JP6608413B2 - 不斉補助基 - Google Patents
不斉補助基 Download PDFInfo
- Publication number
- JP6608413B2 JP6608413B2 JP2017209854A JP2017209854A JP6608413B2 JP 6608413 B2 JP6608413 B2 JP 6608413B2 JP 2017209854 A JP2017209854 A JP 2017209854A JP 2017209854 A JP2017209854 A JP 2017209854A JP 6608413 B2 JP6608413 B2 JP 6608413B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- alkyl
- aryl
- formula
- oligonucleotide
- 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.)
- Active
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 88
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 71
- 108091034117 Oligonucleotide Proteins 0.000 claims description 66
- 125000003118 aryl group Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 47
- 125000003342 alkenyl group Chemical group 0.000 claims description 46
- 125000000304 alkynyl group Chemical group 0.000 claims description 43
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 239000002777 nucleoside Substances 0.000 claims description 26
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 13
- 230000000903 blocking effect Effects 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 9
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 10
- 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
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 239000000178 monomer Substances 0.000 description 71
- 150000001875 compounds Chemical class 0.000 description 61
- -1 tert-butyl (tertiary butyl) Chemical group 0.000 description 58
- 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 50
- 239000012069 chiral reagent Substances 0.000 description 46
- 238000000034 method Methods 0.000 description 33
- 239000000126 substance Substances 0.000 description 32
- 108020004707 nucleic acids Proteins 0.000 description 29
- 150000007523 nucleic acids Chemical class 0.000 description 29
- 102000039446 nucleic acids Human genes 0.000 description 29
- 239000000543 intermediate Substances 0.000 description 27
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 25
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 25
- 229940029575 guanosine Drugs 0.000 description 25
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 24
- 229910052698 phosphorus Inorganic materials 0.000 description 22
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 21
- 235000000346 sugar Nutrition 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 16
- 125000004437 phosphorous atom Chemical group 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 230000003213 activating effect Effects 0.000 description 12
- IXOBSTQVVZZJLV-RBUKOAKNSA-N (1s)-2-[methyl(diphenyl)silyl]-1-[(2s)-pyrrolidin-2-yl]ethanol Chemical compound C([C@H]1[C@H](O)C[Si](C)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1 IXOBSTQVVZZJLV-RBUKOAKNSA-N 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 10
- 238000010511 deprotection reaction Methods 0.000 description 10
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000012039 electrophile Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000011669 selenium Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- VSYNDOLFWJVQNK-WMZOPIPTSA-N (1r)-2,2-diphenyl-1-[(2s)-pyrrolidin-2-yl]ethanol Chemical compound C=1C=CC=CC=1C([C@@H](O)[C@H]1NCCC1)C1=CC=CC=C1 VSYNDOLFWJVQNK-WMZOPIPTSA-N 0.000 description 8
- CBURWGINZWRUOM-NWDGAFQWSA-N (1r)-2-(4-nitrophenyl)-1-[(2s)-pyrrolidin-2-yl]ethanol Chemical compound C([C@@H](O)[C@H]1NCCC1)C1=CC=C([N+]([O-])=O)C=C1 CBURWGINZWRUOM-NWDGAFQWSA-N 0.000 description 8
- QQCCOFYRRVMYRV-IOWSJCHKSA-N (1s)-2-(4-methylphenyl)sulfonyl-1-[(2s)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C[C@@H](O)[C@H]1N(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCC1 QQCCOFYRRVMYRV-IOWSJCHKSA-N 0.000 description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 150000008163 sugars Chemical class 0.000 description 8
- QQCCOFYRRVMYRV-JSOSNVBQSA-N (1r)-2-(4-methylphenyl)sulfonyl-1-[(2r)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C[C@H](O)[C@@H]1N(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCC1 QQCCOFYRRVMYRV-JSOSNVBQSA-N 0.000 description 7
- IMSIQOPPUWTOCM-WMZOPIPTSA-N (r)-9h-fluoren-9-yl-[(2s)-pyrrolidin-2-yl]methanol Chemical compound C([C@H]1[C@H](O)C2C3=CC=CC=C3C3=CC=CC=C32)CCN1 IMSIQOPPUWTOCM-WMZOPIPTSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- VSYNDOLFWJVQNK-SJLPKXTDSA-N (1s)-2,2-diphenyl-1-[(2r)-pyrrolidin-2-yl]ethanol Chemical compound C=1C=CC=CC=1C([C@H](O)[C@@H]1NCCC1)C1=CC=CC=C1 VSYNDOLFWJVQNK-SJLPKXTDSA-N 0.000 description 6
- CBURWGINZWRUOM-NEPJUHHUSA-N (1s)-2-(4-nitrophenyl)-1-[(2r)-pyrrolidin-2-yl]ethanol Chemical compound C([C@H](O)[C@@H]1NCCC1)C1=CC=C([N+]([O-])=O)C=C1 CBURWGINZWRUOM-NEPJUHHUSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 5
- 229930024421 Adenine Natural products 0.000 description 5
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 5
- 0 CCCC(C)CCC(C(C(C)C)*(CC)CC)C1C(C2)C2CC1 Chemical compound CCCC(C)CCC(C(C(C)C)*(CC)CC)C1C(C2)C2CC1 0.000 description 5
- 229960000643 adenine Drugs 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229940104302 cytosine Drugs 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 229910052711 selenium Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 229940113082 thymine Drugs 0.000 description 5
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 4
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 4
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 125000004452 carbocyclyl group Chemical group 0.000 description 4
- 125000005884 carbocyclylalkyl group Chemical group 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 229940035893 uracil Drugs 0.000 description 4
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- MAVVIXJITPFFIQ-UHFFFAOYSA-N benzhydryl(chloromethyl)silane Chemical compound C=1C=CC=CC=1C([SiH2]CCl)C1=CC=CC=C1 MAVVIXJITPFFIQ-UHFFFAOYSA-N 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 3
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 150000007976 iminium ions Chemical class 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000001668 nucleic acid synthesis Methods 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 2
- DAAXYQZSKBPJOX-FQEVSTJZSA-N (2S)-2-amino-3-[4-[5-[3-(4-hydroxyphenyl)-4-methoxyphenyl]-1,2,4-oxadiazol-3-yl]phenyl]propanoic acid Chemical compound COC1=C(C=C(C=C1)C2=NC(=NO2)C3=CC=C(C=C3)C[C@@H](C(=O)O)N)C4=CC=C(C=C4)O DAAXYQZSKBPJOX-FQEVSTJZSA-N 0.000 description 2
- LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 2
- AEVBPXDFDKBGLT-YOUFYPILSA-N (2s,3s,4r,5r)-n-[2-[4-(diethoxyphosphorylmethyl)anilino]-2-oxoethyl]-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C1=CC(CP(=O)(OCC)OCC)=CC=C1NC(=O)CNC(=O)[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 AEVBPXDFDKBGLT-YOUFYPILSA-N 0.000 description 2
- TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 2
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 2
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 2
- SZCBDIVMCGFVPW-UHFFFAOYSA-N 1-[4-(aminomethyl)-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridin-3-yl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OC)=C1 SZCBDIVMCGFVPW-UHFFFAOYSA-N 0.000 description 2
- FKGZYFHAFBWWPJ-UHFFFAOYSA-N 1-phenyl-1h-imidazol-1-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=NC=C[NH+]1C1=CC=CC=C1 FKGZYFHAFBWWPJ-UHFFFAOYSA-N 0.000 description 2
- IWYHWZTYVNIDAE-UHFFFAOYSA-N 1h-benzimidazol-1-ium;trifluoromethanesulfonate Chemical compound OS(=O)(=O)C(F)(F)F.C1=CC=C2NC=NC2=C1 IWYHWZTYVNIDAE-UHFFFAOYSA-N 0.000 description 2
- WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 2
- HNFMVVHMKGFCMB-UHFFFAOYSA-N 3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine Chemical compound NC1=NC=CC=C1C1=NC2=CC=C(C=3C=CC=CC=3)N=C2N1C1=CC=C(C2(N)CCC2)C=C1 HNFMVVHMKGFCMB-UHFFFAOYSA-N 0.000 description 2
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 2
- SJQRQOKXQKVJGJ-UHFFFAOYSA-N 5-(2-aminoethylamino)naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1S(O)(=O)=O SJQRQOKXQKVJGJ-UHFFFAOYSA-N 0.000 description 2
- GONFBOIJNUKKST-UHFFFAOYSA-N 5-ethylsulfanyl-2h-tetrazole Chemical compound CCSC=1N=NNN=1 GONFBOIJNUKKST-UHFFFAOYSA-N 0.000 description 2
- MITGKKFYIJJQGL-UHFFFAOYSA-N 9-(4-chlorobenzoyl)-6-methylsulfonyl-2,3-dihydro-1H-carbazol-4-one Chemical compound ClC1=CC=C(C(=O)N2C3=CC=C(C=C3C=3C(CCCC2=3)=O)S(=O)(=O)C)C=C1 MITGKKFYIJJQGL-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 2
- ZNSPHKJFQDEABI-NZQKXSOJSA-N Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 Chemical compound Nc1nc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)cc(n1)N1CCC2(CN[C@@H](C2)C(O)=O)CC1 ZNSPHKJFQDEABI-NZQKXSOJSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229910005965 SO 2 Inorganic materials 0.000 description 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 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- NPUXORBZRBIOMQ-RUZDIDTESA-N [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]-2-pyrrolidinyl]methanol Chemical compound C=1C(OCC=2C=CC(CN3[C@H](CCC3)CO)=CC=2)=CC(C)=CC=1CS(=O)(=O)C1=CC=CC=C1 NPUXORBZRBIOMQ-RUZDIDTESA-N 0.000 description 2
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000010549 co-Evaporation Methods 0.000 description 2
- 239000012612 commercial material Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229940125876 compound 15a Drugs 0.000 description 2
- 229940126212 compound 17a Drugs 0.000 description 2
- 229940125890 compound Ia Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 description 2
- 150000003949 imides Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- YRCHYHRCBXNYNU-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 YRCHYHRCBXNYNU-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- UQZZQHGRZPTZME-UHFFFAOYSA-N oxazaphospholidine Chemical compound C1CPNO1 UQZZQHGRZPTZME-UHFFFAOYSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
- 125000000101 thioether group Chemical group 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 229940045145 uridine Drugs 0.000 description 2
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 2
- FJPKCRYEBMRPMW-XZWHSSHBSA-N (1R)-2-(4-nitrophenyl)-1-[(2S)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)C[C@@H](O)[C@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 FJPKCRYEBMRPMW-XZWHSSHBSA-N 0.000 description 1
- MOAHPTDEPLSLPI-AARKOHAPSA-N (1R)-2-[methyl(diphenyl)silyl]-1-[(2R)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C[Si](C[C@H](O)[C@@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MOAHPTDEPLSLPI-AARKOHAPSA-N 0.000 description 1
- CPQGQIUKYVZJQB-QZCRLSDHSA-N (1S)-2,2-diphenyl-1-[(2R)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C1(=CC=CC=C1)C([C@H](O)[C@@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)C1=CC=CC=C1 CPQGQIUKYVZJQB-QZCRLSDHSA-N 0.000 description 1
- FJPKCRYEBMRPMW-IHLOFXLRSA-N (1S)-2-(4-nitrophenyl)-1-[(2R)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)C[C@H](O)[C@@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 FJPKCRYEBMRPMW-IHLOFXLRSA-N 0.000 description 1
- MOAHPTDEPLSLPI-PQQNNWGCSA-N (1S)-2-[methyl(diphenyl)silyl]-1-[(2S)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C[Si](C[C@@H](O)[C@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 MOAHPTDEPLSLPI-PQQNNWGCSA-N 0.000 description 1
- VCNBSPPYALVHMK-RRPNLBNLSA-N (1S)-2-trimethylsilyl-1-[(2S)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C[Si](C[C@@H](O)[C@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)(C)C VCNBSPPYALVHMK-RRPNLBNLSA-N 0.000 description 1
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- CPQGQIUKYVZJQB-GIWKVKTRSA-N (1r)-2,2-diphenyl-1-[(2s)-1-tritylpyrrolidin-2-yl]ethanol Chemical compound C=1C=CC=CC=1C([C@@H](O)[C@H]1N(CCC1)C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 CPQGQIUKYVZJQB-GIWKVKTRSA-N 0.000 description 1
- BGWFJHBPHRTUOJ-HSZRJFAPSA-N (2r)-1-tritylpyrrolidine-2-carbaldehyde Chemical compound O=C[C@H]1CCCN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BGWFJHBPHRTUOJ-HSZRJFAPSA-N 0.000 description 1
- SLTBMTIRYMGWLX-XMMPIXPASA-N (2r)-2-[(4-chloroanilino)carbamoylamino]-3-(1h-indol-3-yl)-n-(2-phenylethyl)propanamide Chemical compound C1=CC(Cl)=CC=C1NNC(=O)N[C@@H](C(=O)NCCC=1C=CC=CC=1)CC1=CNC2=CC=CC=C12 SLTBMTIRYMGWLX-XMMPIXPASA-N 0.000 description 1
- BGWFJHBPHRTUOJ-QHCPKHFHSA-N (2s)-1-tritylpyrrolidine-2-carbaldehyde Chemical compound O=C[C@@H]1CCCN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BGWFJHBPHRTUOJ-QHCPKHFHSA-N 0.000 description 1
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
- GBBJBUGPGFNISJ-YDQXZVTASA-N (4as,7r,8as)-9,9-dimethyltetrahydro-4h-4a,7-methanobenzo[c][1,2]oxazireno[2,3-b]isothiazole 3,3-dioxide Chemical compound C1S(=O)(=O)N2O[C@@]32C[C@@H]2C(C)(C)[C@]13CC2 GBBJBUGPGFNISJ-YDQXZVTASA-N 0.000 description 1
- FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 1
- RXNPEQZHMGFNAY-GEALJGNFSA-N (5R)-4-[(1S,6R)-5-[(2S)-2-(4-chlorophenyl)-3-(propan-2-ylamino)propanoyl]-2,5-diazabicyclo[4.1.0]heptan-2-yl]-5-methyl-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one Chemical compound C[C@@H]1CC(=O)NC2=C1C(=NC=N2)N3CCN([C@H]4[C@@H]3C4)C(=O)[C@H](CNC(C)C)C5=CC=C(C=C5)Cl RXNPEQZHMGFNAY-GEALJGNFSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 description 1
- ACQLNNLTRUKJEH-GIWKVKTRSA-N (R)-9H-fluoren-9-yl-[(2S)-1-tritylpyrrolidin-2-yl]methanol Chemical compound C1=CC=CC=2C3=CC=CC=C3C(C12)[C@@H](O)[C@H]1N(CCC1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 ACQLNNLTRUKJEH-GIWKVKTRSA-N 0.000 description 1
- DPRJPRMZJGWLHY-HNGSOEQISA-N (e,3r,5s)-7-[5-(4-fluorophenyl)-3-propan-2-yl-1-pyrazin-2-ylpyrazol-4-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)/C=C/C=1C(C(C)C)=NN(C=2N=CC=NC=2)C=1C1=CC=C(F)C=C1 DPRJPRMZJGWLHY-HNGSOEQISA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- ZQPJNJKCPJDTIQ-UHFFFAOYSA-N 1-(chloromethylsulfonyl)-4-methylbenzene Chemical compound CC1=CC=C(S(=O)(=O)CCl)C=C1 ZQPJNJKCPJDTIQ-UHFFFAOYSA-N 0.000 description 1
- YCGQPIRMLGEWMW-UHFFFAOYSA-N 1-[1-butyl-4-(3-methoxyphenyl)-2-oxo-1,8-naphthyridin-3-yl]-3-[4-[(dimethylamino)methyl]-2,6-di(propan-2-yl)phenyl]urea;hydrochloride Chemical compound Cl.CC(C)C=1C=C(CN(C)C)C=C(C(C)C)C=1NC(=O)NC=1C(=O)N(CCCC)C2=NC=CC=C2C=1C1=CC=CC(OC)=C1 YCGQPIRMLGEWMW-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- XGDRLCRGKUCBQL-UHFFFAOYSA-N 1h-imidazole-4,5-dicarbonitrile Chemical compound N#CC=1N=CNC=1C#N XGDRLCRGKUCBQL-UHFFFAOYSA-N 0.000 description 1
- MOKKMYFSTPXQKE-UHFFFAOYSA-N 2-(dimethylamino)acetonitrile;trifluoromethanesulfonic acid Chemical compound C[NH+](C)CC#N.[O-]S(=O)(=O)C(F)(F)F MOKKMYFSTPXQKE-UHFFFAOYSA-N 0.000 description 1
- WAYFZYZAFJBXFJ-UHFFFAOYSA-N 2-chloro-1,3,2-oxazaphospholidine Chemical class ClP1NCCO1 WAYFZYZAFJBXFJ-UHFFFAOYSA-N 0.000 description 1
- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 1
- DUSHQROJSFJSPX-UHFFFAOYSA-N 2-piperidin-1-ylacetonitrile;trifluoromethanesulfonic acid Chemical compound [O-]S(=O)(=O)C(F)(F)F.N#CC[NH+]1CCCCC1 DUSHQROJSFJSPX-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ONSASHBHHZNQQZ-UHFFFAOYSA-N 2-pyrrolidin-1-ium-1-ylacetonitrile;trifluoromethanesulfonate Chemical compound N#CC[NH+]1CCCC1.[O-]S(=O)(=O)C(F)(F)F ONSASHBHHZNQQZ-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- QAJJXHRQPLATMK-UHFFFAOYSA-N 4,5-dichloro-1h-imidazole Chemical compound ClC=1N=CNC=1Cl QAJJXHRQPLATMK-UHFFFAOYSA-N 0.000 description 1
- TXEBWPPWSVMYOA-UHFFFAOYSA-N 4-[3-[(1-amino-2-chloroethyl)amino]propyl]-1-[[3-(2-chlorophenyl)phenyl]methyl]-5-hydroxyimidazolidin-2-one Chemical compound NC(CCl)NCCCC1NC(=O)N(Cc2cccc(c2)-c2ccccc2Cl)C1O TXEBWPPWSVMYOA-UHFFFAOYSA-N 0.000 description 1
- MIUOBAHGBPSRKY-UHFFFAOYSA-N 5-(4-nitrophenyl)-2h-tetrazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NNN=N1 MIUOBAHGBPSRKY-UHFFFAOYSA-N 0.000 description 1
- KUZSBKJSGSKPJH-VXGBXAGGSA-N 5-[(9R)-6-[(3R)-3-methylmorpholin-4-yl]-11-oxa-1,3,5-triazatricyclo[7.4.0.02,7]trideca-2,4,6-trien-4-yl]pyrazin-2-amine Chemical compound C[C@@H]1COCCN1c1nc(nc2N3CCOC[C@H]3Cc12)-c1cnc(N)cn1 KUZSBKJSGSKPJH-VXGBXAGGSA-N 0.000 description 1
- GXGKKIPUFAHZIZ-UHFFFAOYSA-N 5-benzylsulfanyl-2h-tetrazole Chemical compound C=1C=CC=CC=1CSC=1N=NNN=1 GXGKKIPUFAHZIZ-UHFFFAOYSA-N 0.000 description 1
- KUEFXPHXHHANKS-UHFFFAOYSA-N 5-nitro-1h-1,2,4-triazole Chemical compound [O-][N+](=O)C1=NC=NN1 KUEFXPHXHHANKS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 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 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229930182476 C-glycoside Natural products 0.000 description 1
- 150000000700 C-glycosides Chemical class 0.000 description 1
- QUMCIHKVKQYNPA-RUZDIDTESA-N C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC Chemical compound C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC QUMCIHKVKQYNPA-RUZDIDTESA-N 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- WUZBOJXXYMKMMF-UHFFFAOYSA-N COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F Chemical compound COC1=CC2=NC=3N(C(N(C(C=3N2C=C1)=O)CCC)=O)CCCCNC(=O)C1=CC=C(C=C1)S(=O)(=O)F WUZBOJXXYMKMMF-UHFFFAOYSA-N 0.000 description 1
- HXPOFOOMWKMXHG-UHFFFAOYSA-N C[Mg]C[SiH](C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound C[Mg]C[SiH](C1=CC=CC=C1)C1=CC=CC=C1 HXPOFOOMWKMXHG-UHFFFAOYSA-N 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- NHAOZNGYIICRJH-RBUKOAKNSA-N C[Si](C[C@H]1O[P-]N2[C@H]1CCC2)(c1ccccc1)c1ccccc1 Chemical compound C[Si](C[C@H]1O[P-]N2[C@H]1CCC2)(c1ccccc1)c1ccccc1 NHAOZNGYIICRJH-RBUKOAKNSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 1
- 229930182820 D-proline Natural products 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- PQIPFCFHSJBFSV-UHFFFAOYSA-N [9-(2-carboxyphenyl)-6-(dimethylamino)xanthen-3-ylidene]-dimethylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C(O)=O PQIPFCFHSJBFSV-UHFFFAOYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000007825 activation reagent Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000006323 alkenyl amino group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000005108 alkenylthio group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000006319 alkynyl amino group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 125000005109 alkynylthio group Chemical group 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000000732 arylene group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- BYKCUMSOQIPHSR-UHFFFAOYSA-N boron;n-ethyl-n-propan-2-ylpropan-2-amine Chemical group [B].CCN(C(C)C)C(C)C BYKCUMSOQIPHSR-UHFFFAOYSA-N 0.000 description 1
