KR20030084444A - Ｐｎａ 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 - Google Patents
Ｐｎａ 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 Download PDFInfo
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- KR20030084444A KR20030084444A KR1020020023157A KR20020023157A KR20030084444A KR 20030084444 A KR20030084444 A KR 20030084444A KR 1020020023157 A KR1020020023157 A KR 1020020023157A KR 20020023157 A KR20020023157 A KR 20020023157A KR 20030084444 A KR20030084444 A KR 20030084444A
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- 238000000034 method Methods 0.000 title claims abstract description 42
- 239000000178 monomer Substances 0.000 title abstract description 71
- 238000003786 synthesis reaction Methods 0.000 title abstract description 21
- 230000015572 biosynthetic process Effects 0.000 title abstract description 20
- 230000008569 process Effects 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 55
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 54
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 15
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims abstract description 14
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims abstract description 13
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 11
- 229940113082 thymine Drugs 0.000 claims abstract description 8
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229930024421 Adenine Natural products 0.000 claims abstract description 7
- 229960000643 adenine Drugs 0.000 claims abstract description 7
- 229940104302 cytosine Drugs 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 150000007522 mineralic acids Chemical group 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 6
- 235000008206 alpha-amino acids Nutrition 0.000 claims abstract 11
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims abstract 4
- 229940035893 uracil Drugs 0.000 claims abstract 2
- 239000002585 base Substances 0.000 claims description 69
- 125000003277 amino group Chemical group 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 19
- 239000011347 resin Substances 0.000 claims description 18
- 229920005989 resin Polymers 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 235000001014 amino acid Nutrition 0.000 claims description 9
- 150000001413 amino acids Chemical class 0.000 claims description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 150000001371 alpha-amino acids Chemical class 0.000 claims 10
- 239000000539 dimer Substances 0.000 claims 2
- 238000007112 amidation reaction Methods 0.000 abstract description 16
- 238000007363 ring formation reaction Methods 0.000 abstract description 8
- 230000007062 hydrolysis Effects 0.000 abstract description 7
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 7
- 150000003141 primary amines Chemical class 0.000 abstract description 3
- 108010009736 Protein Hydrolysates Proteins 0.000 abstract 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 abstract 1
- -1 DNA and RNA Chemical class 0.000 description 103
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 125000006239 protecting group Chemical group 0.000 description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 52
- 108091093037 Peptide nucleic acid Proteins 0.000 description 42
- 238000002360 preparation method Methods 0.000 description 40
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 24
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
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- 108020004414 DNA Proteins 0.000 description 17
- LREXRKBIOMBDFW-UHFFFAOYSA-N 1-(1,3-benzothiazol-2-ylsulfonyl)piperazin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1CNCCN1S(=O)(=O)C1=NC2=CC=CC=C2S1 LREXRKBIOMBDFW-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 11
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 11
