KR20020013498A - 신규 뉴클레오시드 및 올리고뉴클레오티드 유사체 - Google Patents
신규 뉴클레오시드 및 올리고뉴클레오티드 유사체 Download PDFInfo
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- KR20020013498A KR20020013498A KR1020017009992A KR20017009992A KR20020013498A KR 20020013498 A KR20020013498 A KR 20020013498A KR 1020017009992 A KR1020017009992 A KR 1020017009992A KR 20017009992 A KR20017009992 A KR 20017009992A KR 20020013498 A KR20020013498 A KR 20020013498A
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- South Korea
- Prior art keywords
- group
- amino
- ethylene
- compound
- oxo
- Prior art date
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- 108091034117 Oligonucleotide Chemical class 0.000 title claims abstract description 67
- 239000002777 nucleoside Substances 0.000 title description 6
- 125000003835 nucleoside group Chemical class 0.000 title description 3
- -1 Oxo-pyrimidin-1-yl Chemical group 0.000 claims abstract description 302
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 125000006239 protecting group Chemical group 0.000 claims abstract description 31
- 239000000126 substance Substances 0.000 claims abstract description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
- 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims abstract description 12
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 236
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 31
- 125000002252 acyl group Chemical group 0.000 claims description 29
- 125000003277 amino group Chemical group 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 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 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 239000005977 Ethylene Substances 0.000 claims description 18
- 150000008300 phosphoramidites Chemical class 0.000 claims description 18
- 125000001931 aliphatic group Chemical group 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 12
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 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 claims description 9
- 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 claims description 9
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 9
- 229940045145 uridine Drugs 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 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 description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 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 claims description 6
- 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 claims description 5
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 5
- 125000005426 adeninyl group Chemical group N1=C(N=C2N=CNC2=C1N)* 0.000 claims description 5
- 229940029575 guanosine Drugs 0.000 claims description 5
- 125000005499 phosphonyl group Chemical group 0.000 claims description 5
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 4
- 229960005305 adenosine Drugs 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 125000005159 cyanoalkoxy group Chemical group 0.000 claims description 3
- BBAMTDMNXVSCRU-UHFFFAOYSA-N (4-chlorophenyl) dihydrogen phosphate Chemical group OP(O)(=O)OC1=CC=C(Cl)C=C1 BBAMTDMNXVSCRU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical group NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 claims description 2
- SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical group NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 claims description 2
- TUDKBZAMOFJOSO-UHFFFAOYSA-N 2-methoxy-7h-purin-6-amine Chemical compound COC1=NC(N)=C2NC=NC2=N1 TUDKBZAMOFJOSO-UHFFFAOYSA-N 0.000 claims 1
- CFIBTBBTJWHPQV-UHFFFAOYSA-N 2-methyl-n-(6-oxo-3,7-dihydropurin-2-yl)propanamide Chemical compound N1C(NC(=O)C(C)C)=NC(=O)C2=C1N=CN2 CFIBTBBTJWHPQV-UHFFFAOYSA-N 0.000 claims 1
- 102000015636 Oligopeptides Human genes 0.000 claims 1
- 108010038807 Oligopeptides Proteins 0.000 claims 1
- FMKLITBCOZWOEX-UHFFFAOYSA-N n-(5-methyl-2-oxo-1h-pyrimidin-6-yl)benzamide Chemical compound CC1=CNC(=O)N=C1NC(=O)C1=CC=CC=C1 FMKLITBCOZWOEX-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
- 230000000692 anti-sense effect Effects 0.000 abstract description 8
- 238000002360 preparation method Methods 0.000 abstract description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 224
