+

WO2017018360A1 - Nucléoside artificiel, nucléotide artificiel et oligonucléotide artificiel - Google Patents

Nucléoside artificiel, nucléotide artificiel et oligonucléotide artificiel Download PDF

Info

Publication number
WO2017018360A1
WO2017018360A1 PCT/JP2016/071637 JP2016071637W WO2017018360A1 WO 2017018360 A1 WO2017018360 A1 WO 2017018360A1 JP 2016071637 W JP2016071637 W JP 2016071637W WO 2017018360 A1 WO2017018360 A1 WO 2017018360A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
hydroxy
substituted
amino
protecting
Prior art date
Application number
PCT/JP2016/071637
Other languages
English (en)
Japanese (ja)
Inventor
友輔 入山
Original Assignee
日産化学工業株式会社
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 日産化学工業株式会社 filed Critical 日産化学工業株式会社
Publication of WO2017018360A1 publication Critical patent/WO2017018360A1/fr

Links

Images

Classifications

    • 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
    • C07H19/067—Pyrimidine radicals with ribosyl as the saccharide radical
    • 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
    • C07H19/167—Purine radicals with ribosyl as the saccharide radical
    • 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
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • 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
    • A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • 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
    • A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • 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
    • A61K31/7076—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 containing purines, e.g. adenosine, adenylic acid
    • 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
    • A61K31/7076—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 containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—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 containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • 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