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- OOCUOKHIVGWCTJ-UHFFFAOYSA-N chloromethyl(trimethyl)silane Chemical compound C[Si](C)(C)CCl OOCUOKHIVGWCTJ-UHFFFAOYSA-N 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 229940120124 dichloroacetate Drugs 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-UHFFFAOYSA-N hexopyranose Chemical group OCC1OC(O)C(O)C(O)C1O WQZGKKKJIJFFOK-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- BTJRKNUKPQBLAL-UHFFFAOYSA-N hydron;4-methylmorpholine;chloride Chemical compound Cl.CN1CCOCC1 BTJRKNUKPQBLAL-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- PHVXTQIROLEEDB-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-n-pyrrolidin-3-ylbenzamide Chemical compound CC1=CC=CC=C1C1CN(CC=2C=CC(=CC=2)C(=O)N(CCC=2C(=CC=CC=2)Cl)C2CNCC2)CCC1 PHVXTQIROLEEDB-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N oxane-2,3,4,5-tetrol Chemical compound OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 125000005545 phthalimidyl group Chemical group 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65844—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a five-membered ring which may be condensed with another ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/11—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/213—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Saccharide Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Description
式(I’)において、G1およびG2は、上と同じである。すなわち、G1およびG2は、独立に、水素原子、ニトロ基、ハロゲン原子、シアノ基、式(II)もしくは(III)の基であるか、または、G1およびG2の両方は、一緒になって、式(IV)の基を形成する。
(S)−2−(メチルジフェニルシリル)−1−((S)−ピロリジン−2−イル)エタノール(III−a)
(R)−2−(メチルジフェニルシリル)−1−((R)−1−ピロリジン−2−イル)エタノール(III−b)
(S)−2−(トリメチルシリル)−1−((S)−1−ピロリジン−2−イル)エタノール(V−a)
(R)−2,2−ジフェニル−1−((S)−ピロリジン−2−イル)エタノール(VII−a)
(S)−2,2−ジフェニル−1−((R)−ピロリジン−2−イル)エタノール(VII−b)
(R)−2−(4−ニトロフェニル)−1−((S)−ピロリジン−2−イル)エタノール(IX−a)
(S)−2−(4−ニトロフェニル)−1−((R)−ピロリジン−2−イル)エタノール(IX−b)
(R)−(9H−フルオロレン−9−イル)((S)−ピロリジン−2−イル)メタノール(XI−a)
(S)−2−トシル−1−((S)−1−トリチルピロリジン−2−イル)エタノール(XIII−a)
(R)−2−トシル−1−((R)−1−トリチルピロリジン−2−イル)エタノール(XIII−b)
の1つから選択されるものである。
Y1は、O、NRd、S、またはSeである。
Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)である。
Reは、独立に、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、またはヘテロアリール−Y2−、あるいは、Na+、Li+、またはK+である陽イオンである。
Y2は、O、NRd、またはSである。
本明細書において開示されるすべての刊行物および特許出願は、各々の個々の刊行物または特許出願が具体的かつ個別に参照により援用されると示されているのと同じ程度に参照によりその全文が本明細書に援用される。
(S)−2−(メチルジフェニルシリル)−1−((S)−ピロリジン−2−イル)エタノール(III−a)
(R)−2−(メチルジフェニルシリル)−1−((R)−1−ピロリジン−2−イル)エタノール(III−b)
(S)−2−(トリメチルシリル)−1−((S)−1−ピロリジン−2−イル)エタノール(V−a)
(R)−2,2−ジフェニル−1−((S)−ピロリジン−2−イル)エタノール(VII−a)
(S)−2,2−ジフェニル−1−((R)−ピロリジン−2−イル)エタノール(VII−b)
(R)−2−(4−ニトロフェニル)−1−((S)−ピロリジン−2−イル)エタノール(IX−a)
(S)−2−(4−ニトロフェニル)−1−((R)−ピロリジン−2−イル)エタノール(IX−b)
(R)−(9H−フルオロレン−9−イル)((S)−ピロリジン−2−イル)メタノール(XI−a)
(S)−2−トシル−1−((S)−1−トリチルピロリジン−2−イル)エタノール(XIII−a)
(R)−2−トシル−1−((R)−1−トリチルピロリジン−2−イル)エタノール(XIII−b)
の1つから選択されるものである。
Y1は、O、NRd、S、またはSeである。
Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)である。
Reは、独立に、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、またはヘテロアリール−Y2−、あるいは、Na+、Li+、またはK+である陽イオンである。
Y2は、O、NRd、またはSである。
アルキルの好ましい例はC1−10アルキル基であり、アルケニルの好ましい例はC2−10アルケニルであり、アルキニルの好ましい例はC2−10アルキニルであり、アリールの好ましい例はC6−14アリールであり、ヘテロアリールの好ましい例はC6−14ヘテロアリールである。
アキラルH−ホスホネート部分を第1の活性化試薬で処理して第1の中間体を形成する。一実施形態では、第1の活性化試薬は、縮合工程の間に反応混合物に添加される。第1の活性化試薬の使用は、反応に使用される溶媒などの反応条件に依存する。第1の活性化試薬の例は、ホスゲン、クロロ蟻酸トリクロロメチル、ビス(トリクロロメチル)カーボネート(BTC)、塩化オキサリル、Ph3PCl2、(PhO)3PCl2、N,N’−ビス(2−オキソ−3−オキサゾリジニル)ホスフィン酸クロリド(BopCl)、1,3−ジメチル−2−(3−ニトロ−1,2,4−トリアゾール−1−イル)−2−ピロリジン−1−イル−1,3,2−ジアザホスホリジニウムヘキサフルオロホスフェート(MNTP)、または3−ニトロ−1,2,4−トリアゾール−1−イル−トリス(ピロリジン−1−イル)ホスホニウムヘキサフルオロホスフェート(PyNTP)である。
第1の活性化工程の後に、活性化したアキラルH−ホスホネート部分は、キラル試薬(式(I)または(I’)によって表される)と反応して、式(Va)、(Vb)、(Va’)、または(Vb’)のキラル中間体を形成する。
式Va((Vb)、(Va’)、または(Vb’))のキラル中間体を、第2の活性化試薬およびヌクレオシドで処理して、濃縮中間体を形成する。ヌクレオシドは凝固していてもよい。第2の活性化試薬の例は、4,5−ジシアノイミダゾール(DCI)、4,5−ジクロロイミダゾール、1−フェニルイミダゾリウムトリフラート(PhIMT)、ベンズイミダゾリウムトリフラート(BIT)、ベンズトリアゾール、3−ニトロ−1,2,4−トリアゾール(NT)、テトラゾール、5−エチルチオテトラゾール(ETT)、5−ベンジルチオテトラゾール(BTT)、5−(4−ニトロフェニル)テトラゾール、N−シアノメチルピロリジニウムトリフラート(CMPT)、N−シアノメチルピペリジニウムトリフラート、N−シアノメチルジメチルアンモニウムトリフラートである。式Va((Vb)、(Va’)、または(Vb’))のキラル中間体は、モノマーとして単離することができる。通常、Va((Vb)、(Va’)、または(Vb’))のキラル中間体は単離されず、同じポットでヌクレオシドまたは修飾ヌクレオシドとの反応を受けて、濃縮中間体であるキラルホスフィット化合物を提供する。その他の実施形態では、この方法を固相合成によって実施する場合、化合物を含む固相支持体を濾過して副生成物、不純物、および/または試薬から分離する。
最終核酸が二量体よりも大きい場合、未反応の−OH部分をブロッキング基でキャッピングし、化合物中のキラル補助剤もブロッキング基でキャッピングして、キャッピングされた濃縮中間体を形成することができる。最終核酸が二量体である場合、キャッピング工程は必要ではない。
化合物は、求電子物質との反応によって修飾される。キャッピングした濃縮中間体に、修飾工程を実施することができる。本方法の一部の実施形態では、修飾工程は、硫黄求電子剤、セレン求電子剤またはホウ素化剤を用いて実施される。修飾工程の好ましい例は、酸化および硫化の工程である。
S8(式B)、Z1−S−S−Z2、またはZ1−S−V−Z2。
Se(式G)、Z3−Se−Se−Z4、またはZ3−Se−V−Z4
キャッピングした濃縮中間体をデブロッキングして、成長する核酸鎖の5’末端のブロッキング基を除去して化合物を得る。化合物を所望により鎖伸長サイクルに再び入らせて、濃縮中間体、キャッピングした濃縮中間体、修飾しキャッピングした濃縮中間体、および5’−脱保護し修飾しキャッピングした中間体を形成する。少なくとも1ラウンドの鎖伸長サイクルの後、5’−脱保護して修飾してキャッピングした中間体を、キラル補助剤配位子およびその他の保護基、例えば、核酸塩基、修飾核酸塩基、糖および修飾糖保護基の除去によりさらにデブロッキングして、核酸を得る。その他の実施形態では、5’−OH部分を含むヌクレオシドは、本明細書に記載されるような以前の鎖伸長サイクルからの中間体である。さらに他の実施形態では、5’−OH部分を含むヌクレオシドは、別の公知の核酸合成方法から得られる中間体である。固相支持体を使用する実施形態では、リン原子修飾核酸を次に固相支持体から切断する。ある種の実施形態では、精製目的のために核酸は固相支持体に付着させたままにされ、その後、精製の後に固相支持体から切断される。
ac:アセチル
bz:ベンゾイル
CSO:(1S)−(+)−(10−カンファースルホニル)オキサジリジン
DBU:1,8−ジアザビシクロ[5.4.0]ウンデカ−7−エン
DCA:ジクロロ酢酸
DCM:ジクロロメタン、CH2Cl2
DMTr:4,4’−ジメトキシトリチル
Tr:トリチル、トリフェニルメチル
MeIm:N−メチルイミダゾール
NIS:N−ヨードスクシンイミド
pac:フェノキシアセチル
Ph:フェニル
PhIMT:N−フェニルイミダゾリウムトリフラート
POS:3−フェニル−1,2,4−ジチアゾリン−5−オン
TBS:tert−ブチルジメチルシリル
TBDPS:tert−ブチルジフェニルシリル
TOM:トリイソプロピルシロキシメチル
TFA:トリフルオロ酢酸
1H NMR(300MHz,CDCl3)δ 7.48−7.08(25H,m),4.33−4.23(1H,m),3.16−2.89(3H,m),2.84(1H,brs),1.70−1.54(1H,m),1.35(1H,dd,J=14.7,6.3Hz),1.10(1H,dd,J=14.7,8.1Hz),1.18−1.05(1H,m),1.04−0.90(1H,m),0.34(3H,s),−0.17−−0.36(1H,m)。
1H NMR(300MHz,CDCl3)δ 7.57−7.52(5H,m),7.38−7.33(5H,m),3.77(1H,ddd,J=8.9,5.4,3.5Hz),3.01(1H,dt,J=7.4,3.6Hz),2.97−2.79(2H,m),2.27(2H,brs),1.76−1.53(4H,m),1.38(1H,dd,J=15.0,9.0Hz),1.24(1H,dd,J=15.0,5.4Hz),0.65(3H,s);13C NMR(100.4MHz,CDCl3)δ 137.4,137.1,134.6,134.5,129.1,127.8,69.5,64.1,47.0,25.8,24.0,19.6,−3.4.MALDI TOF−MS m/z C19H26NOSiに対する計算値[M+H]+ 312.18、実測値312.06。
1H NMR(300MHz,CDCl3)δ 7.48−7.12(25H,m),4.33−4.24(1H,m),3.16−2.89(3H,m),2.86(1H,brs),1.69−1.52(1H,m),1.35(1H,dd,J=14.4,6.0Hz),1.10(1H,dd,J=14.4,8.4Hz),1.18−1.05(1H,m),1.03−0.89(1H,m),0.33(3H,s),−0.19−−0.39(1H,m);13C NMR(75.5MHz,CDCl3)δ 144.5,137.5,136.8,134.6,134.3,129.8,129.0,127.8,127.7,127.4,126.1,77.9,71.7,65.1,53.5,25.0,24.8,19.6,−4.0.MALDI TOF−MS m/z C38H40NOSiに対する計算値[M+H]+ 554.29、実測値554.09。
1H NMR(300MHz,CDCl3)δ 7.58−7.52(5H,m),7.38−7.33(5H,m),3.78(1H,ddd,J=9.0,5.1,3.6Hz),3.00(1H,dt,J=7.4,3.3Hz),2.97−2.78(2H,m),2.19(2H,brs),1.76−1.53(4H,m),1.38(1H,dd,J=14.6,9.0Hz),1.24(1H,dd,J=14.6,5.1Hz),0.66(3H,s);13C NMR(75.5MHz,CDCl3)δ 137.5,137.1,134.5,134.4,129.0,127.7,69.2,64.2,46.9,25.8,24.0,19.7,−3.4.MALDI TOF−MS m/z C19H26NOSiに対する計算値[M+H]+ 312.18、実測値312.09。
1H NMR(300MHz,CDCl3)δ 7.58−7.51(5H,m),7.31−7.14(10H,m),4.13(1H,dt,J=7.5,3.0Hz),3.39−3.31(1H,m),3.20−2.99(2H,m),2.84(1H,s),1.74−1.57(1H,m),1.29−1.10(2H,m),0.74(1H,dd,J=14.4,7.2Hz),0.46(1H,dd,J=14.4,7.2Hz),−0.15(9H,s).MALDI TOF−MS m/z C28H36NOSiに対する計算値[M+H]+ 430.26、実測値430.09。
1H NMR(300MHz,CDCl3)δ 3.76(1H,ddd,J=8.8,5.7,3.3Hz),3.08(1H,dt,J=7.8,3.3Hz),3.02−2.87(2H,m),2.48(2H,brs),1.81−1.58(4H,m),0.83(1H,dd,J=14.7,8.7Hz),0.68(1H,dd,J=14.7,6.0Hz),0.05(9H,s);13C NMR(75.5MHz,CDCl3)δ 69.6,64.3,46.9,25.8,23.9,22.0,−0.8.MALDI TOF−MS m/z C9H22NOSiに対する計算値[M+H]+ 188.15、実測値188.00。
1H NMR(300MHz,CDCl3)δ 7.45−7.01(23H,m),6.67−6.61(2H,m),4.80(1H,d,J=10.8Hz),3.63(1H,d,J=10.8Hz),3.36−3.27(1H,m),3.23−3.09(1H,m),3.02−2.89(1H,m),2.66(1H,s),1.90−1.75(1H,m),1.32−1.04(2H,m),0−−0.18(1H,m)。
1H NMR(300MHz,CDCl3)δ 7.44−7.38(2H,m),7.33−7.14(8H,m),4.46(1H,dd,J=9.9,3.3Hz),3.91(1H,d,J=9.9Hz),3.02−2.88(2H,m),2.81−2.69(1H,m),2.52(2H,brs),1.88−1.56(4H,m);13C NMR(75.5MHz,CDCl3)δ 142.3,142.0,128.6,128.5,128.4,128.2,126.5,126.4,73.5,60.1,55.8,46.6,25.8,23.4.MALDI TOF−MS m/z C18H22NOに対する計算値[M+H]+ 268.17、実測値268.06。
1H NMR(300MHz,CDCl3)δ 7.44−7.37(6H,m),7.30−7.01(17H,m),6.66−6.61(2H,m),4.80(1H,d,J=10.8Hz),3.63(1H,d,J=10.8Hz),3.36−3.28(1H,m),3.22−3.09(1H,m),3.01−2.89(1H,m),2.66(1H,s),1.90−1.75(1H,m),1.29−1.04(2H,m),0.00−−0.19(1H,m);13C NMR(75.5MHz,CDCl3)δ 144.2,142.9,141.6,130.0,128.5,128.4,127.9,127.8,127.4,126.4,126.2,77.9,75.9,61.9,55.4,53.4,24.7,24.5.MALDI TOF−MS m/z C37H36NOに対する計算値[M+H]+ 510.28、実測値510.11。
1H NMR(300MHz,CDCl3)δ 7.45−7.14(10H,m),4.45(1H,dd,J=9.9,3.3Hz),3.91(1H,d,J=9.9Hz),3.00−2.89(2H,m),2.82−2.71(1H,m),2.40(2H,brs),1.87−1.55(4H,m);13C NMR(75.5MHz,CDCl3)δ 142.3,142.0,128.5,128.3,128.1,126.3,126.2,73.4,60.1,55.9,46.5,25.8,23.5.MALDI TOF−MS m/z C18H22NOに対する計算値[M+H]+ 268.17、実測値268.03。
1H NMR(300MHz,CDCl3)δ 8.09−8.03(2H,m),7.49−7.43(6H,m),7.28−7.09(11H,m),4.23(1H,ddd,J=8.3,5.6,3.0Hz),3.43−3.33(1H,m),3.23−3.11(1H,m),3.07−2.96(1H,m),2.83(1H,brs),2.74(1H,dd,J=13.8,8.4Hz),2.49(1H,dd,J=13.8,5.1Hz),1.83−1.67(1H,m),1.41−1.17(2H,m),0.27−0.08(1H,m);13C NMR(75.5MHz,CDCl3)δ 147.3,146.3,144.3,129.8,129.6,127.5,126.3,123.4,77.9,74.8,63.5,53.2,39.5,25.0,24.9.MALDI TOF−MS m/z C31H31N2O3に対する計算値[M+H]+ 479.23、実測値479.08。
1H NMR(300MHz,CDCl3)δ 8.15(2H,d,J=8.7Hz),7.42(2H,d,J=8.7Hz),3.86−3.79(1H,m),3.16−3.07(1H,m),2.99−2.68(6H,m),1.84−1.68(4H,m);13C NMR(75.5MHz,CDCl3)δ 147.4,146.2,129.9,123.2,72.4,62.0,46.6,40.4,25.7,24.4.MALDI TOF−MS m/z C12H17N2O3に対する計算値[M+H]+ 237.12、実測値237.01。
1H NMR(300MHz,CDCl3)δ 8.09−8.04(2H,m),7.49−7.43(6H,m),7.28−7.09(11H,m),4.22(1H,ddd,J=8.4,5.6,3.0Hz),3.43−3.33(1H,m),3.24−3.10(1H,m),3.08−2.94(1H,m),2.81(1H,brs),2.75(1H,dd,J=14.0,8.1Hz),2.49(1H,dd,J=14.0,5.1Hz),1.81−1.67(1H,m),1.40−1.16(2H,m),0.26−0.09(1H,m);13C NMR(75.5MHz,CDCl3)δ 147.3,144.3,129.8,129.6,129.4,126.3,123.5,77.9,74.8,63.5,53.2,39.5,25.0,24.9.MALDI TOF−MS m/z C31H31N2O3に対する計算値[M+H]+ 479.23、実測値479.08。
1H NMR(300MHz,CDCl3)δ 8.19−8.13(2H,m),7.45−7.39(2H,m),3.83(1H,ddd,J=7.7,5.4,3.9Hz),3.14(1H,dt,J=7.7,3.9Hz),3.01−2.87(2H,m),2.83(1H,d,J=3.3Hz),2.81(1H,s),2.62(2H,brs),1.79−1.72(4H,m);13C NMR(75.5MHz,CDCl3)δ 147.3,146.5,130.0,123.5,72.7,61.7,46.7,40.1,25.8,24.2.MALDI TOF−MS m/z C12H17N2O3に対する計算値[M+H]+ 237.12、実測値237.02。
1H NMR(300MHz,CDCl3)δ 7.70(1H,d,J=7.5Hz),7.66(1H,d,J=7.8Hz),7.55(2H,d,J=7.5Hz),7.44−7.09(18H,m),6.87−6.62(1H,m),4.55−4.48(1H,m),4.06(1H,d,J=7.5Hz),3.43−3.34(1H,m),3.18−3.06(1H,m),2.98−2.88(1H,m),2.85(1H,brs),1.42−1.24(1H,m),1.18−1.04(1H,m),0.53−0.39(1H,m),−0.02−−0.20(1H,m);MALDI TOF−MS m/z C37H34NOに対する計算値[M+H]+ 508.26、実測値508.12。
1H NMR(300MHz,CDCl3)δ 7.76(2H,d,J=7.5Hz),7.68(2H,t,J=8.0Hz),7.43−7.35(2H,m),7.34−7.25(2H,m),4.28(1H,d,J=6.3Hz),4.03(1H,dd,J=6.5,4.2Hz),3.19−3.11(1H,m),2.97−2.88(1H,m),2.86−2.76(1H,m),2.02(2H,brs),1.77−1.53(3H,m),1.38−1.23(1H,m);MALDI TOF−MS m/z C18H20NOに対する計算値[M+H]+ 266.15、実測値266.04。
1H NMR(600MHz,CDCl3)δ 7.66(2H,d,J=8.4Hz),7.48−7.44(6H,m),7.35(2H,d,J=7.2Hz),7.21−7.13(9H,m),4.39−4.36(1H,m),3.33(1H,s),3.24−3.20(1H,m),3.19−3.10(2H,m),2.98−2.92(2H,m),2.49(3H,s),1.55−1.49(1H,m),1.33−1.26(1H,m),1.12−1.04(1H,m),0.22−0.14(1H,m);13C NMR(150.9MHz,CDCl3)δ 144.6,144.5,136.3,129.9,129.5,128.1,127.5,126.2,78.0,69.1,63.9,60.2,52.6,25.5,24.7,21.7。
1H NMR(600MHz,CDCl3)δ 7.82(2H,d,J=8.4Hz),7.37(2H,d,J=8.4Hz),4.01(1H,ddd,J=12.0,5.1,3.0Hz),3.32(1H,dd,J=14.4,3.0Hz),3.25(1H,dd,J=14.4,9.0Hz),3.16(1H,dt,J=7.8,5.1Hz),2.90−2.82(2H,m),2.46(3H,s),2.04(2H,brs),1.78−1.63(3H,m),1.62−1.55(1H,m);13C NMR(150.9MHz,CDCl3)δ 144.5,136.7,129.7,127.7,67.4,61.8,60.1,46.7,25.7,21.4.MALDI TOF−MS m/z C13H20NO3Sに対する計算値[M+H]+ 270.12、実測値270.04。
1H NMR(600MHz,CDCl3)δ 7.66(2H,d,J=8.4Hz),7.47−7.44(6H,m),7.35(2H,d,J=7.8Hz),7.21−7.13(9H,m),4.37(1H,dt,J=8.6,2.4Hz),3.33(1H,s),3.23−3.20(1H,m),3.19−3.12(2H,m),2.98−2.92(2H,m),2.49(3H,s),1.56−1.49(1H,m),1.32−1.26(1H,m),1.11−1.03(1H,m),0.23−0.15(1H,m);13C NMR(150.9MHz,CDCl3)δ 144.6,144.5,136.3,129.9,129.6,128.1,127.6,126.2,78.0,69.1,63.9,60.2,52.6,25.5,24.7,21.7。
1H NMR(600MHz,CDCl3)δ 7.82(2H,d,J=8.4Hz),7.37(2H,d,J=8.4Hz),4.01(1H,ddd,J=9.0,5.1,3.0Hz),3.32(1H,dd,J=14.4,3.0Hz),3.25(1H,dd,J=14.4,9.0Hz),3.17(1H,dt,J=7.2,5.1Hz),2.89−2.83(2H,m),2.46(3H,s),2.04(2H,brs),1.79−1.64(3H,m),1.62−1.55(1H,m);13C NMR(150.9MHz,CDCl3)δ 144.8,136.6,129.8,127.9,67.7,61.8,60.1,46.8,25.9,25.8,21.6.MALDI TOF−MS m/z C13H20NO3Sに対する計算値[M+H]+ 270.12、実測値270.05。
1H NMR(300MHz,CDCl3)δ 8.77(1H,brs),7.99(1H,s),7.54−6.98(24H,m),6.81−6.73(4H,m),6.35(1H,dd,J=8.0,6.3Hz),4.89−4.73(4H,m),4.68(2H,brs),4.05−3.98(1H,m),3.75(6H,s),3.62−3.46(1H,m),3.41−3.20(3H,m),3.18−3.04(1H,m),3.08(2H,t,J=6.6Hz),2.58−2.36(2H,m),1.94−1.59(2H,m),1.56(1H,dd,J=15.0,8.7Hz),1.43(1H,dd,J=15.0,5.7Hz),1.33−1.16(2H,m),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 153.5(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.80(1H,brs),7.96(1H,s),7.54−6.96(24H,m),6.79−6.71(4H,m),6.19(1H,t,J=6.6Hz),4.90−4.73(4H,m),4.66(2H,brs),4.16−4.08(1H,m),3.76(6H,s),3.60−3.36(2H,m),3.29(1H,d,J=3.9Hz),3.27−3.12(2H,m),3.09(2H,t,J=6.6Hz),2.59−2.46(1H,m),2.07−1.97(1H,m),1.94−1.41(5H,m),1.36−1.18(1H,m),0.65(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.1(1P,s)。
1H NMR(600MHz,CDCl3)δ 8.71(1H,s),8.12(1H,s),8.04(2H,d,J=7.8Hz),7.62−7.15(23H,m),6.80−6.75(4H,m),6.37(1H,dd,J=7.8,6.0Hz),4.94−4.88(1H,m),4.80(1H,ddd,J=12.0,6.0,5.4Hz),4.07−4.04(1H,m),3.76(6H,s),3.58−3.49(1H,m),3.41−3.34(1H,m),3.33(1H,dd,J=10.8,4.8Hz),3.25(1H,dd,J=10.8,4.8Hz),3.13−3.06(1H,m),2.66−2.58(1H,m),2.40−2.35(1H,m),1.91−1.84(1H,m),1.73−1.66(1H,m),1.56(1H,dd,J=15.0,9.0Hz),1.44(1H,dd,J=15.0,5.4Hz),1.47−1.41(1H,m),1.30−1.23(1H,m),0.63(3H,s);31P NMR(243.0MHz,CDCl3)δ 151.8(1P,s)。
1H NMR(300MHz,CDCl3)δ 9.06(1H,brs),8.76(1H,s),8.12(1H,s),8.07−7.99(2H,m),7.64−7.14(22H,m),6.83−6.75(4H,m),6.25(1H,t,J=6.6Hz),4.86−4.75(2H,m),4.20−4.15(1H,m),3.77(6H,s),3.61−3.38(2H,m),3.36(1H,dd,J=10.2,4.2Hz),3.27(1H,dd,J=10.2,4.2Hz),3.27−3.13(1H,m),2.71−2.59(1H,m),2.12−2.01(1H,m),1.94−1.42(5H,m),1.36−1.20(1H,m),0.67(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.3(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.33(1H,brs),8.17(1H,d,J=7.5Hz),7.52−7.22(19H,m),7.07(1H,d,J=7.5Hz),6.88−6.81(4H,m),6.20(1H,t,J=6.2Hz),4.81−4.64(2H,m),3.93−3.87(1H,m),3.79(6H,s),3.59−3.43(1H,m),3.39−3.29(3H,m),3.16−3.02(1H,m),2.69−2.52(2H,m),2.12−2.00(1H,m),1.91−1.50(3H,m),1.47−1.32(2H,m),1.27−1.16(7H,m),0.60(3H,s);31P NMR(121.5MHz,CDCl3)δ 154.8(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.33(1H,d,J=7.5Hz),8.23(1H,brs),7.57−7.22(19H,m),7.12(1H,d,J=7.5Hz),6.88−6.81(4H,m),6.15(1H,dd,J=6.6,4.2Hz),4.82−4.63(2H,m),4.03−3.97(1H,m),3.80(6H,s),3.55−3.26(4H,m),3.19−3.05(1H,m),2.59(1H,quintet,J=6.9Hz),2.39−2.27(1H,m),2.21−2.10(1H,m),1.90−1.56(3H,m),1.50−1.32(2H,m),1.26−1.17(7H,m),0.66(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.58−7.23(21H,m),6.86−6.79(4H,m),6.35(1H,dd,J=8.1,5.7Hz),4.79−4.67(2H,m),3.83−3.78(1H,m),3.78(6H,s),3.59−3.43(1H,m),3.34(1H,dd,J=10.5,2.4Hz),3.35−3.24(1H,m),3.20(1H,dd,J=10.5,2.4Hz),3.16−3.02(1H,m),2.36−2.26(1H,m),2.15−2.02(1H,m),1.92−1.77(1H,m),1.74−1.59(1H,m),1.52(1H,dd,J=14.7,9.0Hz),1.40(3H,s),1.45−1.15(3H,m),0.60(3H,s);31P NMR(121.5MHz,CDCl3)δ 153.7(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.46(1H,brs),7.59−7.20(20H,m),6.86−6.79(4H,m),6.26(1H,t,J=6.8Hz),4.78−4.65(2H,m),4.01−3.95(1H,m),3.78(6H,s),3.55−3.40(1H,m),3.42(1H,dd,J=10.5,2.7Hz),3.40−3.28(1H,m),3.22(1H,dd,J=10.5,3.0Hz),3.19−3.06(1H,m),2.16−1.95(2H,m),1.90−1.54(3H,m),1.49−1.35(1H,m),1.43(3H,s),1.34−1.17(2H,m),0.67(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.66(1H,s),8.13(1H,s),8.03(2H,d,J=7.2Hz),7.64−7.16(23H,m),6.79(4H,d,J=8.7Hz),6.08(1H,d,J=6.3Hz),4.91−4.81(1H,m),4.77−4.69(1H,m),4.64−4.57(1H,m),4.15−4.10(1H,m),3.76(6H,s),3.60−3.23(4H,m),3.35(3H,s),3.14−3.00(1H,m),1.90−1.19(6H,m),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.8(1P,s)。
1H NMR(300MHz,CDCl3)δ 9.12(1H,brs),8.73(1H,s),8.24(1H,s),8.07−8.01(2H,m),7.62−7.17(22H,m),6.83−6.77(4H,m),6.12(1H,d,J=4.8Hz),4.84−4.73(2H,m),4.43(1H,t,J=4.8Hz),4.25−4.19(1H,m),3.77(6H,s),3.55−3.20(4H,m),3.28(3H,s),3.16−3.03(1H,m),1.90−1.17(6H,m),0.65(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.0(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.49(1H,d,J=7.2Hz),7.58−7.20(19H,m),6.96(1H,d,J=7.2Hz),6.90−6.82(4H,m),5.98(1H,s),4.84(1H,dd,J=13.1,7.5Hz),4.59(1H,dt,J=8.3,4.5Hz),4.19−4.13(1H,m),3.79(6H,s),3.78−3.72(1H,m),3.63−3.40(3H,m),3.55(3H,s),3.36−3.24(1H,m),3.09−2.95(1H,m),2.59(1H,septet,J=6.9Hz),1.85−1.53(5H,m),1.48−1.37(1H,m),1.24−1.17(6H,m),0.59(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.62(1H,d,J=7.5Hz),7.57−7.23(19H,m),7.02(1H,d,J=7.5Hz),6.89−6.81(4H,m),5.92(1H,s),4.90(1H,dt,J=9.0,5.7Hz),4.61(1H,dt,J=8.7,4.8Hz),4.25−4.17(1H,m),3.81(6H,s),3.67(1H,d,J=4.5Hz),3.62−3.25(4H,m),3.38(3H,s),3.16−3.02(1H,m),2.58(1H,septet,J=6.9Hz),1.87−1.40(6H,m),1.26−1.14(6H,m),0.64(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.67(1H,brs),8.01(1H,s),7.56−7.16(24H,m),6.83−6.74(4H,m),6.08(1H,d,J=6.9Hz),4.85−4.76(1H,m),4.84(2H,t,J=6.6Hz),4.65−4.56(1H,m),4.59(2H,brs),4.48(1H,dd,J=6.6,5.1Hz),4.09−4.05(1H,m),3.75(6H,s),3.60−3.42(2H,m),3.40−3.26(2H,m),3.35(3H,s),3.18−3.05(1H,m),3.08(2H,t,J=6.6Hz),1.89−1.49(3H,m),1.48−1.16(3H,m),0.59(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.9(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.74(1H,brs),8.09(1H,s),7.56−6.94(24H,m),6.84−6.71(4H,m),6.09(1H,d,J=4.8Hz),4.83−4.70(2H,m),4.83(2H,t,J=6.6Hz),4.63(2H,brs),4.35(1H,t,J=5.0Hz),4.23−4.16(1H,m),3.75(6H,s),3.58−3.19(4H,m),3.32(3H,s),3.16−3.04(1H,m),3.07(2H,t,J=6.6Hz),1.90−1.55(3H,m),1.48−1.15(3H,m),0.64(3H,s);31P NMR(121.5MHz,CDCl3)δ 154.6(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.91(1H,d,J=7.8Hz),7.58−7.20(19H,m),6.88−6.80(4H,m),5.96(1H,d,J=3.3Hz),5.19(1H,d,J=7.8Hz),4.88−4.78(1H,m),4.66−4.57(1H,m),4.03−3.95(1H,m),3.90−3.74(1H,m),3.78(6H,s),3.77−3.71(1H,m),3.58−3.29(2H,m),3.45(3H,s),3.13−2.82(2H,m),1.88−1.53(3H,m),1.49−1.16(3H,m),0.60(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.3(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.10(1H,d,J=8.4Hz),7.58−7.20(19H,m),6.87−6.79(4H,m),5.89(1H,d,J=1.5Hz),5.21(1H,d,J=8.4Hz),4.92−4.82(1H,m),4.73−4.63(1H,m),4.15−4.08(1H,m),3.89−3.73(1H,m),3.78(6H,s),3.66−3.62(1H,m),3.57−3.27(2H,m),3.30(3H,s),3.17−2.82(2H,m),1.89−1.55(3H,m),1.55−1.40(1H,m),1.35−1.15(2H,m),0.66(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.5(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.64(1H,s),8.14(1H,s),8.06−8.01(2H,m),7.63−7.07(23H,m),6.78−6.70(4H,m),6.12(1H,dd,J=18.0,2.4Hz),5.24−5.01(2H,m),4.94−4.84(1H,m),4.17−4.06(1H,m),3.73(6H,s),3.55−3.40(3H,m),3.30−3.22(1H,m),3.03−2.88(1H,m),1.92−1.19(6H,m),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 150.5(1P,d,J=7.7Hz)。
