WO1996030383A1 - Polyamides de polyester d'acide nucleique - Google Patents
Polyamides de polyester d'acide nucleique Download PDFInfo
- Publication number
- WO1996030383A1 WO1996030383A1 PCT/AT1996/000056 AT9600056W WO9630383A1 WO 1996030383 A1 WO1996030383 A1 WO 1996030383A1 AT 9600056 W AT9600056 W AT 9600056W WO 9630383 A1 WO9630383 A1 WO 9630383A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nucleotide
- carboxylic acid
- formula
- chlorine
- hydroxyl
- Prior art date
Links
- 108020004707 nucleic acids Proteins 0.000 title abstract description 8
- 150000007523 nucleic acids Chemical class 0.000 title abstract description 8
- 102000039446 nucleic acids Human genes 0.000 title abstract description 8
- 239000004952 Polyamide Substances 0.000 title description 2
- 229920002647 polyamide Polymers 0.000 title description 2
- 229920000728 polyester Polymers 0.000 title description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 150000001733 carboxylic acid esters Chemical class 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract 2
- -1 Nucleotide carboxylic acid esters Chemical class 0.000 claims description 15
- 239000002773 nucleotide Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000003729 nucleotide group Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229920002601 oligoester Polymers 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000000178 monomer Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 238000010348 incorporation Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 150000002148 esters Chemical class 0.000 description 7
- 229940045145 uridine Drugs 0.000 description 5
- 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 4
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 108020004394 Complementary RNA Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
Classifications
-
- 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
Definitions
- Natural nucleic acids have a 3 '-5' linkage, which is the basis for the formation of the double helix and thus for the biological function of nucleic acids. Such nucleic acids are easily cleaved by hydrolysis of the phosphoric ester bond. When using nucleotides for molecular biological, diagnostic and therapeutic purposes, the production of nuclease-resistant compounds is therefore always an important goal.
- oligonucleotide analogs which are not linked by 3 '-5'- but 2' -5-'- are also able to pair with natural RNA or DNA, especially if the The number of atoms between the two sugar rings of the nucleosides is 3, but special attention is paid to the type of linking elements. Too great flexibility of such a link between two nucleoside units can lead to a severe restriction or even to the loss of the binding ability. On the other hand, rigidization that is too rigid or too sterically demanding can have the same negative effect.
- the present invention relates to nucleotide carboxylic acid esters and amides of the general formula I
- R 5 is a hydrogen, chlorine or bromine atom, a hydroxyl, amino, monomethoxytritylamino, mercapto, methylamino, dimethylamino, phenylamino or hydroxylamino group
- R 9 hydrogen, fluorine, chlorine, or bromine or iodine atom, a methyl, trifluoro, ethyl, ethyl or hydroxymethyl group, and the salts of compounds of general form I with acids or bases.
- the invention includes Nukleotidoligoester and -oligoamide with the above St ⁇ * ⁇ jJ structure with a number of from 2 to 200 nucleotide units.
- oligonucleotide analogs of the subject invention can be prepared from the suitably protected monomers by conventional condensation processes after the carboxylic acid has been activated beforehand.
- Binding experiments with natural nucleic acids show that oligonucleotides of the present invention are suitable for pairing with natural nucleic acids.
- Molecular dynamics Studies show that esters and amide bonds are superior to other bridging compounds.
- the invention includes the use of such nucleotide oligoesters and oligoamides as therapeutic agents, for diagnostic purposes and as research reagents.
- the best way to investigate the binding behavior of a short Watson-Crick complementary strand is with the additional cooperative "support" of a third polymer strand that forms the pair of Hoogsteen.
- the artificial dinucleotide 4 was thus examined under salt and buffer conditions that allow triplex formation.
- the transformation temperature of the 2Poly-U / artificial dinucleotide system was 15 ° C. It could thus be shown that such 2'-5 'ester-linked artificial nucleotides recognize natural 3'-5'-phosphate-linked oligonucleotides and can interact with them.
- ester modification showed the highest affinity for the complementary RNA strand. More flexible linking systems such as ether modification did not show a high affinity for the counterpart, but the hybrid double strand dissolved after a short time and the strands became entangled.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne de nouveaux oligonucléides de structure modifiée, leur procédé de production et leur utilisation. Ces analogues d'oligonucléides se caractérisent par une liaison 2'-5' et non par la liaison 3'-5' des oligonucléotides naturels. Le nombre d'atomes entre les deux noyaux sucre est de 3 et la liaison est constituée d'un ester d'acide carboxylique ou d'un amide d'acide carboxylique. Ces oligonucléotides modifiés peuvent entrer en interaction avec de l'acide nucléique naturel. Le s oligomères décrits peuvent être utilisés comme médicaments potentiels.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU49311/96A AU4931196A (en) | 1995-03-24 | 1996-03-25 | Nucleic acid polyester polyamides |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ATA538/95 | 1995-03-24 | ||
