JP2019518778A5 - - Google Patents
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- JP2019518778A5 JP2019518778A5 JP2018567264A JP2018567264A JP2019518778A5 JP 2019518778 A5 JP2019518778 A5 JP 2019518778A5 JP 2018567264 A JP2018567264 A JP 2018567264A JP 2018567264 A JP2018567264 A JP 2018567264A JP 2019518778 A5 JP2019518778 A5 JP 2019518778A5
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- JP
- Japan
- Prior art keywords
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- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 82
- 238000000034 method Methods 0.000 claims description 64
- 239000003795 chemical substances by application Substances 0.000 claims description 40
- 108091034117 Oligonucleotide Proteins 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 239000002773 nucleotide Substances 0.000 claims description 20
- 125000003729 nucleotide group Chemical group 0.000 claims description 20
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 16
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 8
- 239000006227 byproduct Substances 0.000 claims description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical group C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 claims description 4
- GVZJRBAUSGYWJI-UHFFFAOYSA-N 2,5-bis(3-dodecylthiophen-2-yl)thiophene Chemical compound C1=CSC(C=2SC(=CC=2)C2=C(C=CS2)CCCCCCCCCCCC)=C1CCCCCCCCCCCC GVZJRBAUSGYWJI-UHFFFAOYSA-N 0.000 claims description 4
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 claims description 4
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 claims description 4
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 claims description 4
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 4
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 4
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 4
- 229930024421 Adenine Natural products 0.000 claims description 4
- 229960000643 adenine Drugs 0.000 claims description 4
- 229940104302 cytosine Drugs 0.000 claims description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- IXGZXXBJSZISOO-UHFFFAOYSA-N s-(2-phenylacetyl)sulfanyl 2-phenylethanethioate Chemical group C=1C=CC=CC=1CC(=O)SSC(=O)CC1=CC=CC=C1 IXGZXXBJSZISOO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 229940113082 thymine Drugs 0.000 claims description 4
- 229940035893 uracil Drugs 0.000 claims description 4
- 238000004064 recycling Methods 0.000 claims description 3
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- YWZHEXZIISFIDA-UHFFFAOYSA-N 5-amino-1,2,4-dithiazole-3-thione Chemical group NC1=NC(=S)SS1 YWZHEXZIISFIDA-UHFFFAOYSA-N 0.000 claims description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006242 amine protecting group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 238000005987 sulfurization reaction Methods 0.000 claims description 2
- 229940075420 xanthine Drugs 0.000 claims description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000003134 recirculating effect Effects 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 0 **OC1[C@@](*)(CO*)OC2(*)C1C2* Chemical compound **OC1[C@@](*)(CO*)OC2(*)C1C2* 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical group C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- IIFWTJATQRKFCB-UHFFFAOYSA-N CCC(c(cccc1)c1N=O)=O Chemical compound CCC(c(cccc1)c1N=O)=O IIFWTJATQRKFCB-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662354433P | 2016-06-24 | 2016-06-24 | |
| US62/354,433 | 2016-06-24 | ||
| PCT/US2017/038643 WO2017223258A1 (en) | 2016-06-24 | 2017-06-22 | Synthesis of thiolated oligonucleotides without a capping step |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019518778A JP2019518778A (ja) | 2019-07-04 |
| JP2019518778A5 true JP2019518778A5 (https=) | 2020-07-30 |
| JP7235512B2 JP7235512B2 (ja) | 2023-03-08 |
Family
ID=59276874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018567264A Active JP7235512B2 (ja) | 2016-06-24 | 2017-06-22 | キャッピング工程を有さないチオール化オリゴヌクレオチドの合成 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11142545B2 (https=) |
| EP (1) | EP3475292B1 (https=) |
| JP (1) | JP7235512B2 (https=) |
| KR (2) | KR102722183B1 (https=) |
| CN (1) | CN109689668B (https=) |
| ES (1) | ES2999138T3 (https=) |
| WO (1) | WO2017223258A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10436802B2 (en) | 2014-09-12 | 2019-10-08 | Biogen Ma Inc. | Methods for treating spinal muscular atrophy |
| CA3195922A1 (en) | 2017-07-10 | 2019-01-17 | Geron Corporation | Improved process for preparing imetelstat |
| US11629347B2 (en) | 2019-05-06 | 2023-04-18 | University Of Massachusetts | Anti-C9ORF72 oligonucleotides and related methods |
| CN110468171B (zh) * | 2019-09-20 | 2021-10-29 | 凯莱英医药集团（天津）股份有限公司 | 核酸的合成方法 |
| CN120505310A (zh) | 2020-02-28 | 2025-08-19 | Ionis制药公司 | 用于调节smn2的化合物和方法 |
| CN114685572B (zh) * | 2022-06-02 | 2022-08-30 | 上海百力格生物技术有限公司 | 用于mgb核酸探针合成的氧化剂组合物及探针的合成方法 |
| US20260001902A1 (en) | 2022-09-19 | 2026-01-01 | Bachem Holding Ag | Improved oligonucleotide synthesis |
| WO2025028656A1 (ja) | 2023-08-02 | 2025-02-06 | 日東電工株式会社 | オリゴヌクレオチドを製造する方法 |
| WO2025038661A1 (en) * | 2023-08-14 | 2025-02-20 | Arrowhead Pharmaceuticals, Inc. | Oligonucleotide synthesis methods |
| WO2025165064A1 (ko) * | 2024-02-02 | 2025-08-07 | 에스티팜 주식회사 | 올리고뉴클레오티드 합성을 위한 개선된 방법 |
| WO2025234897A1 (ru) * | 2024-05-07 | 2025-11-13 | Акционерное общество "ГЕНЕРИУМ" | Способ получения тиофосфатных олигонуклеотидов для терапевтического применения |
| WO2025235761A1 (en) | 2024-05-09 | 2025-11-13 | Biogen Ma Inc. | Reagents and processes for preparing oligonucleotides |
| WO2026082783A1 (en) | 2024-10-17 | 2026-04-23 | F. Hoffmann-La Roche Ag | Synthesis of thiolated oligonucleotides without capping and without recirculation of the thiolating agent |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6087491A (en) * | 1993-01-08 | 2000-07-11 | Hybridon, Inc. | Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks |
| US5614621A (en) * | 1993-07-29 | 1997-03-25 | Isis Pharmaceuticals, Inc. | Process for preparing oligonucleotides using silyl-containing diamino phosphorous reagents |
| US6809195B1 (en) * | 2000-08-16 | 2004-10-26 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotides |
| EP1386925A1 (en) * | 2002-07-31 | 2004-02-04 | Girindus AG | Method for preparing oligonucleotides |
| EP3470072A1 (en) | 2005-06-23 | 2019-04-17 | Biogen MA Inc. | Compositions and methods for modulation of smn2 splicing |
| ES2699827T3 (es) | 2009-06-17 | 2019-02-13 | Biogen Ma Inc | Composiciones y métodos para la modulación de corte y empalme de SMN2 en un sujeto |
| US8642755B2 (en) * | 2009-06-30 | 2014-02-04 | Agilent Technologies, Inc. | Use of thioacetic acid derivatives in the sulfurization of oligonucleotides with phenylacetyl disulfide |
| WO2013086207A1 (en) * | 2011-12-06 | 2013-06-13 | The Ohio State University | Non-ionic, low osmolar contrast agents for delivery of antisense oligonucleotides and treatment of disease |
| WO2015061246A1 (en) * | 2013-10-21 | 2015-04-30 | Isis Pharmaceuticals, Inc. | Method for solution phase detritylation of oligomeric compounds |
| HUE050704T2 (hu) | 2014-04-01 | 2020-12-28 | Biogen Ma Inc | Összetételek a SOD-1 expressziójának modulálására |
| EA035817B1 (ru) * | 2015-03-10 | 2020-08-14 | Адуро Байотек, Инк. | Композиции и способы для активации сигналинга, зависимого от "гена стимулятора интерферона" |
| JOP20190218A1 (ar) * | 2017-03-22 | 2019-09-22 | Boehringer Ingelheim Int | مركبات ثنائية النيوكليوتيدات حلقية معدلة |
-
2017
- 2017-06-22 CN CN201780051170.4A patent/CN109689668B/zh active Active
- 2017-06-22 JP JP2018567264A patent/JP7235512B2/ja active Active
- 2017-06-22 ES ES17735311T patent/ES2999138T3/es active Active
- 2017-06-22 EP EP17735311.7A patent/EP3475292B1/en active Active
- 2017-06-22 KR KR1020237031095A patent/KR102722183B1/ko active Active
- 2017-06-22 WO PCT/US2017/038643 patent/WO2017223258A1/en not_active Ceased
- 2017-06-22 US US16/312,819 patent/US11142545B2/en active Active
- 2017-06-22 KR KR1020197001173A patent/KR20190020743A/ko not_active Ceased
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