1H NMR(300MHz,CDCl3)δ 9.07(1H,brs),8.80(1H,s),8.24(1H,s),8.08−8.01(2H,m),7.66−7.15(22H,m),6.81−6.75(4H,m),6.14(1H,dd,J=18.0,1.8Hz),5.16−4.91(3H,m),4.28−4.21(1H,m),3.76(6H,s),3.57−3.11(5H,m),1.82−1.16(6H,m),0.65(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.8(1P,d,J=5.6Hz)。
1H NMR(300MHz,CDCl3)δ 8.66(1H,brs),8.41(1H,d,J=7.5Hz),7.55−7.20(19H,m),7.01(1H,d,J=7.5Hz),6.89−6.81(4H,m),6.06(1H,d,J=15.9Hz),4.85(1H,dd,J=51.4,3.9Hz),4.84(1H,dd,J=12.9,7.5Hz),4.77−4.59(1H,m),4.15−4.08(1H,m),3.79(6H,s),3.63−3.29(4H,m),3.10−2.96(1H,m),2.65(1H,septet,J=6.9Hz),1.85−1.53(3H,m),1.48−1.17(3H,m),1.21(3H,d,J=4.8Hz),1.19(3H,d,J=4.8Hz),0.59(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.5(1P,d,J=6.6Hz)。
化合物10bを、化合物10aと同様の方法で、III−aの代わりにIII−bを用いることによって得た。
1H NMR(300MHz,CDCl3)δ 8.53(1H,d,J=7.5Hz),7.57−7.23(20H,m),7.10(1H,d,J=7.5Hz),6.89−6.81(4H,m),6.10(1H,d,J=15.9Hz),5.00−4.92(1H,m),4.84(1H,dd,J=51.5,3.3Hz),4.75−4.58(1H,m),4.24(1H,d,J=9.3Hz),3.81(6H,s),3.65−3.39(3H,m),3.32−3.06(2H,m),2.59(1H,septet,J=6.9Hz),1.88−1.53(4H,m),1.49−1.34(2H,m),1.27−1.18(6H,m),0.65(3H,s);31P NMR(121.5MHz,CDCl3)δ 159.0(1P,d,J=4.4)。
1H NMR(300MHz,CDCl3)δ 8.74(1H,brs),8.03(1H,s),7.55−6.94(24H,m),6.80−6.69(4H,m),6.21(1H,dd,J=14.9,3.6Hz),5.34(1H,dt,J=52.3,3.6Hz),5.01−4.75(2H,m),4.84(1H,t,J=6.6Hz),4.62(2H,brs),4.15−4.07(1H,m),3.73(6H,s),3.59−3.29(4H,m),3.15−3.00(1H,m),3.07(2H,t,J=6.6Hz),1.90−1.49(3H,m),1.47−1.12(3H,m),0.58(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.6(1P,d,J=10.9Hz)。
1H NMR(300MHz,CDCl3)δ 8.81(1H,brs),8.06(1H,s),7.55−6.95(24H,m),6.77−6.69(4H,m),6.06(1H,d,J=17.1Hz),5.24−5.08(1H,m),5.04−4.80(2H,m),4.87(1H,t,J=6.6Hz),4.62(2H,brs),4.25−4.19(1H,m),3.73(6H,s),3.58−3.02(5H,m),3.10(2H,t,J=6.6Hz),1.90−1.56(3H,m),1.50−1.15(3H,m),0.63(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.0(1P,d,J=4.4Hz)。
1H NMR(300MHz,CDCl3)δ 7.85(1H,d,J=8.1Hz),7.58−7.20(19H,m),6.87−6.79(4H,m),5.98(1H,d,J=16.5Hz),5.23(1H,d,J=8.1Hz),4.86−4.61(3H,m),3.99(1H,d,J=6.9Hz),3.76(6H,d,J=3.0Hz),3.56−3.34(4H,m),3.10−2.96(1H,m),1.88−1.74(1H,m),1.72−1.52(2H,m),1.48−1.16(3H,m),0.61(3H,s);31P NMR(121.5MHz,CDCl3)δ 154.3(1P,d,J=8.9Hz)。
1H NMR(300MHz,CDCl3)δ 8.01(1H,d,J=8.4Hz),7.58−7.20(19H,m),6.87−6.79(4H,m),6.03(1H,d,J=16.2Hz),5.29(1H,d,J=8.4Hz),4.96(1H,dd,J=13.1,7.5Hz),4.80−4.54(2H,m),4.15(1H,d,J=9.0Hz),3.78(6H,s),3.61−3.39(3H,m),3.37−3.25(1H,m),3.23−3.09(1H,m),1.91−1.56(3H,m),1.51−1.13(3H,m),0.66(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.9(1P,d,J=4.4Hz)。
1H NMR(300MHz,CDCl3)δ 8.82(1H,brs),8.49(1H,s),8.10(1H,s),7.58−7.17(19H,m),6.83−6.73(4H,m),6.11(1H,d,J=6.6Hz),5.15(1H,dd,J=6.6,5.4Hz),4.98−4.77(4H,m),4.18−4.11(1H,m),3.76(6H,s),3.59−3.25(4H,m),3.16−3.02(1H,m),2.62(3H,s),1.91−1.53(3H,m),1.49−1.18(3H,m),0.96−0.80(3H,m),0.90(18H,s),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.7(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.56(1H,brs),8.55(1H,s),8.13(1H,s),7.57−7.17(19H,m),6.82−6.73(4H,m),6.16(1H,d,J=5.7Hz),5.06(1H,t,J=5.6Hz),4.93(1H,d,J=5.1Hz),4.83(1H,d,J=5.1Hz),4.81−4.69(2H,m),4.27−4.19(1H,m),3.76(6H,s),3.55−3.40(2H,m),3.33−3.16(2H,m),3.12−2.97(1H,m),2.63(3H,s),1.88−1.52(3H,m),1.45−1.16(3H,m),0.91−0.79(3H,m),0.86(18H,s),0.64(3H,s);31P NMR(121.5MHz,CDCl3)δ 154.8(1P,s)。
1H NMR(300MHz,CDCl3)δ 10.04(1H,brs),8.30(1H,d,J=7.5Hz),7.51−7.21(19H,m),6.99(1H,d,J=7.5Hz),6.89−6.81(4H,m),6.12(1H,d,J=3.3Hz),5.07(1H,d,J=4.8Hz),5.05(1H,d,J=4.8Hz),4.84−4.75(1H,m),4.62−4.52(1H,m),4.31−4.25(1H,m),4.08−4.01(1H,m),3.78(6H,d,J=3.0Hz),3.55−3.23(4H,m),3.10−2.96(1H,m),2.24(3H,s),1.84−1.49(3H,m),1.46−0.96(24H,m),0.58(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.5(1P,s)。
1H NMR(300MHz,CDCl3)δ 10.19(1H,brs),8.46(1H,d,J=7.5Hz),7.54−7.23(19H,m),7.01(1H,d,J=7.5Hz),6.88−6.79(4H,m),6.19(1H,d,J=1.8Hz),5.11(1H,d,J=4.8Hz),5.07(1H,d,J=4.8Hz),4.81−4.71(1H,m),4.60−4.51(1H,m),4.26−4.18(2H,m),3.79(6H,s),3.63−3.55(1H,m),3.48−3.28(2H,m),3.21−2.94(2H,m),2.26(3H,s),1.81−1.49(3H,m),1.43−0.96(24H,m),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.4(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.70(1H,s),7.63−7.13(21H,m),6.84−6.76(4H,m),5.77(1H,d,J=8.4Hz),5.41−5.33(1H,m),4.90(2H,s),4.78−4.68(2H,m),3.86(1H,brs),3.75(3H,s),3.74(3H,s),3.56−3.41(2H,m),3.32−2.90(3H,m),1.92−1.10(9H,m),0.97−0.87(21H,m),0.52(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.1(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.77(1H,s),7.56−7.15(21H,m),6.82−6.75(4H,m),5.86(1H,d,J=7.5Hz),5.26−5.17(1H,m),4.95(1H,d,J=5.4Hz),4.85(1H,d,J=5.4Hz),4.78−4.71(1H,m),4.59−4.49(1H,m),4.10−4.05(1H,m),3.74(6H,s),3.52−3.37(2H,m),3.30−3.18(1H,m),3.11−2.85(2H,m),1.85−1.15(9H,m),0.93−0.84(21H,m),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 152.3(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.76(1H,d,J=8.1Hz),7.55−7.18(20H,m),6.88−6.80(4H,m),6.11(1H,d,J=6.0Hz),5.32(1H,d,J=8.1Hz),4.99(1H,d,J=5.1Hz),4.93(1H,d,J=5.1Hz),4.84−4.75(1H,m),4.54−4.46(1H,m),4.38(1H,t,J=5.7Hz),3.87−3.83(1H,m),3.78(3H,s),3.77(3H,s),3.56−3.42(1H,m),3.39−3.28(1H,m),3.36(1H,dd,J=11.0,2.7Hz),3.25(1H,dd,J=11.0,2.7Hz),3.16−3.03(1H,m),1.88−1.12(6H,m),1.08−0.97(21H,m),0.59(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.6(1P,s)。
1H NMR(600MHz,CDCl3)δ 7.87(1H,d,J=7.8Hz),7.52−7.48(4H,m),7.38−7.21(16H,m),6.83−6.79(4H,m),6.14(1H,d,J=4.8Hz),5.33(1H,d,J=7.8Hz),4.99(1H,d,J=5.4Hz),4.89(1H,d,J=5.4Hz),4.67(1H,dd,J=13.8,7.2Hz),4.52(1H,dt,J=10.4,4.8Hz),4.31(1H,t,J=4.8Hz),4.06−4.03(1H,m),3.78(3H,s),3.77(3H,s),3.47(1H,dd,J=10.4,2.4Hz),3.47−3.39(1H,m),3.22−3.17(2H,m),3.00(1H,ddd,J=19.5,10.4,4.8Hz),1.82−1.74(1H,m),1.68−1.58(1H,m),1.56(1H,dd,J=14.4,8.4Hz),1.38(1H,dd,J=14.4,7.2Hz),1.31−1.25(1H,m),1.26−1.17(1H,m),1.08−0.98(21H,m),0.63(3H,s);31P NMR(243.0MHz,CDCl3)δ 154.3(1P,s)。
1H NMR(300MHz,CDCl3)δ 9.10(1H,brs),8.76(1H,s),8.32(1H,s),8.04(2H,d,J=7.2Hz),7.64−7.18(22H,m),6.84(4H,d,J=8.7Hz),6.10(1H,s),4.76(1H,d J=6.9Hz),4.58(1H,s),4.61−4.51(1H,m),3.91(1H,d,J=7.8Hz),3.77(1H,d,J=7.8Hz),3.75(6H,s),3.50(1H,s),3.47−3.33(1H,m),3.31−3.19(1H,m),3.03−2.88(1H,m),1.84−1.09(6H,m),0.51(3H,s);31P NMR(121.5MHz,CDCl3)δ 152.9(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.81(1H,s),8.30(1H,s),8.07−8.00(2H,m),7.64−7.17(22H,m),6.86−6.79(4H,m),6.12(1H,s),4.81−4.72(1H,m),4.62(1H,d J=7.2Hz),4.57(1H,s),3.94(1H,d,J=7.8Hz),3.89(1H,d,J=7.8Hz),3.77(6H,s),3.48(2H,s),3.46−3.32(1H,m),3.24−3.13(1H,m),3.10−2.97(1H,m),1.84−1.49(3H,m),1.42−1.09(3H,m),0.58(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.3(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.88(1H,brs),7.58−7.18(20H,m),6.88−6.80(4H,m),5.65(1H,s),4.69−4.60(1H,m),4.52(1H,d,J=6.6Hz),4.49(1H,s),3.81−3.74(1H,m),3.75(3H,s),3.73(3H,s),3.64(1H,d,J=8.1Hz),3.56(1H,d,J=11.1Hz),3.53(1H,d,J=8.1Hz),3.46(1H,d,J=11.1Hz),3.56−3.40(1H,m),3.32−3.20(1H,m),3.14−3.00(1H,m),1.85−1.12(6H,m),1.60(3H,s),1.19(6H,d,J=6.9Hz),0.55(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.9(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.86(1H,brs),7.56−7.19(20H,m),6.88−6.79(4H,m),5.69(1H,s),4.86−4.76(1H,m),4.46(1H,s),4.45(1H,d,J=7.5Hz),3.80−3.75(1H,m),3.79(6H,s),3.74(1H,d,J=8.1Hz),3.69(1H,d,J=8.1Hz),3.51(1H,d,J=11.1Hz),3.44−3.30(1H,m),3.39(1H,d,J=11.1Hz),3.29−3.17(1H,m),3.11−2.97(1H,m),1.86−1.52(3H,m),1.64(3H,s),1.45−1.10(3H,m),1.21(6H,d,J=6.6Hz),0.62(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.71(1H,brs),8.16(1H,s),7.50−7.17(21H,m),7.09−7.01(3H,m),6.86−6.79(4H,m),6.03(1H,s),4.84(2H,t,J=6.6Hz),4.72(2H,s),4.68(1H,d,J=7.2Hz),4.55−4.46(1H,m),4.50(1H,s),3.90(1H,d,J=7.8Hz),3.77(1H,d,J=7.8Hz),3.75(6H,s),3.51(1H,d,J=10.8Hz),3.47(1H,d,J=10.8Hz),3.45−3.21(2H,m),3.08(2H,t,J=6.6Hz),3.03−2.89(1H,m),1.80−1.08(6H,m),0.47(3H,s);31P NMR(121.5MHz,CDCl3)δ 153.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.86(1H,brs),8.13(1H,s),7.55−7.17(21H,m),7.08−6.98(3H,m),6.95−6.78(4H,m),6.01(1H,s),4.86(2H,t,J=6.6Hz),4.82−4.73(1H,m),4.70(2H,s),4.64(1H,d,J=7.5Hz),4.49(1H,s),3.94(1H,d,J=7.8Hz),3.89(1H,d,J=7.8Hz),3.77(6H,s),3.46(2H,s),3.45−3.30(1H,m),3.24−3.12(1H,m),3.09(2H,t,J=6.6Hz),3.09−2.96(1H,m),1.81−1.50(3H,m),1.41−1.06(3H,m),0.58(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.4(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.71(1H,d,J=0.9Hz),7.50−7.17(20H,m),6.87−6.80(4H,m),5.61(1H,s),4.69−4.60(1H,m),4.55(1H,d,J=6.9Hz),4.41(1H,s),3.74(3H,s),3.73(3H,s),3.64(1H,d,J=7.8Hz),3.55(1H,d,J=7.8Hz),3.53(1H,d,J=10.8Hz),3.46(1H,d,J=10.8Hz),3.56−3.42(1H,m),3.35−3.24(1H,m),3.13−3.00(1H,m),1.85−1.45(3H,m),1.55(3H,d,J=0.9Hz),1.41−1.12(3H,m),0.56(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.1(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.69(1H,s),7.56−7.19(20H,m),6.88−6.79(4H,m),5.66(1H,s),4.87−4.77(1H,m),4.47(1H,d,J=7.8Hz),4.40(1H,s),3.78(6H,s),3.74(1H,d,J=7.8Hz),3.68(1H,d,J=7.8Hz),3.50(1H,d,J=10.8Hz),3.46−3.32(1H,m),3.39(1H,d,J=10.8Hz),3.30−3.19(1H,m),3.12−2.98(1H,m),1.85−1.56(3H,m),1.59(3H,s),1.46−1.12(3H,m),0.63(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.1(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.62−7.18(21H,m),6.84(4H,d,J=8.7Hz),6.07(1H,d,J=5.7Hz),4.86−4.76(1H,m),4.63−4.54(1H,m),4.20(1H,t,J=5.4Hz),3.95−3.89(1H,m),3.78(6H,s),3.78−3.71(2H,m),3.60−3.48(2H,m),3.44−3.02(5H,m),3.31(3H,s),1.88−1.15(6H,m),1.35(3H,s),0.58(3H,s);31P NMR(121.5MHz,CDCl3)δ 156.3(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.71(1H,d,J=1.2Hz),7.55−7.22(20H,m),6.86−6.78(4H,m),5.99(1H,d,J=3.9Hz),4.78−4.62(2H,m),4.13−4.08(1H,m),4.07−4.02(1H,m),3.77(6H,s),3.77−3.70(1H,m),3.65−3.56(1H,m),3.52−3.36(4H,m),3.33−3.14(2H,m),3.29(3H,s),3.08−2.94(1H,m),1.86−1.72(1H,m),1.71−1.55(2H,m),1.30(3H,d,J=1.2Hz),1.47−1.16(3H,m)0.64(3H,s);31P NMR(121.5MHz,CDCl3)δ 155.6(1P,s)。
1H NMR(300MHz,CDCl3)δ 7.57(1H,d,J=0.9Hz),7.37−6.94(20H,m),6.87−6.78(4H,m),6.48(1H,dd,J=8.6,5.7Hz),5.42(1H,dd,J=11.0,5.1Hz),4.81−4.71(1H,m),4.02(1H,d,J=11.0Hz),3.83(1H,d,J=2.1Hz),3.79(6H,s),3.61−3.41(2H,m),3.24−3.09(1H,m),3.16(1H,dd,J=10.8,2.4Hz),3.02(1H,dd,J=10.8,2.4Hz),2.54−2.44(1H,m),2.34−2.22(1H,m),1.94−1.79(1H,m),1.74−1.56(1H,m),1.38(3H,s),1.38−1.28(2H,m);31P NMR(121.5MHz,CDCl3)δ 160.9(1P,s)。
化合物22bを、化合物22aと同様の方法で、VII−aの代わりにVII−bを用いることによって得た。
1H NMR(300MHz,CDCl3)δ 7.57(1H,d,J=1.5Hz),7.43−7.11(20H,m),6.85−6.78(4H,m),6.48(1H,dd,J=7.5,5.7Hz),5.58(1H,dd,J=11.4,5.1Hz),4.82−4.73(1H,m),4.17−4.02(2H,m),3.78(6H,s),3.56−3.40(3H,m),3.32(1H,dd,J=10.7,2.4Hz),3.22−3.07(1H,m),2.26−2.04(2H,m),1.95−1.81(1H,m),1.74−1.56(1H,m),1.40(3H,d,J=1.5Hz),1.44−1.34(2H,m);31P NMR(121.5MHz,CDCl3)δ 162.2(1P,s)。
1H NMR(300MHz,CDCl3)δ 9.22(1H,brs),8.05−7.99(2H,m),7.52(1H,d,J=1.2Hz),7.41−7.19(11H,m),6.87−6.79(4H,m),6.37(1H,dd,J=8.4,5.7Hz),4.88−4.75(2H,m),3.86−3.80(1H,m),3.79(6H,s),3.64−3.49(2H,m),3.27−3.12(3H,m),2.97(2H,d,J=6.6Hz),2.51−2.41(1H,m),2.33−2.20(1H,m),2.03−1.75(2H,m),1.72−1.59(1H,m),1.46−1.36(1H,m),1.40(3H,s);31P NMR(121.5MHz,CDCl3)δ 157.5(1P,s)。
1H NMR(300MHz,CDCl3)δ 8.67(1H,brs),8.18−8.11(2H,m),7.57(1H,d,J=1.2Hz),7.47−7.22(11H,m),6.86−6.79(4H,m),6.29(1H,t,J=6.6Hz),4.87(1H,dt,J=7.5,5.7Hz),4.80−4.72(1H,m),4.11−4.05(1H,m),3.79(6H,s),3.67−3.47(2H,m),3.43(1H,dd,J=10.8,2.7Hz),3.27(1H,dd,J=10.8,2.4Hz),3.25−3.13(1H,m),3.07−2.99(2H,m),2.19−2.12(2H,m),2.03−1.62(3H,m),1.46−1.30(1H,m),1.41(3H,s);31P NMR(121.5MHz,CDCl3)δ 158.1(1P,s)。
1H NMR(600MHz,CDCl3)δ 7.76(2H,d,J=9.0Hz),7.62(1H,d,J=1.2Hz),7.40(2H,d,J=7.2Hz),7.32−7.23(10H,m),6.85(4H,d,J=8.4Hz),6.41(1H,dd,J=8.4,5.4Hz),4.94(1H,dd,J=12.3,5.4Hz),4.84−4.79(1H,m),4.03−4.01(1H,m),3.79(6H,s),3.59−3.53(1H,m),3.52−3.44(2H,m),3.41(1H,dd,J=14.7,7.2Hz),3.37−3.30(2H,m),3.13(1H,ddd,J=19.3,10.3,4.1Hz),2.50−2.44(1H,m),2.39(3H,s),2.35−2.29(1H,m),1.91−1.72(2H,m),1.64−1.59(1H,m),1.40(3H,s),1.12−1.05(1H,m);31P NMR(243.0MHz,CDCl3)δ 154.2(1P,s)。
キラル−オリゴの自動化された固相合成を、表1に示されるサイクルに従って実施した。合成の後、樹脂を25%NH3水溶液(1mL)を用いて55℃で12時間処理した。混合物を室温まで放冷し、膜濾過によって樹脂を除去した。濾液を減圧下で濃縮乾固した。残渣をH2O(3mL)に溶解し、0.3mL/分の速度で50℃の0.1M酢酸トリエチルアンモニウム緩衝液(pH7.0)中、アセトニトリル(0〜50%/30分)の直線勾配で、RP−UPLC−MSによって分析した。
実施例のモノマーは、化学的に安定であった。モノマーの単離収率は、80%を上回り、これは従来の方法のものよりも高かった。
Claims (24)
- 固相支持体上のオリゴヌクレオチドであって、次の構造を有するオリゴヌクレオチド
G3およびG4の両方は、一緒になって4個の炭素原子を有するヘテロ原子含有環を形成し、
G5は、ヒドロキシル基の保護基であり、
それぞれのR2は、独立に、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRbであり、ここで、Rbは、ブロッキング部分であり、
Y1は、O、NRd、S、またはSeであり、
Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
Reは、独立に、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、またはヘテロアリール−Y2−、あるいは、Na+、Li+、またはK+である陽イオンであり、
Y2は、O、S,NRd(Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、又はカルバメートである)であり、
それぞれのBsは、独立に、以下の式(VI)〜(XI)
- 固相支持体上のオリゴヌクレオチドであって、次の構造を有するオリゴヌクレオチド
G3およびG4の両方は、一緒になって4個の炭素原子を有するヘテロ原子含有環を形成し、
G5は、ヒドロキシル基の保護基であり、
Xは、OまたはSであり、
それぞれのR2は、独立に、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRbであり、ここで、Rbは、ブロッキング部分であり、
Y1は、O、NRd、S、またはSeであり、
Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
Reは、独立に、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、またはヘテロアリール−Y2−、あるいは、Na+、Li+、またはK+である陽イオンであり、
Y2は、O、S,NRd(Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、又はカルバメートである)であり、
それぞれのBsは、独立に、以下の式(VI)〜(XI)
- 固相支持体上のオリゴヌクレオチドであって、次の構造を有するオリゴヌクレオチド
G3およびG4の両方は、一緒になって4個の炭素原子を有するヘテロ原子含有環を形成し、
G5は、ヒドロキシル基の保護基であり、
Xは、OまたはSであり、
nは、1〜150であり、
それぞれのR2は、独立に、水素、−OH、−SH、−NRdRd、−N3、ハロゲン、アルキル、アルケニル、アルキニル、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRbであり、ここで、Rbは、ブロッキング部分であり、
Y1は、O、NRd、S、またはSeであり、
Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、カルバメート、−P(O)(Re)2、または−HP(O)(Re)であり、
Reは、独立に、水素、アルキル、アリール、アルケニル、アルキニル、アルキル−Y2−、アルケニル−Y2−、アルキニル−Y2−、アリール−Y2−、またはヘテロアリール−Y2−、あるいは、Na+、Li+、またはK+である陽イオンであり、
Y2は、O、S,NRd(Rdは、独立に、水素、アルキル、アルケニル、アルキニル、アリール、アシル、置換シリル、又はカルバメートである)であり、
それぞれのBsは、独立に、以下の式(VI)〜(XI)
- Xは、Sである、請求項2または請求項3に記載のオリゴヌクレオチド。
- Xは、Oである、請求項2または請求項3に記載のオリゴヌクレオチド。
- nは、10〜50である、請求項3〜請求項5のいずれかに記載のオリゴヌクレオチド。
- 請求項1〜請求項6のいずれかに記載のオリゴヌクレオチドであって、
R2は、水素、ハロゲン、アルキル−Y1−、アルケニル−Y1−、アルキニル−Y1−、アリール−Y1−、ヘテロアリール−Y1−、−ORb、または−SRbであり、ここで、Y1は、Oである、オリゴヌクレオチド。 - 請求項7に記載のオリゴヌクレオチドであって、
R2は、ハロゲン、である、オリゴヌクレオチド。 - 請求項8に記載のオリゴヌクレオチドであって、
R2は、F(フッ素原子)である、オリゴヌクレオチド。 - 請求項7に記載のオリゴヌクレオチドであって、
R2は、アルキル−Y1−である、オリゴヌクレオチド。 - 請求項7に記載のオリゴヌクレオチドであって、
R2は、−OMeである、オリゴヌクレオチド。 - 請求項1〜請求項11のいずれかに記載のオリゴヌクレオチドであって、
G5は、4,4’−ジメトキシトリチル基である、オリゴヌクレオチド。 - 請求項13に記載のオリゴヌクレオチドであって、
R8は、メチル、イソプロピル、フェニル、ベンジルまたはフェノキシメチルであり、R9及びR10は、独立に、C1−4アルキルである、オリゴヌクレオチド。 - 請求項1〜請求項14のいずれかに記載のオリゴヌクレオチドであって、
G1は、水素原子である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(III)で示される基であり、G31〜G33は、独立に、C1−4アルキル基、C6−14アリール基、C7−14アラルキル基、C1−4アルキルC6−14アリール基、C1−4アルコキシC6−14アリール基、またはC6−14アリールC1−4アルキル基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(III)で示される基であり、G31〜G33は、独立に、C1−4アルキル基、C6アリール基、C7−10アラルキル基、C1−4アルキルC6アリール基、C1−4アルコキシC6アリール基、またはC6アリールC1−4アルキル基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(III)で示される基であり、G31〜G33は、独立に、C1−4アルキル基、又はC6アリール基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(III)で示される基であり、G31〜G33は、独立に、C1−4アルキル基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(III)で示される基であり、G31及びG33は、C6アリール基であり、G32は、C1−4アルキル基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(V)で示される基であり、G51〜G53は、独立に、水素原子、ニトロ基、メチル基またはメトキシ基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G2は式(V)で示される基であり、G51およびG53の各々が水素原子であり、G52は、4−メチル基である、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G1およびG2は、一緒になって式(IV)の基を形成する、オリゴヌクレオチド。 - 請求項1〜請求項15のいずれかに記載のオリゴヌクレオチドであって、
G1およびG2は、一緒になって式(IV)の基を形成し、G41〜G46の各々が水素原子である、オリゴヌクレオチド。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261671652P | 2012-07-13 | 2012-07-13 | |
US61/671,652 | 2012-07-13 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015500697A Division JP6268157B2 (ja) | 2012-07-13 | 2013-07-12 | 不斉補助基 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019150815A Division JP7030749B2 (ja) | 2012-07-13 | 2019-08-21 | 不斉補助基 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018058845A JP2018058845A (ja) | 2018-04-12 |
JP6608413B2 true JP6608413B2 (ja) | 2019-11-20 |
Family
ID=49915731
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015500697A Active JP6268157B2 (ja) | 2012-07-13 | 2013-07-12 | 不斉補助基 |
JP2017209854A Active JP6608413B2 (ja) | 2012-07-13 | 2017-10-30 | 不斉補助基 |
JP2019150815A Active JP7030749B2 (ja) | 2012-07-13 | 2019-08-21 | 不斉補助基 |
JP2022026049A Active JP7390417B2 (ja) | 2012-07-13 | 2022-02-22 | 不斉補助基 |
JP2023196280A Pending JP2024023334A (ja) | 2012-07-13 | 2023-11-17 | 不斉補助基 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015500697A Active JP6268157B2 (ja) | 2012-07-13 | 2013-07-12 | 不斉補助基 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019150815A Active JP7030749B2 (ja) | 2012-07-13 | 2019-08-21 | 不斉補助基 |
JP2022026049A Active JP7390417B2 (ja) | 2012-07-13 | 2022-02-22 | 不斉補助基 |
JP2023196280A Pending JP2024023334A (ja) | 2012-07-13 | 2023-11-17 | 不斉補助基 |
Country Status (15)
Country | Link |
---|---|
US (5) | US9598458B2 (ja) |
EP (2) | EP2872485B1 (ja) |
JP (5) | JP6268157B2 (ja) |
KR (1) | KR101850319B1 (ja) |
CN (2) | CN107011400B (ja) |
AU (5) | AU2013288048A1 (ja) |
BR (1) | BR112015000784A8 (ja) |
CA (1) | CA2879023C (ja) |
DK (1) | DK2872485T3 (ja) |
ES (1) | ES2862073T3 (ja) |
PL (1) | PL2872485T3 (ja) |
PT (1) | PT2872485T (ja) |
RU (1) | RU2693381C2 (ja) |
SG (1) | SG11201500239VA (ja) |
WO (1) | WO2014010250A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020015735A (ja) * | 2012-07-13 | 2020-01-30 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | 不斉補助基 |
Families Citing this family (72)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102282155B (zh) | 2008-12-02 | 2017-06-09 | 日本波涛生命科学公司 | 磷原子修饰的核酸的合成方法 |
IN2012DN00720A (ja) | 2009-07-06 | 2015-06-19 | Ontorii Inc | |
DK2620428T3 (da) | 2010-09-24 | 2019-07-01 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
JP6128529B2 (ja) | 2011-07-19 | 2017-05-17 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | 官能化核酸の合成のための方法 |