- 230000002194 synthesizing effect Effects 0.000 description 11
- 239000007821 HATU Substances 0.000 description 10
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical class O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QSNHRCZHENQCLL-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethylamino]acetate Chemical compound C1=CC=C2SC(S(=O)(=O)NCCNCC(=O)OCC)=NC2=C1 QSNHRCZHENQCLL-UHFFFAOYSA-N 0.000 description 6
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
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- 230000000295 complement effect Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- HSILAFDVJZUQPI-UHFFFAOYSA-N 1,3-benzothiazole-2-sulfonyl chloride Chemical compound C1=CC=C2SC(S(=O)(=O)Cl)=NC2=C1 HSILAFDVJZUQPI-UHFFFAOYSA-N 0.000 description 4
- PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical compound NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 4
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
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- 150000002148 esters Chemical class 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000010647 peptide synthesis reaction Methods 0.000 description 4
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
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- DAKPYWQCZPUAQH-UHFFFAOYSA-N 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[2-[6-[(4-methoxyphenyl)methoxycarbonylamino]purin-9-yl]acetyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1COC(=O)NC1=NC=NC2=C1N=CN2CC(=O)N(CC(O)=O)CCNS(=O)(=O)C1=NC2=CC=CC=C2S1 DAKPYWQCZPUAQH-UHFFFAOYSA-N 0.000 description 3
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
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- 125000004122 cyclic group Chemical group 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- FSCFFGNXMFCNDM-JTQLQIEISA-N ethyl (2s)-2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethylamino]propanoate Chemical compound C1=CC=C2SC(S(=O)(=O)NCCN[C@@H](C)C(=O)OCC)=NC2=C1 FSCFFGNXMFCNDM-JTQLQIEISA-N 0.000 description 3
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- NHMQTWBYSNVLLN-UHFFFAOYSA-N 1,2-dimethoxyethane;1-methylpyrrolidin-2-one Chemical compound COCCOC.CN1CCCC1=O NHMQTWBYSNVLLN-UHFFFAOYSA-N 0.000 description 2
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- HDBMKJBXZGPQPI-UHFFFAOYSA-N 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound C1=CC=C2SC(S(=O)(=O)NCCN(C(=O)OC(C)(C)C)CC(O)=O)=NC2=C1 HDBMKJBXZGPQPI-UHFFFAOYSA-N 0.000 description 2
- XOYQFFCTNCYDHO-UHFFFAOYSA-N 2-methylsulfanylethyl n-[1-[2-[4-(1,3-benzothiazol-2-ylsulfonyl)-3-oxopiperazin-1-yl]-2-oxoethyl]-2-oxopyrimidin-4-yl]carbamate Chemical compound O=C1N=C(NC(=O)OCCSC)C=CN1CC(=O)N1CC(=O)N(S(=O)(=O)C=2SC3=CC=CC=C3N=2)CC1 XOYQFFCTNCYDHO-UHFFFAOYSA-N 0.000 description 2
- JGWIAOLXBVNFMU-UHFFFAOYSA-N 2-methylsulfanylethyl n-[9-[2-[4-(1,3-benzothiazol-2-ylsulfonyl)-3-oxopiperazin-1-yl]-2-oxoethyl]purin-6-yl]carbamate Chemical compound C1=CC=C2SC(S(=O)(=O)N3CCN(CC3=O)C(=O)CN3C=4N=CN=C(C=4N=C3)NC(=O)OCCSC)=NC2=C1 JGWIAOLXBVNFMU-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
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- TZKPROHXCJKXHP-UHFFFAOYSA-N benzhydryl n-[9-[2-[4-(1,3-benzothiazol-2-ylsulfonyl)-3-oxopiperazin-1-yl]-2-oxoethyl]-6-oxo-3h-purin-2-yl]carbamate Chemical compound N=1C=2N(CC(=O)N3CC(=O)N(CC3)S(=O)(=O)C=3SC4=CC=CC=C4N=3)C=NC=2C(=O)NC=1NC(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 TZKPROHXCJKXHP-UHFFFAOYSA-N 0.000 description 2
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- KFCHRYMBOXGXPU-UHFFFAOYSA-N ethyl 2-[[2-[2-(benzhydryloxycarbonylamino)-6-oxo-3h-purin-9-yl]acetyl]-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl]amino]acetate Chemical compound N=1C2=CC=CC=C2SC=1S(=O)(=O)NCCN(CC(=O)OCC)C(=O)CN1C=NC(C(N2)=O)=C1N=C2NC(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 KFCHRYMBOXGXPU-UHFFFAOYSA-N 0.000 description 2
