ES2234563T5 - Nuevos análogos de nucleósidos y oligonucleótidos - Google Patents

Nuevos análogos de nucleósidos y oligonucleótidos Download PDF

Info

Publication number
ES2234563T5
ES2234563T5 ES00902887.9T ES00902887T ES2234563T5 ES 2234563 T5 ES2234563 T5 ES 2234563T5 ES 00902887 T ES00902887 T ES 00902887T ES 2234563 T5 ES2234563 T5 ES 2234563T5
Authority
ES
Spain
Prior art keywords
group
carbon atoms
nhbz
substituted
compound
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
ES00902887.9T
Other languages
English (en)
Other versions
ES2234563T3 (es
Inventor
Masakatsu Kaneko
Koji Morita
Takeshi Imanishi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mitsubishi Chemical Foods Corp
Daiichi Sankyo Co Ltd
Original Assignee
Mitsubishi Chemical Foods Corp
Daiichi Sankyo Co Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=12398349&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2234563(T5) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Mitsubishi Chemical Foods Corp, Daiichi Sankyo Co Ltd filed Critical Mitsubishi Chemical Foods Corp
Publication of ES2234563T3 publication Critical patent/ES2234563T3/es
Application granted granted Critical
Publication of ES2234563T5 publication Critical patent/ES2234563T5/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • 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
    • 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
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • 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
    • 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
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Pulmonology (AREA)
  • AIDS & HIV (AREA)
  • Physics & Mathematics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
(continuación)
Ej. del comp. núm.
A R1 R2 R3a R4a
1-6
CH2 H H OH OH
1-7
CH2 H H NH2 H
1-8
CH2 H H NH2 NH2
1-9
CH2 H H NH2 Cl
1-10
CH2 H H NH2 F
1-11
CH2 H H NH2 Br
1-12
CH2 H H NH2 OH
1-13
CH2 H H OMe H
1-14
CH2 H H OMe OMe
1-15
CH2 H H OMe NH2
1-16
CH2 H H Cl H
1-17
CH2 H H Br H
1-18
CH2 H H F H
1-19
CH2 H H Cl Cl
1-20
CH2 H H SH H
1-21
CH2 Bn H NHBz H
1-22
CH2 Bn H OH NHCOCH(CH3)2
1-23
CH2 Bn Bn NHBz H
1-24
CH2 Bn Bn OH NHCOCH(CH3)2
1-25
CH2 PMB H NHBz H
1-26
CH2 PMB H OH NHCOCH(CH3)2
1-27
CH2 PMB PMB NHBz H
1-28
CH2 PMB PMB OH NHCOCH(CH3)2
1-29
CH2 Tr H NHBz H
1-30
CH2 MMTr H NHBz H
1-31
CH2 DMTr H NHBz H
1-32
CH2 TMTr H NHBz H
1-33
CH2 Tr H OH NHCOCH(CH3)2
1-34
CH2 MMTr H OH NHCOCH(CH3)2
1-35
CH2 DMTr H OH NHCOCH(CH3)2
1-36
CH2 TMTr H OH NHCOCH(CH3)2
1-37
CH2 TMS H NHBz H
1-38
CH2 TBDMS H NHBz H
1-39
CH2 TBDPS H NHBz H
1-40
CH2 TIPS H NHBz H
1-41
CH2 TMS H OH NHCOCH(CH3)2
1-42
CH2 TBDMS H OH NHCOCH(CH3)2
1-43
CH2 TBDPS H OH NHCOCH(CH3)2
1-44
CH2 TIPS H OH NHCOCH(CH3)2
1-177
CH2 H H OH NHCOCH(CH3)2
1-178
CH2 H H NHBz H
1-185
CH2 DMTr P(N(iPr)2)(OC2H4CN) OH NHCOCH(CH3)2
1-186
CH2 DMTr P(N(iPr)2)(OC2H4CN) NHBz H
9
(continuación)
imagen8
[Tabla 2]
Ej. del comp. núm.
A R1 R2 R5 R6
2-1
CH2 H H OH H
2-2
CH2 H H OH CH3
2-3
CH2 H H NH2 H
2-4
CH2 H H NH2 CH3
2-5
CH2 H H NH2 F
2-6
CH2 H H Cl H
2-7
CH2 H H OMe H
2-8
CH2 H H SH H
2-9
CH2 Bn H OH H
2-10
CH2 Bn Bn OH H
2-11
CH2 PMB H OH H
2-12
CH2 PMB PMB OH H
2-13
CH2 Tr H OH H
2-14
CH2 MMTr H OH H
2-15
CH2 DMTr H OH H
2-16
CH2 TMTr H OH H
2-17
CH2 TMS H OH H
2-18
CH2 TBDMS H OH H
2-19
CH2 TBDPS H OH H
2-20
CH2 TIPS H OH H
2-21
CH2 Bn H OH CH3
2-22
CH2 Bn Bn OH CH3
2-23
CH2 PMB H OH CH3
2-24
CH2 PMB PMB OH CH3
2-25
CH2 Tr H OH CH3
2-26
CH2 MMTr H OH CH3
2-27
CH2 DMTr H OH CH3
2-28
CH2 TMTr H OH CH3
2-29
CH2 TMS H OH CH3
10
(continuación)
Ej. del comp. núm.