CA2879066C (en) | 2012-07-13 | 2019-08-13 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
WO2014012081A2 (en) | 2012-07-13 | 2014-01-16 | Ontorii, Inc. | Chiral control |
US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
KR20220106232A (ko) | 2014-01-16 | 2022-07-28 | 웨이브 라이프 사이언시스 리미티드 | 키랄 디자인 |
RU2708237C2 (ru) | 2014-08-22 | 2019-12-05 | Общество с ограниченной ответственностью "НооГен" | Модифицированные олигонуклеотиды и способ их получения |
WO2016096938A1 (en) | 2014-12-16 | 2016-06-23 | Roche Innovation Center Copenhagen A/S | Chiral toxicity screening method |
BR112017011510B1 (pt) | 2014-12-17 | 2023-12-05 | Proqr Therapeutics Ii B.V. | Construto de oligonucleotídeo para a edição direcionada ao sítio de um nucleotídeo adenosina em uma sequência de rna alvo em uma célula eucariótica e uso do mesmo |
MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
SG10201912902TA (en) | 2015-10-09 | 2020-02-27 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
CN114685589A (zh) * | 2016-03-13 | 2022-07-01 | 波涛生命科学有限公司 | 用于亚磷酰胺和寡核苷酸合成的组合物和方法 |
CN114085836B (zh) | 2016-03-14 | 2024-01-26 | 豪夫迈·罗氏有限公司 | 用于减少pd-l1表达的寡核苷酸 |
KR102372122B1 (ko) * | 2016-03-18 | 2022-03-07 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 아실-보호된 l-lna-구아노신 단량체 |
EA201892366A1 (ru) | 2016-04-18 | 2019-03-29 | Сарепта Терапьютикс, Инк. | Антисмысловые олигомеры и способы их применения для лечения заболеваний, связанных с геном кислой альфа-глюкозидазы |
KR102329187B1 (ko) | 2016-04-29 | 2021-11-22 | 사렙타 쎄러퓨틱스, 인코퍼레이티드 | 인간 lmna를 표적화하는 올리고뉴클레오타이드 유사체 |
MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
CN109311925B (zh) * | 2016-05-12 | 2022-06-03 | 罗氏创新中心哥本哈根有限公司 | 立体限定的氧杂氮杂磷杂环戊烷亚磷酰胺单体与核苷或寡核苷酸的增强的偶联 |
US10882884B2 (en) | 2016-05-18 | 2021-01-05 | Eth Zurich | Stereoselective synthesis of phosphorothioate oligoribonucleotides |
CN109562122A (zh) | 2016-06-03 | 2019-04-02 | 波涛生命科学有限公司 | 寡核苷酸、组合物及其方法 |
AU2017281497B2 (en) | 2016-06-22 | 2023-04-06 | Proqr Therapeutics Ii B.V. | Single-stranded RNA-editing oligonucleotides |
JP2019525742A (ja) | 2016-06-30 | 2019-09-12 | サレプタ セラピューティクス, インコーポレイテッド | 筋ジストロフィーに対するエクソンスキッピングオリゴマー |
MX2018016253A (es) | 2016-07-05 | 2019-09-09 | Biomarin Tech Bv | Oligonucleotidos de conmutacion o modulacion de empalme de pre-arnm que comprenden radicales de andamio biciclicos, con caracteristicas mejoradas para el tratamiento de trastornos geneticos. |
JP2019532027A (ja) | 2016-08-17 | 2019-11-07 | ソルスティス バイオロジクス,リミティッド | ポリヌクレオチド構築物 |
NZ751483A (en) | 2016-09-01 | 2022-07-01 | Proqr Therapeutics Ii Bv | Chemically modified single-stranded rna-editing oligonucleotides |
EP3544987A4 (en) * | 2016-11-23 | 2020-11-18 | Wave Life Sciences Ltd. | COMPOSITIONS AND SYNTHESIS OF PHOSPHORAMIDITES AND OLIGONUCLEOTIDES |
CN117298290A (zh) | 2016-12-19 | 2023-12-29 | 萨勒普塔医疗公司 | 用于肌肉萎缩症的外显子跳跃寡聚体缀合物 |
CA3046793A1 (en) | 2016-12-19 | 2018-06-28 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
MX2019006879A (es) | 2016-12-19 | 2019-08-01 | Sarepta Therapeutics Inc | Conjugados de oligomeros de omision de exon para distrofia muscular. |
KR20180076661A (ko) * | 2016-12-28 | 2018-07-06 | 엘지디스플레이 주식회사 | 표시 장치용 기판과 그를 포함하는 표시 장치 |
CA3058966A1 (en) | 2017-04-14 | 2018-10-18 | Tollnine, Inc. | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
US11603532B2 (en) | 2017-06-02 | 2023-03-14 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
CA3065523A1 (en) | 2017-06-02 | 2018-12-06 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
US11718638B2 (en) | 2017-06-21 | 2023-08-08 | Wave Life Sciences Ltd. | Compounds, compositions and methods for synthesis |
EP3645544B1 (en) | 2017-06-28 | 2023-05-10 | Roche Innovation Center Copenhagen A/S | Multiple coupling&oxidation method |
US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
SG11202000274RA (en) | 2017-08-08 | 2020-02-27 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
CA3072110A1 (en) * | 2017-09-18 | 2019-03-21 | Wave Life Sciences Ltd. | Technologies for oligonucleotide preparation |
EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
JP2020536058A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス, インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
JP2020536057A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス, インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
US20200248178A1 (en) | 2017-09-28 | 2020-08-06 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
SG11202001783YA (en) | 2017-10-12 | 2020-03-30 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
US11555189B2 (en) | 2017-10-18 | 2023-01-17 | Sarepta Therapeutics, Inc. | Antisense oligomer compounds |
WO2019187691A1 (ja) | 2018-03-26 | 2019-10-03 | 株式会社カネカ | コラゲナーゼ活性を有するポリペプチド及びその製造方法 |
US10765760B2 (en) | 2018-05-29 | 2020-09-08 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
EP4219717A3 (en) | 2018-06-13 | 2023-12-20 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystrophy |
TW202020153A (zh) | 2018-07-27 | 2020-06-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
KR20210091180A (ko) | 2018-11-02 | 2021-07-21 | 바이오마린 테크놀로지스 비.브이. | 디스트로핀 엑손 스키핑을 위한 이중특이적 안티센스 올리고뉴클레오타이드 |
EA202191601A1 (ru) | 2018-12-13 | 2022-01-19 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
CN113748116A (zh) * | 2019-03-20 | 2021-12-03 | 波涛生命科学有限公司 | 可用于寡核苷酸制备的技术 |
WO2020196890A1 (ja) | 2019-03-28 | 2020-10-01 | 味の素株式会社 | ホスホロチオエート化部位を有するオリゴヌクレオチドの製造方法 |
JP2022529342A (ja) * | 2019-04-16 | 2022-06-21 | ロシュ イノベーション センター コペンハーゲン エーエス | ヌクレオチドp(v)モノマーを調製するための新規の方法 |
WO2020214763A1 (en) | 2019-04-18 | 2020-10-22 | Sarepta Therapeutics, Inc. | Compositions for treating muscular dystrophy |
KR20230016201A (ko) | 2020-05-22 | 2023-02-01 | 웨이브 라이프 사이언시스 리미티드 | 이중 가닥 올리고뉴클레오티드 조성물 및 이와 관련된 방법 |
EP4370677A1 (en) | 2021-07-16 | 2024-05-22 | Academisch Ziekenhuis Leiden h.o.d.n. LUMC | Oligonucleotide for inhibiting quaking activity |
AU2022358322A1 (en) | 2021-09-30 | 2024-05-16 | Sarepta Therapeutics, Inc. | Antisense oligonucleotides having one or more abasic units |
WO2023154528A1 (en) * | 2022-02-11 | 2023-08-17 | Wave Life Sciences Ltd. | Stereoselective technologies for chiral compounds |
WO2023152371A1 (en) | 2022-02-14 | 2023-08-17 | Proqr Therapeutics Ii B.V. | Guide oligonucleotides for nucleic acid editing in the treatment of hypercholesterolemia |
TW202400187A (zh) | 2022-05-06 | 2024-01-01 | 萊登大學醫院 萊登大學醫學中心 | 寡核苷酸 |
WO2024013361A1 (en) | 2022-07-15 | 2024-01-18 | Proqr Therapeutics Ii B.V. | Oligonucleotides for adar-mediated rna editing and use thereof |
WO2024013360A1 (en) | 2022-07-15 | 2024-01-18 | Proqr Therapeutics Ii B.V. | Chemically modified oligonucleotides for adar-mediated rna editing |
WO2024022911A1 (en) | 2022-07-25 | 2024-02-01 | Vico Therapeutics B.V. | Antisense oligonucleotides for treating a disease or condition associated with an abnormal processing of app |
WO2024064237A2 (en) | 2022-09-21 | 2024-03-28 | Sarepta Therapeutics, Inc. | Dmd antisense oligonucleotide-mediated exon skipping efficiency |
GB202215614D0 (en) | 2022-10-21 | 2022-12-07 | Proqr Therapeutics Ii Bv | Heteroduplex rna editing oligonucleotide complexes |
WO2024110565A1 (en) | 2022-11-24 | 2024-05-30 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for the treatment of hereditary hfe-hemochromatosis |
GB202218090D0 (en) | 2022-12-01 | 2023-01-18 | Proqr Therapeutics Ii Bv | Antisense oligonucleotides for the treatment of aldehyde dehydrogenase 2 deficiency |
WO2024121373A1 (en) | 2022-12-09 | 2024-06-13 | Proqr Therapeutics Ii B.V. | Antisense oligonucleotides for the treatment of cardiovascular disease |
Family Cites Families (703)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2878264A (en) | 1959-03-17 | Substituted amino alcohols | ||
CH372667A (de) | 1957-09-26 | 1963-10-31 | Robins Co Inc A H | Verfahren zur Herstellung von 3-Aryl-3-pyrrolidinolen |
US3135766A (en) | 1961-10-03 | 1964-06-02 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
US3484473A (en) | 1967-05-12 | 1969-12-16 | Buckman Labor Inc | Methylene bisesters of thiolsulfonic acids |
DE1934150A1 (de) | 1968-07-10 | 1970-01-15 | Pennwalt Corp | Neue 1-Alkanoyloxy-1,2,4,5-tetrahydro-3H,3-benzazepine |
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US3745162A (en) | 1970-08-31 | 1973-07-10 | Robins Co Inc A H | 1,2,3,4-tetrahydroisoquinoline-2-(thio)-carboxamides |
GB1448437A (en) | 1973-02-24 | 1976-09-08 | Beecham Group Ltd | Diphenylpropylamines |
US4022791A (en) | 1975-06-03 | 1977-05-10 | Pfizer Inc. | 2-Aminomethyl-3,4-dihydronaphthalenes |
GB1504424A (en) | 1975-08-09 | 1978-03-22 | Beecham Group Ltd | Isoquinoline-derived aminoethers |
BR7807288A (pt) | 1977-11-08 | 1979-06-12 | Genentech Inc | Processo para sintese de polinucleotidos |
DD133885B1 (de) | 1978-01-04 | 1981-02-25 | Hans Lehmann | Mittel zur bekaempfung von phytopathogenen bakterien und pilzen |
US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
US4668777A (en) | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
US4542142A (en) | 1982-11-22 | 1985-09-17 | Roussel Uclaf | Insecticidal cyclopropane carboxylic acid derivatives with 3-unsaturated-side chain |
DE3329892A1 (de) | 1983-08-18 | 1985-03-07 | Köster, Hubert, Prof. Dr., 2000 Hamburg | Verfahren zur herstellung von oligonucleotiden |
US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
US5643889A (en) | 1984-07-11 | 1997-07-01 | Temple University-Of The Commonwealth System Of Pennsylvania | Cholesterol conjugates of 2'5'-oligoadenylate derivatives and antiviral uses thereof |
FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
FR2576898B1 (fr) | 1985-02-01 | 1988-01-08 | Lafon Labor | Derives de 3-phenyl-tetrahydropyridine, procede de preparation et utilisation en therapeutique |
US4659774A (en) | 1985-11-01 | 1987-04-21 | American Hoechst Corporation | Support for solid-phase oligonucleotide synthesis |
US4666777A (en) | 1985-12-23 | 1987-05-19 | The Dow Chemical Company | Structured latex core-shell polymer particles suitable for use in the preparation of composite sheets |
US4735949A (en) | 1986-02-18 | 1988-04-05 | Warner-Lambert Company | Disubstituted-7-pyrrolidinonaphthyridine antibacterial agents |
US4840956A (en) | 1986-02-18 | 1989-06-20 | Warner-Lambert Company | Novel disubstituted-7-pyrrolidinoquinoline antibacterial agents |
IL83663A0 (en) | 1986-10-27 | 1988-01-31 | Robins Co Inc A H | Preparation of 3-pyrrolidinols |
AU598946B2 (en) | 1987-06-24 | 1990-07-05 | Howard Florey Institute Of Experimental Physiology And Medicine | Nucleoside derivatives |
EP0302349B1 (en) | 1987-07-30 | 1993-09-29 | Bar Ilan University | Biologically active carboxylic acid esters |
US4923901A (en) | 1987-09-04 | 1990-05-08 | Millipore Corporation | Membranes with bound oligonucleotides and peptides |
US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
US4945158A (en) | 1988-08-12 | 1990-07-31 | American Cyanamid Company | Antidiabetic phosphonates |
US4943629A (en) | 1988-08-12 | 1990-07-24 | American Cyanamid Company | Antidiabetic alpha-substituted phosphonates |
US5262530A (en) | 1988-12-21 | 1993-11-16 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
US5047524A (en) | 1988-12-21 | 1991-09-10 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
US5141813A (en) | 1989-08-28 | 1992-08-25 | Clontech Laboratories, Inc. | Multifunctional controlled pore glass reagent for solid phase oligonucleotide synthesis |
US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
CA2029273A1 (en) | 1989-12-04 | 1991-06-05 | Christine L. Brakel | Modified nucleotide compounds |
US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
AU658134B2 (en) | 1989-12-28 | 1995-04-06 | Virginia Commonwealth University | Sigma receptor ligands and the use thereof |
US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
US5506212A (en) | 1990-01-11 | 1996-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides with substantially chirally pure phosphorothioate linkages |
US7101993B1 (en) | 1990-01-11 | 2006-09-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides containing 2′-O-modified purines |
US5635488A (en) | 1991-10-15 | 1997-06-03 | Isis Pharmaceuticals, Inc. | Compounds having phosphorodithioate linkages of high chiral purity |
US5620963A (en) | 1991-10-15 | 1997-04-15 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating protein kinase C having phosphorothioate linkages of high chiral purity |
US6339066B1 (en) | 1990-01-11 | 2002-01-15 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate βI, βII, γ, δ, Ε, ζ and η isoforms of human protein kinase C |
US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US5914396A (en) | 1990-01-11 | 1999-06-22 | Isis Pharmaceuticals, Inc. | 2'-O-modified nucleosides and phosphoramidites |
US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US5852188A (en) | 1990-01-11 | 1998-12-22 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
WO1991010671A1 (en) | 1990-01-11 | 1991-07-25 | Isis Pharmaceuticals, Inc. | Compositions and methods for detecting and modulating rna activity and gene expression |
US5212295A (en) | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
US5151510A (en) | 1990-04-20 | 1992-09-29 | Applied Biosystems, Inc. | Method of synethesizing sulfurized oligonucleotide analogs |
US5292875A (en) | 1990-04-20 | 1994-03-08 | Lynx Therapeutics, Inc. | Method of synthesizing sulfurized oligonucleotide analogs |
JPH06500075A (ja) | 1990-05-23 | 1994-01-06 | アイシス・ファーマシューティカルス・インコーポレーテッド | Rnaの5´キャップ構造の修飾によりrna活性を変調させるための組成物および方法 |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
US5783682A (en) | 1990-07-27 | 1998-07-21 | Isis Pharmaceuticals, Inc. | Oligonucleotide mimics having nitrogen-containing linkages |
US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
US6087482A (en) | 1990-07-27 | 2000-07-11 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US6121433A (en) | 1990-07-27 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having nitrogen-containing linkages |
WO1994022886A1 (en) | 1993-03-30 | 1994-10-13 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
JPH0874B2 (ja) | 1990-07-27 | 1996-01-10 | アイシス・ファーマシューティカルス・インコーポレーテッド | 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド |
US5223618A (en) | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
US5834607A (en) | 1990-07-27 | 1998-11-10 | Isis Pharmaceuticals, Inc. | Amines and methods of making and using the same |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
US5998603A (en) | 1994-09-29 | 1999-12-07 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analogs, and oligomers thereof |
US5792844A (en) | 1990-07-27 | 1998-08-11 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent nitrogen atoms |
US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
US5512668A (en) | 1991-03-06 | 1996-04-30 | Polish Academy Of Sciences | Solid phase oligonucleotide synthesis using phospholane intermediates |
US7015315B1 (en) | 1991-12-24 | 2006-03-21 | Isis Pharmaceuticals, Inc. | Gapped oligonucleotides |
US20020183502A1 (en) | 1991-05-21 | 2002-12-05 | Mesmaeker Alain De | Backbone-modified oligonucleotide analogs and methods for using same |
US6414112B1 (en) | 1991-05-24 | 2002-07-02 | Ole Buchardt | Peptide nucleic acids having 2,6-diaminopurine nucleobases |
JPH04348077A (ja) | 1991-05-24 | 1992-12-03 | Nec Corp | 薄膜トランジスタ |
GB2272443B (en) | 1991-06-10 | 1995-10-25 | Lucky Ltd | Nucleotide and amino acid sequences of Korean hepatitis C virus |
US5646267A (en) | 1991-08-05 | 1997-07-08 | Polish Academy Of Sciences | Method of making oligonucleotides and oligonucleotide analogs using phospholanes and enantiomerically resolved phospholane analogues |
US5359052A (en) | 1991-08-05 | 1994-10-25 | Polish Academy Of Sciences | Chalcophospholanes useful in the synthesis of oligonucleoside phosphorothioates, phosphorodithioates and related selenates |
US6369209B1 (en) | 1999-05-03 | 2002-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
US7119184B2 (en) | 1991-08-12 | 2006-10-10 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
US5576302A (en) | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
US5599797A (en) | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5654284A (en) | 1991-10-15 | 1997-08-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating RAF kinase having phosphorothioate linkages of high chiral purity |
WO1993008296A1 (en) | 1991-10-15 | 1993-04-29 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
US5661134A (en) | 1991-10-15 | 1997-08-26 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity |
US5607923A (en) | 1991-10-15 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity |
EP0538194B1 (de) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
US6235887B1 (en) | 1991-11-26 | 2001-05-22 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines |
US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
DK0618925T4 (da) | 1991-12-24 | 2012-07-09 | Isis Pharmaceuticals Inc | Antisense-oligonukleotider |
GB9213601D0 (en) | 1992-06-26 | 1992-08-12 | Mastico Robert A | Protein based delivery system |
US7067497B2 (en) | 1992-09-29 | 2006-06-27 | Isis Pharmaceuticals, Inc. | Modulation of telomere length by oligonucleotides having a G-core sequence |
US6444656B1 (en) | 1992-12-23 | 2002-09-03 | Biochem Pharma, Inc. | Antiviral phosphonate nucleotides |
US6005107A (en) | 1992-12-23 | 1999-12-21 | Biochem Pharma, Inc. | Antiviral compounds |
JPH08508714A (ja) | 1993-01-25 | 1996-09-17 | ハイブライドン インコーポレイテッド | オリゴヌクレオチド・アルキルホスホネートおよびアルキルホスホノチオエート |
EP0691979A1 (en) | 1993-03-31 | 1996-01-17 | Sanofi | Novel 5'-substituted nucleosides and oligomers produced therefrom |
JPH08508489A (ja) | 1993-03-31 | 1996-09-10 | スターリング ウィンスロップ インコーポレイティド | 二官能価ヌクレオシド、それらのオリゴマーならびにそれらの製造方法及び使用方法 |
US5955591A (en) | 1993-05-12 | 1999-09-21 | Imbach; Jean-Louis | Phosphotriester oligonucleotides, amidites and method of preparation |
US6015886A (en) | 1993-05-24 | 2000-01-18 | Chemgenes Corporation | Oligonucleotide phosphate esters |
EP0628394B1 (en) | 1993-06-10 | 1998-08-26 | Idemitsu Petrochemical Co. Ltd. | Injection molding die |
