JP2013541334A5 - - Google Patents

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Publication number

JP2013541334A5

JP2013541334A5 JP2013529298A JP2013529298A JP2013541334A5 JP 2013541334 A5 JP2013541334 A5 JP 2013541334A5 JP 2013529298 A JP2013529298 A JP 2013529298A JP 2013529298 A JP2013529298 A JP 2013529298A JP 2013541334 A5 JP2013541334 A5 JP 2013541334A5

Authority

JP

Japan

Prior art keywords

independently

occurrence

duplex agent

irna duplex

irna

Prior art date

2011-09-14

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.)

Pending

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• 239000003795 chemical substances by application Substances 0.000 claims 28
• 125000003729 nucleotide group Chemical group 0.000 claims 14
• 229910052760 oxygen Inorganic materials 0.000 claims 13
• 230000000692 anti-sense effect Effects 0.000 claims 12
• 229910052717 sulfur Inorganic materials 0.000 claims 11
• 108091081021 Sense strand Proteins 0.000 claims 10
• 239000002773 nucleotide Substances 0.000 claims 8
• 229910052799 carbon Inorganic materials 0.000 claims 7
• 239000003446 ligand Substances 0.000 claims 5
• 108091034117 Oligonucleotide Proteins 0.000 claims 4
• 150000001875 compounds Chemical class 0.000 claims 4
• 238000000034 method Methods 0.000 claims 4
• 238000012986 modification Methods 0.000 claims 4
• 230000004048 modification Effects 0.000 claims 4
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 4
• 125000002947 alkylene group Chemical group 0.000 claims 3
• 239000002777 nucleoside Substances 0.000 claims 3
• 108091033319 polynucleotide Proteins 0.000 claims 3
• 239000002157 polynucleotide Substances 0.000 claims 3
• 102000040430 polynucleotide Human genes 0.000 claims 3
• 150000003431 steroids Chemical class 0.000 claims 3
• 239000000126 substance Substances 0.000 claims 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 2
• 125000003275 alpha amino acid group Chemical group 0.000 claims 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• 150000001720 carbohydrates Chemical class 0.000 claims 2
• -1 cationic lipid Chemical class 0.000 claims 2
• 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 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
• 125000000623 heterocyclic group Chemical group 0.000 claims 2
• 229910052739 hydrogen Inorganic materials 0.000 claims 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
• 150000002632 lipids Chemical class 0.000 claims 2
• 108020004999 messenger RNA Proteins 0.000 claims 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 150000004713 phosphodiesters Chemical group 0.000 claims 2
• 150000008300 phosphoramidites Chemical class 0.000 claims 2
• OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical group OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 2
• 229920000642 polymer Polymers 0.000 claims 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• 239000007787 solid Substances 0.000 claims 2
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 2
• PUDXUJRJLRLJIU-QYVSTXNMSA-N (2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)oxolan-3-ol Chemical compound COCCO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 PUDXUJRJLRLJIU-QYVSTXNMSA-N 0.000 claims 1
• NEVQCHBUJFYGQO-DNRKLUKYSA-N 1-[(2r,3r,4r,5r)-4-hydroxy-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound COCCO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C)=C1 NEVQCHBUJFYGQO-DNRKLUKYSA-N 0.000 claims 1
• GUEIFVRYWPOXHJ-DNRKLUKYSA-N 4-amino-1-[(2r,3r,4r,5r)-4-hydroxy-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolan-2-yl]-5-methylpyrimidin-2-one Chemical compound COCCO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C(C)=C1 GUEIFVRYWPOXHJ-DNRKLUKYSA-N 0.000 claims 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims 1
• 229910019142 PO4 Inorganic materials 0.000 claims 1
• 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 claims 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 1
• 235000012000 cholesterol Nutrition 0.000 claims 1
• 230000000295 complement effect Effects 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 229910052736 halogen Inorganic materials 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 238000001727 in vivo Methods 0.000 claims 1
• 238000001361 intraarterial administration Methods 0.000 claims 1
• 238000007918 intramuscular administration Methods 0.000 claims 1
• 238000007912 intraperitoneal administration Methods 0.000 claims 1
• 238000001990 intravenous administration Methods 0.000 claims 1
• 230000001926 lymphatic effect Effects 0.000 claims 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 1
• 229910052757 nitrogen Inorganic materials 0.000 claims 1
• 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
• 239000010452 phosphate Substances 0.000 claims 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 claims 1
• 108090000765 processed proteins & peptides Proteins 0.000 claims 1
• 125000006239 protecting group Chemical group 0.000 claims 1
• 108090000623 proteins and genes Proteins 0.000 claims 1
• 238000007920 subcutaneous administration Methods 0.000 claims 1
• 150000003505 terpenes Chemical class 0.000 claims 1
• 235000007586 terpenes Nutrition 0.000 claims 1
• 229940104230 thymidine Drugs 0.000 claims 1
• 239000011782 vitamin Substances 0.000 claims 1
• 229940088594 vitamin Drugs 0.000 claims 1
• 229930003231 vitamin Natural products 0.000 claims 1
• 235000013343 vitamin Nutrition 0.000 claims 1
• 150000003722 vitamin derivatives Chemical class 0.000 claims 1