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- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
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- KZRKLQCNUIUBSK-UHFFFAOYSA-N benzyl n-[9-[2-[4-(1,3-benzothiazol-2-ylsulfonyl)-3-oxopiperazin-1-yl]-2-oxoethyl]purin-6-yl]carbamate Chemical compound N=1C=NC=2N(CC(=O)N3CC(=O)N(CC3)S(=O)(=O)C=3SC4=CC=CC=C4N=3)C=NC=2C=1NC(=O)OCC1=CC=CC=C1 KZRKLQCNUIUBSK-UHFFFAOYSA-N 0.000 description 1
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- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
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- AKIVBPMKPCQWFD-UHFFFAOYSA-N ethyl 2-(2-aminoethylamino)acetate Chemical compound CCOC(=O)CNCCN AKIVBPMKPCQWFD-UHFFFAOYSA-N 0.000 description 1
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- CNCGUMZWKBHJMF-UHFFFAOYSA-N ethyl 2-[2-(1,3-benzothiazol-2-ylsulfonylamino)ethyl-[2-[6-[(4-methoxyphenyl)methoxycarbonylamino]purin-9-yl]acetyl]amino]acetate Chemical compound N=1C2=CC=CC=C2SC=1S(=O)(=O)NCCN(CC(=O)OCC)C(=O)CN(C1=NC=N2)C=NC1=C2NC(=O)OCC1=CC=C(OC)C=C1 CNCGUMZWKBHJMF-UHFFFAOYSA-N 0.000 description 1
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- 229910052736 halogen Inorganic materials 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229960002050 hydrofluoric acid Drugs 0.000 description 1
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- 239000002198 insoluble material Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 125000006357 methylene carbonyl group Chemical group [H]C([H])([*:1])C([*:2])=O 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- PSACHCMMPFMFAJ-UHFFFAOYSA-N nmm n-methylmorpholine Chemical compound CN1CCOCC1.CN1CCOCC1 PSACHCMMPFMFAJ-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
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- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
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- 239000000376 reactant Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
- C07D277/76—Sulfur atoms attached to a second hetero atom
- C07D277/80—Sulfur atoms attached to a second hetero atom to a nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
-
- 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
Priority Applications (20)
| Application Number | Priority Date | Filing Date | Title |
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| KR1020020023157A KR20030084444A (ko) | 2002-04-26 | 2002-04-26 | Ｐｎａ 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
| US10/424,181 US6969766B2 (en) | 2002-04-26 | 2003-04-25 | PNA monomer and precursor |
| DK09015826.2T DK2174936T3 (da) | 2002-04-26 | 2003-04-28 | Pna-monomer og prækursor |
| EP03718981A EP1501812B1 (en) | 2002-04-26 | 2003-04-28 | Pna monomer and precursor |
| EP09015826.2A EP2174936B1 (en) | 2002-04-26 | 2003-04-28 | PNA monomer and precursor |
| AT03718981T ATE453631T1 (de) | 2002-04-26 | 2003-04-28 | Pna-monomer und vorstufe |
| CNB038127652A CN100347161C (zh) | 2002-04-26 | 2003-04-28 | Pna单体和前体 |
| DE60330766T DE60330766D1 (de) | 2002-04-26 | 2003-04-28 | Pna-monomer und vorstufe |
| JP2003587791A JP4417728B2 (ja) | 2002-04-26 | 2003-04-28 | Ｐｎａ単量体および前駆体 |
| AU2003223014A AU2003223014A1 (en) | 2002-04-26 | 2003-04-28 | Pna monomer and precursor |
| DK03718981.8T DK1501812T3 (da) | 2002-04-26 | 2003-04-28 | PNA-monomer og prækursor |
| KR1020047006648A KR100555204B1 (ko) | 2002-04-26 | 2003-04-28 | 피앤에이 단량체와 그의 전구체 |
| PCT/IB2003/001595 WO2003091231A1 (en) | 2002-04-26 | 2003-04-28 | Pna monomer and precursor |
| US11/182,935 US7371859B2 (en) | 2002-04-26 | 2005-07-15 | PNA monomer and precursor |
| US11/182,672 US7125994B2 (en) | 2002-04-26 | 2005-07-15 | PNA monomer and precursor |
| US11/182,936 US7179896B2 (en) | 2002-04-26 | 2005-07-15 | Method of making PNA oligomers |