US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
US5643989A (en) | 1993-10-29 | 1997-07-01 | Azdel, Inc. | Fiber reinforced functionalized polyolefin composites |
US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
DE4435728A1 (de) | 1994-01-19 | 1995-07-20 | Boehringer Mannheim Gmbh | Biotinsilan-Verbindungen und diese Verbindungen enthaltende Bindematrix |
US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
BR9506861A (pt) | 1994-02-22 | 1997-09-23 | Novo Nordisk As | Processo para preparar e produzir uma variante de uma enzima lipolítica originária variante de enzima liplítica construção de dna vetor célula hospedeira aditivo detergente e composição detergente |
US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
AU2445795A (en) | 1994-05-11 | 1995-12-05 | Novo Nordisk A/S | An enzyme with endo-1,3(4)-beta -glucanase activity |
US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
EP0685475B1 (en) | 1994-05-31 | 1999-01-13 | Bayer Ag | Amino-benzofuryl-and thienyl-derivatives |
HRP950288A2 (en) | 1994-05-31 | 1997-08-31 | Bayer Ag | Oxalylamino-benzofuran- and benzothienyl-derivatives |
US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
DK0772619T4 (da) | 1994-07-15 | 2011-02-21 | Univ Iowa Res Found | Immunmodulatoriske oligonukleotider |
ATE202569T1 (de) | 1994-09-07 | 2001-07-15 | Hybridon Inc | Prodrug-oligonukleotide |
US5681940A (en) | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
AU4514696A (en) | 1994-12-22 | 1996-07-10 | Hybridon, Inc. | Synthesis of stereospecific oligonucleotide phosphorothioates |
GB9501465D0 (en) | 1995-01-25 | 1995-03-15 | King S College London | Nucleoside phosphorothioate derivatives,synthesis and use thereof |
US6166197A (en) | 1995-03-06 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions |
AU5359496A (en) | 1995-03-06 | 1996-09-23 | Isis Pharmaceuticals, Inc. | Improved process for the synthesis of 2'-o-substituted pyrimidines and oligomeric compounds therefrom |
DE69638104D1 (de) | 1995-04-27 | 2010-02-11 | Takara Bio Inc | Für Lacto-N-biosidase kodierendes Gen |
MX9708663A (es) | 1995-05-11 | 1998-02-28 | Applied Research Systems | Inhibidor de actividad il-6. |
JPH11507020A (ja) | 1995-05-19 | 1999-06-22 | グリコメド・インコーポレイテッド | 活性化したグリコシド化合物の収集およびその生物学的使用 |
AU5871196A (en) | 1995-05-23 | 1996-12-24 | Hybridon, Inc. | Methods and compounds for the synthesis of oligonucleotides and the oligonucleotides thereby produced |
ATE194990T1 (de) | 1995-05-23 | 2000-08-15 | Hybridon Inc | Synthon für stereoselektive oligonukleotid- synthese |
AU698739B2 (en) | 1995-06-06 | 1998-11-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5932450A (en) | 1995-06-07 | 1999-08-03 | Gen-Probe Incorporated | Enzymatic synthesis of oligonucleotides using digestible templates |
US5824503A (en) | 1995-06-29 | 1998-10-20 | Takara Shuzo Co, Ltd. | Gene encoding endoglycoceramidase activator |
US5795765A (en) | 1995-06-29 | 1998-08-18 | Takara Shuzo Co., Ltd. | Gene encoding endoglycoceramidase |
US6017700A (en) | 1995-08-04 | 2000-01-25 | Bayer Corporation | Cationic oligonucleotides, and related methods of synthesis and use |
US5936080A (en) | 1996-05-24 | 1999-08-10 | Genta Incorporated | Compositions and methods for the synthesis of organophosphorus derivatives |
WO1997009443A1 (en) | 1995-09-05 | 1997-03-13 | Michigan State University | PROCESS FOR THE ISOLATION AND PURIFICATION OF TAXOL AND TAXANES FROM TAXUS spp |
US5734041A (en) | 1995-10-20 | 1998-03-31 | Mcgill University | Preparation of chiral phosphorothioate oligomers |
US6476216B1 (en) | 1995-10-20 | 2002-11-05 | Mcgill University | Preparation of phosphorothioate oligomers |
US6160109A (en) | 1995-10-20 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Preparation of phosphorothioate and boranophosphate oligomers |
US7018793B1 (en) | 1995-12-07 | 2006-03-28 | Diversa Corporation | Combinatorial screening of mixed populations of organisms |
US6214805B1 (en) | 1996-02-15 | 2001-04-10 | The United States Of America As Represented By The Department Of Health And Human Services | RNase L activators and antisense oligonucleotides effective to treat RSV infections |
AU708535B2 (en) | 1996-02-15 | 1999-08-05 | Cleveland Clinic Foundation, The | RNase L activators and antisense oligonucleotides effective to treat RSV infections |
GB9604669D0 (en) | 1996-03-05 | 1996-05-01 | Ciba Geigy Ag | Chemical compounds |
US5824669A (en) | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
DE69738254T2 (de) | 1996-05-10 | 2008-08-14 | Novozymes A/S | Methode zur bereitstellung von dna sequenzen |
US5856465A (en) | 1996-05-24 | 1999-01-05 | Polska Akademia Nauk Centrum Badan Molekularnych I Makromolekularnych | Compositions and methods for the synthesis of chirally pure organophosphorus nucleoside derivatives |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
DE19622783A1 (de) | 1996-06-07 | 1997-12-11 | Hoechst Ag | Isolierung der Biosynthesegene für Pseudo-Oligosaccharide aus Streptomyces glaucescens GLA.O und ihre Verwendung |
DE69736667T2 (de) | 1996-07-16 | 2007-09-06 | Gen-Probe Inc., San Diego | Verfahren zum nachweis und amplifikation von nukleinsäuresequenzen unter verbrauch von modifizierten oligonukleotiden mit erhöhter zielschmelztemperatur (tm) |
CA2261566A1 (en) | 1996-07-24 | 1998-01-29 | Buchardt, Dorte | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
WO1998007734A1 (en) | 1996-08-21 | 1998-02-26 | Hybridon, Inc. | Oligonucleotide prodrugs |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
GB9621522D0 (en) | 1996-10-16 | 1996-12-04 | Biocompatibles Ltd | Synthesis of phosphorus compounds |
US6639062B2 (en) | 1997-02-14 | 2003-10-28 | Isis Pharmaceuticals, Inc. | Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom |
US6172209B1 (en) | 1997-02-14 | 2001-01-09 | Isis Pharmaceuticals Inc. | Aminooxy-modified oligonucleotides and methods for making same |
US6369237B1 (en) | 1997-03-07 | 2002-04-09 | President And Fellows Of Harvard College | DNA glycosylase inhibitors, and uses related thereto |
US6015887A (en) | 1997-04-11 | 2000-01-18 | Isis Pharmaceuticals, Inc. | Chiral peptide nucleic acids and methods for preparing same |
US6468983B2 (en) | 1997-04-21 | 2002-10-22 | The Cleveland Clinic Foundation | RNase L activators and antisense oligonucleotides effective to treat telomerase-expressing malignancies |
PL184612B1 (pl) | 1997-04-25 | 2002-11-29 | Pan | Sposób wytwarzania modyfikowanych P chiralnych analogów nukleotydów |
CA2291839A1 (en) | 1997-05-28 | 1998-12-03 | Peter E. Nielsen | Conjugated peptide nucleic acids having enhanced cellular uptake |
BR9810946A (pt) | 1997-06-27 | 2000-09-26 | Procter & Gamble | "acetais cìclicos pró-fragrância" |
AU8512598A (en) | 1997-07-25 | 1999-02-16 | Hybridon, Inc. | Oligonuclotides having 3' terminal stereospecific phosphorothioates |
US6383808B1 (en) | 2000-09-11 | 2002-05-07 | Isis Pharmaceuticals, Inc. | Antisense inhibition of clusterin expression |
GB9717158D0 (en) | 1997-08-13 | 1997-10-22 | King S College London | Solution synthesis of oligonucleotides and their phosphorothioate analogues |
US6767739B2 (en) | 2001-07-30 | 2004-07-27 | Isis Pharmaceuticals Inc. | Antisense modulation of microsomal triglyceride transfer protein expression |
US6750344B1 (en) | 1997-09-05 | 2004-06-15 | Isis Pharmaceuticals, Inc. | Amine compounds and combinatorial libraries comprising same |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
DE19741715A1 (de) | 1997-09-22 | 1999-03-25 | Hoechst Ag | Pentopyranosyl-Nucleosid, seine Herstellung und Verwendung |
US6232463B1 (en) | 1997-10-09 | 2001-05-15 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US6617438B1 (en) | 1997-11-05 | 2003-09-09 | Sirna Therapeutics, Inc. | Oligoribonucleotides with enzymatic activity |
US6528640B1 (en) | 1997-11-05 | 2003-03-04 | Ribozyme Pharmaceuticals, Incorporated | Synthetic ribonucleic acids with RNAse activity |
US6080543A (en) | 1997-12-08 | 2000-06-27 | E. & J. Gallo Winery | Detection of fungal pathogens |
US6582936B1 (en) | 1997-12-12 | 2003-06-24 | The Regents Of The University Of California | Methods for making nucleic acids |
US6248519B1 (en) | 1998-03-11 | 2001-06-19 | E & J Gallo Winery | Detection of fermentation-related microorganisms |
US7045610B2 (en) | 1998-04-03 | 2006-05-16 | Epoch Biosciences, Inc. | Modified oligonucleotides for mismatch discrimination |
AU3884199A (en) | 1998-05-06 | 1999-11-23 | Ottawa Health Research Institute | Methods for the prevention and treatment of parasitic infections and related diseases using cpg oligonucleotides |
DE69927495T2 (de) | 1998-05-14 | 2006-07-06 | Coley Pharmaceutical Group, Inc., Wellesley | Verfahren zur regulieren der hämatopoese mit hilfe von cpg-oligonukleotiden |
US6242589B1 (en) | 1998-07-14 | 2001-06-05 | Isis Pharmaceuticals, Inc. | Phosphorothioate oligonucleotides having modified internucleoside linkages |
US6867294B1 (en) | 1998-07-14 | 2005-03-15 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
AU764532B2 (en) | 1998-07-27 | 2003-08-21 | University Of Iowa Research Foundation, The | Stereoisomers of CpG oligonucleotides and related methods |
DK1104306T3 (da) | 1998-08-10 | 2006-05-22 | Antigenics Inc | Præparater af CpG- og saponinadjuvanser og fremgangsmåder til anvendelse deraf |
WO2000023444A1 (en) | 1998-10-21 | 2000-04-27 | Abbott Laboratories | 5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds |
US6995259B1 (en) | 1998-10-23 | 2006-02-07 | Sirna Therapeutics, Inc. | Method for the chemical synthesis of oligonucleotides |
US6451524B1 (en) | 1998-11-25 | 2002-09-17 | Isis Pharmaceuticals, Inc. | Identification of disease predictive nucleic acids |
AU1742600A (en) | 1998-11-25 | 2000-06-13 | Isis Pharmaceuticals, Inc. | Identification of disease predictive nucleic acids |
WO2000037658A2 (en) | 1998-12-21 | 2000-06-29 | Genencor International, Inc. | Chemically modified enzymes with multiple charged variants |
CA2702148C (en) | 1999-01-06 | 2014-03-04 | Genenews Inc. | Method of profiling gene expression in a human subject having an infectious disease |
US6265172B1 (en) | 1999-02-08 | 2001-07-24 | University Of Kentucky | Diagnostic test and therapy for manganese superoxide dismutate (mNsod) associated diseases |
US6121437A (en) | 1999-03-16 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Phosphate and thiophosphate protecting groups |
US6506594B1 (en) | 1999-03-19 | 2003-01-14 | Cornell Res Foundation Inc | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
GB9907245D0 (en) | 1999-03-29 | 1999-05-26 | Goldsborough Andrew | Cleavage of nucleic acids from solid supports |
JP3072345B1 (ja) | 1999-03-31 | 2000-07-31 | 農林水産省家畜衛生試験場長 | 豚丹毒菌の組換えサブユニットワクチン |
US5998148A (en) | 1999-04-08 | 1999-12-07 | Isis Pharmaceuticals Inc. | Antisense modulation of microtubule-associated protein 4 expression |
US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
US6300069B1 (en) | 1999-05-03 | 2001-10-09 | Qiagen Gmbh | Generation and amplification of nucleic acids from ribonucleic acids |
US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
US6066500A (en) | 1999-06-25 | 2000-05-23 | Isis Pharmaceuticals Inc. | Antisense modulation of Beta catenin expression |
US6271004B1 (en) | 1999-06-25 | 2001-08-07 | Display Systems Biotech A/S | Method for improved reverse transcription at high temperatures |
US6414135B1 (en) | 1999-07-07 | 2002-07-02 | Isis Pharmaceuticals, Inc. | C3′-methylene hydrogen phosphonate monomers and related compounds |
US20030092647A1 (en) | 2001-08-08 | 2003-05-15 | Crooke Rosanne M. | Antisense modulation of cholesteryl ester transfer protein expression |
US6147200A (en) | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
US7264932B2 (en) | 1999-09-24 | 2007-09-04 | Applera Corporation | Nuclease inhibitor cocktail |
SK287400B6 (sk) | 1999-09-25 | 2010-08-09 | University Of Iowa Research Foundation | Prostriedok s obsahom imunostimulačnej nukleovej kyseliny a jeho použitie na stimuláciu imunitnej reakcie |
US6949520B1 (en) | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
IL148844A0 (en) | 1999-09-27 | 2002-09-12 | Coley Pharm Group Inc | Methods related to immunostimulatory nucleic acid-induced interferon |
US20020082227A1 (en) | 1999-09-30 | 2002-06-27 | Scott Henry | Use of oligonucleotides for inhibition of complement activation |
WO2001025488A2 (en) | 1999-10-06 | 2001-04-12 | Quark Biotech, Inc. | Method for enrichment of natural antisense messenger rna |
GB9924285D0 (en) | 1999-10-14 | 1999-12-15 | Avecia Ltd | Process |
US20010055761A1 (en) | 1999-10-29 | 2001-12-27 | Agilent Technologies | Small scale dna synthesis using polymeric solid support with functionalized regions |
FR2800750B1 (fr) | 1999-11-05 | 2003-01-31 | Centre Nat Rech Scient | Proteines membranaires ctl (choline transporter like) impliquees dans le transport de la choline |
AU1656601A (en) | 1999-11-12 | 2001-06-12 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
US6322985B1 (en) | 1999-12-27 | 2001-11-27 | Technion Research And Development Foundation Ltd. | Abundant, well distributed and hyperpolymorphic simple sequence repeats in prokaryote genomes and use of same for prokaryote classification and typing |
WO2001050117A1 (en) | 1999-12-30 | 2001-07-12 | Cabot Corporation | Sensors with improved properties |
WO2001050349A1 (en) | 1999-12-30 | 2001-07-12 | Rutgers, The State University Of New Jersey | Electronic document customization and transformation utilizing user feedback |
US6649750B1 (en) | 2000-01-05 | 2003-11-18 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotide compounds |
US6159697A (en) | 2000-01-19 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Antisense modulation of Smad7 expression |
US7585847B2 (en) | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
US6495677B1 (en) | 2000-02-15 | 2002-12-17 | Kanda S. Ramasamy | Nucleoside compounds |
US6936432B2 (en) | 2000-03-01 | 2005-08-30 | Message Pharmaceuticals | Bacterial RNase P proteins and their use in identifying antibacterial compounds |
GB0004889D0 (en) | 2000-03-01 | 2000-04-19 | Avecia Ltd | Synthesis of oligonucleotides |
EP1265840A2 (en) | 2000-03-17 | 2002-12-18 | Corixa Corporation | Novel amphipathic aldehydes and their use as adjuvants and immunoeffectors |
BR0110112A (pt) | 2000-04-20 | 2003-02-11 | Hoffmann La Roche | Derivados de pirrolidina e piperidina e seu uso para o tratamento de distúrbios neurodegenerativos |
DE10019756A1 (de) | 2000-04-20 | 2001-10-25 | Bayer Ag | Verfahren zur Herstellung von superabsorbierenden Polymeren aus Polyacrylnitrilen |
WO2001085751A1 (en) | 2000-05-09 | 2001-11-15 | Reliable Biopharmaceutical, Inc. | Polymeric compounds useful as prodrugs |
US6492171B2 (en) | 2000-05-16 | 2002-12-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of TERT expression |
US6815542B2 (en) | 2000-06-16 | 2004-11-09 | Ribapharm, Inc. | Nucleoside compounds and uses thereof |
JP3074398U (ja) | 2000-06-27 | 2001-01-12 | ドンウー キヨン ジュシクヘサ | 自動車内装形オゾン発生装置 |
ATE384731T1 (de) | 2000-08-03 | 2008-02-15 | Hoffmann La Roche | Nukleinsäurebindende verbindungen mit pyrazolo 3, 4-d pyrimidinanalogen von purin-2,6-diamin und ihre verwendung |
US6725412B1 (en) | 2000-08-15 | 2004-04-20 | Dolby Laboratories Licensing Corporation | Low latency data encoder |
US6809195B1 (en) | 2000-08-16 | 2004-10-26 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotides |
US6559279B1 (en) | 2000-09-08 | 2003-05-06 | Isis Pharmaceuticals, Inc. | Process for preparing peptide derivatized oligomeric compounds |
DK1366077T3 (da) | 2000-09-15 | 2011-09-12 | Coley Pharm Gmbh | Fremgangsmåde til screening i store mængder af CpG-baserede immunoagonister/-antagonister |
EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
GB0024752D0 (en) | 2000-10-10 | 2000-11-22 | Univ Belfast | Oxidative halogenation of aromatic compounds |
PL208755B1 (pl) | 2000-10-18 | 2011-06-30 | Glaxosmithkline Biolog Sa | Kompozycja immunogenna oraz zastosowanie połączenia saponiny, oligonukleotydu immunostymulującego i lipopolisacharydu |
US6372492B1 (en) | 2000-10-30 | 2002-04-16 | Isis Pharmaceuticals, Inc. | Antisense modulation of talin expression |
US6682889B1 (en) | 2000-11-08 | 2004-01-27 | Becton, Dickinson And Company | Amplification and detection of organisms of the Chlamydiaceae family |
NL1016978C2 (nl) | 2000-12-22 | 2002-06-25 | Robert Jan Colenbrander | Inrichting en werkwijze voor het verpakken en bereiden van voedsel en werkwijze voor het vervaardigen van een dergelijke inrichting. |
EP2360166A1 (en) | 2001-01-22 | 2011-08-24 | Merck Sharp & Dohme Corp. | Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase |
US8008459B2 (en) | 2001-01-25 | 2011-08-30 | Evolva Sa | Concatemers of differentially expressed multiple genes |
ATE501251T1 (de) | 2001-01-25 | 2011-03-15 | Evolva Ltd | Zellbibliothek |
AU2002224668B2 (en) | 2001-01-26 | 2007-09-20 | Commonwealth Scientific And Industrial Research Organisation | Methods and means for producing efficient silencing construct using recombinational cloning |
US20050277133A1 (en) | 2001-05-18 | 2005-12-15 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
WO2002097134A2 (en) | 2001-05-25 | 2002-12-05 | Isis Pharmaceuticals, Inc. | Modified peptide nucleic acid |
GB0113523D0 (en) | 2001-06-04 | 2001-07-25 | Torotrak Dev Ltd | An Hydraulic control circuit for a continuosly variable transmission |
US20030069410A1 (en) | 2001-06-14 | 2003-04-10 | Isis Pharmaceuticals, Inc. | Methods for preparing oligonucleotides having chiral phosphorothioate linkages |
US20050019915A1 (en) | 2001-06-21 | 2005-01-27 | Bennett C. Frank | Antisense modulation of superoxide dismutase 1, soluble expression |
CN1931365A (zh) | 2001-06-29 | 2007-03-21 | 希龙公司 | Hcv e1e2疫苗组合物 |
EP1499627A2 (en) | 2001-07-03 | 2005-01-26 | ISIS Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
US7205399B1 (en) | 2001-07-06 | 2007-04-17 | Sirna Therapeutics, Inc. | Methods and reagents for oligonucleotide synthesis |
US6440739B1 (en) | 2001-07-17 | 2002-08-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of glioma-associated oncogene-2 expression |