A R1 R2 R5 R6
2-30
CH2 TBDMS H OH CH3
2-31
CH2 TBDPS H OH CH3
2-32
CH2 TIPS H OH CH3
2-33
CH2 Bn H NHBz H
2-34
CH2 Bn Bn NHBz H
2-35
CH2 PMB H NHBz H
2-36
CH2 PMB PMB NHBz H
2-37
CH2 Tr H NHBz H
2-38
CH2 MMTr H NHBz H
2-39
CH2 DMTr H NHBz H
2-40
CH2 TMTr H NHBz H
2-41
CH2 TMS H NHBz H
2-42
CH2 TBDMS H NHBz H
2-43
CH2 TBDPS H NHBz H
2-44
CH2 TIPS H NHBz H
2-45
CH2 Bn H NHBz CH3
2-46
CH2 Bn Bn NHBz CH3
2-47
CH2 PMB H NHBz CH3
2-48
CH2 PMB PMB NHBz CH3
2-49
CH2 Tr H NHBz CH3
2-50
CH2 MMTr H NHBz CH3
2-51
CH2 DMTr H NHBz CH3
2-52
CH2 TMTr H NHBz CH3
2-53
CH2 TMS H NHBz CH3
2-54
CH2 TBDMS H NHBz CH3
2-55
CH2 TBDPS H NHBz CH3
2-56
CH2 TIPS H NHBz CH3
2-225
CH2 H H NHBz H
2-226
CH2 H H NHBz CH3
2-233
CH2 DMTr P(N(iPr)2)(OC2H4CN) OH H
2-234
CH2 DMTr P(N(iPr)2)(OC2H4CN) OH CH3
2-235
CH2 DMTr P(N(iPr)2)(OC2H4CN) NHBz H
2-236
CH2 DMTr P(N(iPr)2)(OC2H4CN) NHBz CH3
2-249
CH2 DMTr P(N(iPr)2)(OCH3) OH H
2-250
CH2 DMTr P(N(iPr)2)(OCH3) OH CH3
2-251
CH2 DMTr P(N(iPr)2)(OCH3) NHBz H
2-252
CH2 DMTr P(N(iPr)2)(OCH3) NHBz CH3
En la Tabla 1 y Tabla 2 anteriores, los compuestos preferidos incluyen los compuestos (1-5), (1-7), (1-23), (1-24), (131), (1-35), (1-39), (1-43), (1-177), (1-178), (1-185), (1-186), (1-193), (1-194), (1-201), (1-202), (2-1), (2-2), (2-3), (24), (2-10), (2-15), (2-19), (2-22), (2-27), (2-31), (2-34), (2-39), (2-43), (2-46), (2-51), (2-55), (2-225), (2-226), (2-233), (2-234), (2-235) o (2-236), los compuestos que se prefieren más pueden incluir 2'-O,4'-C-etilenguanosina (1-5), 2'-O,4'-C-etilenadenosina (1-7), 3',5'-di-O-bencil-2'-O,4'-C-etilen-6-N-benzoiladenosina (1-23), 3',5'-di-O-bencil-2'-O,4'-C-etilen-2-N-isobutirilguanosina (1-24),
11 5
10
15
20
25
30
5'-O-dimetoxitritil-2'-O,4'-C-etilen-6-N-benzoiladenosina (1-31), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-2-N-isobutirilguanosina (1-35), 2'-O,4'-C-etilen-2-N-isobutirilguanosina (1-177), 2'-O,4'-C-etilen-6-N-benzoiladenosina (1-178), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-2-N-isobutirilguanosina-3'-O-(2-cianoetil N,N-diisopropilo)fosforamidita (1-185), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-6-N-benzoiladenosina-3'-O-(2-cianoetil N,N-diisopropilo)fosforamidita (1-186), 2'-O,4'-C-etilenuridina (2-1), 2'-O,4'-C-etilen-5-metiluridina (2-2), 2'-O,4'-C-etilencitidina (2-3), 2'-O,4'-C-etilen-5-metilcitidina (2-4), 3',5'-di-O-bencil-2'-O,4'-C-etilenuridina (2-10), 5'-O-dimetoxitritil-2'-O,4'-C-etilenuridina (2-15), 3',5'-di-O-bencil-2'-O,4'-C-etilen-5-metiluridina (2-22), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-5-metiluridina (2-27), 3',5'-di-O-bencil-2'-O,4'-C-etilen-4-N-benzoilcitidina (2-34), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-4-N-benzoilcitidina (2-39), 3',5'-di-O-bencil-2'-O,4'-C-etilen-4-N-benzoil-5-metilcitidina (2-46), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-4-N-benzoil-5-metilcitidina (2-51), 2'-O,4'-C-etilen-4-N-benzoilcitidina (2-225), 2'-O,4'-C-etilen-4-N-benzoil-5-metilcitidina (2-226), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-uridina-3'-O-(2-cianoetil N,N-diisopropilo)fosforamidita (2-233), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-5-metiluridina-3'-O-(2-cianoetil N,N-diisopropilo)fosforamidita (2-234), 5'-O-dimetoxitritil-2'-O,4'-C-etilen-4-N-benzoilcitidina-3'-O-(2-cianoetil N,N-diisopropilo)fosforamidita (2-235), y 5'-O-dimetoxitritil-2'-O,4'-C-etilen-4-N-benzoil-5-metilcitidina-3'-O-(2-cianoetil N,N-diisopropilo)fosforamidita (2-236).
El compuesto (1) de la presente invención se puede producir de acuerdo con el Procedimiento A que se describe a continuación.
imagen9
En el Procedimiento A, X representa un grupo protector; Y representa un grupo protector; A tiene el mismo significado tal y como se ha definido anteriormente; mientras B1 representa un grupo purin-9-ilo, un grupo purin-9-ilo sustituido o un grupo 2-oxo-pirimidin-1-ilo sustituido, dichos sustituyentes se seleccionan entre R3 y R4 anteriores pero con la exclusión de un grupo amino desprotegido de "un grupo amino que se puede proteger"; mientras B2 representa un grupo purin-9-ilo, un grupo purin-9-ilo sustituido o un grupo 2-oxo-pirimidin-1-ilo sustituido, dichos sustituyentes se eligen entre R3 y R4 anteriores pero con la exclusión de los grupos aminos protegidos de "un grupo amino que se puede proteger"; R7 representa un grupo que forma un grupo saliente; y R8 representa un grupo acilo
12
imagen10
imagen11
imagen12
imagen13
El tiempo de reacción es desde 0 ºC hasta 50 ºC, se prefiere desde 10 ºC hasta 40 ºC.
El tiempo de reacción es desde 10 minutos hasta 24 horas, se prefiere desde 10 minutos hasta 15 horas. Después de la reacción, se obtiene el compuesto deseado (1c) de la presente reacción, por ejemplo, mediante la concentración de la mezcla de reacción, la adición de un solvente orgánico inmiscible con agua tal como acetato de
5 etilo, el lavado con agua, la separación de una fase orgánica que contiene el compuesto deseado, el secado sobre sulfato de magnesio anhídrido y la eliminación por destilación del solvente.
El producto deseado obtenido de este modo se puede purificar más, si es necesario, mediante un procedimiento convencional, por ejemplo, recristalización, y cromatografía de columna de gel de sílice y similares.
El intermediario (3) descrito anteriormente se puede preparar mediante los Procedimientos del B al D que se 10 describen a continuación.
imagen14
En los Procedimientos B y C, X e Y tienen el mismo significado tal y como se ha definido anteriormente; R9 representa un grupo que forma un grupo saliente.
15 El grupo que forma el grupo saliente de R9 puede incluir el grupo descrito en R7 anterior, preferentemente un grupo trifluorometansulfonilo.
