DK2176280T4 - 6-Disubstituerede bicykliske nukleinsyreanaloge - Google Patents
6-Disubstituerede bicykliske nukleinsyreanaloge Download PDFInfo
- Publication number
- DK2176280T4 DK2176280T4 DK08781239.2T DK08781239T DK2176280T4 DK 2176280 T4 DK2176280 T4 DK 2176280T4 DK 08781239 T DK08781239 T DK 08781239T DK 2176280 T4 DK2176280 T4 DK 2176280T4
- Authority
- DK
- Denmark
- Prior art keywords
- compound
- oligomeric compound
- group
- nucleosides
- groups
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (12)
1. Bicyklisk nukleosid med formlen II: 11.
i hvilken: Bx er en heterocyklisk basedel; én af T-ι og T2 er H eller en hydroxylbeskyttende gruppe, og den anden af Ti og T2 er H, en hydroxylbeskyttende gruppe eller en reaktiv phosphorholdig gruppe; qi og q2 er hver methyl; hvor den reaktive phosphorholdige gruppe er phosphoramidit, H-phosphonat, phosphattriester eller en phosphorholdig chiral hjælpegruppe.
2. Bicyklisk nukleosid ifølge krav 1, hvor Ti er 4,4'-dimethoxytrityl, og T2 er diisopropylcyanoethoxy-phosphoramidit.
3. Bicyklisk nukleosid ifølge krav 1 eller krav 2, hvor Bx er uracil, 5-propynyl-uracil, 5-thiazolo-uracil, thymin, cytosin, 5-methylcytosin, 5-propynyl-cytosin, 5-thiazolo-cytosin, adenin, guanin, 2,6-diaminopurin eller anden pyrimidin, substitueret pyrimidin, purin eller substitueret purin.
4. Oligomer forbindelse omfattende i det mindste ét bicyklisk nukleosid med formlen IV:
IV. hvor uafhængigt for hver af det mindst ene bicykliske nukleosid med formlen IV: Bx er en heterocyklisk basedel; T3 og Τ4 er hver uafhængigt en internukleosid-forbindende gruppe, der forbinder det bicykliske nucleosid med formlen IV til den oligomere forbindelse, eller én af T3 og T4 er en internukleosid-forbindende gruppe, der forbinder det bicykliske nukleosid med formlen IV til den oligomere forbindelse, og den anden af T3 og T4 er H, en hydroxylbeskyttende gruppe, en forbundet konjugatgruppe eller en 5'- eller 3'-terminalgruppe; qi og q2 er hver methyl, og hvor den oligomere forbindelse indeholder fra 8 til ca. 40 forbundne nukleosider, og hvor udtrykket "oligomer forbindelse" henviser til en polymer med i det mindste en region, der er i stand til at hybridisere til et nukleinsyremolekyle.
5. Oligomer forbindelse ifølge krav 4 indeholdende mindst én 3'- eller 5'-terminalgruppe.
6. Oligomer forbindelse ifølge krav 4 eller krav 5, hvor hver internukleosid-forbindende gruppe uafhængigt er en phosphodiester eller phosphorthioat.
7. Oligomer forbindelse ifølge ethvert af kravene 4-6 indeholdende mindst én region af mindst to tilstødende bicykliske nukleosider med formlen beliggende ved enten 3'- eller 5'-enden af den oligomere forbindelse.
8. Oligomer forbindelse ifølge ethvert af kravene 4-7 indeholdende en gapped oligomer forbindelse med mindst to regioner, hvor hver region indeholder fra 1 til ca. 5 tilstødende bicykliske nukleosider med den angivne formel, hvor én af regionerne af bicykliske nukleosider med den angivne formel befinder sig eksternt ved 5'-enden, og den anden af regionerne er beliggende eksternt ved 3'-enden, og hvor de to eksterne regioner er adskilt med en intern region indeholdende fra ca. 6 til ca. 14 monomere underenheder.
9. Oligomer forbindelse ifølge krav 8, hvor i det væsentlige hver monomer underenhed i den interne region er et 3-D-2'-deoxyribonukleosid.
10. In vitro-fremgangsmåde til inhibering af genekspression, hvilken fremgangsmåde omfatter kontakt mellem én eller flere celler eller et væv og en oligomer forbindelse ifølge ethvert af kravene 4-9.
11. Oligomer forbindelse ifølge ethvert af kravene 4-9 til anvendelse ved en in vivo-fremgangsmåde til inhibering af genekspression, hvilken fremgangsmåde omfatter kontakt mellem én eller flere celler, et væv eller et dyr og en oligomer forbindelse ifølge ethvert af kravene 4-9.
12. Oligomer forbindelse ifølge ethvert af kravene 4-9 til anvendelse ved medicinsk terapi.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94813407P | 2007-07-05 | 2007-07-05 | |
PCT/US2008/068922 WO2009006478A2 (en) | 2007-07-05 | 2008-07-01 | 6-disubstituted bicyclic nucleic acid analogs |
Publications (2)
Publication Number | Publication Date |
---|---|
DK2176280T3 DK2176280T3 (da) | 2012-03-05 |
DK2176280T4 true DK2176280T4 (da) | 2015-07-20 |
Family
ID=40087523
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK08781239.2T DK2176280T4 (da) | 2007-07-05 | 2008-07-01 | 6-Disubstituerede bicykliske nukleinsyreanaloge |
Country Status (9)
Country | Link |
---|---|
US (1) | US8278283B2 (da) |
EP (1) | EP2176280B2 (da) |
CN (1) | CN101796062B (da) |
AT (1) | ATE538127T1 (da) |
AU (1) | AU2008272918B2 (da) |
CA (1) | CA2692579C (da) |
DK (1) | DK2176280T4 (da) |
ES (1) | ES2376507T5 (da) |
WO (1) | WO2009006478A2 (da) |
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-
2008
- 2008-07-01 ES ES08781239.2T patent/ES2376507T5/es active Active
- 2008-07-01 CA CA2692579A patent/CA2692579C/en not_active Expired - Fee Related
- 2008-07-01 DK DK08781239.2T patent/DK2176280T4/da active
- 2008-07-01 AT AT08781239T patent/ATE538127T1/de active
- 2008-07-01 AU AU2008272918A patent/AU2008272918B2/en not_active Ceased
- 2008-07-01 WO PCT/US2008/068922 patent/WO2009006478A2/en active Application Filing
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- 2008-07-01 CN CN200880105715.6A patent/CN101796062B/zh active Active
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DK2176280T3 (da) | 2012-03-05 |
WO2009006478A3 (en) | 2009-02-19 |
AU2008272918A1 (en) | 2009-01-08 |
US8278283B2 (en) | 2012-10-02 |
CA2692579C (en) | 2016-05-03 |
WO2009006478A2 (en) | 2009-01-08 |
CN101796062B (zh) | 2014-07-30 |
US20110053881A1 (en) | 2011-03-03 |
EP2176280B1 (en) | 2011-12-21 |
ATE538127T1 (de) | 2012-01-15 |
AU2008272918B2 (en) | 2012-09-13 |
ES2376507T3 (es) | 2012-03-14 |
CA2692579A1 (en) | 2009-01-08 |
EP2176280A2 (en) | 2010-04-21 |
EP2176280B2 (en) | 2015-06-24 |
ES2376507T5 (es) | 2015-08-31 |
CN101796062A (zh) | 2010-08-04 |
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