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- 238000006243 chemical reaction Methods 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- 239000002904 solvent Substances 0.000 description 126
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 74
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 60
- 238000010898 silica gel chromatography Methods 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 239000003153 chemical reaction reagent Substances 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 45
- 239000000203 mixture Substances 0.000 description 43
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 229920006395 saturated elastomer Polymers 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 33
- 235000017557 sodium bicarbonate Nutrition 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000007864 aqueous solution Substances 0.000 description 26
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 24
- 238000007796 conventional method Methods 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- 239000003960 organic solvent Substances 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 230000035484 reaction time Effects 0.000 description 22
- 238000001953 recrystallisation Methods 0.000 description 22
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000002585 base Substances 0.000 description 21
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 20
- 150000008282 halocarbons Chemical class 0.000 description 20
- 239000003638 chemical reducing agent Substances 0.000 description 19
- 239000002994 raw material Substances 0.000 description 19
- 239000007858 starting material Substances 0.000 description 19
- 238000001035 drying Methods 0.000 description 18
- 238000005406 washing Methods 0.000 description 18
- 150000002170 ethers Chemical class 0.000 description 17
- 239000012442 inert solvent Substances 0.000 description 17
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 239000003377 acid catalyst Substances 0.000 description 16
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- 235000011054 acetic acid Nutrition 0.000 description 15
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- HJOVHMDZYOCNQW-UHFFFAOYSA-N isophorone Chemical compound CC1=CC(=O)CC(C)(C)C1 HJOVHMDZYOCNQW-UHFFFAOYSA-N 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 150000001408 amides Chemical class 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 125000005129 aryl carbonyl group Chemical group 0.000 description 12
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- 239000003054 catalyst Substances 0.000 description 11
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 11
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- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 8
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- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
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Abstract
Description
화합물 | 올리고뉴클레오티드 (2) | 올리고뉴클레오티드 (3) |
올리고뉴클레오티드 (4) | 48 | 44 |
올리고뉴클레오티드 (1) | 61 | 75 |
Claims (13)
- 하기 화학식 1:[화학식 1][식 중, R1및 R2는 동일 또는 상이하며, 수소원자, 히드록실기의 보호기, 인산기, 보호된 인산기 또는 -P(R3)R4[식 중, R3및 R4는 동일 또는 상이하며, 히드록실기, 보호된 히드록실기, 메르캅토기, 보호된 메르캅토기, 아미노기, 탄소수 1 내지 4 개의 알콕시기, 탄소수 1 내지 4 개의 알킬티오기, 탄소수 1 내지 5 개의 시아노알콕시기 또는 탄소수 1 내지 4 개의 알킬기로 치환된 아미노기를 나타냄] 를 나타내고,A 는 탄소수 1 내지 4 개의 알킬렌기를 나타내고,B 는 푸린-9-일기, 2-옥소-피리미딘-1-일기 또는 하기 α군에서 선택되는 치환기를 갖는 치환 푸린-9-일기 또는 치환 2-옥소-피리미딘-1-일기를 나타냄] 으로 표시되는 화합물 및 그의 염;(α군)히드록실기,보호된 히드록실기,탄소수 1 내지 4 개의 알콕시기,메르캅토기,보호된 메르캅토기,탄소수 1 내지 4 개의 알킬티오기,아미노기,보호된 아미노기,탄소수 1 내지 4 개의 알킬기로 치환된 아미노기,탄소수 1 내지 4 개의 알킬기, 및할로겐원자.
- 제 1 항에 있어서, R1이 수소원자, 지방족 아실기, 방향족 아실기, 1 내지 3 개의 아릴기로 치환된 메틸기, 저급 알킬, 저급 알콕시, 할로겐 또는 시아노기로 아릴환이 치환된 1 내지 3 개의 아릴기로 치환된 메틸기, 또는 실릴기인 화합물 및 그의 염.
- 제 1 항에 있어서, R1이 수소원자, 아세틸기, 벤조일기, 벤질기, p-메톡시벤질기, 디메톡시트리틸기, 모노메톡시트리틸기 또는 tert-부틸디페닐실릴기인 화합물 및 그의 염.
- 제 1 항 내지 제 3 항 중 어느 한 항에 있어서, R2가 수소원자, 지방족 아실기, 방향족 아실기, 1 내지 3 개의 아릴기로 치환된 메틸기, 저급 알킬, 저급 알콕시, 할로겐 또는 시아노기로 아릴환이 치환된 1 내지 3 개의 아릴기로 치환된 메틸기, 실릴기, 포스포르아미다이트기, 포스포닐기, 인산기 또는 보호된 인산기인 화합물 및 그의 염.
- 제 1 항 내지 제 3 항 중 어느 한 항에 있어서, R2가 수소원자, 아세틸기, 벤조일기, 벤질기, p-메톡시벤질기, tert-부틸디페닐실릴기, -P(OC2H4CN)(NCH(CH3)2), -P(OCH3)(NCH(CH3)2), 포스포닐기, 또는 2-클로로페닐 또는 4-클로로페닐인산기인 화합물 및 그의 염.
- 제 1 항 내지 제 5 항 중 어느 한 항에 있어서, A 가 메틸렌기인 화합물 및 그의 염.