17
imagen15
5
10
15
20
25
30
35
40
45
50
(Etapa B-3)
La presente etapa consiste en preparar el compuesto (10) mediante la reacción del compuesto (9) preparado en la Etapa B-2 con un agente reductor en un solvente inerte.
El solvente que se puede utilizar en el presente documento puede incluir hidrocarburos halogenados tales como cloruro de metileno, cloroformo, 1,2-dicloroetano o tetracloruro de carbono; hidrocarburos alifáticos tales como hexano, heptano, ligroína y éter de petróleo; hidrocarburos aromáticos tales como benceno, tolueno y xileno; éteres tales como éter de dietilo, éter de diisopropilo, tetrahidrofurano, dioxano, dimetoxietano y dimetiléter de dietilenglicol; y cetonas tales como acetona, metiletilcetona, metilisobutilcetona isoforona y ciclohexanona; preferentemente hidrocarburos halogenados (en particular cloruro de metileno).
El agente reductor que se puede utilizar en el presente documento puede incluir hidruro de diisobutilaluminio e hidruro de trietoxialuminio, preferentemente hidruro de diisobutilaluminio.
La temperatura de reacción varía dependiendo del material de partida, el solvente y el agente reductor, pero por lo general es desde -100 ºC hasta -50 ºC, preferentemente desde -90 ºC hasta -70 ºC.
El tiempo de reacción varía dependiendo del material de partida, el solvente, el agente reductor y el tiempo de reacción, pero por lo general es desde 30 minutos hasta 12 horas, preferentemente desde 1 hora hasta 5 horas.
Después de la reacción, se obtiene el compuesto deseado (10) de la presente reacción, por ejemplo, mediante la concentración de la mezcla de reacción, la adición de un solvente orgánico inmiscible con agua tal como acetato de etilo, el lavado con agua, la separación de una fase orgánica que contiene el compuesto deseado, el secado sobre sulfato de magnesio anhídrido y la eliminación por destilación del solvente.
El producto deseado obtenido se puede purificar más, si es necesario, mediante un procedimiento convencional, por ejemplo, recristalización, y cromatografía de columna de gel de sílice y similares.
(Etapa B-4)
La presente etapa consiste en preparar el compuesto (3a), uno de los materiales de partida del Procedimiento A mediante la reacción del compuesto (10) preparado en la Etapa B-3 con un agente reductor en un solvente inerte.
El solvente que se puede utilizar en el presente documento puede incluir alcoholes tales como metanol, etanol, npropanol, isopropanol, n-butanol, isobutanol, t-butanol, alcohol isoamílico, dietilenglicol, glicerina, octanol, ciclohexanol y etilglicol de metilo; y ácido acético; preferentemente alcoholes (en particular etanol).
El agente reductor que se puede utilizar en el presente documento puede incluir hidroboruros de metal alcalino tales como hidroboruro de sodio y hidroboruro de litio; compuestos de hidruro de aluminio tales como hidruro de aluminio litio e hidruro de trietóxido de aluminio litio; y borano; preferentemente hidroboruro de sodio.
La temperatura de reacción varía dependiendo del material de partida, el solvente y el agente reductor pero por lo general es desde 0 ºC hasta 50 ºC, preferentemente desde 10 ºC hasta 40 ºC.
El tiempo de reacción varía dependiendo del material de partida, el solvente, el agente reductor y el tiempo de reacción, pero por lo general es desde 10 minutos hasta 12 horas, preferentemente desde 30 minutos hasta 5 horas.
Después de la reacción, se obtiene el compuesto deseado (3a) de la presente reacción, por ejemplo, mediante la descomposición del agente reductor, la concentración de la mezcla de reacción, la adición de un solvente orgánico inmiscible con agua tal como acetato de etilo, el lavado con agua, la separación de una fase orgánica que contiene el compuesto deseado, el secado sobre sulfato de magnesio anhídrido y la eliminación por destilación del solvente.
El producto deseado obtenido de este modo se puede purificar más, si es necesario, mediante un procedimiento convencional, por ejemplo, recristalización, y cromatografía de columna de gel de sílice y similares.
(Procedimiento C)
(Etapa C-1)
La presente etapa consiste en preparar el compuesto (11) mediante la reacción del compuesto (7) preparado en el procedimiento anterior con un agente oxidante en un solvente inerte.
El solvente que se puede utilizar en el presente documento puede incluir hidrocarburos alifáticos tales como hexano, heptano, ligroína y éter de petróleo; hidrocarburos aromáticos tales como benceno, tolueno y xileno; hidrocarburos halogenados tales como cloruro de metileno, cloroformo, tetracloruro de carbono, dicloroetano, clorobenceno y diclorobenceno; ésteres tales como formato de etilo, acetato de etilo, acetato de propilo, acetato de butilo y carbonato de dietilo; éteres tales como éter de dietilo, éter de diisopropilo, tetrahidrofurano, dioxano, dimetoxietano, dimetileter de dietilenglicol; y cetonas tales como acetona, metiletilcetona, metilisobutilcetona, isoforona y
19 5
10
15
20
25
30
35
40
45
50
ciclohexanona; preferentemente hidrocarburos halogenados (en particular el cloruro de metileno).
El agente oxidante que se puede utilizar en el presente documento puede incluir el reactivo de Swern para la oxidación, el reactivo de Dess-Martin para la oxidación, un complejo de trióxido de cromo tal como complejo de hidrocloruro de piridina/trióxido de cromo (clorocromato de piridina y dicromato de piridina), preferentemente el reactivo de Swern para la oxidación (principalmente, sulfóxido de dimetilo/cloruro de oxalilo).
La temperatura de reacción varía dependiendo del material de partida, el solvente y el agente oxidante, pero por lo general es desde -100 ºC hasta -50 ºC, preferentemente desde -100 ºC hasta -70 ºC.
El tiempo de reacción varía dependiendo del material de partida, el solvente, el agente oxidante y el tiempo de reacción, pero por lo general es desde 30 minutos hasta 12 horas, preferentemente desde 1 hora hasta 5 horas.
Después de la reacción, se obtiene el compuesto deseado (11) de la presente reacción, por ejemplo, mediante la descomposición del agente oxidante, la concentración de la mezcla de reacción, la adición de un solvente orgánico inmiscible con agua tal como acetato de etilo, el lavado con agua, la separación de una fase orgánica que contiene el compuesto deseado, el secado sobre sulfato de magnesio anhídrido y la eliminación por destilación del solvente.
El producto deseado obtenido de este modo se puede purificar más, si es necesario, mediante un procedimiento convencional, por ejemplo, la recristalización, y la cromatografía de columna de gel de sílice y similares.