US7425545B2 (en) | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
US7888324B2 (en) | 2001-08-01 | 2011-02-15 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
US6455308B1 (en) | 2001-08-01 | 2002-09-24 | Isis Pharmaceuticals, Inc. | Antisense modulation of serum amyloid A4 expression |
US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
US7259150B2 (en) | 2001-08-07 | 2007-08-21 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein (a) expression |
US7354909B2 (en) | 2001-08-14 | 2008-04-08 | The United States Of America As Represented By Secretary Of The Department Of Health And Human Services | Method for rapid generation of mature dendritic cells |
EP1418877A2 (en) | 2001-08-24 | 2004-05-19 | Massachusetts Institute Of Technology | Reagents that facilitate the purification of compounds synthesized on a solid support |
US7049122B2 (en) | 2001-09-21 | 2006-05-23 | Academia Sinica | Mutant-type lipases and applications thereof |
US6933288B2 (en) | 2002-02-04 | 2005-08-23 | Isis Pharmaceuticals, Inc. | Pyranosyl cytosines: pharmaceutical formulations and methods |
JP4348044B2 (ja) | 2002-02-12 | 2009-10-21 | 株式会社キラルジェン | 立体規則性の高いジヌクレオシドホスホロチオエートの製造法 |
US20030159938A1 (en) | 2002-02-15 | 2003-08-28 | George Hradil | Electroplating solution containing organic acid complexing agent |
US20040149587A1 (en) | 2002-02-15 | 2004-08-05 | George Hradil | Electroplating solution containing organic acid complexing agent |
US20050096284A1 (en) | 2002-02-20 | 2005-05-05 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
US8232383B2 (en) | 2002-02-20 | 2012-07-31 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
JP2005525358A (ja) | 2002-02-28 | 2005-08-25 | ビオタ インコーポレーティッド | ヌクレオチド模倣体およびそのプロドラッグ |
WO2003073989A2 (en) | 2002-02-28 | 2003-09-12 | Biota, Inc. | Nucleoside 5'-monophosphate mimics and their prodrugs |
US7288376B2 (en) | 2002-03-22 | 2007-10-30 | Council Of Scientific And Industrial Research | Method of detection of SP-A2 gene variants useful for prediction of predisposition to aspergillosis |
US20040102394A1 (en) | 2002-11-23 | 2004-05-27 | Isis Pharmaceuticals Inc. | Modulation of huntingtin interacting protein 2 expression |
US7247621B2 (en) | 2002-04-30 | 2007-07-24 | Valeant Research & Development | Antiviral phosphonate compounds and methods therefor |
WO2003097662A1 (en) | 2002-05-15 | 2003-11-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
AU2003237249A1 (en) | 2002-05-24 | 2003-12-12 | Isis Pharmaceuticals, Inc. | Oligonucleotides having modified nucleoside units |
AU2003241621A1 (en) | 2002-05-24 | 2003-12-12 | Isis Pharmaceuticals, Inc. | Oligonucleotides having modified nucleoside units |
US7507808B2 (en) | 2002-12-12 | 2009-03-24 | Isis Pharmaceuticals, Inc. | Modulation of endothelial lipase expression |
AU2003248708A1 (en) | 2002-06-17 | 2003-12-31 | Isis Pharmaceuticals, Inc. | Oligomeric compounds that include carbocyclic nucleosides and their use in gene modulation |
CA2488856A1 (en) | 2002-06-20 | 2003-12-31 | Cytos Biotechnology Ag | Packaged virus-like particles for use as adjuvants: method of preparation and use |
WO2004003228A1 (en) | 2002-07-01 | 2004-01-08 | Unisearch Limited | Genotyping method |
EP1520022B1 (en) | 2002-07-10 | 2015-07-22 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Rna-interference by single-stranded rna molecules |
US20040023905A1 (en) | 2002-07-31 | 2004-02-05 | Isis Pharmaceuticals Inc. | Antisense modulation of LAR expression |
US20080274989A1 (en) | 2002-08-05 | 2008-11-06 | University Of Iowa Research Foundation | Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof |
US20050042646A1 (en) | 2002-08-05 | 2005-02-24 | Davidson Beverly L. | RNA interference suppresion of neurodegenerative diseases and methods of use thereof |
US20050255086A1 (en) | 2002-08-05 | 2005-11-17 | Davidson Beverly L | Nucleic acid silencing of Huntington's Disease gene |
WO2004014933A1 (en) | 2002-08-07 | 2004-02-19 | University Of Massachusetts | Compositions for rna interference and methods of use thereof |
WO2004014312A2 (en) | 2002-08-08 | 2004-02-19 | Sirna Therapeutics, Inc. | Small-mer compositions and methods of use |
AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
US7414116B2 (en) | 2002-08-23 | 2008-08-19 | Illumina Cambridge Limited | Labelled nucleotides |
CN1694959B (zh) | 2002-09-13 | 2013-09-18 | 雷普利瑟公司 | 非序列互补的抗病毒寡核苷酸 |
US7030230B2 (en) | 2002-10-25 | 2006-04-18 | Isis Pharmaceuticals, Inc. | Process of purifying phosphoramidites |
EP1556077A2 (en) | 2002-10-29 | 2005-07-27 | Coley Pharmaceutical Group, Ltd | Use of cpg oligonucleotides in the treatment of hepatitis c virus infection |
CA2505090A1 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Conjugated oligomeric compounds and their use in gene modulation |
AU2003291721A1 (en) | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | Phosphorous-linked oligomeric compounds and their use in gene modulation |
CA2504694C (en) | 2002-11-05 | 2013-10-01 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
EP1560840B1 (en) | 2002-11-05 | 2015-05-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
US7381527B2 (en) | 2002-11-06 | 2008-06-03 | Council Of Scientific And Industrial Research | Method of detection of SP-A2 gene variants |
WO2004044181A2 (en) | 2002-11-13 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
EP2284266B1 (en) | 2002-11-14 | 2013-11-06 | Thermo Fisher Scientific Biosciences Inc. | siRNA targeting tp53 |
DK2216407T3 (en) | 2003-03-07 | 2016-03-29 | Alnylam Pharmaceuticals Inc | therapeutic compositions |
AU2003225705A1 (en) | 2003-03-07 | 2004-09-30 | Ribapharm Inc. | Cytidine analogs and methods of use |
AU2003225410A1 (en) | 2003-03-21 | 2004-10-11 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
GB0306657D0 (en) | 2003-03-24 | 2003-04-30 | Avecia Ltd | Process and compounds |
EP1606398A1 (en) | 2003-03-26 | 2005-12-21 | Cytos Biotechnology AG | Melan-a peptide analogue-virus-like-particle conjugates |
US7537767B2 (en) | 2003-03-26 | 2009-05-26 | Cytis Biotechnology Ag | Melan-A- carrier conjugates |
ITRM20030149A1 (it) | 2003-04-02 | 2004-10-03 | Giuliani Spa | Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico |
US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
US20050261237A1 (en) | 2003-04-25 | 2005-11-24 | Boojamra Constantine G | Nucleoside phosphonate analogs |
AU2004233989A1 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
WO2004096233A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Nucleoside phosphonate conjugates |
US7407965B2 (en) | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
US7470724B2 (en) | 2003-04-25 | 2008-12-30 | Gilead Sciences, Inc. | Phosphonate compounds having immuno-modulatory activity |
US7432261B2 (en) | 2003-04-25 | 2008-10-07 | Gilead Sciences, Inc. | Anti-inflammatory phosphonate compounds |
CN101410120A (zh) | 2003-04-25 | 2009-04-15 | 吉里德科学公司 | 抗炎的膦酸酯化合物 |
ATE490788T1 (de) | 2003-04-25 | 2010-12-15 | Gilead Sciences Inc | Antivirale phosphonate analoge |
US7452901B2 (en) | 2003-04-25 | 2008-11-18 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
US20090247488A1 (en) | 2003-04-25 | 2009-10-01 | Carina Cannizzaro | Anti-inflammatory phosphonate compounds |
WO2005002626A2 (en) | 2003-04-25 | 2005-01-13 | Gilead Sciences, Inc. | Therapeutic phosphonate compounds |
US7045306B2 (en) | 2003-04-28 | 2006-05-16 | The General Hospital Corporation | Method for identifying compounds in vitro that modulate the dysregulation of transcription of transcription mediated by mutant huntingtin protein |
US7214491B2 (en) | 2003-05-07 | 2007-05-08 | E. I. Du Pont De Nemours And Company | Δ-12 desaturase gene suitable for altering levels of polyunsaturated fatty acids in oleaginous yeasts |
JP4179562B2 (ja) | 2003-05-14 | 2008-11-12 | 独立行政法人科学技術振興機構 | ハンチンチン遺伝子の発現抑制 |
CA2524495A1 (en) | 2003-06-03 | 2005-01-13 | Eli Lilly And Company | Modulation of survivin expression |
BRPI0411514A (pt) | 2003-06-20 | 2006-08-01 | Coley Pharm Gmbh | antagonistas de receptor toll-like de molécula pequena |
US7683036B2 (en) | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
JP2005089441A (ja) | 2003-08-08 | 2005-04-07 | Toudai Tlo Ltd | 立体規則性の高いリン原子修飾ヌクレオチド類縁体の製造法 |
JP2011088935A (ja) | 2003-08-08 | 2011-05-06 | Chiralgen Ltd | リン原子修飾ヌクレオチド類縁体の製造のための光学活性ヌクレオシド3’−ホスホロアミダイト |
US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
MXPA06001976A (es) | 2003-08-21 | 2006-05-31 | Univ Griffith | Nuevas sulfenamidas. |
JP2007502778A (ja) | 2003-08-21 | 2007-02-15 | グリフィス ユニバーシティ | 新規スルフェンアミドオキシド |
DE602004029904D1 (de) | 2003-08-27 | 2010-12-16 | Biota Scient Management | Neue tricyclische nukleoside oder nukleotide als therapeutische mittel |
WO2005021570A1 (ja) | 2003-08-28 | 2005-03-10 | Gene Design, Inc. | N−0結合性架橋構造型新規人工核酸 |
JP4616175B2 (ja) | 2003-09-02 | 2011-01-19 | 株式会社キラルジェン | 5’−ホスフィチル化モノマーおよびh−ホスホネートオリゴヌクレオチド誘導体の製造方法 |
JP4580870B2 (ja) | 2003-09-02 | 2010-11-17 | 株式会社キラルジェン | リボヌクレオチド又はリボヌクレオチド誘導体の製造方法 |
US20050053981A1 (en) | 2003-09-09 | 2005-03-10 | Swayze Eric E. | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
US20050074801A1 (en) | 2003-09-09 | 2005-04-07 | Monia Brett P. | Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry |
CN101293908B (zh) | 2003-09-09 | 2015-05-06 | 杰龙公司 | 用于端粒酶抑制的改性寡核苷酸 |
US7947658B2 (en) | 2003-09-12 | 2011-05-24 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
GB0323968D0 (en) | 2003-10-13 | 2003-11-19 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
WO2005042018A2 (en) | 2003-10-30 | 2005-05-12 | Coley Pharmaceutical Gmbh | C-class oligonucleotide analogs with enhanced immunostimulatory potency |
US20050239102A1 (en) | 2003-10-31 | 2005-10-27 | Verdine Gregory L | Nucleic acid binding oligonucleotides |
US7846436B2 (en) | 2003-11-28 | 2010-12-07 | Chemgenes Corporation | Oligonucleotides and related compounds |
AU2003300239A1 (en) | 2003-12-29 | 2005-07-21 | Galapagos Genomics N.V. | Modulators of bone homeostasis identified in a high-throughput screen |
JP4945129B2 (ja) | 2004-01-27 | 2012-06-06 | 株式会社キラルジェン | フルオラス担体およびそれを用いたオリゴヌクレオチド誘導体の製造方法 |
US20050176045A1 (en) | 2004-02-06 | 2005-08-11 | Dharmacon, Inc. | SNP discriminatory siRNA |
WO2005076744A2 (en) | 2004-02-18 | 2005-08-25 | Frutarom Ltd. | Method for the preparation of peptide-oligonucleotide conjugates |
JP3976742B2 (ja) | 2004-02-27 | 2007-09-19 | 江守商事株式会社 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
WO2005085272A1 (ja) | 2004-03-05 | 2005-09-15 | Takeshi Wada | ボラノホスフェートモノマーおよびそれを用いたオリゴヌクレオチド誘導体の製造方法 |
WO2005092909A1 (ja) * | 2004-03-25 | 2005-10-06 | Toudai Tlo, Ltd. | 立体規則性の高いリボヌクレオチド類縁体及びデオキシリボヌクレオチド類縁体の製造法 |
US20050267300A1 (en) | 2004-04-05 | 2005-12-01 | Muthiah Manoharan | Processes and reagents for oligonucleotide synthesis and purification |
US20050244869A1 (en) | 2004-04-05 | 2005-11-03 | Brown-Driver Vickie L | Modulation of transthyretin expression |
TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
WO2005116268A2 (en) | 2004-05-27 | 2005-12-08 | The Government Of The United States Of America As Represented By The Secretary, Department Of Health | Differential expression of molecules associated with acute stroke |
US7759318B1 (en) | 2004-05-28 | 2010-07-20 | Isis Pharmaceuticals, Inc. | Identification of novel pathways, genes and promoter motifs regulating adipogenesis |
EP1766071A4 (en) | 2004-06-03 | 2009-11-11 | Isis Pharmaceuticals Inc | DOUBLE-STRONG COMPOSITIONS WITH DIFFERENTLY MODIFIED STRANDS FOR USE IN GENE MODULATION |
DE602005026386D1 (de) | 2004-06-28 | 2011-03-31 | Univ Western Australia | Antisense-oligonukleotide zur induktion von exon-skipping sowie verfahren zur verwendung davon |
SI2409713T1 (sl) | 2004-08-10 | 2015-10-30 | Genzyme Corporation | Oligonukleotidi za uporabo pri uravnavanju nivojev lipoproteinov in holesterola pri ljudeh |
WO2006022323A1 (ja) | 2004-08-26 | 2006-03-02 | Nippon Shinyaku Co., Ltd. | ホスホロアミダイト化合物及びオリゴrnaの製法 |
US20070066551A1 (en) | 2004-09-07 | 2007-03-22 | Keefe Anthony D | Aptamer medicinal chemistry |
US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
US20090203132A1 (en) | 2004-09-09 | 2009-08-13 | Swayze Eric E | Pyrrolidinyl groups for attaching conjugates to oligomeric compounds |
EP2397563A3 (en) | 2004-09-17 | 2012-07-18 | Isis Pharmaceuticals, Inc. | Enhanced antisense oligonucleotides |
AU2005295756B2 (en) | 2004-10-13 | 2012-02-02 | Isis Parmaceuticals, Inc. | Antisense modulation of PTP1B expression |
US7622451B2 (en) | 2004-11-03 | 2009-11-24 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
US8212012B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
AU2005301957B2 (en) | 2004-11-03 | 2012-02-23 | Department Of Health And Human Services | Novobiocin analogues as anticancer agents |
US9120774B2 (en) | 2004-11-03 | 2015-09-01 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
US8212011B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues |
KR100721928B1 (ko) | 2004-11-05 | 2007-05-28 | 주식회사 바이오씨에스 | CpG 올리고데옥시뉴클레오티드를 함유하는 피부질환의치료 또는 예방용 약학적 조성물 |
EP1657307A1 (en) | 2004-11-16 | 2006-05-17 | Immunotech S.A. | Oligonucleotides that induce the secretion of GM-CSF |
AU2005313883B2 (en) | 2004-12-09 | 2011-03-31 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering RNAs |
WO2006065751A2 (en) | 2004-12-13 | 2006-06-22 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Cpg oligonucleotide prodrugs, compositions thereof and associated therapeutic methods |
WO2006066260A2 (en) | 2004-12-17 | 2006-06-22 | Thiosense, Inc. | Compositions of and methods for producing phosphorus-chiral monomers and oligomers |
US20070099851A1 (en) | 2004-12-30 | 2007-05-03 | Linn Gregory S | Stable analogues of ribose-1-phosphate and methods for treating diabetes and other metabolic disorders |
US20060183763A1 (en) | 2004-12-31 | 2006-08-17 | Pfizer Inc | Novel pyrrolidyl derivatives of heteroaromatic compounds |
CN100485034C (zh) | 2005-01-28 | 2009-05-06 | 权滢周 | 从分支杆菌中提取的用于刺激免疫功能,治疗免疫相关性疾病,过敏性皮炎和/或保护正常免疫细胞的寡核苷酸 |
WO2006091915A2 (en) | 2005-02-24 | 2006-08-31 | Coley Pharmaceutical Group, Inc. | Immunostimulatory oligonucleotides |
WO2006137953A1 (en) | 2005-04-01 | 2006-12-28 | The Regents Of The Univerisity Of California | Phosphono-pent-2-en-1-yl nucleosides and analogs |
US8097597B2 (en) | 2005-05-05 | 2012-01-17 | Antisense Pharma Gmbh | Use of low doses of oligonucleotides antisense to TGF-β genes in the treatment of brain tumors |
US7902352B2 (en) | 2005-05-06 | 2011-03-08 | Medtronic, Inc. | Isolated nucleic acid duplex for reducing huntington gene expression |
WO2006121960A2 (en) | 2005-05-06 | 2006-11-16 | Medtronic, Inc. | Methods and sequences to suppress primate huntington gene expression |
EP2644700A1 (en) | 2005-06-23 | 2013-10-02 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of SMN2 splicing |
US9133517B2 (en) | 2005-06-28 | 2015-09-15 | Medtronics, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin |
EP1896586A2 (en) | 2005-06-28 | 2008-03-12 | Medtronic, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin |
US20090162316A1 (en) | 2005-07-05 | 2009-06-25 | Harvard University | Liver targeted conjugates |
JP4984634B2 (ja) | 2005-07-21 | 2012-07-25 | ソニー株式会社 | 物理情報取得方法および物理情報取得装置 |
PL1924252T3 (pl) | 2005-07-28 | 2012-02-29 | Id Fish Tech Inc | Sposób ulepszania przepuszczalności komórki dla obcych cząstek |
CA2620856C (en) | 2005-08-29 | 2017-11-28 | Isis Pharmaceuticals, Inc. | Methods for use in modulating mir-122a |
US8501703B2 (en) | 2005-08-30 | 2013-08-06 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
US7700567B2 (en) | 2005-09-29 | 2010-04-20 | Supergen, Inc. | Oligonucleotide analogues incorporating 5-aza-cytosine therein |
US20070077993A1 (en) | 2005-09-30 | 2007-04-05 | Midgley Timothy M | Method and apparatus for collecting user game play data and crediting users in a gaming environment |
ES2542989T3 (es) | 2005-10-12 | 2015-08-13 | Idera Pharmaceuticals, Inc. | Compuestos oligonucleótidos inmuno reguladores (IRO) para modular la respuesta inmune basada en receptor semejante a Toll |
US9308252B2 (en) | 2005-10-27 | 2016-04-12 | Cook Biotech, Inc. | Extracellular matrix materials as vaccine adjuvants for diseases associated with infectious pathogens or toxins |
CN101466834B (zh) | 2005-10-28 | 2013-09-25 | 东曹株式会社 | 制备类胡萝卜素合成性微生物的方法和生产类胡萝卜素的方法 |
CA2627025A1 (en) | 2005-10-28 | 2007-05-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of huntingtin gene |
EP1963502A4 (en) | 2005-11-11 | 2010-04-07 | Pfizer | COMBINATIONS AND METHOD FOR USE OF AN IMMUNOMODULATIVE OLIGODESOXYNUCLEOTIDE |
WO2007064291A1 (en) | 2005-11-30 | 2007-06-07 | Jyoti Chattopadhyaya | Method and compounds for rna synthesis |
CA2632968A1 (en) | 2005-12-02 | 2007-06-07 | Isis Pharmaceuticals, Inc. | Antibacterial 4,5-substituted aminoglycoside analogs having multiple substituents |
US8076303B2 (en) | 2005-12-13 | 2011-12-13 | Spring Bank Pharmaceuticals, Inc. | Nucleotide and oligonucleotide prodrugs |
MY151455A (en) | 2005-12-21 | 2014-05-30 | Pfizer Prod Inc | Carbonylamino pyrrolopyrazoles, potent kinase inhibitors |
AU2007210038B2 (en) | 2006-01-26 | 2013-01-10 | Ionis Pharmaceuticals, Inc. | Compositions and their uses directed to huntingtin |
DK2314594T3 (da) | 2006-01-27 | 2014-10-27 | Isis Pharmaceuticals Inc | 6-modificerede bicykliske nukleinsyreanaloger |
PT2405002E (pt) | 2006-02-15 | 2015-01-05 | Adiutide Pharmaceuticals Gmbh | Composições e métodos para formulações de oligonucleotídeos |
US7759470B2 (en) | 2006-02-20 | 2010-07-20 | Roche Diagnostics Operations, Inc. | Labeling reagent |
US8383660B2 (en) | 2006-03-10 | 2013-02-26 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
AU2007234451A1 (en) | 2006-03-31 | 2007-10-11 | Atom Acquisition, Llc | Reagents useful for synthesizing rhodamine-labeled oligonucleotides |
US8088582B2 (en) | 2006-04-06 | 2012-01-03 | Ibis Biosciences, Inc. | Compositions for the use in identification of fungi |
DE602007008222D1 (de) | 2006-04-20 | 2010-09-16 | Hoffmann La Roche | Diazepanderivate als modulatoren von chemokinrezeptoren |