| US11/183,025 US7371860B2 (en) | 2002-04-26 | 2005-07-15 | PNA monomer and precursor |
| US11/183,034 US7145006B2 (en) | 2002-04-26 | 2005-07-15 | PNA monomer and precursor |
| US11/182,977 US7411065B2 (en) | 2002-04-26 | 2005-07-15 | PNA monomer and precursor |
| JP2009006471A JP4927105B2 (ja) | 2002-04-26 | 2009-01-15 | Ｐｎａ単量体および前駆体 |
Applications Claiming Priority (1)
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|---|---|---|---|
| KR1020020023157A KR20030084444A (ko) | 2002-04-26 | 2002-04-26 | Ｐｎａ 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
Publications (1)
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| KR1020020023157A KR20030084444A (ko) | 2002-04-26 | 2002-04-26 | Ｐｎａ 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
| KR1020047006648A KR100555204B1 (ko) | 2002-04-26 | 2003-04-28 | 피앤에이 단량체와 그의 전구체 |
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| KR1020047006648A KR100555204B1 (ko) | 2002-04-26 | 2003-04-28 | 피앤에이 단량체와 그의 전구체 |
Country Status (10)
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020004980A1 (ko) * | 2018-06-27 | 2020-01-02 | 주식회사 시선바이오머티리얼스 | Ｐｎａ 올리고머의 제조방법 |
| WO2021133032A1 (ko) * | 2019-12-24 | 2021-07-01 | 주식회사 시선바이오머티리얼스 | 개질된 감마탄소 골격 화합물 및 이의 제조방법 |
| WO2021133033A1 (ko) * | 2019-12-24 | 2021-07-01 | 주식회사 시선바이오머티리얼스 | 용액공정상 pna 올리고머의 제조방법 |
Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| ES2804764T3 (es) | 2009-06-01 | 2021-02-09 | Halo Bio Rnai Therapeutics Inc | Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos |
| WO2011060320A1 (en) | 2009-11-13 | 2011-05-19 | Avi Biopharma, Inc. | Antisense antiviral compound and method for treating influenza viral infection |
| WO2011064552A1 (en) | 2009-11-30 | 2011-06-03 | Isis Innovation Limited | Conjugates for delivery of biologically active compounds |
| WO2011112516A1 (en) | 2010-03-08 | 2011-09-15 | Ico Therapeutics Inc. | Treating and preventing hepatitis c virus infection using c-raf kinase antisense oligonucleotides |
| EP2545173A2 (en) | 2010-03-12 | 2013-01-16 | Sarepta Therapeutics, Inc. | Antisense modulation of nuclear hormone receptors |
| AU2011248625B2 (en) | 2010-04-26 | 2017-01-05 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-tRNA synthetase |
| JP6294074B2 (ja) | 2010-04-27 | 2018-03-14 | エータイアー ファーマ， インコーポレイテッド | イソロイシルｔＲＮＡ合成酵素のタンパク質フラグメントに関連した治療用、診断用および抗体組成物の革新的発見 |
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| CA2797393C (en) | 2010-04-29 | 2020-03-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of valyl trna synthetases |
| AU2011248227B2 (en) | 2010-05-03 | 2016-12-01 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-tRNA synthetases |
| CN103096925A (zh) | 2010-05-03 | 2013-05-08 | Atyr医药公司 | 与精氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的创新发现 |
| ES2668207T3 (es) | 2010-05-03 | 2018-05-17 | Atyr Pharma, Inc. | Descubrimiento innovador de composiciones terapéuticas, de diagnóstico y de anticuerpos relacionadas con fragmentos de proteínas de metionil-ARNt sintetasas |
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| US8945541B2 (en) | 2010-05-14 | 2015-02-03 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-beta-tRNA synthetases |
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| EP2575856B1 (en) | 2010-05-27 | 2017-08-16 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-trna synthetases |
| WO2012021247A2 (en) | 2010-07-12 | 2012-02-16 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-trna synthetases |
| CA2808539C (en) | 2010-08-25 | 2021-05-25 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of tyrosyl-trna synthetases |
| EP2732035A2 (en) | 2011-07-15 | 2014-05-21 | Sarepta Therapeutics, Inc. | Methods and compositions for manipulating translation of protein isoforms from alternative initiation start sites |