(Etapa C-2)
La presente etapa consiste en preparar el compuesto (12) mediante la reacción del compuesto (11) preparado en la Etapa C-1 con un reactivo aumentador de carbono en un solvente inerte.
El solvente que se puede utilizar en el presente documento puede incluir hidrocarburos alifáticos tal como hexano, heptano, ligroína y éter de petróleo; hidrocarburos aromáticos tales como benceno, tolueno y xileno; hidrocarburos halogenados tales como cloruro de metileno, cloroformo, tetracloruro de carbono, dicloroetano, clorobenceno y diclorobenceno; ésteres tales como formato de etilo, acetato de etilo, acetato de propilo, acetato de butilo y carbonato de dietilo; éteres tales como éter de dietilo, éter de diisopropilo, tetrahidrofuran, dioxano, dimetoxietano, dimetiléter de dietilenglicol; y cetonas tales como acetona, metiletilcetona, metilisobutilcetona, isoforona y ciclohexanona; preferentemente hidrocarburos halogenados (en particular el cloruro de metileno).
El reactivo que se puede utilizar en el presente documento puede incluir el reactivo de Wittig, el reactivo de Horner-Emmons, el reactivo de la reacción de Peterson, el agente de reacción del sistema TiCl4-CH2Cl2-Zn y el reactivo de Tebbe, preferentemente el reactivo de Wittig, el reactivo de Horner-Emmons y el reactivo de Tebbe.
La temperatura de reacción varía dependiendo del material de partida, el solvente y el reactivo aumentador de carbono, pero por lo general es desde -20 ºC hasta 20 ºC, preferentemente 0 ºC.
El tiempo de reacción varía dependiendo del material de partida, el solvente, el reactivo aumentador de carbono y el tiempo de reacción, pero por lo general es desde 30 minutos hasta 12 horas, preferentemente desde 1 hora hasta 5 horas.
Después de la reacción, se obtiene el compuesto deseado (12) de la presente reacción, por ejemplo, mediante la concentración de la mezcla de reacción, la adición de un solvente orgánico inmiscible con agua tal como acetato de etilo, el lavado con agua, la separación de una fase orgánica que contiene el compuesto deseado, el secado sobre sulfato de magnesio anhídrido y la eliminación por destilación del solvente.
El producto deseado obtenido de este modo se puede purificar más, si es necesario, mediante un procedimiento convencional, por ejemplo, la recristalización, y la cromatografía de columna de gel de sílice y similares.
(Etapa C-3)
La presente etapa consiste en preparar el compuesto (3a) mediante la introducción selectiva de un grupo hidroxilo a un carbono terminal de un compuesto de olefina (12) preparado en la Etapa C-2 en un solvente inerte.
El solvente que se puede utilizar en el presente documento puede incluir hidrocarburos alifáticos tales como hexano, heptano, ligroína y éter de petróleo; hidrocarburos aromáticos tales como benceno, tolueno y xileno; hidrocarburos halogenados tales como cloruro de metileno, cloroformo, tetracloruro de carbono, dicloroetano, clorobenceno y diclorobenceno; ésteres tales como formato de etilo, acetato de etilo, acetato de propilo, acetato de butilo y carbonato de dietilo; éteres tales como éter de dietilo, éter de diisopropilo, tetrahidrofurano, dioxano, dimetoxietano y dimetiléter de dietilenglicol; y cetonas tales como acetona, metiletilcetona, metilisobutilcetona, isoforona y ciclohexanona; preferentemente éteres (en particular tetrahidrofurano).
El reactivo de la reacción que se puede utilizar en el presente documento puede incluir borano, disiamilo borano, texil borano, 9-BBN (9-borabiciclo[3.3.1]nonano), preferentemente 9-BBN.
20
imagen16
imagen17
imagen18
imagen19
imagen20
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32

Claims (1)

  1. imagen1
    imagen2
    imagen3
ES00902887.9T 1999-02-12 2000-02-10 Nuevos análogos de nucleósidos y oligonucleótidos Expired - Lifetime ES2234563T5 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP3386399 1999-02-12
JP3386399 1999-02-12
PCT/JP2000/000725 WO2000047599A1 (fr) 1999-02-12 2000-02-10 Nouveaux analogues de nucleosides et d'oligonucleotides

Publications (2)

Publication Number Publication Date
ES2234563T3 ES2234563T3 (es) 2005-07-01
ES2234563T5 true ES2234563T5 (es) 2018-01-17

Family

ID=12398349

Family Applications (1)

Application Number Title Priority Date Filing Date
ES00902887.9T Expired - Lifetime ES2234563T5 (es) 1999-02-12 2000-02-10 Nuevos análogos de nucleósidos y oligonucleótidos

Country Status (26)

Country Link
US (4) US7335765B2 (es)
EP (1) EP1152009B2 (es)
JP (1) JP3420984B2 (es)
KR (1) KR100573231B1 (es)
CN (1) CN1273478C (es)
AT (1) ATE287897T2 (es)
AU (1) AU758956B2 (es)
BR (1) BRPI0008131B8 (es)
CA (1) CA2361318C (es)
CZ (1) CZ296576B6 (es)
DE (1) DE60017711T3 (es)
DK (1) DK1152009T4 (es)
ES (1) ES2234563T5 (es)
HK (1) HK1040084B (es)
HU (1) HU228398B1 (es)
ID (1) ID30093A (es)
IL (2) IL144338A0 (es)
NO (1) NO320441B1 (es)
NZ (1) NZ513402A (es)
PL (1) PL208245B1 (es)
PT (1) PT1152009E (es)
RU (1) RU2233844C2 (es)
TR (2) TR200604211T1 (es)
TW (1) TW513438B (es)
WO (1) WO2000047599A1 (es)
ZA (1) ZA200106544B (es)

Families Citing this family (449)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7119184B2 (en) * 1991-08-12 2006-10-10 Isis Pharmaceuticals, Inc. Oligonucleotides having A-DNA form and B-DNA form conformational geometry
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
JP4148662B2 (ja) * 2000-08-10 2008-09-10 第一三共株式会社 ヌクレオシド及びオリゴヌクレオチド類縁体を含有する核酸試薬及び医薬
JP4151751B2 (ja) * 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
WO2002028875A2 (en) * 2000-10-04 2002-04-11 Cureon A/S Improved synthesis of purine locked nucleic acid analogues
GB0114719D0 (en) * 2001-06-15 2001-08-08 Glaxo Group Ltd Compound
WO2003033696A1 (fr) * 2001-10-18 2003-04-24 Sankyo Company, Limited Compose antisens vegf
ES2431586T3 (es) * 2002-02-13 2013-11-27 Takeshi Imanishi Análogos de nucleósidos y derivado de oligonucleótido que comprende un análogo de nucleótido del mismo
US20040219565A1 (en) 2002-10-21 2004-11-04 Sakari Kauppinen Oligonucleotides useful for detecting and analyzing nucleic acids of interest
CA2504929C (en) 2002-11-05 2014-07-22 Charles Allerson Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
EP1562971B1 (en) 2002-11-05 2014-02-12 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2141233B1 (en) 2002-11-18 2016-10-19 Roche Innovation Center Copenhagen A/S Antisense design
AU2013201786B2 (en) * 2002-11-18 2015-04-02 Roche Innovation Center Copenhagen A/S Amino-LNA, thio-LNA and alpha-L-oxy-LN
JP5132025B2 (ja) * 2002-11-19 2013-01-30 第一三共株式会社 新規２’，５’−オリゴアデニル酸類縁体
TWI347948B (en) * 2002-11-19 2011-09-01 Sankyo Co Novel 2',5'-oligoadenylic acid compositions
EP2530153B1 (en) * 2002-11-25 2016-03-16 Masafumi Matsuo ENA nucleic acid drugs modifying splicing in mRNA precursor
ES2385828T3 (es) 2003-06-20 2012-08-01 Exiqon A/S Sondas, bibliotecas y kits para análisis de mezclas de ácidos nucleicos y procedimientos para construirlos
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
US7427672B2 (en) * 2003-08-28 2008-09-23 Takeshi Imanishi Artificial nucleic acids of n-o bond crosslinkage type
US20050053981A1 (en) * 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
US7480382B2 (en) * 2003-09-30 2009-01-20 Microsoft Corporation Image file container
GB0324854D0 (en) * 2003-10-24 2003-11-26 Expresson Biosystems Ltd App/ena antisense
DK1688493T3 (da) 2003-11-07 2008-11-17 Daiichi Sankyo Co Ltd Fremgangsmåde til detektering af genetisk polymorfisme
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
WO2005116207A1 (ja) * 2004-05-28 2005-12-08 Sankyo Company, Limited テロメラーゼ阻害ｅｎａオリゴヌクレオチド
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
US7884086B2 (en) 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
WO2006059507A1 (ja) * 2004-11-30 2006-06-08 Sankyo Company, Limited 11β-HSD1アンチセンス化合物
US20090264635A1 (en) 2005-03-25 2009-10-22 Applera Corporation Methods and compositions for depleting abundant rna transcripts
EP2338992A3 (en) 2005-08-29 2011-10-12 Regulus Therapeutics, Inc Antisense compounds having enhanced anti-microRNA activity
US9862770B2 (en) 2005-10-19 2018-01-09 Ibc Pharmaceuticals, Inc. Multivalent antibody complexes targeting IGF-1R show potent toxicity against solid tumors
US8883162B2 (en) * 2005-10-19 2014-11-11 Ibc Pharmaceuticals, Inc. Multivalent antibody complexes targeting IGF-1R show potent toxicity against solid tumors
US20100226884A1 (en) 2009-01-20 2010-09-09 Immunomedics, Inc. Novel Class of Monospecific and Bispecific Humanized Antibodies that Target the Insulin-like Growth Factor Type I Receptor (IGF-1R)
JP5623016B2 (ja) 2005-12-01 2014-11-12 プロネイ・セラピューティクス・インコーポレイテッドＰｒｏｎａｉｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． 癌治療法およびそれに用いる医薬組成物
AU2006323745B2 (en) * 2005-12-09 2012-11-22 Riken Method for replicating nucleic acids and novel unnatural base pairs
CN103301475B (zh) 2005-12-28 2016-08-03 斯克里普斯研究所 药物组合物和表达载体以及调节基因表达的方法和核酸分子的应用
EP2314594B1 (en) 2006-01-27 2014-07-23 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
CA2640058C (en) 2006-01-27 2018-04-24 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
KR101441700B1 (ko) 2006-05-05 2014-09-18 아이시스 파마수티컬즈 인코포레이티드 Ｐｃｓｋ９ 발현을 조절하는 화합물 및 방법
EP2527442A3 (en) 2006-05-05 2013-03-06 Isis Pharmaceuticals, Inc. Compounds and methods for modulating gene expression
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
ES2389737T3 (es) 2006-05-11 2012-10-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en 5'
JP5665317B2 (ja) 2006-10-18 2015-02-04 アイシス ファーマシューティカルズ， インコーポレーテッド アンチセンス化合物
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
MX2009005527A (es) * 2006-11-27 2009-06-08 Isis Pharmaceuticals Inc Metodos para el tratamiento de hipercolesterolemia.