CN101432440B (zh) | 2006-04-24 | 2013-08-21 | 西格马食品可变资本有限公司 | 通过实时聚合酶链反应检测和多重、同时量化病原体的方法 |
EP2018436A2 (en) | 2006-04-25 | 2009-01-28 | Immune Disease Institute Inc. | Targeted delivery to leukocytes using non-protein carriers |
GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
EP2023936A4 (en) | 2006-05-05 | 2010-11-24 | Isis Pharmaceuticals Inc | COMPOSITIONS AND THEIR USES ASSOCIATED WITH THE ALPHA PTPR RECEPTOR |
US8188059B2 (en) | 2006-05-05 | 2012-05-29 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of GCGR |
US20090012120A1 (en) | 2006-05-10 | 2009-01-08 | Board Of Trustees Of Michigan State University | Synthesis of N-heterocycles, beta-amino acids, and allyl amines via aza-payne mediated reaction of ylides and hydroxy aziridines |
CN101490074B (zh) | 2006-05-11 | 2013-06-26 | Isis制药公司 | 5’-修饰的双环核酸类似物 |
US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
KR101065760B1 (ko) | 2006-05-31 | 2011-09-19 | 오사카 유니버시티 | 면역자극 올리고뉴클레오티드 및 그 의약 용도 |
US8097596B2 (en) | 2006-06-30 | 2012-01-17 | Lakewood-Amedex, Inc. | Compositions and methods for the treatment of muscle wasting |
CA2662704A1 (en) | 2006-07-07 | 2008-01-10 | University Of Massachusetts | Rna silencing compositions and methods for the treatment of huntington's disease |
WO2008008476A2 (en) | 2006-07-12 | 2008-01-17 | The Regents Of The University Of California | Transducible delivery of nucleic acids by reversible phosphotriester charge neutralization protecting groups |
WO2008011453A2 (en) | 2006-07-20 | 2008-01-24 | Amgen Inc. | SUBSTITUTED AZOLE AROMATIC HETEROCYCLES AS INHIBITORS OF LLβ-HSD-1 |
GB0614947D0 (en) | 2006-07-27 | 2006-09-06 | Isis Innovation | Epitope reduction therapy |
WO2008017081A1 (en) | 2006-08-04 | 2008-02-07 | Isis Pharmaceuticals, Inc. | Compositions and methods for the modulation of jnk proteins |
AT504194B1 (de) | 2006-09-07 | 2008-07-15 | Oesterr Rotes Kreuz | Bakteriennachweis |
US8138330B2 (en) | 2006-09-11 | 2012-03-20 | Sigma-Aldrich Co. Llc | Process for the synthesis of oligonucleotides |
KR101251707B1 (ko) | 2006-09-27 | 2013-04-11 | 콜리 파마슈티칼 게엠베하 | 면역 자극 활성이 증강된 소수성 T 유사체를 함유하는 CpG 올리고뉴클레오티드 유사체 |
JP5665317B2 (ja) | 2006-10-18 | 2015-02-04 | アイシス ファーマシューティカルズ, インコーポレーテッド | アンチセンス化合物 |
JP2010507681A (ja) | 2006-10-23 | 2010-03-11 | アイアールエム・リミテッド・ライアビリティ・カンパニー | カテプシンプロテアーゼ阻害剤 |
AU2007353120A1 (en) | 2006-10-26 | 2008-11-20 | Coley Pharmaceutical Gmbh | Oligoribonucleotides and uses thereof |
FR2908414B1 (fr) | 2006-11-13 | 2012-01-20 | Centre Nat Rech Scient | Immobilisation de proteines membranaires sur un support par l'intermediaire d'une molecule amphiphile |
CN101534824A (zh) | 2006-11-17 | 2009-09-16 | 艾博特公司 | 作为化学活素受体拮抗剂的氨基吡咯烷 |
US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
EP2455471A3 (en) | 2006-11-27 | 2012-09-12 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
AU2007333146A1 (en) | 2006-12-12 | 2008-06-19 | Idera Pharmaceuticals, Inc. | Synthetic agonists of TLR9 |
UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
US20100190837A1 (en) | 2007-02-15 | 2010-07-29 | Isis Pharmaceuticals, Inc. | 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom |
CN101679979A (zh) | 2007-03-24 | 2010-03-24 | 基酶有限公司 | 施用与人载脂蛋白b互补的反义寡核苷酸 |
US7960353B2 (en) | 2007-05-10 | 2011-06-14 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
ES2542511T3 (es) | 2007-05-11 | 2015-08-06 | Adynxx, Inc. | Expresión génica y dolor |
CA2688008A1 (en) | 2007-05-24 | 2008-11-27 | Kyorin Pharmaceutical Co., Ltd. | Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in substituent at 14-position |
GB0710186D0 (en) | 2007-05-29 | 2007-07-04 | Texas Instr Denmark | PWM loop with minimum allasing error property |
WO2008150729A2 (en) | 2007-05-30 | 2008-12-11 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
NZ581364A (en) | 2007-06-05 | 2011-10-28 | Nsab Af Neurosearch Sweden Ab | Disubstituted phenylpyrrolidines as modulators of cortical catecholaminergic neurotransmission |
ES2386492T3 (es) | 2007-06-08 | 2012-08-21 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos carbocíclicos |
WO2008151833A2 (en) | 2007-06-13 | 2008-12-18 | Hochschule Mannheim | Compounds for the modulation of huntingtin aggregation, methods and means for identifying such compounds |
ATE462787T1 (de) | 2007-06-18 | 2010-04-15 | Commissariat Energie Atomique | Reversibles sirna-silencing eines mutierten und endogenen huntington-wildtypgens und dessen anwendung zur behandlung von morbus huntington |
GB0712494D0 (en) | 2007-06-27 | 2007-08-08 | Isis Innovation | Substrate reduction therapy |
US8278283B2 (en) | 2007-07-05 | 2012-10-02 | Isis Pharmaceuticals, Inc. | 6-disubstituted or unsaturated bicyclic nucleic acid analogs |
US8188261B2 (en) | 2007-07-09 | 2012-05-29 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory RNA (SIMRA) compounds |
TWI413530B (zh) | 2007-07-20 | 2013-11-01 | Kao Corp | 有機聚矽氧 |
US8008011B2 (en) | 2007-07-31 | 2011-08-30 | University Of Saskatchewan | Genetic variation in pro-melanin-concentrating hormone gene affects carcass traits in cattle |
US7812003B2 (en) | 2007-08-02 | 2010-10-12 | Safe Stephen H | Antisense microRNA and uses therefor |
AU2008286735A1 (en) | 2007-08-15 | 2009-02-19 | Idera Pharmaceuticals, Inc. | Toll like receptor modulators |
CA2701128A1 (en) | 2007-10-01 | 2009-04-09 | Isis Pharmaceuticals, Inc. | Antisense modulation of fibroblast growth factor receptor 4 expression |
KR100886139B1 (ko) | 2007-11-13 | 2009-02-27 | 주식회사 삼천리제약 | 올리고뉴클레오타이드의 제조방법 |
PE20091669A1 (es) | 2007-12-21 | 2009-12-06 | Exelixis Inc | Benzofuropirimidinonas |
TWI340765B (en) | 2007-12-26 | 2011-04-21 | Ind Tech Res Inst | Oligonucleotide sequences and dna chip for identifying filamentous microorganisms and the identification method thereof |
WO2009089689A1 (en) | 2008-01-15 | 2009-07-23 | Mediatek Inc. | Multimedia presenting system, multimedia processing apparatus thereof, and method for presenting video and audio signals |
WO2009089659A1 (en) | 2008-01-18 | 2009-07-23 | Shanghai Targetdrug Co., Ltd. | Pyrollidine-based compounds |
EP2240768A1 (en) | 2008-02-04 | 2010-10-20 | Galapagos N.V. | Target sequences and methods to identify the same, useful in treatment of neurodegenerative diseases |
JP2009190983A (ja) | 2008-02-12 | 2009-08-27 | Tokyo Institute Of Technology | オリゴヌクレオチド誘導体 |
EP2282744B1 (en) | 2008-03-21 | 2018-01-17 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising tricyclic nucleosides and methods for their use |
WO2009120878A2 (en) | 2008-03-26 | 2009-10-01 | Alnylam Pharmaceuticals, Inc. | Non-natural ribonucleotides, and methods of use thereof |
EP2271351A4 (en) | 2008-04-03 | 2016-08-31 | Spring Bank Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTIONS |
EP2262820B1 (de) | 2008-04-04 | 2013-06-19 | Universität Hamburg | Verfahren zur stereoselektiven synthese von phosphorverbindungen |
US9290534B2 (en) | 2008-04-04 | 2016-03-22 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds having at least one neutrally linked terminal bicyclic nucleoside |
EP2297341A4 (en) | 2008-05-09 | 2013-01-09 | Univ British Columbia | METHOD AND COMPOSITIONS FOR TREATING MORBUS HUNTINGTON |
US8679750B2 (en) | 2008-05-09 | 2014-03-25 | The University Of British Columbia | Methods and compositions for the treatment of Huntington'S disease |
CA2724418A1 (en) | 2008-05-15 | 2009-11-19 | Dynavax Technologies Corporation | Long term disease modification using immunostimulatory oligonucleotides |
WO2009143390A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc. | Methods for modulating expression of rbp4 |
WO2009143391A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc | Methods for modulation expression of creb |
US8541387B2 (en) | 2008-05-22 | 2013-09-24 | Isis Pharmaceuticals, Inc. | Modulation of SMRT expression |
WO2009148605A2 (en) | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
JP2011526931A (ja) | 2008-07-03 | 2011-10-20 | エグゼリクシス, インコーポレイテッド | Cdkモジュレーター |
US8410070B2 (en) | 2008-09-12 | 2013-04-02 | University Of Louisville Research Foundation, Inc. | Compositions and methods for treating cancer, inhibiting proliferation, and inducing cell death |
WO2010030858A1 (en) | 2008-09-15 | 2010-03-18 | Enanta Pharmaceuticals, Inc. | 4'-allene-substituted nucleoside derivatives |
CN102196740A (zh) * | 2008-09-22 | 2011-09-21 | 戴曼加拿大采集无限责任公司 | 带有一体结合的拉出载运器的手提箱 |
WO2010039543A2 (en) | 2008-09-23 | 2010-04-08 | Traversa Therapeutics, Inc. | Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating rna interference |
DK2361256T3 (da) | 2008-09-24 | 2013-07-01 | Isis Pharmaceuticals Inc | Cyclohexenyl-nukleinsyreanaloger |
EP2356129B1 (en) | 2008-09-24 | 2013-04-03 | Isis Pharmaceuticals, Inc. | Substituted alpha-l-bicyclic nucleosides |
JP2012504962A (ja) | 2008-10-07 | 2012-03-01 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | テロメラーゼ阻害剤およびその使用方法 |
CA2962219C (en) | 2008-10-22 | 2020-08-25 | Quark Pharmaceuticals, Inc. | Methods for treating eye disorders |
EP2358398A2 (en) | 2008-10-24 | 2011-08-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
US20120059045A1 (en) | 2008-10-24 | 2012-03-08 | Isis Pharmaceuticals, Inc. | Methods of using oligomeric compounds comprising 2'-substituted nucleosides |
CN102282155B (zh) | 2008-12-02 | 2017-06-09 | 日本波涛生命科学公司 | 磷原子修饰的核酸的合成方法 |
WO2010072831A1 (en) | 2008-12-23 | 2010-07-01 | Girindus America, Inc | Sulfurizing reagents and their use for oligonucleotides synthesis |
WO2010080953A1 (en) | 2009-01-08 | 2010-07-15 | Isis Pharmaceuticals, Inc. | Transgenic murine model of human lipoprotein metabolism, hypercholesterolemia and cardiovascular disease |
KR20100087540A (ko) | 2009-01-28 | 2010-08-05 | 삼성전자주식회사 | 잉크젯 기록용 잉크 조성물 |
US20120264806A1 (en) | 2009-02-06 | 2012-10-18 | Bennett C Frank | Oligomeric compounds and excipients |
US8202974B2 (en) | 2009-02-10 | 2012-06-19 | Idera Pharmaceuticals, Inc. | Synthetic RNA-based agonists of TLR7 |
JP5766617B2 (ja) | 2009-02-20 | 2015-08-19 | ユニバーシティ・オブ・カンザス | 修飾された糖部分を有するノボビオシン類似体 |
US8975389B2 (en) | 2009-03-02 | 2015-03-10 | Alnylam Pharmaceuticals, Inc. | Nucleic acid chemical modifications |
US9107933B2 (en) | 2009-03-16 | 2015-08-18 | Isis Pharmaceuticals, Inc. | Compositions and methods of targeting apolipoprotein B for the reduction of apolipoprotein C-III |
WO2010113937A1 (ja) | 2009-03-31 | 2010-10-07 | 武田薬品工業株式会社 | ヌクレオシドの製造方法 |
WO2010118263A1 (en) | 2009-04-08 | 2010-10-14 | University Of Massachusetts | Single-nucleotide polymorphism (snp) targeting therapies for the treatment of huntington's disease |
US20120156138A1 (en) | 2009-04-14 | 2012-06-21 | Smith Larry J | Methods and Compositions for the Treatment of Medical Conditions Involving Cellular Reprogramming |
WO2010129853A2 (en) | 2009-05-07 | 2010-11-11 | The Regents Of The University Of California | TRANSDUCIBLE DELIVERY OF NUCLEIC ACIDS USING MODIFIED dsRNA BINDING DOMAINS |
AU2010256836A1 (en) | 2009-06-01 | 2012-01-19 | The Regents Of The University Of California | Nucleic acid delivery compositions and methods of use thereof |
RU2560182C2 (ru) | 2009-06-05 | 2015-08-20 | Инфекшес Дизиз Рисерч Инститьют | Синтетические глюкопиранозиллипидные адъюванты |
TR201816256T4 (tr) | 2009-06-17 | 2018-11-21 | Biogen Ma Inc | Bir süjede smn2 uç birleştirmesinin modülasyonu için bileşimler ve yöntemler. |
JP5670097B2 (ja) | 2009-06-19 | 2015-02-18 | 花王株式会社 | 二層分離型毛髪化粧料 |
US20120108800A1 (en) | 2009-06-23 | 2012-05-03 | Shumpei Murata | Method for synthesizing nucleic acid |
IN2012DN00720A (ja) | 2009-07-06 | 2015-06-19 | Ontorii Inc | |
US8329024B2 (en) | 2009-07-06 | 2012-12-11 | Ada Technologies, Inc. | Electrochemical device and method for long-term measurement of hypohalites |
US8927513B2 (en) | 2009-07-07 | 2015-01-06 | Alnylam Pharmaceuticals, Inc. | 5′ phosphate mimics |
EP2451974A2 (en) | 2009-07-08 | 2012-05-16 | Idera Pharmaceuticals, Inc. | Oligonucleotide-based compounds as inhibitors of toll-like receptors |
EP2458005A1 (en) | 2009-07-23 | 2012-05-30 | Galaxy Pharma Inc. | Fgf21 cis-element binding substance |
WO2011015572A1 (en) | 2009-08-03 | 2011-02-10 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
WO2011015573A1 (en) | 2009-08-03 | 2011-02-10 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
UA107360C2 (en) | 2009-08-05 | 2014-12-25 | Biogen Idec Inc | Bicyclic aryl sphingosine 1-phosphate analogs |
EP2462153B1 (en) | 2009-08-06 | 2015-07-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
US8927553B2 (en) | 2009-08-10 | 2015-01-06 | Daljit Singh Dhanoa | Deuterium-enriched alkyl sulfonamides and uses thereof |
ES2772825T3 (es) | 2009-09-11 | 2020-07-08 | Ionis Pharmaceuticals Inc | Modulación de la expresión de huntingtina |
CN102574888A (zh) | 2009-09-16 | 2012-07-11 | 株式会社启拉坚 | 用于rna及其衍生物的合成的新型保护基 |
WO2011038288A1 (en) | 2009-09-25 | 2011-03-31 | Isis Pharmaceuticals, Inc. | Modulation of ttc39 expression to increase hdl |
AP2012006192A0 (en) | 2009-10-15 | 2012-04-30 | Pfizer | PyrroloÄ2,3-DÜ pyrimidine compounds. |
TWI475051B (zh) | 2009-11-18 | 2015-03-01 | Kao Corp | Organic polysiloxane |
JP5809408B2 (ja) | 2009-11-25 | 2015-11-10 | 花王株式会社 | 毛髪化粧料 |
WO2011075560A1 (en) | 2009-12-17 | 2011-06-23 | Merck Sharp & Dohme Corp. | Aminopyrimidines as syk inhibitors |
JP2013515953A (ja) | 2009-12-28 | 2013-05-09 | アチラ ラボズ プライベート リミテッド | 診断用ゲル組成物、前記診断用ゲル組成物の製造方法 |
WO2011085271A2 (en) | 2010-01-08 | 2011-07-14 | Isis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
US8750507B2 (en) | 2010-01-25 | 2014-06-10 | Cisco Technology, Inc. | Dynamic group creation for managed key servers |
AU2011213563B2 (en) | 2010-02-08 | 2015-12-24 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
DK2534248T3 (en) | 2010-02-08 | 2018-11-19 | Ionis Pharmaceuticals Inc | SELECTIVE REDUCTION OF ALLELVARIANS |
JP5922587B2 (ja) | 2010-02-10 | 2016-05-24 | グラクソスミスクライン エルエルシー | 6−アミノ−2−{[(1s)−1−メチルブチル]オキシ}−9−[5−(1−ピペリジニル)ペンチル]−7,9−ジヒドロ−8h−プリン−8−オンマレイン酸塩 |
CN102918052A (zh) | 2010-03-05 | 2013-02-06 | 国立大学法人东京大学 | 硫代磷酸核糖核苷的制造方法 |
WO2011127175A1 (en) | 2010-04-06 | 2011-10-13 | Isis Pharmaceuticals, Inc. | Modulation of cd130 (gp130) expression |
CA2795750A1 (en) | 2010-04-07 | 2011-10-13 | Isis Pharmaceuticals, Inc. | Modulation of cetp expression |
WO2011133871A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | 5'-end derivatives |
WO2011139699A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
EP3173419A1 (en) | 2010-04-28 | 2017-05-31 | Ionis Pharmaceuticals, Inc. | Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom |
WO2011139911A2 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
EP2563921B1 (en) | 2010-04-30 | 2016-11-23 | Cellectis | Method for modulating double-strand break-induced homologous recombination |
GB201008902D0 (en) | 2010-05-27 | 2010-07-14 | Imp Innovations Ltd | Membrane enhanced polymer sythesis |
US20130253168A1 (en) | 2010-08-31 | 2013-09-26 | Steven L. Colletti | Novel single chemical entities and methods for delivery of oligonucleotides |
DK2620428T3 (da) | 2010-09-24 | 2019-07-01 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
WO2012043633A1 (ja) | 2010-09-30 | 2012-04-05 | 独立行政法人国立精神・神経医療研究センター | 優性変異遺伝子発現抑制剤 |
KR101381048B1 (ko) | 2010-10-20 | 2014-04-14 | 씨제이제일제당 (주) | O-포스포세린 생산 균주 및 이로부터 생산된 o-포스포세린으로부터 l-시스테인 또는 이의 유도체의 생산방법 |
WO2012058210A1 (en) | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA) |
ES2633565T3 (es) | 2010-11-12 | 2017-09-22 | The General Hospital Corporation | ARN no codificantes asociados a polycomb |
JP6093924B2 (ja) | 2010-11-30 | 2017-03-15 | 株式会社Wave Life Sciences Japan | 2’−o−修飾rna |
US20140050778A1 (en) | 2010-12-28 | 2014-02-20 | University Of Rochester | Nucleic acid binding compounds, methods of making, and use thereof |
US10017764B2 (en) | 2011-02-08 | 2018-07-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
US9181544B2 (en) | 2011-02-12 | 2015-11-10 | University Of Iowa Research Foundation | Therapeutic compounds |
WO2012151324A1 (en) | 2011-05-02 | 2012-11-08 | Isis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with usher syndrome |
FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
CN103958519A (zh) | 2011-07-19 | 2014-07-30 | 爱达荷州大学 | 用于靶向核酸的探针和方法的实施方式 |
JP6128529B2 (ja) | 2011-07-19 | 2017-05-17 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | 官能化核酸の合成のための方法 |
WO2013022984A1 (en) | 2011-08-11 | 2013-02-14 | Isis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
US9976138B2 (en) | 2011-08-29 | 2018-05-22 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
US20140080896A1 (en) | 2011-08-30 | 2014-03-20 | The Regents Of The University Of California | Identification of small molecules that facilitate therapeutic exon skipping |
EP2751284B1 (en) | 2011-08-31 | 2017-01-11 | The University Of Manchester | Method for diagnosing a neurodegenerative disease. |
US20140255936A1 (en) | 2011-09-09 | 2014-09-11 | Mayo Foundation For Medical Education And Research | Detecting frontotemporal dementia and amyotrophic lateral sclerosis |
ES2832531T3 (es) | 2011-11-30 | 2021-06-10 | Sarepta Therapeutics Inc | Oligonucleótidos para el tratamiento de enfermedades por expansión de repeticiones |
EP2790736B1 (en) | 2011-12-12 | 2018-01-31 | Oncoimmunin, Inc. | In vivo delivery of oligonucleotides |
AU2012353330B2 (en) | 2011-12-16 | 2018-04-19 | National University Corporation Tokyo Medical And Dental University | Chimeric double-stranded nucleic acid |
CN104114605B (zh) | 2011-12-20 | 2018-06-22 | 沙特阿美技术公司 | 聚合物合成的方法 |
CN102675386B (zh) | 2011-12-24 | 2014-07-02 | 河南科技大学 | 一种龙胆苦苷分离提纯方法 |
WO2013134558A1 (en) | 2012-03-07 | 2013-09-12 | The Texas A & M University System | Cancer treatment targeting non-coding rna overexpression |
EP3210993B1 (en) | 2012-03-13 | 2018-12-12 | Gilead Sciences, Inc. | 2'- substituted carba-nucleoside analogs for antiviral treatment |
KR20130114435A (ko) | 2012-04-09 | 2013-10-17 | 삼성전자주식회사 | 다수의 전극을 갖는 생분자 검출 장치 |
SI2841578T1 (sl) | 2012-04-23 | 2017-12-29 | Biomarin Technologies B.V. | Rna modulirajoči oligonukleotidi z izboljšanimi karakteristikami za zdravljenje nevromuskularnih motenj |
EA031301B1 (ru) | 2012-05-22 | 2018-12-28 | Иденикс Фармасьютикалз Ллс | D-аминокислотные химические соединения для лечения заболеваний печени |
