HUP0400151A2 - Activators for oligonucleotide synthesis - Google Patents
Activators for oligonucleotide synthesis Download PDFInfo
- Publication number
- HUP0400151A2 HUP0400151A2 HU0400151A HUP0400151A HUP0400151A2 HU P0400151 A2 HUP0400151 A2 HU P0400151A2 HU 0400151 A HU0400151 A HU 0400151A HU P0400151 A HUP0400151 A HU P0400151A HU P0400151 A2 HUP0400151 A2 HU P0400151A2
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- HU
- Hungary
- Prior art keywords
- substituted
- unsubstituted
- group
- atom
- groups
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- 239000012190 activator Substances 0.000 title claims description 33
- 238000002515 oligonucleotide synthesis Methods 0.000 title description 3
- 108091034117 Oligonucleotide Proteins 0.000 claims description 118
- 239000002777 nucleoside Substances 0.000 claims description 62
- 125000001931 aliphatic group Chemical group 0.000 claims description 58
- 238000000034 method Methods 0.000 claims description 55
- -1 nucleoside phosphoramidite Chemical class 0.000 claims description 54
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 125000006239 protecting group Chemical group 0.000 claims description 43
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 40
- 150000007530 organic bases Chemical class 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
- 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 32
- 150000008300 phosphoramidites Chemical class 0.000 claims description 31
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 29
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 29
- 238000003786 synthesis reaction Methods 0.000 claims description 28
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 25
- 230000015572 biosynthetic process Effects 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 238000005859 coupling reaction Methods 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 19
- 125000004434 sulfur atom Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 229910052698 phosphorus Inorganic materials 0.000 claims description 16
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 125000004437 phosphorous atom Chemical group 0.000 claims description 13
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 238000009833 condensation Methods 0.000 claims description 12
- 230000005494 condensation Effects 0.000 claims description 12
- 230000008878 coupling Effects 0.000 claims description 12
- 238000010168 coupling process Methods 0.000 claims description 12
- 230000003647 oxidation Effects 0.000 claims description 11
- 238000007254 oxidation reaction Methods 0.000 claims description 11
- 150000003512 tertiary amines Chemical class 0.000 claims description 11
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 238000005987 sulfurization reaction Methods 0.000 claims description 10
- 125000006242 amine protecting group Chemical group 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000000178 monomer Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000005647 linker group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000007822 coupling agent Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 239000000539 dimer Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 150000003222 pyridines Chemical class 0.000 claims description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
- 125000004961 1-arylpyrazolyl group Chemical group 0.000 claims description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- 150000003857 carboxamides Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- 150000002537 isoquinolines Chemical class 0.000 claims description 3
- 150000002780 morpholines Chemical class 0.000 claims description 3
- 150000004885 piperazines Chemical class 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 claims description 3
- 150000003216 pyrazines Chemical class 0.000 claims description 3
- 150000003230 pyrimidines Chemical class 0.000 claims description 3
- 150000003235 pyrrolidines Chemical class 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 150000003248 quinolines Chemical class 0.000 claims description 3
- 150000003252 quinoxalines Chemical class 0.000 claims description 3