Definitions

  • R 1 is a hydrogen atom, a C1-3 alkyl group, an acetyl group, a benzyl group, a tert-butoxycarbonyl group or a benzyloxycarbonyl group. To 3. The compound as described in any one of these, or its salt. 5).
  • R 4 is a hydrogen atom; To 4. The compound or its salt as described in any one of these. 6).
  • R 2 and R 3 are hydrogen atoms; To 5. The compound as described in any one of these, or its salt. 7).
  • 1. R 1 is a methyl group To 6.
  • 1. Z 1 is a hydrogen atom or a hydroxy protecting group To 7. The compound as described in any one of these, or its salt. 9.
  • Z 2 is a hydrogen atom or a phosphorus-containing group To 9. The compound as described in any one of these, or its salt.
  • 11. 1. Z 2 is a hydrogen atom, a cyanoethoxy (diisopropylamino) phosphino group or a hydroxyphosphinyl group.
  • 12 1. Z 2 is a hydroxy protecting group To 9. The compound as described in any one of these, or its salt.
  • the “C2-9 aromatic heterocycle” means that the ring has one or more heteroatoms arbitrarily selected from an oxygen atom, a sulfur atom and a nitrogen atom in the ring, and the number of carbon atoms constituting the ring is 2
  • An aromatic monocyclic or condensed ring such as purine, pyrimidine, thiophene, furan, isobenzofuran, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridazine, indolizine, indole, isoindole, isoquinoline Quinoline, naphthyridine, quinoxaline, quinazoline, pteridine and the like.
  • Examples thereof include a dimethylamino group, a diethylamino group, an N, N-diisopropylamino group, an N-methyl-N-ethylamino group, and an N-isopropyl-N-ethylamino group.
  • C1-6 alkylaminocarbonyl group means a group in which the “C1-6 alkylamino group” is bonded to a carbonyl group.
  • the aromatic acyl group is a C6-10 aromatic carbocyclic group or a C2-9 aromatic heterocyclic group (the C6-10 aromatic carbocyclic group and the C2-9 aromatic heterocyclic group are unsubstituted Or a monovalent substituent bonded to a carbonyl group, such as a benzoyl group, ⁇ -Naphthoyl group, ⁇ -naphthoyl group, 2-bromobenzoyl group, 4-chlorobenzoyl group, 2,4,6-trimethylbenzoyl group, 4-toluoyl group, 4-anisoyl group, 2-carboxybenzoyl group, 3-carboxy Benzoyl group, 4-carboxybenzoyl group, 4-nitrobenzoyl group, 2-nitrobenzoyl group, 2- (methoxycarbonyl) benzoyl group, 4-phenylbenzoyl group, 2-pyridy Rucarbonyl group, 4-methoxy-2-pyridyl
  • An aromatic sulfonyl group is a C6-10 aromatic carbocyclic group or a C2-9 aromatic heterocyclic group (the C6-10 aromatic carbocyclic group and C2-9 aromatic heterocyclic group are Means a monovalent substituent bonded to a sulfonyl group, such as benzenesulfonyl, which is substituted or substituted with one or more substituents selected from the substituent group B alone or differently Group, p-toluenesulfonyl group and the like.
  • Bx is preferably a purin-9-yl group or a 2-oxo-pyrimidin-1-yl group.
  • the purin-9-yl group and the 2-oxo-pyrimidin-1-yl group may be unsubstituted, alone or differently from the group consisting of halogen atoms, C1-6 alkyl groups, amino groups, hydroxy groups and sulfanyl groups. It may be substituted with one or more selected substituents.
  • the amino group may be unsubstituted or may be substituted with an amino group protecting group.
  • the hydroxy group may be unsubstituted or substituted with a hydroxy protecting group.
  • the sulfanyl group may be unsubstituted or substituted with a sulfanyl group protecting group. Specific examples include the following.
  • Z 2 is preferably a hydroxy protecting group as an intermediate. Therefore, the hydroxy protecting group is not limited as long as it can stably protect the hydroxy group during nucleic acid synthesis, and the type and structure of the protecting group are the same or different in each artificial nucleotide and artificial nucleoside. May be.
  • the hydroxy protecting group is preferably an acetyl group, a tert-butyl group, a tert-butoxymethyl group, a methoxymethyl group, a tetrahydropyranyl group, 1-ethoxyethyl.
  • R 2 and R 3 each independently represents a hydrogen atom, a halogen atom, a cyano group, a C 1-6 alkyl group or a C 2-6 alkenyl group.
  • the C1-6 alkyl group and the C2-6 alkenyl group are unsubstituted, or one or more substituents selected from the group consisting of a halogen atom, a C1-6 alkoxy group, and a cyano group, alone or differently.
  • R 2 is preferably a hydrogen atom or a C1-3 alkyl group, more preferably a hydrogen atom.
  • R 3 is preferably a hydrogen atom or a C1-3 alkyl group, more preferably a hydrogen atom.
  • the phosphate ester moiety is a group represented by the formula: —OP ( ⁇ O) (OH) 2 or a modification group thereof.
  • the modifying group one or more of —O— and ⁇ O of the phosphate ester moiety may be substituted with a sulfur atom or —N (R X ) —, and one or more of OH is a hydrogen atom, —SH , —N (R X ) 2 , or an alkyl group.
  • R X is a hydrogen atom or an amino group protecting group.
  • the 5 ′ and / or 3 ′ end groups may each independently contain a substituted or unsubstituted 1 to 3 phosphate ester moiety.
  • modifications include, for example, 2′-O-methylation, 2′MOE (2′-O—CH 2 —CH 2 —O—CH 3 ), 2′-O-aminopropyl (AP), Examples thereof include 2′-fluorination and 2′-O-methylcarbamoylethyl (MCE).
  • Modifications with 4′-CH 2 —O-2 ′ LNA, Locked Nucleic Acid), AmNA (Amide BNA) (Bridged Nucleic Acid, see WO2011 / 052436) and the like can be mentioned.
  • One or more hydrogen, carbon and / or other atoms of the artificial oligonucleotide can be replaced with isotopes of hydrogen, carbon and / or other atoms, respectively.
  • isotopes, preparation methods, and the like are the same as those of the above-described artificial nucleosides and artificial nucleotides.
  • the artificial oligonucleotide of this embodiment contains a pharmaceutically acceptable salt thereof. Specific examples of the salt are the same as those in the above-described artificial nucleoside and artificial nucleotide.
  • Step I Protection reaction Compound B can be obtained by protecting the hydroxy groups at the 3′-position and 5′-position of compound A with a hydroxy-protecting group by a protection reaction known to those skilled in the art.
  • P 1 and P 2 of Compound B may be the same or different.
  • compound B can be obtained by simultaneous protection in one reaction.
  • P 1 and P 2 are different, the difference between the 3′-position and the 5′-position is used to introduce either P 1 or P 2 first , and then the other one. By introducing the compound B, the compound B can be obtained.
  • protection reactions known to those skilled in the art reference can be made to the Protective Groups in Organic Synthesis 4th edition.
  • Step IV 5′-position protection reaction
  • Compound E can be obtained by selectively protecting the hydroxy group at the 5′-position of compound D with a hydroxy-protecting group by a protection reaction known to those skilled in the art. It is known to those skilled in the art that the selective protection reaction of the 5′-hydroxy group can generally be achieved by utilizing a bulky protecting group.
  • protection reaction known to those skilled in the art reference can be made to the Protective Groups in Organic Synthesis 4th edition.
  • An example of the 5′-position protection reaction is a method of reacting with various triarylmethyl halides in the presence of a base in a solvent.
  • MS was measured by ESI (electrospray ionization) method under the following condition 1 unless otherwise specified.
  • ESI + means ESI positive ion mode
  • ESI ⁇ means ESI negative ion mode.
  • Condition 1 Device: AB SCIEX TripleTOF 5600
  • Eluent composition The mixture ratio of acetonitrile and water was linearly changed to 98/2 in 12 minutes after the start of measurement at 2/98. Thereafter, the mixing ratio of acetonitrile and water was fixed at 98/2 for 3 minutes.
  • Flow rate 0.3 mL / min
  • Detection wavelength 254 nm
  • Step 3 Synthesis of Compound 4 Under a nitrogen atmosphere, a tetrahydrofuran solution (5 mL) of compound 3 (130 mg, 0.24 mmol) was added to a tetrahydrofuran (THF) solution (0.8 ml, 0.8 mmol) of 1M tetrabutylammonium fluoride (TBAF). ) was added and stirred for 2 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • THF tetrahydrofuran
  • Step 2 Synthesis of Compound 12 Under a nitrogen atmosphere, Compound 11 (40 mg, 0.076 mmol) and 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane 2,4-disulfide (50 mg 0.13 mmol) was added toluene (8 mL), and the mixture was stirred at 90 ° C. for 30 minutes. The reaction mixture was concentrated, and the resulting crude product was purified by silica gel chromatography to give compound 12 (38 mg, 91%) as a white solid.
  • Step 1 Synthesis of Compound 16
  • Compound 15 (synthesized according to the method described in International Publication No. 2014/109384) (30 mg, 54.5 ⁇ mol), 2,4-bis (4-methoxyphenyl)-under nitrogen atmosphere
  • Toluene (4 mL) was added to 1,3-dithia-2,4-diphosphetane 2,4-disulfide (200 mg, 520.0 ⁇ mol), and the mixture was stirred at 90 ° C. for 30 minutes.
  • the reaction mixture was concentrated, and the resulting crude product was purified by silica gel chromatography to give compound 15 (10 mg, 32%) as a white solid.
  • Oligonucleotides prepared from the nucleoside analogs or nucleotide analogs of the present invention exhibit excellent binding affinity for single-stranded RNA and nuclease resistance. Therefore, since the oligonucleotide is considered to have very good persistence in the body, the nucleoside analog or nucleotide analog of the present invention is very useful as a material for synthesizing nucleic acid pharmaceuticals such as antisense oligonucleotides. Useful.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un nucléoside artificiel, ou un nucléotide artificiel, qui est un composé représenté par la formule (I) ou un sel de celui-ci. Dans la formule (I), Bx représente une base pyrimidine, une base thioxypyrimidine, ou une base purine, R1, R2, R3 et R4 représentent des atomes d'hydrogène, des groupes alkyles C1-6 et analogues, Z1 et Z2 représentent des atomes d'hydrogène, des groupes protecteurs de groupe hydroxyle, des groupes contenant du phosphore et analogues.
PCT/JP2016/071637 2015-07-24 2016-07-22 Nucléoside artificiel, nucléotide artificiel et oligonucléotide artificiel WO2017018360A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015-146682 2015-07-24
JP2015146682A JP2018140938A (ja) 2015-07-24 2015-07-24 人工ヌクレオシド及び人工ヌクレオチド並びに人工オリゴヌクレオチド