US20100292301A1 (en) * 2007-02-28 2010-11-18 Elena Feinstein Novel sirna structures
AU2008260277C1 (en) 2007-05-30 2014-04-17 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
US8278426B2 (en) 2007-06-08 2012-10-02 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
EP2173358B1 (en) * 2007-06-22 2015-10-21 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
WO2009006478A2 (en) 2007-07-05 2009-01-08 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
CA2700953A1 (en) 2007-10-02 2009-04-09 Amgen Inc. Increasing erythropoietin using nucleic acids hybridizable to micro-rna and precursors thereof
CN103898110A (zh) * 2007-10-03 2014-07-02 夸克制药公司 新siRNA结构
US8546556B2 (en) * 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
WO2009074990A2 (en) * 2007-12-12 2009-06-18 Quark Pharmaceuticals, Inc. Rtp801l sirna compounds and methods of use thereof
US8614311B2 (en) 2007-12-12 2013-12-24 Quark Pharmaceuticals, Inc. RTP801L siRNA compounds and methods of use thereof
WO2009090639A2 (en) * 2008-01-15 2009-07-23 Quark Pharmaceuticals, Inc. Sirna compounds and methods of use thereof
WO2009100320A2 (en) 2008-02-07 2009-08-13 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
CN102016036B (zh) 2008-02-11 2015-04-08 阿克赛医药公司 经修饰的RNAi多核苷酸及其用途
US20110028531A1 (en) * 2008-03-20 2011-02-03 Elena Feinstein Novel sirna compounds for inhibiting rtp801
US9290534B2 (en) 2008-04-04 2016-03-22 Ionis Pharmaceuticals, Inc. Oligomeric compounds having at least one neutrally linked terminal bicyclic nucleoside
US8278287B2 (en) * 2008-04-15 2012-10-02 Quark Pharmaceuticals Inc. siRNA compounds for inhibiting NRF2
US8222221B2 (en) 2008-06-04 2012-07-17 The Board Of Regents Of The University Of Texas System Modulation of gene expression through endogenous small RNA targeting of gene promoters
WO2009147684A2 (en) 2008-06-06 2009-12-10 Quark Pharmaceuticals, Inc. Compositions and methods for treatment of ear disorders
TWI455944B (zh) 2008-07-01 2014-10-11 Daiichi Sankyo Co Ltd 雙股多核苷酸
WO2010008582A2 (en) 2008-07-18 2010-01-21 Rxi Pharmaceuticals Corporation Phagocytic cell drug delivery system
JP2011529686A (ja) 2008-07-29 2011-12-15 ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム ポリグルタミンタンパク質発現の選択的阻害
CN107083386A (zh) * 2008-08-25 2017-08-22 埃克斯雷德制药有限公司 阻止结缔组织生长因子的反义核苷酸及其用途
WO2010033247A2 (en) 2008-09-22 2010-03-25 Rxi Pharmaceuticals Corporation Reduced size self-delivering rnai compounds
US8501805B2 (en) 2008-09-24 2013-08-06 Isis Pharmaceuticals, Inc. Substituted alpha-L-bicyclic nucleosides
RU2604489C2 (ru) * 2008-10-03 2016-12-10 КьюРНА,Инк.,US Лечение заболеваний, связанных с аполипопротеином-а1, путем ингибирования природного антисмыслового транскрипта аполипопротеина-а1
WO2010059226A2 (en) 2008-11-19 2010-05-27 Rxi Pharmaceuticals Corporation Inhibition of map4k4 through rnai
CA2745329C (en) 2008-12-04 2022-07-12 Opko Curna, Llc Treatment of erythropoietin (epo) related diseases by inhibition of natural antisense transcript to epo
MX2011005912A (es) 2008-12-04 2011-06-17 Opko Curna Llc Tratamiento de enfermedades relacionadas con factor de crecimiento endotelial vascular por inhibicion de transcrito antisentido natural para factor de crecimiento endotelial vascular.
CN107338251A (zh) 2008-12-04 2017-11-10 库尔纳公司 通过抑制肿瘤抑制基因的天然反义转录物治疗肿瘤抑制基因相关性疾病
US8592386B2 (en) 2008-12-17 2013-11-26 Sarepta Therapeutics, Inc. Antisense compositions and methods for modulating contact hypersensitivity or contact dermatitis
WO2010080452A2 (en) 2008-12-18 2010-07-15 Quark Pharmaceuticals, Inc. siRNA COMPOUNDS AND METHODS OF USE THEREOF
WO2010078536A1 (en) 2009-01-05 2010-07-08 Rxi Pharmaceuticals Corporation Inhibition of pcsk9 through rnai
WO2010090762A1 (en) 2009-02-04 2010-08-12 Rxi Pharmaceuticals Corporation Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
ES2560107T3 (es) 2009-02-12 2016-02-17 Curna, Inc. Tratamiento de enfermedades relacionadas con el factor neurotrófico derivado de cerebro (BDNF) por inhibición de transcrito antisentido natural para BDNF
WO2010107733A2 (en) 2009-03-16 2010-09-23 Curna, Inc. Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2
EP2408920B1 (en) 2009-03-17 2017-03-08 CuRNA, Inc. Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1
US8815586B2 (en) 2009-04-24 2014-08-26 The Board Of Regents Of The University Of Texas System Modulation of gene expression using oligomers that target gene regions downstream of 3′ untranslated regions
DE102009019476A1 (de) * 2009-05-04 2010-11-11 Biametrics Marken Und Rechte Gmbh Wiedererkennbarer Träger für optische Meßverfahren
US9155754B2 (en) 2009-05-06 2015-10-13 Curna, Inc. Treatment of ABCA1 gene related diseases by inhibition of a natural antisense transcript to ABCA1
JP6250930B2 (ja) 2009-05-06 2017-12-20 クルナ・インコーポレーテッド トリステトラプロリン（ｔｔｐ）に対する天然アンチセンス転写物の抑制によるｔｔｐ関連疾患の治療
CA3185821A1 (en) 2009-05-08 2010-11-11 Curna, Inc. Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to dmd family
CA2762369C (en) 2009-05-18 2021-12-28 Joseph Collard Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor
KR101703695B1 (ko) 2009-05-22 2017-02-08 큐알엔에이, 인크. 전사 인자 ｅ3(ｔｆｅ3)에 대한 천연 안티센스 전사체의 억제에 의해 ｔｆｅ3 및 인슐린 수용체 기질 2(ｉｒｓ2)의 치료
CA2764683A1 (en) 2009-05-28 2010-12-02 Joseph Collard Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene
EP2440214A4 (en) 2009-06-08 2013-07-31 Quark Pharmaceuticals Inc METHODS OF TREATING CHRONIC RENAL DISEASE