- 150000008584 quinuclidines Chemical class 0.000 claims description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 3
- 125000005270 trialkylamine group Chemical group 0.000 claims description 3
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 150000004713 phosphodiesters Chemical class 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 2
- MQCHTHJRANYSEJ-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-1-(3-methylphenyl)benzimidazole-5-carboxamide Chemical class CC1=CC=CC(N2C3=CC=C(C=C3N=C2)C(=O)NCC=2C(=CC=CC=2)Cl)=C1 MQCHTHJRANYSEJ-UHFFFAOYSA-N 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 150000003557 thiazoles Chemical class 0.000 claims 2
- 150000003918 triazines Chemical class 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 108091028664 Ribonucleotide Proteins 0.000 claims 1
- 239000005547 deoxyribonucleotide Substances 0.000 claims 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 239000002336 ribonucleotide Substances 0.000 claims 1
- 125000002652 ribonucleotide group Chemical group 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 21
- 150000003536 tetrazoles Chemical class 0.000 description 15
- 239000002585 base Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical group C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000004793 Polystyrene Substances 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 6
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 238000001818 capillary gel electrophoresis Methods 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 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 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- YWZHEXZIISFIDA-UHFFFAOYSA-N 5-amino-1,2,4-dithiazole-3-thione Chemical compound NC1=NC(=S)SS1 YWZHEXZIISFIDA-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical group CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 239000002342 ribonucleoside Substances 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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 4
- JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical compound C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 239000002360 explosive Substances 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000006574 non-aromatic ring group Chemical group 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 230000002028 premature Effects 0.000 description 3
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 3
- 239000013638 trimer Substances 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-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
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 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 description 2
- 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 2
- GONFBOIJNUKKST-UHFFFAOYSA-N 5-ethylsulfanyl-2h-tetrazole Chemical compound CCSC=1N=NNN=1 GONFBOIJNUKKST-UHFFFAOYSA-N 0.000 description 2
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-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
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
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- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
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- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical class COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
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- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical group NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 description 1
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- 125000003386 piperidinyl group Chemical group 0.000 description 1
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- 150000003212 purines Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- IXGZXXBJSZISOO-UHFFFAOYSA-N s-(2-phenylacetyl)sulfanyl 2-phenylethanethioate Chemical compound C=1C=CC=CC=1CC(=O)SSC(=O)CC1=CC=CC=C1 IXGZXXBJSZISOO-UHFFFAOYSA-N 0.000 description 1
- XTDHBAVVPOKCKF-UHFFFAOYSA-N s-(benzoyltrisulfanyl) benzenecarbothioate Chemical compound C=1C=CC=CC=1C(=O)SSSSC(=O)C1=CC=CC=C1 XTDHBAVVPOKCKF-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
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- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