Publications (1)

Publication Number Publication Date
WO2017018360A1 true WO2017018360A1 (fr) 2017-02-02

Family

ID=57884687

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/071637 WO2017018360A1 (fr) 2015-07-24 2016-07-22 Nucléoside artificiel, nucléotide artificiel et oligonucléotide artificiel

Country Status (3)

Country Link
JP (1) JP2018140938A (fr)
TW (1) TW201718617A (fr)
WO (1) WO2017018360A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019142897A1 (fr) * 2018-01-22 2019-07-25 三菱瓦斯化学株式会社 Composé, résine, composition et procédé de formation de motif
EP3587432A4 (fr) * 2017-02-21 2021-01-06 Osaka University Composé d'acide nucléique et oligonucléotide
WO2021216785A1 (fr) 2020-04-21 2021-10-28 Flagship Pioneering, Inc. Molécules bifonctionnelles et leurs procédés d'utilisation

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039352A1 (fr) * 1997-03-07 1998-09-11 Takeshi Imanishi Nouveaux analogues de bicyclonucleoside et d'oligonucleotide
WO2011052436A1 (fr) * 2009-10-29 2011-05-05 国立大学法人大阪大学 Nucléoside et nucléotide artificiels pontés
WO2011085102A1 (fr) * 2010-01-11 2011-07-14 Isis Pharmaceuticals, Inc. Nucléosides bicycliques à base modifiée et composés oligomères préparés à partir de ceux-ci
WO2011156202A1 (fr) * 2010-06-08 2011-12-15 Isis Pharmaceuticals, Inc. 2'‑amino- et 2'‑thio-nucléosides bicycliques substitués et composés oligomères préparés à partir de ces derniers
WO2014112463A1 (fr) * 2013-01-15 2014-07-24 国立大学法人大阪大学 Nucléoside et nucléotide ayant une structure de sulfonamide

