ES2226135T3 - Nuevos reactivos de transferencia de azufre para la sintesis de oligonucleotidos. - Google Patents
Nuevos reactivos de transferencia de azufre para la sintesis de oligonucleotidos.Info
- Publication number
- ES2226135T3 ES2226135T3 ES98923757T ES98923757T ES2226135T3 ES 2226135 T3 ES2226135 T3 ES 2226135T3 ES 98923757 T ES98923757 T ES 98923757T ES 98923757 T ES98923757 T ES 98923757T ES 2226135 T3 ES2226135 T3 ES 2226135T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- thione
- dithiazol
- group
- sulfur
- 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.)
- Expired - Lifetime
Links
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 61
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 56
- 238000012546 transfer Methods 0.000 title claims abstract description 54
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 44
- 230000015572 biosynthetic process Effects 0.000 title claims description 38
- 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 title claims description 27
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 title 1
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 56
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 55
- 239000011593 sulfur Substances 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- YWZHEXZIISFIDA-UHFFFAOYSA-N 5-amino-1,2,4-dithiazole-3-thione Chemical compound NC1=NC(=S)SS1 YWZHEXZIISFIDA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims description 47
- 239000002777 nucleoside Substances 0.000 claims description 34
- 238000005987 sulfurization reaction Methods 0.000 claims description 33
- 230000008569 process Effects 0.000 claims description 28
- 125000003835 nucleoside group Chemical group 0.000 claims description 25
- 125000000962 organic group Chemical group 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 15
- -1 xanthan hydride Chemical class 0.000 claims description 12
- 229920001285 xanthan gum Polymers 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 3
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
- 150000004678 hydrides Chemical group 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 abstract description 10
- 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 abstract description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 3
- 239000007790 solid phase Substances 0.000 abstract description 3
- 238000005457 optimization Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 150000008300 phosphoramidites Chemical class 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 229940125904 compound 1 Drugs 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 9
- 239000000539 dimer Substances 0.000 description 7
- 150000003833 nucleoside derivatives Chemical class 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 239000000203 mixture Substances 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
- 238000002515 oligonucleotide synthesis Methods 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- PWWSSIYVTQUJQQ-UHFFFAOYSA-N distearyl thiodipropionate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCCCCCCCC PWWSSIYVTQUJQQ-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 125000004354 sulfur functional group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- BPVALDZRWMHTCJ-UHFFFAOYSA-N 1,2,4-dithiazolidine-3,5-dione Chemical compound O=C1NC(=O)SS1 BPVALDZRWMHTCJ-UHFFFAOYSA-N 0.000 description 1
- AEHGOWVFQLOENS-UHFFFAOYSA-N 1-methyl-4-[(4-methylphenyl)sulfonyldisulfanyl]sulfonylbenzene Chemical compound C1=CC(C)=CC=C1S(=O)(=O)SSS(=O)(=O)C1=CC=C(C)C=C1 AEHGOWVFQLOENS-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- KMEMIMRPZGDOMG-UHFFFAOYSA-N 2-cyanoethoxyphosphonamidous acid Chemical compound NP(O)OCCC#N KMEMIMRPZGDOMG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- RZIJZXUDFRSADE-UHFFFAOYSA-N 5-ethoxy-1,2,4-dithiazol-3-one Chemical compound CCOC1=NC(=O)SS1 RZIJZXUDFRSADE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- VBQDSLGFSUGBBE-UHFFFAOYSA-N benzyl(triethyl)azanium Chemical compound CC[N+](CC)(CC)CC1=CC=CC=C1 VBQDSLGFSUGBBE-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 150000002972 pentoses Chemical group 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 239000012688 phosphorus precursor Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000012552 review Methods 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
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/865,666 US6096881A (en) | 1997-05-30 | 1997-05-30 | Sulfur transfer reagents for oligonucleotide synthesis |
| US865666 | 1997-05-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2226135T3 true ES2226135T3 (es) | 2005-03-16 |
Family
ID=25345990
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98923757T Expired - Lifetime ES2226135T3 (es) | 1997-05-30 | 1998-05-26 | Nuevos reactivos de transferencia de azufre para la sintesis de oligonucleotidos. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6096881A (https=) |
