CA2159632A1 - Novel 5'-substituted nucleosides and oligomers produced therefrom - Google Patents
Novel 5'-substituted nucleosides and oligomers produced therefromInfo
- Publication number
- CA2159632A1 CA2159632A1 CA002159632A CA2159632A CA2159632A1 CA 2159632 A1 CA2159632 A1 CA 2159632A1 CA 002159632 A CA002159632 A CA 002159632A CA 2159632 A CA2159632 A CA 2159632A CA 2159632 A1 CA2159632 A1 CA 2159632A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- amino
- lower alkyl
- independently selected
- lower alkoxy
- 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.)
- Abandoned
Links
- 239000002777 nucleoside Substances 0.000 title abstract description 25
- 125000003835 nucleoside group Chemical class 0.000 title abstract description 8
- -1 nucleoside compounds Chemical class 0.000 claims abstract description 48
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 108091034117 Oligonucleotide Chemical class 0.000 claims abstract description 44
- 150000004713 phosphodiesters Chemical class 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 21
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 125000003545 alkoxy group Chemical group 0.000 claims description 58
- 125000003342 alkenyl group Chemical group 0.000 claims description 37
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 20
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 20
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 20
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 20
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 18
- 150000004714 phosphonium salts Chemical class 0.000 claims description 18
- 229910019142 PO4 Inorganic materials 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 235000021317 phosphate Nutrition 0.000 claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 16
- 230000014509 gene expression Effects 0.000 claims description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 13
- 239000010452 phosphate Substances 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 11
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 10
- 229930024421 Adenine Natural products 0.000 claims description 10
- 229960000643 adenine Drugs 0.000 claims description 10
- 229940104302 cytosine Drugs 0.000 claims description 10
- 229940113082 thymine Drugs 0.000 claims description 10
- 229940035893 uracil Drugs 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- 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 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000000692 anti-sense effect Effects 0.000 abstract description 25
- 101710163270 Nuclease Proteins 0.000 abstract description 15
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000002585 base Substances 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 108020004414 DNA Proteins 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 108020004707 nucleic acids Proteins 0.000 description 18
- 150000007523 nucleic acids Chemical class 0.000 description 18
- 102000039446 nucleic acids Human genes 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- 150000003833 nucleoside derivatives Chemical class 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 6
- 238000009396 hybridization Methods 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- ZAZGGJMKOYLNLD-UHFFFAOYSA-N 3-[chloro-[di(propan-2-yl)amino]-dihydroxy-lambda5-phosphanyl]propanenitrile Chemical compound CC(C)N(C(C)C)P(O)(O)(Cl)CCC#N ZAZGGJMKOYLNLD-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- XARVANDLQOZMMJ-CHHVJCJISA-N 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-oxo-2-(2-oxoethylamino)ethylidene]amino]oxy-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)O\N=C(/C(=O)NCC=O)C1=CSC(N)=N1 XARVANDLQOZMMJ-CHHVJCJISA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 108020004491 Antisense DNA Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 3
- 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 3
- 108060002716 Exonuclease Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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- 239000012894 fetal calf serum Substances 0.000 description 3
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 3
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- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- 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
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- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4075093A | 1993-03-31 | 1993-03-31 | |
| US08/040,750 | 1993-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2159632A1 true CA2159632A1 (en) | 1994-10-13 |
Family
ID=21912730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002159632A Abandoned CA2159632A1 (en) | 1993-03-31 | 1994-03-21 | Novel 5'-substituted nucleosides and oligomers produced therefrom |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0691979A1 (ja) |
| JP (1) | JPH08508490A (ja) |
| AU (1) | AU6449294A (ja) |
| CA (1) | CA2159632A1 (ja) |
| HU (1) | HU9501994D0 (ja) |
| WO (1) | WO1994022890A1 (ja) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681940A (en) * | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
| CN103554205A (zh) | 2006-05-05 | 2014-02-05 | Isis制药公司 | 调节gccr的表达的化合物和方法 |
| AU2007249349B2 (en) * | 2006-05-11 | 2012-03-08 | Isis Pharmaceuticals, Inc. | 5'-Modified bicyclic nucleic acid analogs |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| MX2009005527A (es) | 2006-11-27 | 2009-06-08 | Isis Pharmaceuticals Inc | Metodos para el tratamiento de hipercolesterolemia. |