EP2857412B1 (en) | 2012-05-30 | 2017-01-11 | Hokkaido System Science Co., Ltd. | Oligonucleotide synthesis method using highly dispersible liquid-phase support |
CA2879066C (en) | 2012-07-13 | 2019-08-13 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
WO2014012081A2 (en) | 2012-07-13 | 2014-01-16 | Ontorii, Inc. | Chiral control |
DK2872485T3 (da) * | 2012-07-13 | 2021-03-08 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
EP4253395A3 (en) | 2012-08-06 | 2023-11-29 | Alnylam Pharmaceuticals, Inc. | Processes for the preparation of carbohydrate conjugated rna agents |
KR102237882B1 (ko) | 2012-08-15 | 2021-04-07 | 아이오니스 파마수티컬즈, 인코포레이티드 | 변형된 캡핑 프로토콜을 이용하는 올리고머 화합물 제조 방법 |
US20150275208A1 (en) | 2012-10-12 | 2015-10-01 | Isis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
DK2906696T4 (da) | 2012-10-15 | 2023-02-27 | Ionis Pharmaceuticals Inc | Fremgangsmåder til modulering af c9orf72-ekspression |
RU2730677C2 (ru) | 2012-10-15 | 2020-08-24 | Ионис Фармасьютикалз, Инк. | Соединение для модуляции экспрессии гена c9orf72 и его применение |
WO2014062736A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for monitoring c9orf72 expression |
EP2725029A1 (en) | 2012-10-29 | 2014-04-30 | Laboratoire Biodim | New antibacterial compounds and biological applications thereof |
MX2015005500A (es) | 2012-10-29 | 2016-02-09 | Cocrystal Pharma Inc | Nucleotidos de pirimidina y sus profarmacos de monofosfato para el tratamiento de infecciones virales y cancer. |
WO2014069520A1 (ja) | 2012-10-31 | 2014-05-08 | 武田薬品工業株式会社 | 新規修飾核酸 |
CN104837996A (zh) | 2012-11-15 | 2015-08-12 | 罗氏创新中心哥本哈根有限公司 | 抗apob反义缀合物化合物 |
JP6463687B2 (ja) | 2012-11-26 | 2019-02-06 | ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブRoche Innovation Center Copenhagen A/S | Fgfr3の発現の調節のための組成物及び方法 |
WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
CN104955952A (zh) | 2013-01-30 | 2015-09-30 | 弗·哈夫曼-拉罗切有限公司 | Lna寡核苷酸碳水化合物缀合物 |
CA2899924A1 (en) | 2013-02-04 | 2014-08-07 | Isis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
WO2014130607A1 (en) | 2013-02-22 | 2014-08-28 | Sirna Therapeutics, Inc. | SHORT INTERFERING NUCLEIC ACID (siNA) MOLECULES CONTAINING A 2' INTERNUCLEOSIDE LINKAGE |
AU2014222150A1 (en) | 2013-03-01 | 2015-09-10 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
CN105072911A (zh) | 2013-03-28 | 2015-11-18 | 先正达参股股份有限公司 | 控制新烟碱抗性有害生物的方法 |
WO2014154486A1 (en) | 2013-03-28 | 2014-10-02 | Syngenta Participations Ag | Methods of controlling neonicotinoid resistant pests |
SI2992009T1 (sl) | 2013-05-01 | 2020-10-30 | Ionis Pharmaceuticals, Inc. | Sestavki in postopki za moduliranje izražanja apolipoproteina (A) |
DK3004352T3 (da) | 2013-05-24 | 2017-11-27 | Roche Innovation Ct Copenhagen As | Oligonukleotidmodulatorer af b-celle-cll/lymfom 11a (bcl11a) og anvendelser deraf |
JP6477464B2 (ja) | 2013-05-24 | 2019-03-06 | 味の素株式会社 | モルフォリノオリゴヌクレオチドの製造方法 |
ES2700277T3 (es) | 2013-05-30 | 2019-02-14 | Univ Nat Corp Tokyo Medical & Dental | Agentes de doble cadena para el suministro de oligonucleótidos terapéuticos |
WO2014203518A1 (en) | 2013-06-16 | 2014-12-24 | National University Corporation Tokyo Medical And Dental University | Double-stranded antisense nucleic acid with exon-skipping effect |
AU2014284152B2 (en) | 2013-06-21 | 2020-01-23 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
EP3591054A1 (en) | 2013-06-27 | 2020-01-08 | Roche Innovation Center Copenhagen A/S | Antisense oligomers and conjugates targeting pcsk9 |
TWI772856B (zh) | 2013-07-19 | 2022-08-01 | 美商百健Ma公司 | 用於調節τ蛋白表現之組合物 |
AU2014292926B2 (en) | 2013-07-25 | 2020-03-05 | Exicure Operating Company | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
WO2015017675A2 (en) | 2013-07-31 | 2015-02-05 | Isis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
CN105579442A (zh) | 2013-09-06 | 2016-05-11 | 先正达参股股份有限公司 | 杀虫化合物 |
US10385088B2 (en) | 2013-10-02 | 2019-08-20 | Modernatx, Inc. | Polynucleotide molecules and uses thereof |
KR20160067219A (ko) | 2013-10-03 | 2016-06-13 | 모더나 세라퓨틱스, 인코포레이티드 | 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드 |
WO2015051366A2 (en) | 2013-10-04 | 2015-04-09 | Novartis Ag | Novel formats for organic compounds for use in rna interference |
SG10201808903UA (en) | 2013-10-11 | 2018-11-29 | Ionis Pharmaceuticals Inc | Compositions for modulating c9orf72 expression |
US20160230172A1 (en) | 2013-10-14 | 2016-08-11 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
ES2747260T3 (es) | 2013-10-14 | 2020-03-10 | Ionis Pharmaceuticals Inc | Métodos para modular la expresión de transcrito antisentido C9ORF72 |
WO2015070212A1 (en) | 2013-11-11 | 2015-05-14 | Sangamo Biosciences, Inc. | Methods and compositions for treating huntington's disease |
KR20160083876A (ko) | 2013-11-14 | 2016-07-12 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | ApoB 안티센스 접합체 화합물 |
US20150167017A1 (en) | 2013-12-13 | 2015-06-18 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
KR20220106232A (ko) | 2014-01-16 | 2022-07-28 | 웨이브 라이프 사이언시스 리미티드 | 키랄 디자인 |
ES2856403T3 (es) | 2014-03-18 | 2021-09-27 | Univ Massachusetts | Composiciones a base de rAAV y procedimientos para el tratamiento de la esclerosis lateral amiotrofica |
DK3137476T3 (da) | 2014-04-28 | 2019-11-18 | Ionis Pharmaceuticals Inc | Linker-modificerede oligomerforbindelser |
MX2016014102A (es) | 2014-05-01 | 2017-05-03 | Ionis Pharmaceuticals Inc | Composiciones y metodos para modular la expresion de similar a la angiopoyetina tipo 3. |
CA2947035A1 (en) | 2014-05-08 | 2015-11-12 | Sangamo Biosciences, Inc. | Methods and compositions for treating huntington's disease |
US9523093B2 (en) | 2014-05-20 | 2016-12-20 | University Of Iowa Research Foundation | Huntington's disease therapeutic compounds |
US20160017327A1 (en) | 2014-07-11 | 2016-01-21 | The Johns Hopkins University | Phosphorodiamidate morpholino oligomers (pmos) and their use in suppression of mutant huntingtin expression and attenuation of neurotoxicity |
JP2017524357A (ja) | 2014-07-16 | 2017-08-31 | モデルナティエックス インコーポレイテッドModernaTX,Inc. | キメラポリヌクレオチド |
EP2982758A1 (en) | 2014-08-04 | 2016-02-10 | Centre Hospitalier Universitaire Vaudois (CHUV) | Genome editing for the treatment of huntington's disease |
PL3178807T3 (pl) | 2014-08-07 | 2020-08-24 | Takeda Pharmaceutical Company Limited | Lipid kationowy |
WO2016024205A1 (en) | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
WO2016027168A2 (en) | 2014-08-20 | 2016-02-25 | Lifesplice Pharma Llc | Splice modulating oligonucleotides and methods of use thereof |
WO2016037191A1 (en) | 2014-09-05 | 2016-03-10 | Health Research, Inc. | Use of huntingtin-derived plasmids and peptides for active immunization as a huntington's disease (hd) therapeutic |
EP3221329A1 (en) | 2014-11-19 | 2017-09-27 | Roche Innovation Center Copenhagen A/S | Lna gapmer oligonucleotides comprising chiral phosphorothioate linkages |
WO2016096938A1 (en) | 2014-12-16 | 2016-06-23 | Roche Innovation Center Copenhagen A/S | Chiral toxicity screening method |
LT3237618T (lt) | 2014-12-24 | 2019-07-10 | Uniqure Ip B.V. | Rnri sukeltas hantingtino geno slopinimas |
US9688707B2 (en) | 2014-12-30 | 2017-06-27 | Ionis Pharmaceuticals, Inc. | Bicyclic morpholino compounds and oligomeric compounds prepared therefrom |
WO2016112132A1 (en) | 2015-01-06 | 2016-07-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
CN107636159B (zh) | 2015-02-04 | 2022-06-14 | 百时美施贵宝公司 | 选择治疗性分子的方法 |
PE20171766A1 (es) | 2015-02-04 | 2017-12-21 | Hoffmann La Roche | Oligomeros antisentido de tau y usos de estos |
US20180023081A1 (en) | 2015-02-04 | 2018-01-25 | Bristol-Myers Squibb Company | Lna oligonucleotides with alternating flanks |
JP2018506304A (ja) | 2015-02-10 | 2018-03-08 | ジェンザイム・コーポレーション | バリアントRNAi |
JP2018510621A (ja) | 2015-02-13 | 2018-04-19 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | パタチン様ホスホリパーゼドメイン含有3(PNPLA3)iRNA組成物およびその使用方法 |
WO2016138017A1 (en) | 2015-02-23 | 2016-09-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for increasing antisense activity |
US20180036335A1 (en) | 2015-03-03 | 2018-02-08 | Ionis Pharmaceuticals, Inc. | Compositions for modulating mecp2 expression |
WO2016145142A1 (en) | 2015-03-10 | 2016-09-15 | Emory University | Nucleotide and nucleoside therapeutics compositions and uses related thereto |
WO2016154096A1 (en) | 2015-03-20 | 2016-09-29 | Ionis Pharmaceuticals, Inc. | Modulation of smggds expression |
PL3277814T3 (pl) | 2015-04-03 | 2020-11-30 | University Of Massachusetts | Związki oligonukleotydowe ukierunkowane na mrna huntingtyny |
US10851371B2 (en) | 2015-04-10 | 2020-12-01 | Ionis Pharmaceuticals, Inc. | Modulation of SMN expression |
US10407678B2 (en) | 2015-04-16 | 2019-09-10 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
KR102258516B1 (ko) | 2015-04-16 | 2021-05-31 | 아이오니스 파마수티컬즈, 인코포레이티드 | C9orf72 발현을 조절하기 위한 조성물 |
WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
US11414657B2 (en) | 2015-06-29 | 2022-08-16 | Ionis Pharmaceuticals, Inc. | Modified CRISPR RNA and modified single CRISPR RNA and uses thereof |
US10494632B2 (en) | 2015-07-10 | 2019-12-03 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof |
PE20180800A1 (es) | 2015-07-10 | 2018-05-09 | Ionis Pharmaceuticals Inc | Moduladores de diaciglicerol aciltransferasa 2 (dgat2) |
CA3205381A1 (en) | 2015-07-17 | 2017-01-26 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
TW201718620A (zh) | 2015-07-27 | 2017-06-01 | 阿尼拉製藥公司 | 黃嘌呤脫氫酶(XDH)iRNA組成物及其使用方法 |
KR20240074895A (ko) | 2015-07-31 | 2024-05-28 | 알닐람 파마슈티칼스 인코포레이티드 | 트랜스티레틴(TTR) iRNA 조성물 및 TTR-관련 질병을 치료하거나, 예방하기 위한 그의 사용 방법 |
EP3341479B1 (en) | 2015-08-24 | 2019-12-18 | Roche Innovation Center Copenhagen A/S | Lna-g process |
WO2017035340A1 (en) | 2015-08-25 | 2017-03-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder |
KR20180051550A (ko) | 2015-09-02 | 2018-05-16 | 알닐람 파마슈티칼스 인코포레이티드 | 프로그램된 세포사 1 리간드 1 (PD-L1) iRNA 조성물 및 그의 사용 방법 |
WO2017059446A1 (en) | 2015-10-01 | 2017-04-06 | Memorial Sloan-Kettering Cancer Center | Anthranilyl-adenosinemonosulfamate analogs and uses thereof |
US20180273573A1 (en) | 2015-10-01 | 2018-09-27 | Memorial Sloan-Kettering Cancer Center | Inhibitors of menaquinone biosynthesis |
US10577388B2 (en) | 2015-10-02 | 2020-03-03 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugation process |
SG10201912902TA (en) | 2015-10-09 | 2020-02-27 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
WO2017068087A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotide detection method |
WO2017067970A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | In vitro toxicity screening assay |
US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
SI3374509T1 (sl) | 2015-11-12 | 2021-04-30 | F. Hoffmann-La Roche Ag | Oligonukleotidi za indukcijo očetovske ekspresije UBE3A |
CN114685589A (zh) | 2016-03-13 | 2022-07-01 | 波涛生命科学有限公司 | 用于亚磷酰胺和寡核苷酸合成的组合物和方法 |
CN114085836B (zh) | 2016-03-14 | 2024-01-26 | 豪夫迈·罗氏有限公司 | 用于减少pd-l1表达的寡核苷酸 |
KR102372122B1 (ko) | 2016-03-18 | 2022-03-07 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 아실-보호된 l-lna-구아노신 단량체 |
WO2017165489A1 (en) | 2016-03-23 | 2017-09-28 | Emory University | Antiviral agents for treating zika and dengue virus infections |
CA3017532A1 (en) | 2016-04-13 | 2017-10-19 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
US11248019B2 (en) | 2016-04-14 | 2022-02-15 | Hoffmann-La Roche Inc. | Trityl-mono-GalNAc compounds and their use |
MA45290A (fr) | 2016-05-04 | 2019-03-13 | Wave Life Sciences Ltd | Procédés et compositions d'agents biologiquement actifs |
MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
CN109311925B (zh) | 2016-05-12 | 2022-06-03 | 罗氏创新中心哥本哈根有限公司 | 立体限定的氧杂氮杂磷杂环戊烷亚磷酰胺单体与核苷或寡核苷酸的增强的偶联 |
CA3023621C (en) | 2016-05-13 | 2021-07-27 | F. Hoffmann-La Roche Ag | Protein-based sample collection matrices and devices |
US10882884B2 (en) | 2016-05-18 | 2021-01-05 | Eth Zurich | Stereoselective synthesis of phosphorothioate oligoribonucleotides |
CN109562122A (zh) | 2016-06-03 | 2019-04-02 | 波涛生命科学有限公司 | 寡核苷酸、组合物及其方法 |
DK3473270T3 (da) | 2016-06-20 | 2023-01-09 | Genahead Bio Inc | Konjugat af antistof-lægemiddel |
US20190264267A1 (en) | 2016-07-25 | 2019-08-29 | Wave Life Sciences Ltd. | Phasing |
EP3544987A4 (en) | 2016-11-23 | 2020-11-18 | Wave Life Sciences Ltd. | COMPOSITIONS AND SYNTHESIS OF PHOSPHORAMIDITES AND OLIGONUCLEOTIDES |
US11603532B2 (en) | 2017-06-02 | 2023-03-14 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
WO2018223073A1 (en) | 2017-06-02 | 2018-12-06 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
CA3065523A1 (en) | 2017-06-02 | 2018-12-06 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
US11718638B2 (en) | 2017-06-21 | 2023-08-08 | Wave Life Sciences Ltd. | Compounds, compositions and methods for synthesis |
SG11202000274RA (en) | 2017-08-08 | 2020-02-27 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
CA3072110A1 (en) | 2017-09-18 | 2019-03-21 | Wave Life Sciences Ltd. | Technologies for oligonucleotide preparation |
SG11202001783YA (en) | 2017-10-12 | 2020-03-30 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
MX2020010687A (es) | 2018-04-12 | 2021-01-20 | Wave Life Sciences Ltd | Composiciones de oligonucleotidos y metodos de uso de las mismas. |
SG11202010131QA (en) | 2018-05-11 | 2020-11-27 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods of use thereof |
EP3891284A4 (en) | 2018-12-06 | 2023-04-12 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF |
SG11202107318YA (en) | 2019-02-01 | 2021-08-30 | Wave Life Sciences Ltd | Oligonucleotide compositions and methods thereof |
CN113748116A (zh) | 2019-03-20 | 2021-12-03 | 波涛生命科学有限公司 | 可用于寡核苷酸制备的技术 |
US20220307019A1 (en) | 2019-03-25 | 2022-09-29 | National University Corporation Tokyo Medical And Dental University | Double-stranded nucleic acid complex and use thereof |
EP3958872A2 (en) | 2019-04-25 | 2022-03-02 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
EP3959318A4 (en) | 2019-04-25 | 2023-10-25 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE COMPOSITIONS AND METHODS OF USE |
JP2022532169A (ja) | 2019-05-09 | 2022-07-13 | ウェイブ ライフ サイエンシズ リミテッド | オリゴヌクレオチド組成物及びその使用方法 |
US20230220384A1 (en) | 2019-10-06 | 2023-07-13 | Prashant Monian | Oligonucleotide compositions and methods of use thereof |
KR20220070324A (ko) | 2019-10-06 | 2022-05-30 | 웨이브 라이프 사이언시스 리미티드 | 올리고뉴클레오티드 조성물 및 이의 이용 방법 |
-
2013
- 2013-07-12 DK DK13817386.9T patent/DK2872485T3/da active
- 2013-07-12 ES ES13817386T patent/ES2862073T3/es active Active
- 2013-07-12 CA CA2879023A patent/CA2879023C/en active Active
- 2013-07-12 CN CN201610835862.5A patent/CN107011400B/zh active Active
- 2013-07-12 PL PL13817386T patent/PL2872485T3/pl unknown
- 2013-07-12 AU AU2013288048A patent/AU2013288048A1/en not_active Abandoned
- 2013-07-12 JP JP2015500697A patent/JP6268157B2/ja active Active
- 2013-07-12 RU RU2015100197A patent/RU2693381C2/ru not_active Application Discontinuation
- 2013-07-12 KR KR1020157004038A patent/KR101850319B1/ko active IP Right Grant
- 2013-07-12 SG SG11201500239VA patent/SG11201500239VA/en unknown
- 2013-07-12 EP EP13817386.9A patent/EP2872485B1/en active Active
- 2013-07-12 PT PT138173869T patent/PT2872485T/pt unknown
- 2013-07-12 BR BR112015000784A patent/BR112015000784A8/pt not_active Application Discontinuation
- 2013-07-12 CN CN201380037512.9A patent/CN104684893B/zh active Active
- 2013-07-12 EP EP20214250.1A patent/EP3812370A1/en active Pending
- 2013-07-12 US US14/414,604 patent/US9598458B2/en active Active
- 2013-07-12 WO PCT/JP2013/004303 patent/WO2014010250A1/en active Application Filing
-
2016
- 2016-07-08 AU AU2016204770A patent/AU2016204770B2/en active Active
- 2016-10-14 US US15/294,602 patent/US10167309B2/en active Active
-
2017
- 2017-10-30 JP JP2017209854A patent/JP6608413B2/ja active Active
-
2018
- 2018-04-26 AU AU2018202884A patent/AU2018202884B2/en active Active
- 2018-11-06 US US16/182,302 patent/US10696711B2/en active Active
-
2019
- 2019-08-21 JP JP2019150815A patent/JP7030749B2/ja active Active
-
2020
- 2020-05-19 US US16/878,461 patent/US11136346B2/en active Active
- 2020-08-10 AU AU2020213420A patent/AU2020213420B2/en active Active
-
2021
- 2021-09-02 US US17/465,238 patent/US20220127301A1/en active Pending
-
2022
- 2022-02-22 JP JP2022026049A patent/JP7390417B2/ja active Active
-
2023
- 2023-03-20 AU AU2023201700A patent/AU2023201700A1/en active Pending
- 2023-11-17 JP JP2023196280A patent/JP2024023334A/ja active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020015735A (ja) * | 2012-07-13 | 2020-01-30 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | 不斉補助基 |
JP7030749B2 (ja) | 2012-07-13 | 2022-03-07 | ウェイブ ライフ サイエンシズ リミテッド | 不斉補助基 |
JP2022071016A (ja) * | 2012-07-13 | 2022-05-13 | ウェイブ ライフ サイエンシズ リミテッド | 不斉補助基 |
JP7390417B2 (ja) | 2012-07-13 | 2023-12-01 | ウェイブ ライフ サイエンシズ リミテッド | 不斉補助基 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6608413B2 (ja) | 不斉補助基 | |
EP2921499B1 (en) | Method for liquid-phase synthesis of nucleic acids | |
JP7433684B1 (ja) | 疑似固相保護基、それを用いたヌクレオシド保護体又はオリゴヌクレオチド保護体、オリゴアミダイト前駆体の製造方法 | |
WO2022194924A1 (en) | Chiral synthons for the synthesis of chiral phosphorothioates |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171129 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171221 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20180418 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180418 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181002 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190104 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190220 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190405 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20190423 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190821 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20190830 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190924 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20191023 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6608413 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |