ES2479393T3 - Método de síntesis de oligómeros de morfolino - Google Patents
Método de síntesis de oligómeros de morfolino Download PDFInfo
- Publication number
- ES2479393T3 ES2479393T3 ES08850132.5T ES08850132T ES2479393T3 ES 2479393 T3 ES2479393 T3 ES 2479393T3 ES 08850132 T ES08850132 T ES 08850132T ES 2479393 T3 ES2479393 T3 ES 2479393T3
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- morpholino
- group
- compound
- protected
- nitrogen
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 title claims abstract description 112
- 238000001308 synthesis method Methods 0.000 title description 2
- -1 morpholino compound Chemical class 0.000 claims abstract description 101
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 39
- 125000005039 triarylmethyl group Chemical group 0.000 claims abstract description 25
- MCKANBCWFDYIJO-UHFFFAOYSA-N chloro-dihydroxy-imino-$l^{5}-phosphane Chemical group NP(O)(Cl)=O MCKANBCWFDYIJO-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 239000007787 solid Substances 0.000 claims abstract description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 229910052739 hydrogen Chemical group 0.000 claims abstract description 11
- 239000001257 hydrogen Chemical group 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 7
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 186
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 107
- 229910052757 nitrogen Inorganic materials 0.000 claims description 57
- 230000015572 biosynthetic process Effects 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 42
- 238000003786 synthesis reaction Methods 0.000 claims description 39
- 239000000178 monomer Substances 0.000 claims description 38
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 33
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 25
- 239000003153 chemical reaction reagent Substances 0.000 claims description 23
- 238000010511 deprotection reaction Methods 0.000 claims description 23
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 239000007790 solid phase Substances 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 238000000605 extraction Methods 0.000 claims description 9
- POEJZKASYFKLKY-UHFFFAOYSA-N 3-chloropyridin-1-ium;methanesulfonate Chemical group CS([O-])(=O)=O.ClC1=CC=C[NH+]=C1 POEJZKASYFKLKY-UHFFFAOYSA-N 0.000 claims description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical group NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 3
- 150000003852 triazoles Chemical class 0.000 claims description 3
- 229930194542 Keto Natural products 0.000 claims description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- 150000008298 phosphoramidates Chemical class 0.000 claims description 2
- LMWFKCYJTRUATP-UHFFFAOYSA-N pyridin-1-ium-4-carbonitrile;2,2,2-trifluoroacetate Chemical group [O-]C(=O)C(F)(F)F.N#CC1=CC=[NH+]C=C1 LMWFKCYJTRUATP-UHFFFAOYSA-N 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims 3
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical class C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 239000000243 solution Substances 0.000 description 90
- 239000011347 resin Substances 0.000 description 56
- 229920005989 resin Polymers 0.000 description 56
- 238000006243 chemical reaction Methods 0.000 description 38
- 239000000203 mixture Substances 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000002585 base Substances 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 21
- 125000006239 protecting group Chemical group 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- LAZQWLMVJAIYFE-UHFFFAOYSA-N 1-tritylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LAZQWLMVJAIYFE-UHFFFAOYSA-N 0.000 description 14
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 241000894007 species Species 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 238000005859 coupling reaction Methods 0.000 description 13
- 239000006227 byproduct Substances 0.000 description 11
- 230000008878 coupling Effects 0.000 description 11
- 238000010168 coupling process Methods 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000006386 neutralization reaction Methods 0.000 description 9
- MHCMWGPPLOSCJY-UHFFFAOYSA-N 4-$l^{1}-azanylmorpholine Chemical compound [N]N1CCOCC1 MHCMWGPPLOSCJY-UHFFFAOYSA-N 0.000 description 8
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 7
- 108091034117 Oligonucleotide Proteins 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 150000003222 pyridines Chemical class 0.000 description 7
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000007836 KH2PO4 Substances 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- 239000004793 Polystyrene Substances 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 6
- ANCLJVISBRWUTR-UHFFFAOYSA-N diaminophosphinic acid Chemical compound NP(N)(O)=O ANCLJVISBRWUTR-UHFFFAOYSA-N 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 6
- 235000019796 monopotassium phosphate Nutrition 0.000 description 6
- 229920002223 polystyrene Polymers 0.000 description 6
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- RODBEKUWCLMBSW-FGZHOGPDSA-M (3r,5r)-7-[1-cyclohexyl-4-(4-fluorophenyl)-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyheptanoate Chemical compound CC(C)C1=C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=CN1C1CCCCC1 RODBEKUWCLMBSW-FGZHOGPDSA-M 0.000 description 5
- VKKXEIQIGGPMHT-UHFFFAOYSA-N 7h-purine-2,8-diamine Chemical class NC1=NC=C2NC(N)=NC2=N1 VKKXEIQIGGPMHT-UHFFFAOYSA-N 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
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- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000010532 solid phase synthesis reaction Methods 0.000 description 5