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- 229940035893 uracil Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
- C07D213/18—Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
-
- 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
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
-
- 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
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30271701P | 2001-07-03 | 2001-07-03 | |
| PCT/GB2002/003029 WO2003004512A1 (en) | 2001-07-03 | 2002-07-01 | Activators for oligonucleotide synthesis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUP0400151A2 true HUP0400151A2 (en) | 2007-08-28 |
Family
ID=23168928
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU0400151A HUP0400151A2 (en) | 2001-07-03 | 2002-07-01 | Activators for oligonucleotide synthesis |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7501505B2 (enExample) |
| EP (1) | EP1404696B1 (enExample) |
| JP (1) | JP4574167B2 (enExample) |
| KR (1) | KR100898083B1 (enExample) |
| CN (1) | CN100430411C (enExample) |
| AR (1) | AR036122A1 (enExample) |
| AT (1) | ATE317395T1 (enExample) |
| CA (1) | CA2452205C (enExample) |
| DE (1) | DE60209128T2 (enExample) |
| DK (1) | DK1404696T3 (enExample) |
| ES (1) | ES2258151T3 (enExample) |
| HU (1) | HUP0400151A2 (enExample) |
| IL (1) | IL159402A0 (enExample) |
| PL (1) | PL367623A1 (enExample) |
| RU (1) | RU2004102903A (enExample) |
| WO (1) | WO2003004512A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR036122A1 (es) | 2001-07-03 | 2004-08-11 | Avecia Biotechnology Inc | Un complejo de sal que comprende un n-alquilimidazol y una 1,1-dioxo-1,2-dihidro-1l6-benzo [d]-isotiazol-3-ona y un metodo para sintetizar oligonucleotidos utilizando la quimica de fosforamidita |
| ATE362937T1 (de) * | 2002-10-15 | 2007-06-15 | Avecia Biotechnology Inc | Verfahren zur phosphithylierung |
| GB0229443D0 (en) * | 2002-12-18 | 2003-01-22 | Avecia Ltd | Process |
| US8569367B2 (en) | 2004-11-16 | 2013-10-29 | Allergan, Inc. | Ophthalmic compositions and methods for treating eyes |
| EP1874792B1 (en) | 2005-04-27 | 2016-04-13 | Sigma-Aldrich Co. LLC | Activators for oligonucleotide and phosphoramidite synthesis |
| WO2009007736A1 (en) * | 2007-07-12 | 2009-01-15 | Avecia Biotechnology Inc. | Oxidation process |
| KR200457843Y1 (ko) * | 2010-05-26 | 2012-01-10 | 김원제 | 향기 발산 기능을 가지는 악취 차단 커버 |
| CA2805546A1 (en) * | 2010-06-30 | 2012-01-05 | Girindus America, Inc. | A new method of using n-thio compounds for oligonucleotide synthesis |
| US9907826B2 (en) | 2011-12-07 | 2018-03-06 | Allergan, Inc. | Efficient lipid delivery to human tear film using a salt-sensitive emulsion system |
| CN104278030A (zh) * | 2013-07-05 | 2015-01-14 | 上海交通大学医学院 | 小分子化合物Antagomir-31制备方法及应用 |
| RS62930B1 (sr) | 2015-08-05 | 2022-03-31 | Eisai R&D Man Co Ltd | Postupak za pripremu suštinski dijastereomerno čistog fosforodiamidatnog oligomera, fosforodiamidatni oligomer proizveden takvim postupkom i farmaceutska kompozicija koja sadrži fosforodiamidatni oligomer |
| US10072261B1 (en) * | 2016-03-25 | 2018-09-11 | Agilent Technologies, Inc. | Double coupling method for oligonucleotide synthesis |
| WO2018035380A1 (en) | 2016-08-17 | 2018-02-22 | Solstice Biologics, Ltd. | Polynucleotide constructs |
| US11597744B2 (en) | 2017-06-30 | 2023-03-07 | Sirius Therapeutics, Inc. | Chiral phosphoramidite auxiliaries and methods of their use |
| WO2019158007A1 (zh) * | 2018-02-13 | 2019-08-22 | 深圳华大生命科学研究院 | 合成寡核苷酸的方法及系统 |
| EP3983421A1 (en) * | 2019-06-11 | 2022-04-20 | F. Hoffmann-La Roche AG | Process for the preparation of oligonucleotides using modified oxidation protocol |
| JP7657736B2 (ja) * | 2020-01-08 | 2025-04-07 | 日東電工株式会社 | セグメント型アミダイトを用いた核酸合成法 |
| CN117362373B (zh) * | 2022-06-30 | 2026-04-24 | 成都先导药物开发股份有限公司 | 一种dna编码化合物库构建2,4-咪唑烷二酮类化合物的方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US757650A (en) * | 1903-09-30 | 1904-04-19 | Wilfrid Chausse | Means for cleaning the third rails of electrical railways. |
| US3325475A (en) * | 1964-11-16 | 1967-06-13 | Maumee Chemical Company | Organic amine salts of saccharin |
| JPS4822628B1 (enExample) * | 1967-04-15 | 1973-07-07 | ||