| AT53895 | 1995-03-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996030383A1 true WO1996030383A1 (fr) | 1996-10-03 |
Family
ID=3493275
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/AT1996/000056 WO1996030383A1 (fr) | 1995-03-24 | 1996-03-25 | Polyamides de polyester d'acide nucleique |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU4931196A (fr) |
| WO (1) | WO1996030383A1 (fr) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8871737B2 (en) | 2010-09-22 | 2014-10-28 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US8916538B2 (en) | 2012-03-21 | 2014-12-23 | Vertex Pharmaceuticals Incorporated | Solid forms of a thiophosphoramidate nucleotide prodrug |
| US8980865B2 (en) | 2011-12-22 | 2015-03-17 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US9012427B2 (en) | 2012-03-22 | 2015-04-21 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993024508A1 (fr) * | 1992-06-01 | 1993-12-09 | Gilead Sciences, Inc. | Oligomeres aptes a la fixation contenant des liaisons 2', 5' |
| WO1994022891A1 (fr) * | 1993-03-31 | 1994-10-13 | Sterling Winthrop Inc. | Oligonucleotides a liaisons d'amides remplacant les liaisons de phosphodiesters |
-
1996
- 1996-03-25 AU AU49311/96A patent/AU4931196A/en not_active Abandoned
- 1996-03-25 WO PCT/AT1996/000056 patent/WO1996030383A1/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993024508A1 (fr) * | 1992-06-01 | 1993-12-09 | Gilead Sciences, Inc. | Oligomeres aptes a la fixation contenant des liaisons 2', 5' |
| WO1994022891A1 (fr) * | 1993-03-31 | 1994-10-13 | Sterling Winthrop Inc. | Oligonucleotides a liaisons d'amides remplacant les liaisons de phosphodiesters |
Non-Patent Citations (2)
| Title |
|---|
| A.D. MESMAEKER ET AL.: "Synthetic Modifications of Antisense Oligonucleotides: Novel Backbone Replacements with Improved Properties", BULL. SOC. CHIM. BELG., vol. 103, 1994, pages 705 - 17, XP002008196 * |
| C.R. NOE ET AL.: "Novel Three-Atom 2'-5' Linkages in Antisense Nucleotides: Synthesis and Pairing Properties of Dinucleotides with a Carboxylic Ester Linkage", ARCH. PHARM., vol. 328, 1995, pages 743 - 4, XP002008198 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8871737B2 (en) | 2010-09-22 | 2014-10-28 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US9278990B2 (en) | 2010-09-22 | 2016-03-08 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US8980865B2 (en) | 2011-12-22 | 2015-03-17 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US9605018B2 (en) | 2011-12-22 | 2017-03-28 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US8916538B2 (en) | 2012-03-21 | 2014-12-23 | Vertex Pharmaceuticals Incorporated | Solid forms of a thiophosphoramidate nucleotide prodrug |
| US9394330B2 (en) | 2012-03-21 | 2016-07-19 | Alios Biopharma, Inc. | Solid forms of a thiophosphoramidate nucleotide prodrug |
| US9856284B2 (en) | 2012-03-21 | 2018-01-02 | Alios Biopharma, Inc. | Solid forms of a thiophosphoramidate nucleotide prodrug |
| US9012427B2 (en) | 2012-03-22 | 2015-04-21 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
Also Published As
| Publication number | Publication date |
|---|---|
| AU4931196A (en) | 1996-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69027431T2 (de) | Kumarinderivate zur verwendung als nukleotidvernetzungsreagenzien | |
| EP0524997B1 (fr) | Nucleotides de 2'-o-alkyle et polymeres contenant ces nucleotides | |
| EP0399330B1 (fr) | Procédé amide-ester phosphoreux modifié pour la préparation d'acides nucléiques modifiés | |
| DE3855055T2 (de) | Chemische Blockierung durch Phosphithylierung während der Oligonukleotid-Synthese | |
| DE69033495T2 (de) | 2'-modifizierte nukleotide | |
| DE69032167T2 (de) | Ungeladene polymere mit morpholino-einheiten und mit achiralen bindungen zwischen diesen einheiten | |
| DE69719220T2 (de) | Neue nucleotidanaloga | |
| DE3689715T2 (de) | Verfahren und Reagenzien für die In-vitro-Synthese von Oligonukleotiden. | |
| DE3855275T4 (de) | Nichtnukleotides Bindungsreagenz für nukleotide Proben | |
| DE69635744T2 (de) | Modifizierte Nukleinsäuresonden | |
| DE69637256T2 (de) | Synthese von Methoxynukleoside und enzymatische Nukleisäure Moleküle | |
| DE69432315T2 (de) | ANTISENSE NUKLEINSÄUREN ZUR VORBEUGUNG UND BEHANDLUNG VON BESCHWERDEN IN WELCHEN DIE EXPRIMIERUNG VON C-erbB-2 EINE ROLLE SPIELT | |
| DE69632456T2 (de) | Nukleinsäuresynthese unter verwendung von mittels licht abspaltbaren schutzgruppen | |
| DE69724218T2 (de) | Universale feste träger und verfahren zu ihrer verwendung | |
| EP0593901B1 (fr) | Analogues des oligoribonucleotide et ribozymer avec 3'-3'-et 5'-5' liasons terminaler | |
| EP0600965B1 (fr) | Amorces pour la synthese enzymatique matrice-dependante d'acides nucleiques | |
| EP0818460B1 (fr) | Synthèse d'oligonucléotides sur support solide. | |
| DE69828076T3 (de) | Synthese von sulfurierten oligonukleotiden | |
| DE69405396T2 (de) | Verfahren zur synthese von nukleinsäuren auf einem festträger und verbindungen verwendbar als festträger in diesem verfahren | |
| DE69725440T2 (de) | 2-substituierte nukleosid- und oligonukleotid- derivate | |
| DE69824843T2 (de) | Verfahren zur herstellung von modifizierten p-chiralen nucleotid-analoga | |
| DE69733150T2 (de) | Verfahren zur herstellung von nukleotiden oder oligonukleotiden phosphoramitiden | |
| DD141836A5 (de) | Verfahren zur herstellung von polynucleotiden mit bestimmter sequenz | |
| WO1996030383A1 (fr) | Polyamides de polyester d'acide nucleique | |
| DE69402177T2 (de) | Synthese von dimer-blöcken und ihre verwendung bei der zusammensetzung von oligonukleotiden |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU BR CA CN CZ EE HU JP LT LV MX NZ TR US AM AZ BY KG KZ MD RU TJ TM |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: CA |