | 2013-09-20 | 2014-01-09 | Chongxi Yu | ペプチド及び関連化合物の経皮送達システム |
| JP2018197255A (ja) * | 2010-11-15 | 2018-12-13 | ライフ テクノロジーズ コーポレーション | アミン含有トランスフェクション試薬ならびにそれを生成および使用するための方法 |
| JP2022505234A (ja) * | 2018-10-18 | 2022-01-14 | アクイタス セラピューティクス インコーポレイテッド | 活性剤の脂質ナノ粒子送達のための脂質 |
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|---|---|---|---|---|
| US6339173B1 (en) * | 1996-07-22 | 2002-01-15 | Promega Biosciences, Inc. | Amide-based cationic lipids |
| FR2760193B1 (fr) * | 1997-02-28 | 1999-05-28 | Transgene Sa | Lipides et complexes de lipides cationiques et de substances actives, notamment pour la transfection de cellules |
| US6034135A (en) * | 1997-03-06 | 2000-03-07 | Promega Biosciences, Inc. | Dimeric cationic lipids |
| US5877220A (en) * | 1997-03-06 | 1999-03-02 | Genta, Incorporated | Amide-based oligomeric cationic lipids |
| US6395713B1 (en) * | 1997-07-23 | 2002-05-28 | Ribozyme Pharmaceuticals, Inc. | Compositions for the delivery of negatively charged molecules |
| JP4504559B2 (ja) | 1997-08-13 | 2010-07-14 | ビオンテックス ラボラトリーズ ゲーエムベーハー | 新リポポリアミン、その調製および適用 |
| GB9914045D0 (en) * | 1999-06-16 | 1999-08-18 | Smithkline Beecham Plc | Novel compounds |
| WO2001070685A2 (en) * | 2000-03-22 | 2001-09-27 | Solulink, Incorporated | Hydrazine-based and carbonyl-based bifunctional crosslinking reagents |
| US7102024B1 (en) | 2000-08-01 | 2006-09-05 | Schwartz David A | Functional biopolymer modification reagents and uses thereof |
| US6686461B1 (en) * | 2000-03-22 | 2004-02-03 | Solulink Bioscience, Inc. | Triphosphate oligonucleotide modification reagents and uses thereof |
| US7294511B2 (en) * | 2001-03-22 | 2007-11-13 | Chromos Molecular Systems, Inc. | Methods for delivering nucleic acid molecules into cells and assessment thereof |
| DE10117043A1 (de) * | 2001-04-05 | 2002-11-07 | Gerhard Puetz | Verfahren zur Eliminierung von potentiell toxischen und/oder schädlichen Stoffen |
| US20070141724A1 (en) * | 2003-07-29 | 2007-06-21 | Schmidt Jurgen G | Solid phase immobilized trifunctional linker |
| JP4842821B2 (ja) | 2003-09-15 | 2011-12-21 | プロチバ バイオセラピューティクス インコーポレイティッド | ポリエチレングリコール修飾脂質化合物およびその使用 |
| US7158353B2 (en) * | 2003-11-06 | 2007-01-02 | Seagate Technology Llc | Magnetoresistive sensor having specular sidewall layers |
| US7142948B2 (en) | 2004-01-07 | 2006-11-28 | Honeywell International Inc. | Controller interface with dynamic schedule display |
| CA2565633C (en) | 2004-05-05 | 2016-04-26 | Atugen Ag | Lipids, lipid complexes and use thereof |
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| US20060134189A1 (en) * | 2004-11-17 | 2006-06-22 | Protiva Biotherapeutics, Inc | siRNA silencing of apolipoprotein B |
| JP5292572B2 (ja) | 2004-12-27 | 2013-09-18 | サイレンス・セラピューティクス・アーゲー | コーティングされた脂質複合体およびそれらの使用 |
| EP1948674A4 (en) | 2005-11-02 | 2009-02-04 | Protiva Biotherapeutics Inc | MODIFIED SIRNA MOLECULES AND APPLICATIONS THEREOF |
| JP2009544281A (ja) | 2006-07-21 | 2009-12-17 | サイレンス・セラピューティクス・アーゲー | プロテインキナーゼ３の発現を阻害するための手段 |
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| EP3225621A1 (en) | 2008-10-09 | 2017-10-04 | Arbutus Biopharma Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
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| US9035039B2 (en) | 2011-12-22 | 2015-05-19 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing SMAD4 |
| CN106795096B (zh) | 2014-06-25 | 2020-05-29 | 爱康泰生治疗公司 | 用于递送核酸的新型脂质和脂质纳米颗粒制剂 |
| EP3289083A4 (en) | 2015-04-27 | 2018-12-19 | The Trustees Of The University Of Pennsylvania | Nucleoside-modified rna for inducing an adaptive immune response |
| HRP20240865T1 (hr) | 2015-06-29 | 2024-10-11 | Acuitas Therapeutics Inc. | Lipidi i formulacije lipidnih nanočestica za isporuku nukleinskih kiselina |