EP2443238B1 (en) 2009-06-16 2017-03-22 CuRNA, Inc. Treatment of paraoxonase 1 (pon1) related diseases by inhibition of natural antisense transcript to pon1
EP2443237B1 (en) 2009-06-16 2017-02-22 CuRNA, Inc. Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene
EP2446036B1 (en) 2009-06-24 2017-03-01 CuRNA, Inc. Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2
JP5907866B2 (ja) 2009-06-26 2016-04-26 クルナ・インコーポレーテッド ダウン症候群遺伝子に対する天然アンチセンス転写物の抑制によるダウン症候群遺伝子関連疾患の治療
KR101801407B1 (ko) 2009-07-24 2017-11-24 큐알엔에이, 인크. 시르투인 (ｓｉｒｔ)에 대한 천연 안티센스 전사체의 억제에 의한 시르투인 관련된 질환의 치료
US9234199B2 (en) 2009-08-05 2016-01-12 Curna, Inc. Treatment of insulin gene (INS) related diseases by inhibition of natural antisense transcript to an insulin gene (INS)
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
JP6189594B2 (ja) 2009-08-11 2017-08-30 クルナ・インコーポレーテッド アディポネクチン（ａｄｉｐｏｑ）に対する天然アンチセンス転写物の抑制によるアディポネクチン（ａｄｉｐｏｑ）関連疾患の治療
CN102482670B (zh) 2009-08-21 2018-06-15 库尔纳公司 通过抑制‘hsp70-相互作用蛋白的c末端’(chip)的天然反义转录物而治疗chip相关疾病
CA2771172C (en) 2009-08-25 2021-11-30 Opko Curna, Llc Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap
JP6175236B2 (ja) 2009-09-25 2017-08-09 カッパーアールエヌエー，インコーポレイテッド フィラグリン（ｆｌｇ）の発現および活性の調整によるｆｌｇ関連疾患の処置
JPWO2011052715A1 (ja) 2009-10-30 2013-03-21 第一三共株式会社 修飾２本鎖ポリヌクレオチド
US20110110860A1 (en) 2009-11-02 2011-05-12 The Board Of Regents Of The University Of Texas System Modulation of ldl receptor gene expression with double-stranded rnas targeting the ldl receptor gene promoter
WO2011072082A2 (en) 2009-12-09 2011-06-16 Nitto Denko Corporation Modulation of hsp47 expression
EP2862929B1 (en) 2009-12-09 2017-09-06 Quark Pharmaceuticals, Inc. Compositions and methods for treating diseases, disorders or injury of the CNS
EP2513310B1 (en) 2009-12-16 2017-11-01 CuRNA, Inc. Treatment of membrane bound transcription factor peptidase, site 1 (mbtps1) related diseases by inhibition of natural antisense transcript to mbtps1
KR101891352B1 (ko) 2009-12-23 2018-08-24 큐알엔에이, 인크. 간세포 성장 인자(ｈｇｆ)에 대한 천연 안티센스 전사체의 억제에 의한 ｈｇｆ 관련 질환의 치료
US9068183B2 (en) 2009-12-23 2015-06-30 Curna, Inc. Treatment of uncoupling protein 2 (UCP2) related diseases by inhibition of natural antisense transcript to UCP2
JP5982288B2 (ja) 2009-12-29 2016-08-31 カッパーアールエヌエー，インコーポレイテッド 腫瘍タンパク質６３（ｐ６３）に対する天然アンチセンス転写物の阻害による腫瘍タンパク質６３関連疾患の治療
CN102782134B (zh) 2009-12-29 2017-11-24 库尔纳公司 通过抑制核呼吸因子1(nrf1)的天然反义转录物而治疗nrf1相关疾病
RU2016115782A (ru) 2009-12-31 2018-11-28 Курна, Инк. Лечение заболеваний, связанных с субстратом рецептора инсулина 2 (irs2), путем ингибирования природного антисмыслового транскрипта к irs2 и транскрипционному фактору е3 (tfe3)
WO2011082409A2 (en) 2010-01-04 2011-07-07 Curna, Inc. Treatment of interferon regulatory factor 8 (irf8) related diseases by inhibition of natural antisense transcript to irf8
JP5963680B2 (ja) 2010-01-06 2016-08-03 カッパーアールエヌエー，インコーポレイテッド 膵臓発生遺伝子に対する天然アンチセンス転写物の阻害による膵臓発生遺伝子疾患の治療
WO2011084193A1 (en) 2010-01-07 2011-07-14 Quark Pharmaceuticals, Inc. Oligonucleotide compounds comprising non-nucleotide overhangs
DK2524039T3 (en) 2010-01-11 2018-03-12 Curna Inc TREATMENT OF GENDER HORMON-BINDING GLOBULIN (SHBG) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPTS TO SHBG
US8779118B2 (en) 2010-01-11 2014-07-15 Isis Pharmaceuticals, Inc. Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2011091390A2 (en) 2010-01-25 2011-07-28 Opko Curna, Llc Treatment of rnase h1 related diseases by inhibition of natural antisense transcript to rnase h1
WO2011097388A1 (en) 2010-02-03 2011-08-11 Alnylam Pharmaceuticals, Inc. Selective inhibition of polyglutamine protein expression
KR101838308B1 (ko) 2010-02-22 2018-03-13 큐알엔에이, 인크. 피롤린-5-카르복실레이트 환원효소 1(ｐｙｃｒ1)에 대한 천연 안티센스 전사체의 억제에 의한 ｐｙｃｒ1과 관련된 질환의 치료
KR20130008560A (ko) 2010-03-12 2013-01-22 다이이찌 산쿄 가부시키가이샤 마이크로 ｒｎａ를 이용한 심근 세포의 증식 방법
WO2011115818A1 (en) 2010-03-17 2011-09-22 Isis Pharmaceuticals, Inc. 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
RU2615143C2 (ru) 2010-03-24 2017-04-04 Адвирна Самодоставляющие PHKi соединения уменьшенного размера
CN103108642B (zh) 2010-03-24 2015-09-23 雷克西制药公司 皮肤与纤维化症候中的rna干扰
WO2011119871A1 (en) 2010-03-24 2011-09-29 Rxi Phrmaceuticals Corporation Rna interference in ocular indications
KR101877065B1 (ko) 2010-04-02 2018-07-10 큐알엔에이, 인크. 집락 자극 인자 3 (ｃｓｆ3)에 대한 자연 안티센스 전사체의 저해에 의한 집락 자극 인자 3 (ｃｓｆ3) 관련된 질환의 치료
CN102858979B (zh) 2010-04-09 2018-01-26 库尔纳公司 通过抑制成纤维细胞生长因子21(fgf21)的天然反义转录物而治疗fgf21相关疾病
US8993738B2 (en) 2010-04-28 2015-03-31 Isis Pharmaceuticals, Inc. Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
RU2693462C2 (ru) 2010-05-03 2019-07-03 Курна, Инк. Лечение заболеваний, связанных с сиртуином (sirt), путем ингибирования природного антисмыслового транскрипта к сиртуину (sirt)
TWI531370B (zh) 2010-05-14 2016-05-01 可娜公司 藉由抑制ｐａｒ４天然反股轉錄本治療ｐａｒ４相關疾病
NO2576784T3 (es) 2010-05-26 2018-04-14
NO2576783T3 (es) 2010-05-26 2018-04-28
WO2011156278A1 (en) 2010-06-07 2011-12-15 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
HUE054179T2 (hu) 2010-06-23 2021-08-30 Curna Inc Nátriumcsatornás, feszültségfüggõ, alfa alegységgel (SCNA) kapcsolatos betegségek kezelése a természetes antiszensz (SCNA)-transzkripció gátlásával
JP5998131B2 (ja) 2010-07-14 2016-09-28 カッパーアールエヌエー，インコーポレイテッド Ｄｉｓｃｓｌａｒｇｅｈｏｍｏｌｏｇ（ｄｌｇ）ｄｌｇ１への天然アンチセンス転写物の阻害によるｄｌｇ関連疾患の治療