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039352A1 (fr) * 1997-03-07 1998-09-11 Takeshi Imanishi Nouveaux analogues de bicyclonucleoside et d'oligonucleotide
WO2011052436A1 (fr) * 2009-10-29 2011-05-05 国立大学法人大阪大学 Nucléoside et nucléotide artificiels pontés
WO2011085102A1 (fr) * 2010-01-11 2011-07-14 Isis Pharmaceuticals, Inc. Nucléosides bicycliques à base modifiée et composés oligomères préparés à partir de ceux-ci
WO2011156202A1 (fr) * 2010-06-08 2011-12-15 Isis Pharmaceuticals, Inc. 2'‑amino- et 2'‑thio-nucléosides bicycliques substitués et composés oligomères préparés à partir de ces derniers
WO2014112463A1 (fr) * 2013-01-15 2014-07-24 国立大学法人大阪大学 Nucléoside et nucléotide ayant une structure de sulfonamide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KUMAR RAVINDRA ET AL.: "The first analogues of LNA (locked nucleic acids): Phosphorothioate- LNA and 2'-thio-LNA", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 8, 1998, pages 22 19 - 2222, XP004137249, ISSN: 0960-894X *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3587432A4 (fr) * 2017-02-21 2021-01-06 Osaka University Composé d'acide nucléique et oligonucléotide
US11286275B2 (en) 2017-02-21 2022-03-29 Osaka University Nucleic acid compound and oligonucleotide
US11905308B2 (en) 2017-02-21 2024-02-20 Osaka University Nucleic acid compound and oligonucleotide
WO2019142897A1 (fr) * 2018-01-22 2019-07-25 三菱瓦斯化学株式会社 Composé, résine, composition et procédé de formation de motif
JPWO2019142897A1 (ja) * 2018-01-22 2021-02-25 三菱瓦斯化学株式会社 化合物、樹脂、組成物及びパターン形成方法
JP7290114B2 (ja) 2018-01-22 2023-06-13 三菱瓦斯化学株式会社 化合物、樹脂、組成物及びパターン形成方法
WO2021216785A1 (fr) 2020-04-21 2021-10-28 Flagship Pioneering, Inc. Molécules bifonctionnelles et leurs procédés d'utilisation

Also Published As

Publication number Publication date
JP2018140938A (ja) 2018-09-13
TW201718617A (zh) 2017-06-01

Similar Documents

Publication Publication Date Title
US7427672B2 (en) Artificial nucleic acids of n-o bond crosslinkage type
JP6292631B2 (ja) 含窒素複素環構造を有するヌクレオシド及びヌクレオチド
JP4151751B2 (ja) 新規ビシクロヌクレオシド類縁体
JP5030998B2 (ja) ヌクレオシド類縁体およびそのヌクレオチド類縁体を含むオリゴヌクレオチド誘導体
WO2011052436A1 (fr) Nucléoside et nucléotide artificiels pontés
WO2014112463A1 (fr) Nucléoside et nucléotide ayant une structure de sulfonamide
JP7085739B2 (ja) 人工ヌクレオシド及び人工ヌクレオチド並びに人工オリゴヌクレオチド
WO2017018360A1 (fr) Nucléoside artificiel, nucléotide artificiel et oligonucléotide artificiel
US20230340008A1 (en) Bridged nucleoside and nucleotide using same
JP2023110119A (ja) ５’位修飾ヌクレオシドおよびそれを用いたヌクレオチド
JP4255227B2 (ja) Ｎ３’−ｐ５’結合を有する２’，４’−ｂｎａオリゴヌクレオチド
US20230322840A1 (en) Bridged nucleoside and nucleotide
JP7650412B2 (ja) ５′位修飾ヌクレオシドおよびそれを用いたヌクレオチド
JP2019119739A (ja) ヌクレオシド誘導体の製造方法
JP7678994B2 (ja) 架橋型ヌクレオシドおよびそれを用いたヌクレオチド
US20230124641A1 (en) Cross-linked nucleoside and nucleotide using same
WO2024101446A1 (fr) Nucléoside modifié ayant une structure guanidino dans une partie pontée et méthode de production d'oligonucléotide l'utilisant
JP2016149940A (ja) 新規なヌクレオチド類縁体及びオリゴヌクレオチド類縁体
JPWO2003068794A1 (ja) 核酸糖部をｓ型に束縛したヌクレオシド類縁体およびそのヌクレオチド類縁体を含むオリゴヌクレオチド誘導体

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16830465

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: JP

122 Ep: pct application non-entry in european phase

Ref document number: 16830465

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载