| AU2016343803B2 (en) | 2015-10-28 | 2021-04-29 | Acuitas Therapeutics, Inc. | Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids |
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| IL322436A (en) | 2018-09-21 | 2025-09-01 | Acuitas Therapeutics Inc | Systems and methods for producing lipid nanoparticles and liposomes |
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| CN117098541A (zh) | 2020-11-25 | 2023-11-21 | 阿卡格拉医药公司 | 用于递送核酸的脂质纳米粒及相关使用方法 |
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| EP4534525A4 (en) * | 2022-06-02 | 2025-08-20 | Xiamen Sinopeg Biotech Co Ltd | CATIONIC LIPID BASED ON AMINO ACIDS CONTAINING UNSATURATED BONDS |
| CN120737003A (zh) * | 2022-06-02 | 2025-10-03 | 厦门赛诺邦格生物科技股份有限公司 | 一种氨基酸阳离子脂质 |
| CN119630438A (zh) * | 2022-08-12 | 2025-03-14 | 五眼高新技术株式会社 | 溶剂中抗原回收系统及溶剂中抗原回收方法 |
| EP4642787A2 (en) * | 2022-12-27 | 2025-11-05 | Sunvax Mrna Therapeutics | Modular lipid compounds and two- to three-component lipid nanoparticle compositions |
| CN119562942A (zh) * | 2023-06-30 | 2025-03-04 | 厦门赛诺邦格生物科技股份有限公司 | 一种含有两个叔胺基团的阳离子脂质及其应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2426891A (en) * | 1945-09-14 | 1947-09-02 | American Cyanamid Co | N, n'-dioctadecyl-beta-amino-propionamide |
| US4897355A (en) * | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4548955A (en) * | 1985-02-25 | 1985-10-22 | Sogo Pharmaceutical Company Limited | Nylon capsule responding to pH |
| FR2645866B1 (fr) * | 1989-04-17 | 1991-07-05 | Centre Nat Rech Scient | Nouvelles lipopolyamines, leur preparation et leur emploi |
| US5264618A (en) * | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| JPH07502753A (ja) * | 1992-07-13 | 1995-03-23 | ユーカリオン，インコーポレイティド | 脂質化タンパク質類の血管通過輸送および細胞内輸送 |
| US5334761A (en) * | 1992-08-28 | 1994-08-02 | Life Technologies, Inc. | Cationic lipids |
| US5777153A (en) * | 1994-07-08 | 1998-07-07 | Gilead Sciences, Inc. | Cationic lipids |
-
1996
- 1996-07-22 JP JP9506945A patent/JPH11510489A/ja not_active Withdrawn
- 1996-07-22 WO PCT/US1996/012087 patent/WO1997003939A1/en not_active Ceased
- 1996-07-22 EP EP96926111A patent/EP0869937A4/en not_active Withdrawn
- 1996-07-22 US US08/681,297 patent/US6020526A/en not_active Expired - Lifetime
- 1996-07-22 NZ NZ313839A patent/NZ313839A/xx unknown
- 1996-07-22 CA CA002227373A patent/CA2227373A1/en not_active Abandoned
- 1996-07-22 AU AU66494/96A patent/AU707947B2/en not_active Ceased
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003519199A (ja) * | 1999-12-30 | 2003-06-17 | ノバルティス アクチエンゲゼルシャフト | 遺伝子治療のための新規なコロイド合成ベクター |
| JP2018197255A (ja) * | 2010-11-15 | 2018-12-13 | ライフ テクノロジーズ コーポレーション | アミン含有トランスフェクション試薬ならびにそれを生成および使用するための方法 |
| US10406237B2 (en) | 2010-11-15 | 2019-09-10 | Life Technololgies Corporation | Amine-containing transfection reagents and methods for making and using same |
| US11464863B2 (en) | 2010-11-15 | 2022-10-11 | Life Technologies Corporation | Amine-containing transfection reagents and methods for making and using same |
| US12458700B2 (en) | 2010-11-15 | 2025-11-04 | Life Technologies Corporation | Amine-containing transfection reagents and methods for making and using same |
| JP2014001237A (ja) * | 2013-09-20 | 2014-01-09 | Chongxi Yu | ペプチド及び関連化合物の経皮送達システム |
| JP2022505234A (ja) * | 2018-10-18 | 2022-01-14 | アクイタス セラピューティクス インコーポレイテッド | 活性剤の脂質ナノ粒子送達のための脂質 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0869937A1 (en) | 1998-10-14 |
| CA2227373A1 (en) | 1997-02-06 |
| US6020526A (en) | 2000-02-01 |
| AU707947B2 (en) | 1999-07-22 |
| NZ313839A (en) | 1998-12-23 |
| AU6649496A (en) | 1997-02-18 |
| WO1997003939A1 (en) | 1997-02-06 |
| EP0869937A4 (en) | 2004-07-21 |
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