JP2020072732A5 - - Google Patents

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Publication number

JP2020072732A5

JP2020072732A5 JP2020009600A JP2020009600A JP2020072732A5 JP 2020072732 A5 JP2020072732 A5 JP 2020072732A5 JP 2020009600 A JP2020009600 A JP 2020009600A JP 2020009600 A JP2020009600 A JP 2020009600A JP 2020072732 A5 JP2020072732 A5 JP 2020072732A5

Authority

JP

Japan

Prior art keywords

seq

modified oligonucleotide

compound according

modified

compound

Prior art date

2020-01-24

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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• 108091034117 Oligonucleotide Proteins 0.000 claims description 71
• 239000002777 nucleoside Substances 0.000 claims description 67
• 125000003835 nucleoside group Chemical group 0.000 claims description 38
• 230000000295 complement effect Effects 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 150000003833 nucleoside derivatives Chemical class 0.000 claims description 8
• 239000000203 mixture Substances 0.000 claims description 7
• 108020004707 nucleic acids Proteins 0.000 claims description 7
• 102000039446 nucleic acids Human genes 0.000 claims description 7
• 150000007523 nucleic acids Chemical class 0.000 claims description 7
• 206010030113 Oedema Diseases 0.000 claims description 5
• 208000005189 Embolism Diseases 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 208000035475 disorder Diseases 0.000 claims description 4
• 208000001435 Thromboembolism Diseases 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 208000027866 inflammatory disease Diseases 0.000 claims description 3
• -1 phosphorothioate nucleoside Chemical class 0.000 claims description 3
• LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 2
• 206010048962 Brain oedema Diseases 0.000 claims description 2
• 206010051055 Deep vein thrombosis Diseases 0.000 claims description 2
• 206010052139 Eye oedema Diseases 0.000 claims description 2
• 206010061216 Infarction Diseases 0.000 claims description 2
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
• 208000006011 Stroke Diseases 0.000 claims description 2
• 208000007536 Thrombosis Diseases 0.000 claims description 2
• 206010047249 Venous thrombosis Diseases 0.000 claims description 2
• 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 Chemical class 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 description 2
• 208000006752 brain edema Diseases 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 230000007574 infarction Effects 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 150000003839 salts Chemical class 0.000 claims description 2
• 230000008961 swelling Effects 0.000 claims description 2
• 108090000113 Plasma Kallikrein Proteins 0.000 claims 7
• 230000000692 anti-sense effect Effects 0.000 claims 5
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• 206010019860 Hereditary angioedema Diseases 0.000 claims 2
• 125000002619 bicyclic group Chemical group 0.000 claims 2
• 238000004132 cross linking Methods 0.000 claims 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical group P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 2
• 239000002953 phosphate buffered saline Substances 0.000 claims 2
• 208000028185 Angioedema Diseases 0.000 claims 1
• 101001081555 Homo sapiens Plasma protease C1 inhibitor Proteins 0.000 claims 1
• 208000001344 Macular Edema Diseases 0.000 claims 1
• 206010025415 Macular oedema Diseases 0.000 claims 1
• 102100027637 Plasma protease C1 inhibitor Human genes 0.000 claims 1
• 239000005549 deoxyribonucleoside Substances 0.000 claims 1
• 210000000744 eyelid Anatomy 0.000 claims 1
• 201000010230 macular retinal edema Diseases 0.000 claims 1
• 125000001424 substituent group Chemical group 0.000 claims 1
• 238000012986 modification Methods 0.000 description 9
• 230000004048 modification Effects 0.000 description 9
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
• 238000000034 method Methods 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 4
• 108020004999 messenger RNA Proteins 0.000 description 4
• 229930024421 Adenine Natural products 0.000 description 3
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
• 229960000643 adenine Drugs 0.000 description 3
• 229940113082 thymine Drugs 0.000 description 3
• 230000002792 vascular Effects 0.000 description 2
• IHLOTZVBEUFDMD-UUOKFMHZSA-N 7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,2-dioxo-1h-imidazo[4,5-c][1,2,6]thiadiazin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NS(=O)(=O)NC2=O)=C2N=C1 IHLOTZVBEUFDMD-UUOKFMHZSA-N 0.000 description 1
• 206010015993 Eyelid oedema Diseases 0.000 description 1
• 206010042674 Swelling Diseases 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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• 230000000938 luteal effect Effects 0.000 description 1
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• 239000002773 nucleotide Substances 0.000 description 1
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