| IT8148047A0 (it) * | 1981-03-18 | 1981-03-18 | Manetti & Roberts Italo Brit | Composti organici derivati da 2-ami no-5-(o-solfamidofenil)-1,3,4-tiadiazolo loro applicazione terapeutica e procedimento per la loro preparazione |
| DE3430805A1 (de) * | 1984-03-08 | 1985-09-19 | Bayer Ag, 5090 Leverkusen | Mikrobizide mittel |
| DE3639901A1 (de) * | 1986-11-22 | 1988-06-01 | Bayer Ag | Saccharin-salze von substituierten aminen |
| US5034534A (en) | 1988-07-15 | 1991-07-23 | E. I. Du Pont De Nemours And Company | Process for producing saccharin, saccharin analogues or their salts |
| JPH04330093A (ja) * | 1990-07-20 | 1992-11-18 | Takeda Chem Ind Ltd | オリゴリボヌクレオチドの製造法 |
| US5639875A (en) | 1995-02-01 | 1997-06-17 | Hybridon, Inc. | Methods for H-phosphonate syntheis of oligonucleotides using triphosgene |
| AU4800197A (en) * | 1996-10-15 | 1998-05-11 | Nexstar Pharmaceuticals, Inc. | Improved coupling activators for oligonucleotide synthesis |
| US5896999A (en) | 1996-10-16 | 1999-04-27 | United Parcel Service Of America, Inc. | Sorting system |
| US5955600A (en) * | 1996-12-27 | 1999-09-21 | Isis Pharmaceuticals, Inc. | Method for the synthesis of nucleotide or oligonucleotide phosphoramidites |
| US6096881A (en) | 1997-05-30 | 2000-08-01 | Hybridon, Inc. | Sulfur transfer reagents for oligonucleotide synthesis |
| US6274725B1 (en) * | 1998-06-02 | 2001-08-14 | Isis Pharmaceuticals, Inc. | Activators for oligonucleotide synthesis |
| AR036122A1 (es) | 2001-07-03 | 2004-08-11 | Avecia Biotechnology Inc | Un complejo de sal que comprende un n-alquilimidazol y una 1,1-dioxo-1,2-dihidro-1l6-benzo [d]-isotiazol-3-ona y un metodo para sintetizar oligonucleotidos utilizando la quimica de fosforamidita |
| ATE362937T1 (de) * | 2002-10-15 | 2007-06-15 | Avecia Biotechnology Inc | Verfahren zur phosphithylierung |
| GB0229443D0 (en) * | 2002-12-18 | 2003-01-22 | Avecia Ltd | Process |
-
2002
- 2002-06-28 AR ARP020102444A patent/AR036122A1/es unknown
- 2002-07-01 IL IL15940202A patent/IL159402A0/xx unknown
- 2002-07-01 EP EP02748994A patent/EP1404696B1/en not_active Expired - Lifetime
- 2002-07-01 DK DK02748994T patent/DK1404696T3/da active
- 2002-07-01 HU HU0400151A patent/HUP0400151A2/hu unknown
- 2002-07-01 CN CNB02817156XA patent/CN100430411C/zh not_active Expired - Lifetime
- 2002-07-01 RU RU2004102903/04A patent/RU2004102903A/ru not_active Application Discontinuation
- 2002-07-01 WO PCT/GB2002/003029 patent/WO2003004512A1/en not_active Ceased
- 2002-07-01 KR KR1020037016969A patent/KR100898083B1/ko not_active Expired - Lifetime
- 2002-07-01 US US10/482,441 patent/US7501505B2/en not_active Expired - Lifetime
- 2002-07-01 ES ES02748994T patent/ES2258151T3/es not_active Expired - Lifetime
- 2002-07-01 DE DE60209128T patent/DE60209128T2/de not_active Expired - Lifetime
- 2002-07-01 CA CA2452205A patent/CA2452205C/en not_active Expired - Lifetime
- 2002-07-01 PL PL02367623A patent/PL367623A1/xx not_active Application Discontinuation
- 2002-07-01 JP JP2003510678A patent/JP4574167B2/ja not_active Expired - Lifetime
- 2002-07-01 AT AT02748994T patent/ATE317395T1/de not_active IP Right Cessation
-
2008
- 2008-10-06 US US12/287,116 patent/US8093397B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003004512A1 (en) | 2003-01-16 |
| US8093397B2 (en) | 2012-01-10 |
| IL159402A0 (en) | 2004-06-01 |
| JP2004533488A (ja) | 2004-11-04 |
| DE60209128T2 (de) | 2006-10-05 |
| US20090085006A1 (en) | 2009-04-02 |
| EP1404696A1 (en) | 2004-04-07 |
| KR100898083B1 (ko) | 2009-05-18 |
| CA2452205C (en) | 2011-11-08 |
| DE60209128D1 (de) | 2006-04-20 |
| US20060041114A1 (en) | 2006-02-23 |
| CN100430411C (zh) | 2008-11-05 |
| JP4574167B2 (ja) | 2010-11-04 |
| RU2004102903A (ru) | 2005-07-10 |
| DK1404696T3 (da) | 2006-06-06 |
| EP1404696B1 (en) | 2006-02-08 |
| PL367623A1 (en) | 2005-03-07 |
| US7501505B2 (en) | 2009-03-10 |
| ATE317395T1 (de) | 2006-02-15 |
| AR036122A1 (es) | 2004-08-11 |
| KR20040015758A (ko) | 2004-02-19 |
| CA2452205A1 (en) | 2003-01-16 |
| ES2258151T3 (es) | 2006-08-16 |
| CN1549820A (zh) | 2004-11-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FD9A | Lapse of provisional protection due to non-payment of fees |