| US20130085139A1 (en) | 2011-10-04 | 2013-04-04 | Royal Holloway And Bedford New College | Oligomers |
| JP6132849B2 (ja) | 2011-12-08 | 2017-05-31 | サレプタ セラピューティクス， インコーポレイテッド | ヒトｌｍｎａを標的とするオリゴヌクレオチド類似体を使用する早老性ラミノパシーを処置するための方法 |
| US10006909B2 (en) | 2012-09-28 | 2018-06-26 | Vibrant Holdings, Llc | Methods, systems, and arrays for biomolecular analysis |
| EP3041935A1 (en) | 2013-09-05 | 2016-07-13 | Sage Therapeutics, Inc. | Antisense-induced exon2 inclusion in acid alpha-glucosidase |
| US10517898B2 (en) | 2014-11-20 | 2019-12-31 | The Regents Of The University Of California | Compositions and methods related to hematologic recovery |
| MA41795A (fr) | 2015-03-18 | 2018-01-23 | Sarepta Therapeutics Inc | Exclusion d'un exon induite par des composés antisens dans la myostatine |
| WO2016196670A1 (en) | 2015-06-01 | 2016-12-08 | Sarepta Therapeutics, Inc. | Antisense-induced exon exclusion in type vii collagen |
| AU2016312530A1 (en) | 2015-08-24 | 2018-03-01 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotide nanoparticles for the modulation of gene expression and uses thereof |
| BR112018007066A2 (pt) | 2015-10-09 | 2018-10-23 | Sarepta Therapeutics Inc | composições e métodos para tratamento da distrofia muscular de duchene e distúrbios relacionados |
| CA3022874A1 (en) | 2016-02-02 | 2017-08-10 | Olix Pharmaceuticals, Inc. | Treatment of atopic dermatitis and asthma using rna complexes that target il4ra, trpa1, or f2rl1 |
| JP7033547B2 (ja) | 2016-04-18 | 2022-03-10 | サレプタ セラピューティクス， インコーポレイテッド | 酸性アルファ－グルコシダーゼ遺伝子に関連する疾患を処置するためのアンチセンスオリゴマーおよびそれを用いる方法 |
| EA201892467A1 (ru) | 2016-04-29 | 2019-05-31 | Сарепта Терапьютикс, Инк. | Олигонуклеотидные аналоги, нацеленные на lmna человека |
| MA45618A (fr) | 2016-06-30 | 2019-05-08 | Sarepta Therapeutics Inc | Sauts d'exons oligomères pour la dystrophie musculaire |
| WO2018017814A1 (en) | 2016-07-20 | 2018-01-25 | President And Fellows Of Harvard College | Peptidoglycan glycosyltransferase inhibitors of sed proteins for treating bacterial infections |
| WO2018053142A2 (en) | 2016-09-14 | 2018-03-22 | President And Fellows Of Harvard College | Methods and compositions for modulating erythropoiesis |
| WO2018112033A1 (en) | 2016-12-13 | 2018-06-21 | President And Fellows Of Harvard College | Methods and compositions for targeting tumor-infiltrating tregs |
| HUE059843T2 (hu) | 2016-12-19 | 2023-01-28 | Sarepta Therapeutics Inc | Exonátugró oligomerkonjugátumok izomdisztrófiára |
| CN110636866A (zh) | 2016-12-19 | 2019-12-31 | 萨勒普塔医疗公司 | 用于肌肉萎缩症的外显子跳跃寡聚体缀合物 |
| SG10202100491QA (en) | 2016-12-19 | 2021-02-25 | Sarepta Therapeutics Inc | Exon skipping oligomer conjugates for muscular dystrophy |
| WO2018195338A1 (en) | 2017-04-20 | 2018-10-25 | Atyr Pharma, Inc. | Compositions and methods for treating lung inflammation |
| US10538808B2 (en) | 2017-05-26 | 2020-01-21 | Vibrant Holdings, Llc | Photoactive compounds and methods for biomolecule detection and sequencing |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| WO2019067975A1 (en) | 2017-09-28 | 2019-04-04 | Sarepta Therapeutics, Inc. | POLYTHERAPIES FOR TREATING MUSCLE DYSTROPHY |
| JP2020536058A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス， インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
| US20200254002A1 (en) | 2017-09-28 | 2020-08-13 | Sarepta Therapeutics, Inc. | Combination therapies for treating muscular dystrophy |
| WO2019079637A2 (en) | 2017-10-18 | 2019-04-25 | Sarepta Therapeutics, Inc. | ANTISENSE OLIGOMERIC COMPOUNDS |
| US10758629B2 (en) | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| EP4219717A3 (en) | 2018-06-13 | 2023-12-20 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystrophy |
| TW202020153A (zh) | 2018-07-27 | 2020-06-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