- 제 1 항 내지 제 6 항 중 어느 한 항에 있어서, B 가 6-아미노푸린-9-일 (즉, 아데니닐), 아미노기가 보호된 6-아미노푸린-9-일, 2,6-디아미노푸린-9-일, 2-아미노-6-클로로푸린-9-일, 아미노기가 보호된 2-아미노-6-클로로푸린-9-일, 2-아미노-6-플루오로푸린-9-일, 아미노기가 보호된 2-아미노-6-플루오로푸린-9-일, 2-아미노-6-브로모푸린-9-일, 아미노기가 보호된 2-아미노-6-브로모푸린-9-일, 2-아미노-6-히드록시푸린-9-일 (즉, 구아니닐), 아미노기가 보호된 2-아미노-6-히드록시푸린-9-일, 아미노기 및 히드록실기가 보호된 2-아미노-6-히드록시푸린-9-일, 6-아미노-2-메톡시푸린-9-일, 6-아미노-2-클로로푸린-9-일, 6-아미노-2-플루오로푸린-9-일, 2,6-디메톡시푸린-9-일, 2,6-디클로로푸린-9-일, 6-메르캅토푸린-9-일, 2-옥소-4-아미노-피리미딘-1-일 (즉, 시토시닐), 아미노기가 보호된 2-옥소-4-아미노-피리미딘-1-일, 2-옥소-4-아미노-5-플루오로-피리미딘-1-일, 아미노기가 보호된 2-옥소-4-아미노-5-플루오로-피리미딘-1-일, 4-아미노-2-옥소-5-클로로-피리미딘-1-일, 2-옥소-4-메톡시-피리미딘-1-일, 2-옥소-4-메르캅토-피리미딘-1-일, 2-옥소-4-히드록시-피리미딘-1-일 (즉, 우라시닐), 2-옥소-4-히드록시-5-메틸피리미딘-1-일 (즉, 티미닐), 4-아미노-5-메틸-2-옥소-피리미딘-1-일 (즉, 5-메틸시토시닐) 기 또는 아미노기가 보호된 4-아미노-5-메틸-2-옥소-피리미딘-1-일기인 화합물 및 그의 염.
- 제 1 항 내지 제 6 항 중 어느 한 항에 있어서, B 가 6-벤조일아미노푸린-9-일, 아데니닐, 2-이소부티릴아미노-6-히드록시푸린-9-일, 구아니닐, 2-옥소-4-벤조일아미노-피리미딘-1-일, 시토시닐, 2-옥소-5-메틸-4-벤조일아미노-피리미딘-1-일, 5-메틸시토시닐, 우라시닐 또는 티미닐기인 화합물 및 그의 염.
- 하기 군에서 선택되는 화합물 및 그의 염 ;2'-O,4'-C-에틸렌구아노신,2'-O,4'-C-에틸렌아데노신,3',5'-디-O-벤질-2'-O,4'-C-에틸렌-6-N-벤조일아데노신,3',5'-디-O-벤질-2'-O,4'-C-에틸렌-2-N-이소부티릴구아노신,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-6-N-벤조일아데노신,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-2-N-이소부티릴구아노신,2'-O,4'-C-에틸렌-2-N-이소부티릴구아노신,2'-O,4'-C-에틸렌-6-N-벤조일아데노신,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-6-N-벤조일아데노신-3'-O-(2-시아노에틸 N,N-디이소프로필)포스포르아미다이트5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-2-N-이소부티릴구아노신-3'-O-(2-시아노에틸 N,N-디이소프로필)포스포르아미다이트2'-O,4'-C-에틸렌우리딘,2'-O,4'-C-에틸렌-5-메틸우리딘,2'-O,4'-C-에틸렌시티딘,2'-O,4'-C-에틸렌-5-메틸시티딘,3',5'-디-O-벤질-2'-O,4'-C-에틸렌우리딘,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌우리딘,3',5'-디-O-벤질-2'-O,4'-C-에틸렌-5-메틸우리딘,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-5-메틸우리딘,3',5'-디-O-벤질-2'-O,4'-C-에틸렌-4-N-벤조일시티딘,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-4-N-벤조일시티딘,3',5'-디-O-벤질-2'-O,4'-C-에틸렌-4-N-벤조일-5-메틸시티딘,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-4-N-벤조일-5-메틸시티딘,2'-O,4'-C-에틸렌-4-N-벤조일시티딘,2'-O,4'-C-에틸렌-4-N-벤조일-5-메틸시티딘,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-우리딘-3'-O-(2-시아노에틸 N,N-디이소프로필)포스포르아미다이트,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-5-메틸우리딘-3'-O-(2-시아노에틸 N,N-디이소프로필)포스포르아미다이트,5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-4-N-벤조일시티딘-3'-O-(2-시아노에틸 N,N-디이소프로필)포스포르아미다이트, 및5'-O-디메톡시트리틸-2'-O,4'-C-에틸렌-4-N-벤조일-5-메틸시티딘-3'-O-(2-시아노에틸 N,N-디이소프로필)포스포르아미다이트.