| US20100190837A1 (en) * | 2007-02-15 | 2010-07-29 | Isis Pharmaceuticals, Inc. | 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom |
| WO2010048585A2 (en) | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| WO2010048549A2 (en) * | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | 5' and 2' bis-substituted nucleosides and oligomeric compounds prepared therefrom |
| CA2744987C (en) | 2008-12-02 | 2018-01-16 | Chiralgen, Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| BR112012000828A8 (pt) | 2009-07-06 | 2017-10-10 | Ontorii Inc | Novas pró-drogas de ácido nucleico e métodos de uso das mesmas |
| WO2011123621A2 (en) * | 2010-04-01 | 2011-10-06 | Alnylam Pharmaceuticals Inc. | 2' and 5' modified monomers and oligonucleotides |
| WO2011139695A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom |
| WO2011139699A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
| EP2601204B1 (en) | 2010-04-28 | 2016-09-07 | Ionis Pharmaceuticals, Inc. | Modified nucleosides and oligomeric compounds prepared therefrom |
| US20130156845A1 (en) | 2010-04-29 | 2013-06-20 | Alnylam Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
| PE20140608A1 (es) | 2010-09-22 | 2014-06-12 | Alios Biopharma Inc | Analogos de nucleotidos sustituidos |
| WO2012039448A1 (ja) | 2010-09-24 | 2012-03-29 | 株式会社キラルジェン | 不斉補助基 |
| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| EP2742136B1 (en) | 2011-08-11 | 2017-09-27 | Ionis Pharmaceuticals, Inc. | Gapped oligomeric compounds comprising 5'-modified deoxyribonucleosides in the gap and uses thereof |
| PL2794627T3 (pl) | 2011-12-22 | 2019-04-30 | Alios Biopharma Inc | Podstawione nukleozydy, nukleotydy i ich analogi |
| EP2794630A4 (en) | 2011-12-22 | 2015-04-01 | Alios Biopharma Inc | SUBSTITUTED PHOSPHORTHIOAT NUCLEOTIDE ANALOGUE |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| NZ631601A (en) | 2012-03-21 | 2016-06-24 | Alios Biopharma Inc | Solid forms of a thiophosphoramidate nucleotide prodrug |
| WO2013142157A1 (en) | 2012-03-22 | 2013-09-26 | Alios Biopharma, Inc. | Pharmaceutical combinations comprising a thionucleotide analog |
| AU2013288048A1 (en) | 2012-07-13 | 2015-01-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| KR20220139425A (ko) | 2012-07-13 | 2022-10-14 | 웨이브 라이프 사이언시스 리미티드 | 키랄 제어 |
| PL3041854T3 (pl) | 2013-08-08 | 2020-06-29 | The Scripps Research Institute | Sposób miejscowo specyficznego oznakowania enzymatycznego kwasów nukleinowych in vitro przez inkorporację niewystępujących naturalnie nukleotydów |
| EP3095461A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| WO2015108048A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| PT3094728T (pt) | 2014-01-16 | 2022-05-19 | Wave Life Sciences Ltd | Desenho quiral |
| TWI638047B (zh) | 2014-04-09 | 2018-10-11 | 史基普研究協會 | 藉由核酸三磷酸酯轉運子將非天然或經修飾的核苷三磷酸酯輸入至細胞中 |
| WO2015164693A1 (en) | 2014-04-24 | 2015-10-29 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising alpha-beta-constrained nucleic acid |
| WO2015168172A1 (en) | 2014-04-28 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
| AU2017210726B2 (en) | 2016-01-31 | 2023-08-03 | University Of Massachusetts | Branched oligonucleotides |
| EP3464313A4 (en) | 2016-06-06 | 2020-02-26 | Arrowhead Pharmaceuticals, Inc. | MODIFIED NUCLEOTIDES 5 '-CYCLO-PHOSPHONATE |
| SG11202000167SA (en) | 2017-07-11 | 2020-02-27 | Synthorx Inc | Incorporation of unnatural nucleotides and methods thereof |
| MA49770A (fr) | 2017-08-03 | 2021-05-26 | Synthorx Inc | Conjugués de cytokine destinés au traitement de maladies prolifératives et infectieuses |
| EP3752612A4 (en) | 2018-02-12 | 2021-11-10 | Ionis Pharmaceuticals, Inc. | MODIFIED COMPOUNDS AND USES THEREOF |
| AU2019224159A1 (en) | 2018-02-26 | 2020-10-01 | Synthorx, Inc. | IL-15 conjugates and uses thereof |
| CN113412268A (zh) * | 2019-02-01 | 2021-09-17 | 国立大学法人大阪大学 | 5’位修饰核苷和使用其的核苷酸 |
| EP3923974A4 (en) | 2019-02-06 | 2023-02-08 | Synthorx, Inc. | IL-2 CONJUGATES AND METHODS OF USE THEREOF |
| JP2022528840A (ja) | 2019-03-26 | 2022-06-16 | ユニバーシティ・オブ・マサチューセッツ | 安定性が増加した修飾オリゴヌクレオチド |
| CN114207129A (zh) | 2019-06-14 | 2022-03-18 | 斯克利普斯研究所 | 用于在半合成生物体中复制、转录和翻译的试剂和方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69027443T2 (de) * | 1989-10-24 | 1998-03-19 | Gilead Sciences, Inc., Foster City, Calif. | Oligonukleotidanaloga mit neuartigen bindungen |
| HU217036B (hu) * | 1990-08-03 | 1999-11-29 | Sanofi | Eljárás génexpresszió gátlására alkalmas vegyületek előállítására |
| EP0549686A4 (en) * | 1990-09-20 | 1995-01-18 | Gilead Sciences Inc | Modified internucleoside linkages |
| US5672697A (en) * | 1991-02-08 | 1997-09-30 | Gilead Sciences, Inc. | Nucleoside 5'-methylene phosphonates |
-
1994
- 1994-03-21 CA CA002159632A patent/CA2159632A1/en not_active Abandoned
- 1994-03-21 AU AU64492/94A patent/AU6449294A/en not_active Abandoned
- 1994-03-21 JP JP6522131A patent/JPH08508490A/ja active Pending
- 1994-03-21 EP EP94912265A patent/EP0691979A1/en not_active Withdrawn
- 1994-03-21 WO PCT/US1994/002993 patent/WO1994022890A1/en not_active Application Discontinuation
- 1994-03-21 HU HU9501994A patent/HU9501994D0/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0691979A1 (en) | 1996-01-17 |
| AU6449294A (en) | 1994-10-24 |
| JPH08508490A (ja) | 1996-09-10 |
| WO1994022890A1 (en) | 1994-10-13 |
| HU9501994D0 (en) | 1995-09-28 |
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