| US11273137B2 (en) | 2018-09-04 | 2022-03-15 | Board Of Trustees Of Michigan State University | Methods and compositions to prevent and treat disorders associated with mutations in the ODC1 gene |
| WO2020123574A1 (en) | 2018-12-13 | 2020-06-18 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| KR20210144754A (ko) | 2019-03-12 | 2021-11-30 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 암을 치료하기 위한 방법 및 조성물 |
| EP3955966A1 (en) | 2019-04-18 | 2022-02-23 | Sarepta Therapeutics, Inc. | Compositions for treating muscular dystrophy |
| US20220226269A1 (en) | 2019-06-12 | 2022-07-21 | President And Fellows Of Harvard College | Methods and compositions for modulation of an interspecies gut bacterial pathway for levodopa metabolism |
| EP4114946A1 (en) | 2020-03-04 | 2023-01-11 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for sensitization of tumor cells to immune therapy |
| WO2021242826A1 (en) | 2020-05-27 | 2021-12-02 | The Regents Of The University Of California | Compositions and methods for transdifferentiating cells |
| WO2022056454A2 (en) | 2020-09-14 | 2022-03-17 | President And Fellows Of Harvard College | Methods and compositions for treating hpv-positive cancers |
| CA3195231A1 (en) | 2020-09-16 | 2022-03-24 | President And Fellows Of Harvard College | Methods of treating an individual that has failed an anti-pd-1/anti-pd-l1 therapy |
| WO2023055774A1 (en) | 2021-09-30 | 2023-04-06 | Sarepta Therapeutics, Inc. | Antisense oligonucleotides having one or more abasic units |
| WO2023070086A1 (en) | 2021-10-22 | 2023-04-27 | Sarepta Therapeutics, Inc. | Morpholino oligomers for treatment of peripheral myelin protein 22 related diseases |
| WO2023091704A1 (en) | 2021-11-18 | 2023-05-25 | Circularis Biotechnologies, Inc. | Compositions and methods for production of circular nucleic acid molecules |
| WO2023150181A1 (en) | 2022-02-01 | 2023-08-10 | President And Fellows Of Harvard College | Methods and compositions for treating cancer |
| WO2024026474A1 (en) | 2022-07-29 | 2024-02-01 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle |
| WO2024064237A2 (en) | 2022-09-21 | 2024-03-28 | Sarepta Therapeutics, Inc. | Dmd antisense oligonucleotide-mediated exon skipping efficiency |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS574978A (en) * | 1980-06-12 | 1982-01-11 | Sanshin Kagaku Kogyo Kk | Preparation of benzothiazole-2-sulfonamide compound |
| JPH05140115A (ja) * | 1991-11-14 | 1993-06-08 | Sanshin Chem Ind Co Ltd | スルホンアミド系化合物及びゴム組成物 |
| JPH06298749A (ja) * | 1993-02-19 | 1994-10-25 | Asahi Chem Ind Co Ltd | ベンゾチアゾールスルホンアミド誘導体 |
| JPH07215972A (ja) * | 1993-07-05 | 1995-08-15 | Duphar Internatl Res Bv | ５−ｈｔ１ａ−拮抗活性を有する２，３−ジヒドロ−１，４−ベンゾジオキシン−５−イル−ピペラジン誘導体 |
| JPH11199573A (ja) * | 1998-01-07 | 1999-07-27 | Yamanouchi Pharmaceut Co Ltd | ５ｈｔ３受容体作動薬及び新規ベンゾチアゾール誘導体 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2135543A1 (de) * | 1971-07-16 | 1973-01-25 | Boehringer Mannheim Gmbh | Benzthiazolderivate enthaltende arzneimittel |
| IT1059127B (it) * | 1976-04-15 | 1982-05-31 | Montedison Spa | Eteri e tioeteri benzilici o feni lici a catena alifatica lineare con terminale alogenato ad attivi ta ormonica giovanile e acaric/da |
| US4204870A (en) * | 1978-07-25 | 1980-05-27 | Eastman Kodak Company | Photographic products and processes employing novel nondiffusible heterocyclyazonaphthol dye-releasing compounds |
| US6228982B1 (en) * | 1992-05-22 | 2001-05-08 | Benget Norden | Double-stranded peptide nucleic acids |
| DK51092D0 (da) | 1991-05-24 | 1992-04-15 | Ole Buchardt | Oligonucleotid-analoge betegnet pna, monomere synthoner og fremgangsmaade til fremstilling deraf samt anvendelser deraf |
| US6713602B1 (en) * | 1991-05-24 | 2004-03-30 | Ole Buchardt | Synthetic procedures for peptide nucleic acids |
| US5700922A (en) * | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