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- 108020004414 DNA Proteins 0.000 description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
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- 229940059260 amidate Drugs 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000007979 citrate buffer Substances 0.000 description 4
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- 229910021641 deionized water Inorganic materials 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 4
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- 108020004707 nucleic acids Proteins 0.000 description 4
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
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- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 3
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- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
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- 238000005571 anion exchange chromatography Methods 0.000 description 3
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- 238000006731 degradation reaction Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
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- 108091033319 polynucleotide Proteins 0.000 description 3
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- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 3
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- 238000003756 stirring Methods 0.000 description 3
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- 239000001384 succinic acid Substances 0.000 description 3
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- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- CSPHPKQCLCBONW-UHFFFAOYSA-N pyridin-1-ium-1-carbonitrile Chemical class N#C[N+]1=CC=CC=C1 CSPHPKQCLCBONW-UHFFFAOYSA-N 0.000 description 1
- ILAILUUAUWUQNG-UHFFFAOYSA-N pyridin-1-ium-3-carbonitrile;2,2,2-trifluoroacetate Chemical compound OC(=O)C(F)(F)F.N#CC1=CC=CN=C1 ILAILUUAUWUQNG-UHFFFAOYSA-N 0.000 description 1
- ODNFVADIRXKBCY-UHFFFAOYSA-N pyrrolidin-1-yl carbamate Chemical class NC(=O)ON1CCCC1 ODNFVADIRXKBCY-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000002305 strong-anion-exchange chromatography Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 239000001043 yellow dye Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Saccharide Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98819207P | 2007-11-15 | 2007-11-15 | |
| US98820007P | 2007-11-15 | 2007-11-15 | |
| US988200P | 2007-11-15 | ||
| US988192P | 2007-11-15 | ||
| PCT/US2008/012804 WO2009064471A1 (en) | 2007-11-15 | 2008-11-14 | Method of synthesis of morpholino oligomers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2479393T3 true ES2479393T3 (es) | 2014-07-24 |
Family
ID=40293764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08850132.5T Active ES2479393T3 (es) | 2007-11-15 | 2008-11-14 | Método de síntesis de oligómeros de morfolino |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP2207779B1 (https=) |
| JP (3) | JP5512533B2 (https=) |
| KR (1) | KR101617472B1 (https=) |
| CN (1) | CN101861318A (https=) |
| BR (1) | BR122019021332A8 (https=) |
| CA (2) | CA2704261C (https=) |
| DK (1) | DK2207779T3 (https=) |
| ES (1) | ES2479393T3 (https=) |
| HR (1) | HRP20140646T1 (https=) |
| IL (1) | IL205776A0 (https=) |
| MX (1) | MX2010004955A (https=) |
| RU (1) | RU2606627C2 (https=) |
| WO (1) | WO2009064471A1 (https=) |
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-
2008
- 2008-11-14 RU RU2010123958A patent/RU2606627C2/ru not_active Application Discontinuation
- 2008-11-14 WO PCT/US2008/012804 patent/WO2009064471A1/en not_active Ceased
- 2008-11-14 CA CA2704261A patent/CA2704261C/en active Active
- 2008-11-14 CA CA2884340A patent/CA2884340C/en active Active
- 2008-11-14 MX MX2010004955A patent/MX2010004955A/es active IP Right Grant
- 2008-11-14 ES ES08850132.5T patent/ES2479393T3/es active Active
- 2008-11-14 JP JP2010534042A patent/JP5512533B2/ja active Active
- 2008-11-14 CN CN200880116219A patent/CN101861318A/zh active Pending
- 2008-11-14 BR BR122019021332A patent/BR122019021332A8/pt not_active Application Discontinuation
- 2008-11-14 KR KR1020107009620A patent/KR101617472B1/ko active Active
- 2008-11-14 HR HRP20140646AT patent/HRP20140646T1/hr unknown
- 2008-11-14 DK DK08850132.5T patent/DK2207779T3/da active
- 2008-11-14 EP EP08850132.5A patent/EP2207779B1/en active Active
-
2010
- 2010-05-13 IL IL205776A patent/IL205776A0/en unknown
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2014
- 2014-03-26 JP JP2014063314A patent/JP6178744B2/ja active Active
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2016
- 2016-06-30 JP JP2016129716A patent/JP2016196494A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100090681A (ko) | 2010-08-16 |
| WO2009064471A1 (en) | 2009-05-22 |
| CA2704261A1 (en) | 2009-05-22 |
| JP2014159432A (ja) | 2014-09-04 |
| JP6178744B2 (ja) | 2017-08-09 |
| DK2207779T3 (da) | 2014-07-14 |
| CA2884340A1 (en) | 2009-05-22 |
| CN101861318A (zh) | 2010-10-13 |
| RU2606627C2 (ru) | 2017-01-10 |
| BRPI0819828A2 (pt) | 2015-05-26 |
| BRPI0819828A8 (pt) | 2022-12-27 |
| CA2704261C (en) | 2015-05-26 |
| AU2008321409A1 (en) | 2009-05-22 |
| BR122019021332A8 (pt) | 2022-12-06 |
| RU2010123958A (ru) | 2011-12-20 |
| JP5512533B2 (ja) | 2014-06-04 |
| JP2011503184A (ja) | 2011-01-27 |
| CA2884340C (en) | 2017-07-25 |
| KR101617472B1 (ko) | 2016-05-02 |
| EP2207779B1 (en) | 2014-04-09 |
| HK1144424A1 (en) | 2011-02-18 |
| MX2010004955A (es) | 2010-06-30 |
| JP2016196494A (ja) | 2016-11-24 |
| HRP20140646T1 (hr) | 2014-09-26 |
| BR122019021332A2 (https=) | 2015-05-26 |
| IL205776A0 (en) | 2010-11-30 |
| AU2008321409B2 (en) | 2014-08-14 |
| EP2207779A1 (en) | 2010-07-21 |
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