| EP (1) | EP0986571B1 (https=) |
| JP (1) | JP4393594B2 (https=) |
| AT (1) | ATE271065T1 (https=) |
| AU (1) | AU7597498A (https=) |
| CA (1) | CA2291688C (https=) |
| DE (1) | DE69825051T2 (https=) |
| ES (1) | ES2226135T3 (https=) |
| WO (1) | WO1998054198A1 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69910140T2 (de) * | 1998-10-08 | 2004-06-03 | Novartis Ag | Verfahren zur Sulfurierung von Phosphor-enthaltenden Verbindungen |
| US7098325B2 (en) * | 1998-10-08 | 2006-08-29 | Pierre Martin | Process for the sulfurization of a phosphorus-containing compound |
| GB0004889D0 (en) | 2000-03-01 | 2000-04-19 | Avecia Ltd | Synthesis of oligonucleotides |
| CA2714353A1 (en) * | 2000-12-05 | 2002-06-13 | Avecia Biotechnology Inc | Process for the preparation of phosphorothioate oligonucleotides |
| US6768005B2 (en) * | 2000-12-20 | 2004-07-27 | Avecia Limited | Process |
| 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 |
| JP4825375B2 (ja) * | 2001-08-28 | 2011-11-30 | 株式会社 資生堂 | ジチアゾール化合物及びマトリックスメタロプロテアーゼ活性阻害剤、皮膚外用剤 |
| GB0209539D0 (en) * | 2002-04-26 | 2002-06-05 | Avecia Ltd | Monomer Polymer and process |
| JP2007531794A (ja) * | 2004-04-05 | 2007-11-08 | アルニラム ファーマスーティカルズ インコーポレイテッド | オリゴヌクレオチドの合成および精製に使用する方法および反応試薬 |
| CN104086516B (zh) * | 2014-07-18 | 2016-01-06 | 成都樵枫科技发展有限公司 | R-(+)-硫代四氢呋喃-2-甲酸的合成方法 |
| EP3564373A4 (en) | 2016-12-28 | 2020-12-16 | Daiichi Sankyo Company, Limited | THERAPEUTIC DRUG FOR ALPORT SYNDROME |
| WO2019111791A1 (ja) * | 2017-12-07 | 2019-06-13 | 第一三共株式会社 | ジストロフィン遺伝子のイントロンリテンションを解消するアンチセンスオリゴヌクレオチド |
| KR102398295B1 (ko) | 2018-03-09 | 2022-05-17 | 다이이찌 산쿄 가부시키가이샤 | 당원병 Ia형 치료약 |
| CN112218950A (zh) | 2018-06-13 | 2021-01-12 | 第一三共株式会社 | 心肌损伤治疗药 |
| EP3981436A4 (en) | 2019-06-05 | 2024-06-19 | Fukuoka University | Stable target-editing guide rna having chemically modified nucleic acid introduced thereinto |
| JP7715345B2 (ja) | 2019-06-26 | 2025-07-30 | 神戸天然物化学株式会社 | ミオスタチン遺伝子のｍＲＮＡの産生を抑制する核酸医薬 |
| US20220364086A1 (en) | 2019-07-12 | 2022-11-17 | Daiichi Sankyo Company, Limited | ANTISENSE OLIGONUCLEOTIDE CAPABLE OF ALTERING SPLICING OF DUX4 pre-mRNA |
| IL291251B1 (en) | 2019-09-10 | 2026-02-01 | Daiichi Sankyo Co Ltd | Oligonucleotide-galnac conjugate for targeted delivery to the liver and method for its production |
| IL292286A (en) | 2019-10-18 | 2022-06-01 | Daiichi Sankyo Co Ltd | Production method for bicyclic phosphoramidite |
| CA3175125A1 (en) | 2020-03-11 | 2021-09-16 | Biocomber Co., Ltd. | Single-stranded nucleic acid molecule for inducing -1 frameshift and composition |
| CN115916976A (zh) | 2020-07-28 | 2023-04-04 | 神户天然物化学株式会社 | 诱导血管紧张素转换酶2基因外显子跳跃的反义核酸 |
| MX2023006714A (es) | 2020-12-08 | 2023-07-13 | Univ Fukuoka | Acido ribonucleico (arn) guia estable de edicion de objetivo al cual se introduce acido nucleico quimicamente modificado. |
| CA3211057A1 (en) | 2021-02-26 | 2022-09-01 | Knc Laboratories Co., Ltd. | Nucleic acid medicine expressing splicing variant of myostatin |
| US20250188477A1 (en) | 2022-03-16 | 2025-06-12 | Daiichi Sankyo Company, Limited | CHEMICALLY MODIFIED OLIGONUCLEOTIDE HAVING RNAi ACTIVITY |
| EP4495240A1 (en) | 2022-03-16 | 2025-01-22 | Daiichi Sankyo Company, Limited | Sirna for suppressing expression of transferrin receptor-2 |
| WO2025047679A1 (ja) | 2023-08-25 | 2025-03-06 | 学校法人福岡大学 | リン酸部修飾を導入した安定型標的編集ガイドｒｎａ |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3753908A (en) * | 1971-08-30 | 1973-08-21 | Chevron Res | Oxidation inhibited lubricating oil compositions with extreme pressure properties |
| DE4320157A1 (de) * | 1993-06-18 | 1994-12-22 | Bayer Ag | Verwendung von 1,2,4-Dithiazolium-Salzen als Chemotherapeutica |
-
1997
- 1997-05-30 US US08/865,666 patent/US6096881A/en not_active Expired - Lifetime
-
1998
- 1998-05-26 CA CA002291688A patent/CA2291688C/en not_active Expired - Lifetime
- 1998-05-26 WO PCT/US1998/010653 patent/WO1998054198A1/en not_active Ceased
- 1998-05-26 DE DE69825051T patent/DE69825051T2/de not_active Expired - Lifetime
- 1998-05-26 AU AU75974/98A patent/AU7597498A/en not_active Abandoned
- 1998-05-26 JP JP50080299A patent/JP4393594B2/ja not_active Expired - Lifetime
- 1998-05-26 AT AT98923757T patent/ATE271065T1/de not_active IP Right Cessation
- 1998-05-26 EP EP98923757A patent/EP0986571B1/en not_active Expired - Lifetime
- 1998-05-26 ES ES98923757T patent/ES2226135T3/es not_active Expired - Lifetime
Also Published As
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|---|---|
| CA2291688A1 (en) | 1998-12-03 |
| EP0986571A1 (en) | 2000-03-22 |
| WO1998054198A1 (en) | 1998-12-03 |
| US6096881A (en) | 2000-08-01 |
| JP2002501534A (ja) | 2002-01-15 |
| AU7597498A (en) | 1998-12-30 |
| CA2291688C (en) | 2008-01-29 |
| JP4393594B2 (ja) | 2010-01-06 |
| EP0986571B1 (en) | 2004-07-14 |
| WO1998054198A9 (en) | 1999-04-01 |
| DE69825051T2 (de) | 2005-10-06 |
| DE69825051D1 (de) | 2004-08-19 |
| ATE271065T1 (de) | 2004-07-15 |
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