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
Authority: JP; Japan
Prior art keywords: moiety; carbon atoms; lipid; alkyl; construction
Prior art date: 1995-07-21
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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

JP9506945A

Other languages

English (en)

Japanese (ja)

Other versions

JPH11510489A5 (2

Inventor

シュワルツ，デイビッド・アーロン

デイリー，ウィリアム・ジェイ

ドワイヤー，ブライアン・パトリック

スリニバサン，クマール

ブラウン，ボブ・デイル

Original Assignee

ジンタ・インコーポレイテッド

Priority date (The priority date 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 date listed.)

1995-07-21

Filing date

1996-07-22

Publication date

1999-09-14

1996-07-22 Application filed by ジンタ・インコーポレイテッド filed Critical ジンタ・インコーポレイテッド

1999-09-14 Publication of JPH11510489A publication Critical patent/JPH11510489A/ja

2004-09-16 Publication of JPH11510489A5 publication Critical patent/JPH11510489A5/ja

Status Withdrawn legal-status Critical Current

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
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239000000243 solution Substances 0.000 description 20
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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
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239000000706 filtrate Substances 0.000 description 8
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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
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238000001727 in vivo Methods 0.000 description 7
230000003834 intracellular effect Effects 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
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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
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235000001014 amino acid Nutrition 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
229960001230 asparagine Drugs 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
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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
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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
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- 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

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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)
Pharmacology & Pharmacy (AREA)
Nanotechnology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Dispersion Chemistry (AREA)
Epidemiology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Medical Informatics (AREA)
Crystallography & Structural Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (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)

JP9506945A 1995-07-21 1996-07-22 新規アミド基本カチオン性脂質 Withdrawn JPH11510489A (ja)

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 (2)	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 (2)
EP (1)	EP0869937A4 (2)
JP (1)	JPH11510489A (2)
AU (1)	AU707947B2 (2)
CA (1)	CA2227373A1 (2)
NZ (1)	NZ313839A (2)
WO (1)	WO1997003939A1 (2)

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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
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1996
- 1996-07-22 CA CA002227373A patent/CA2227373A1/en not_active Abandoned
- 1996-07-22 EP EP96926111A patent/EP0869937A4/en not_active Withdrawn
- 1996-07-22 WO PCT/US1996/012087 patent/WO1997003939A1/en not_active Ceased
- 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 JP JP9506945A patent/JPH11510489A/ja not_active Withdrawn
- 1996-07-22 AU AU66494/96A patent/AU707947B2/en not_active Ceased

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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
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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
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JP2024174889A (ja) *	2018-10-18	2024-12-17	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
CA2227373A1 (en)	1997-02-06
EP0869937A1 (en)	1998-10-14
AU707947B2 (en)	1999-07-22
US6020526A (en)	2000-02-01
AU6649496A (en)	1997-02-18
EP0869937A4 (en)	2004-07-21
WO1997003939A1 (en)	1997-02-06
NZ313839A (en)	1998-12-23

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Publication	Publication Date	Title
US6020526A (en)	2000-02-01	Amide-based cationic lipids
US6034135A (en)	2000-03-07	Dimeric cationic lipids
US6339173B1 (en)	2002-01-15	Amide-based cationic lipids
WO1997003939A9 (en)	1997-05-22	Novel amide-based cationic lipids
JPH11507352A (ja)	1999-06-29	新規カルバメート基本カチオン性脂質
US6172049B1 (en)	2001-01-09	Phosphonic acid-based cationic lipids
US5877220A (en)	1999-03-02	Amide-based oligomeric cationic lipids
US5906922A (en)	1999-05-25	Delivery of nucleic acids
WO1996040726A9 (en)	1997-02-06	Novel carbamate-based cationic lipids
JP4467084B2 (ja)	2010-05-26	核酸を細胞に導入するための化合物、その製法及びその使用
JP2000501383A (ja)	2000-02-08	トランスフェクション剤としてのリポポリアミン及びその医薬的使用
WO1998039358A9 (en)	1999-02-25	Oligomeric cationic lipids
AU727040B2 (en)	2000-11-30	New lipid compounds and compositions containing them which can be used for the transfer of at least one active substance, in particular a polynucleotide, into a target cell and use in gene therapy
KR20010042318A (ko)	2001-05-25	신규 핵산 전달제, 이를 함유하는 조성물 및 용도