- 하기 화학식 2:[화학식 2][식 중, A 는 탄소수 1 내지 4 개의 알킬렌기를 나타내고,B 는 푸린-9-일기, 2-옥소-피리미딘-1-일기 또는 하기 α군에서 선택되는 치환기를 갖는 치환 푸린-9-일기 또는 치환 2-옥소-피리미딘-1-일기를 나타냄] 로 표시되는 구조를 1 또는 2 이상 함유하는 올리고뉴클레오티드 유사체 및 그의 약리학상 허용되는 염;(α군)히드록실기,보호된 히드록실기,탄소수 1 내지 4 개의 알콕시기,메르캅토기,보호된 메르캅토기,탄소수 1 내지 4 개의 알킬티오기,아미노기,보호된 아미노기,탄소수 1 내지 4 개의 알킬기로 치환된 아미노기,탄소수 1 내지 4 개의 알킬기, 및할로겐원자.
- 제 10 항에 있어서, A 가 메틸렌기인 올리고뉴클레오티드 유사체 및 그의 약리학상 허용되는 염.
- 제 10 항 또는 제 11 항에 있어서, B 가 6-아미노푸린-9-일 (즉, 아데니닐), 아미노기가 보호된 6-아미노푸린-9-일, 2,6-디아미노푸린-9-일, 2-아미노-6-클로로푸린-9-일, 아미노기가 보호된 2-아미노-6-클로로푸린-9-일, 2-아미노-6-플루오로푸린-9-일, 아미노기가 보호된 2-아미노-6-플루오로푸린-9-일, 2-아미노-6-브로모푸린-9-일, 아미노기가 보호된 2-아미노-6-브로모푸린-9-일, 2-아미노-6-히드록시푸린-9-일 (즉, 구아니닐), 아미노기가 보호된 2-아미노-6-히드록시푸린-9-일, 아미노기 및 히드록실기가 보호된 2-아미노-6-히드록시푸린-9-일, 6-아미노-2-메톡시푸린-9-일, 6-아미노-2-클로로푸린-9-일, 6-아미노-2-플루오로푸린-9-일, 2,6-디메톡시푸린-9-일, 2,6-디클로로푸린-9-일, 6-메르캅토푸린-9-일, 2-옥소-4-아미노-피리미딘-1-일 (즉, 시토시닐), 아미노기가 보호된 2-옥소-4-아미노-피리미딘-1-일, 2-옥소-4-아미노-5-플루오로-피리미딘-1-일, 아미노기가 보호된 2-옥소-4-아미노-5-플루오로-피리미딘-1-일, 4-아미노-2-옥소-5-클로로-피리미딘-1-일, 2-옥소-4-메톡시-피리미딘-1-일, 2-옥소-4-메르캅토-피리미딘-1-일, 2-옥소-4-히드록시-피리미딘-1-일 (즉, 우라시닐), 2-옥소-4-히드록시-5-메틸피리미딘-1-일 (즉, 티미닐), 4-아미노-5-메틸-2-옥소-피리미딘-1-일 (즉, 5-메틸시토시닐) 기 또는 아미노기가 보호된 4-아미노-5-메틸-2-옥소-피리미딘-1-일기인 올리고뉴클레오티드 유사체 및 그의 약리학상 허용되는 염.
- 제 10 항 또는 제 11 항에 있어서, B 가 6-벤조일아미노푸린-9-일, 아데니닐, 2-이소부티릴아미노-6-히드록시푸린-9-일, 구아니닐, 2-옥소-4-벤조일아미노-피리미딘-1-일, 시토시닐, 2-옥소-5-메틸-4-벤조일아미노-피리미딘-1-일, 5-메틸시토시닐, 우라시닐 또는 티미닐기인 올리고뉴클레오티드 유사체 및 그의 약리학상 허용되는 염.
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