| US6277603B1 (en) * | 1991-12-24 | 2001-08-21 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
| US6350853B1 (en) * | 1993-04-26 | 2002-02-26 | Peter E. Nielsen | Conjugated peptide nucleic acids having enhanced cellular uptake |
| US5435939A (en) * | 1993-07-07 | 1995-07-25 | Isp Investments Inc. | Stable emulsifiable gel matrix and aqueous macroemulsion prepared therefrom |
| US6133444A (en) * | 1993-12-22 | 2000-10-17 | Perseptive Biosystems, Inc. | Synthons for the synthesis and deprotection of peptide nucleic acids under mild conditions |
| US5539083A (en) * | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
| JP2001518054A (ja) * | 1995-06-07 | 2001-10-09 | パーセプティブ バイオシステムズ，インコーポレーテッド | Ｐｎａ−ｄｎａキメラと、このキメラ合成用のｐｎａシントン |
| DE19532553A1 (de) * | 1995-09-04 | 1997-03-06 | Hoechst Ag | Verfahren zur Herstellung substituierter N-Ethyl-Glycinderivate |
| CN1291892A (zh) * | 1998-01-27 | 2001-04-18 | 阿温蒂斯药物制品公司 | 取代的氧代氮杂杂环基因子Xa抑制剂 |
| DE69933770D1 (de) | 1998-07-09 | 2006-12-07 | Biocept Inc | Verfahren zur verwendung einer universellen bibliothek von peptid-nukleinsäuren zur optimierung der dns-hybridisierung |
| SE9802538D0 (sv) | 1998-07-13 | 1998-07-13 | Astra Ab | New pharmaceutically active compounds |
| KR100464261B1 (ko) * | 2002-01-24 | 2005-01-03 | 주식회사 파나진 | Ｐｎａ 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
| US7211668B2 (en) * | 2003-07-28 | 2007-05-01 | Panagene, Inc. | PNA monomer and precursor |
-
2002
- 2002-04-26 KR KR1020020023157A patent/KR20030084444A/ko not_active Application Discontinuation
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- 2003-04-25 US US10/424,181 patent/US6969766B2/en not_active Expired - Lifetime
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- 2003-04-28 DE DE60330766T patent/DE60330766D1/de not_active Expired - Lifetime
- 2003-04-28 AT AT03718981T patent/ATE453631T1/de not_active IP Right Cessation
- 2003-04-28 WO PCT/IB2003/001595 patent/WO2003091231A1/en active Application Filing
- 2003-04-28 AU AU2003223014A patent/AU2003223014A1/en not_active Abandoned
- 2003-04-28 EP EP09015826.2A patent/EP2174936B1/en not_active Expired - Lifetime
- 2003-04-28 EP EP03718981A patent/EP1501812B1/en not_active Expired - Lifetime
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2005
- 2005-07-15 US US11/182,977 patent/US7411065B2/en not_active Expired - Lifetime
- 2005-07-15 US US11/182,672 patent/US7125994B2/en not_active Expired - Lifetime
- 2005-07-15 US US11/183,025 patent/US7371860B2/en not_active Expired - Lifetime
- 2005-07-15 US US11/182,935 patent/US7371859B2/en not_active Expired - Lifetime
- 2005-07-15 US US11/182,936 patent/US7179896B2/en not_active Expired - Lifetime
- 2005-07-15 US US11/183,034 patent/US7145006B2/en not_active Expired - Lifetime
-
2009
- 2009-01-15 JP JP2009006471A patent/JP4927105B2/ja not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS574978A (en) * | 1980-06-12 | 1982-01-11 | Sanshin Kagaku Kogyo Kk | Preparation of benzothiazole-2-sulfonamide compound |
| JPH05140115A (ja) * | 1991-11-14 | 1993-06-08 | Sanshin Chem Ind Co Ltd | スルホンアミド系化合物及びゴム組成物 |
| JPH06298749A (ja) * | 1993-02-19 | 1994-10-25 | Asahi Chem Ind Co Ltd | ベンゾチアゾールスルホンアミド誘導体 |
| JPH07215972A (ja) * | 1993-07-05 | 1995-08-15 | Duphar Internatl Res Bv | ５−ｈｔ１ａ−拮抗活性を有する２，３−ジヒドロ−１，４−ベンゾジオキシン−５−イル−ピペラジン誘導体 |
| JPH11199573A (ja) * | 1998-01-07 | 1999-07-27 | Yamanouchi Pharmaceut Co Ltd | ５ｈｔ３受容体作動薬及び新規ベンゾチアゾール誘導体 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020004980A1 (ko) * | 2018-06-27 | 2020-01-02 | 주식회사 시선바이오머티리얼스 | Ｐｎａ 올리고머의 제조방법 |
| WO2021133032A1 (ko) * | 2019-12-24 | 2021-07-01 | 주식회사 시선바이오머티리얼스 | 개질된 감마탄소 골격 화합물 및 이의 제조방법 |
| WO2021133033A1 (ko) * | 2019-12-24 | 2021-07-01 | 주식회사 시선바이오머티리얼스 | 용액공정상 pna 올리고머의 제조방법 |
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