EP2412724A1 (en) 2010-07-29 2012-02-01 Centre National de la Recherche Scientifique (C.N.R.S) Regulation of Glypican 4 activity to modulate the fate of stem cells and uses thereof
ES2640755T3 (es) 2010-10-06 2017-11-06 Curna, Inc. Tratamiento de enfermedades relacionadas con la Sialidasa 4 (neu4) mediante inhibición del transcrito antisentido natural al gen neu4
CN103180445B (zh) 2010-10-22 2018-02-16 库尔纳公司 通过抑制α‑L‑艾杜糖醛酸酶(IDUA)的天然反义转录物而治疗IDUA相关疾病
WO2012068340A2 (en) 2010-11-18 2012-05-24 Opko Curna Llc Antagonat compositions and methods of use
CA2818824A1 (en) 2010-11-23 2012-05-31 Joseph Collard Treatment of nanog related diseases by inhibition of natural antisense transcript to nanog
CA2819944A1 (en) 2010-12-02 2012-06-07 Daiichi Sankyo Company, Limited Modified single-stranded polynucleotide
EP3067421B1 (en) 2011-02-08 2018-10-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2012118911A1 (en) 2011-03-03 2012-09-07 Quark Pharmaceuticals, Inc. Oligonucleotide modulators of the toll-like receptor pathway
US9796979B2 (en) 2011-03-03 2017-10-24 Quark Pharmaceuticals Inc. Oligonucleotide modulators of the toll-like receptor pathway
KR101937498B1 (ko) 2011-03-03 2019-04-10 쿠아크 파마수티칼스 인코퍼레이티드 폐 질환 및 손상을 치료하기 위한 조성물 및 방법
US10196637B2 (en) 2011-06-08 2019-02-05 Nitto Denko Corporation Retinoid-lipid drug carrier
TWI658830B (zh) 2011-06-08 2019-05-11 日東電工股份有限公司 Ｈｓｐ47表現調控強化用類視色素脂質體
CA2838588C (en) 2011-06-09 2021-09-14 Curna, Inc. Treatment of frataxin (fxn) related diseases by inhibition of natural antisense transcript to fxn
HUE036963T2 (hu) 2011-06-15 2018-08-28 Grifols Therapeutics Inc Eljárások, kompozíciók és készletek humán immundeficiencia vírus (HIV) meghatározásához
WO2013022990A1 (en) 2011-08-11 2013-02-14 Isis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
KR101991980B1 (ko) 2011-09-06 2019-06-21 큐알엔에이, 인크. 소형 분자로 전압-개폐된 나트륨 채널 (SCNxA)의 알파 아단위에 관련된 질환의 치료
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
SG11201401648RA (en) 2011-11-03 2014-05-29 Quark Pharmaceuticals Inc Methods and compositions for neuroprotection
DK2790736T3 (en) 2011-12-12 2018-05-07 Oncoimmunin Inc In vivo delivery of oligonucleotides
US9737480B2 (en) 2012-02-06 2017-08-22 President And Fellows Of Harvard College ARRDC1-mediated microvesicles (ARMMs) and uses thereof
EP2825648B1 (en) 2012-03-15 2018-09-05 CuRNA, Inc. Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf
WO2013148260A1 (en) 2012-03-30 2013-10-03 Washington University Methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome
WO2013154799A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleosides and oligomeric compounds prepared therefrom
US9221864B2 (en) 2012-04-09 2015-12-29 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
EP3336189A1 (en) 2012-04-20 2018-06-20 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
AU2013262649A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating smn gene family expression
WO2013173608A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating mecp2 expression
KR102028784B1 (ko) 2012-05-16 2019-10-04 트랜슬레이트 바이오 인코포레이티드 유전자 발현을 조절하기 위한 조성물 및 방법
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
JP2013256452A (ja) * 2012-06-11 2013-12-26 Kawaken Fine Chem Co Ltd メラニン産生抑制剤とその組成物
TW201402594A (zh) * 2012-06-18 2014-01-16 Daiichi Sankyo Co Ltd 核苷類似物的製造中間體及其製造方法
US9993522B2 (en) 2012-09-18 2018-06-12 Uti Limited Partnership Treatment of pain by inhibition of USP5 de-ubiquitinase
WO2014059353A2 (en) 2012-10-11 2014-04-17 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
US9029335B2 (en) 2012-10-16 2015-05-12 Isis Pharmaceuticals, Inc. Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2014071406A1 (en) 2012-11-05 2014-05-08 Pronai Therapeutics, Inc. Methods of using biomarkers for the treatment of cancer by modulation of bcl2|expression
CN105143470B (zh) 2013-02-28 2020-06-09 德克萨斯大学系统董事会 用于将癌症分类为易感于tmepai定向疗法以及治疗所述癌症的方法
WO2014143158A1 (en) 2013-03-13 2014-09-18 The Broad Institute, Inc. Compositions and methods for labeling of agents
US9273349B2 (en) 2013-03-14 2016-03-01 Affymetrix, Inc. Detection of nucleic acids
RU2745324C2 (ru) 2013-03-14 2021-03-23 Ионис Фармасьютикалз, Инк. Композиции и способы модулирования экспрессии tau
WO2014176259A1 (en) 2013-04-22 2014-10-30 Icahn School Of Medicine At Mount Sinai Mutations in pdgfrb and notch3 as causes of autosomal dominant infantile myofibromatosis
CR20190269A (es) 2013-05-01 2019-09-13 Ionis Pharmaceuticals Inc COMPOSICIONES Y MÉTODOS PARA MODULAR LA EXPRESIÓN DE TTR Y VHB (Divisonal 2015-0612)
TWI772856B (zh) * 2013-07-19 2022-08-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
EP3052632A4 (en) 2013-10-04 2017-03-29 Rana Therapeutics, Inc. Compositions and methods for treating amyotrophic lateral sclerosis
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
WO2015075166A1 (en) 2013-11-22 2015-05-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treatment of a bacterial infection
EP3079707A4 (en) 2013-12-02 2017-10-18 RXi Pharmaceuticals Corporation Immunotherapy of cancer
WO2015118407A2 (en) 2014-01-29 2015-08-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Oligonucleotides and methods for inhibiting or reducing bacterial biofilms
SG11201608109TA (en) 2014-04-01 2016-10-28 Ionis Pharmaceuticals Inc Compositions for modulating sod-1 expression
EP3647318B1 (en) 2014-04-28 2021-06-30 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
EP3608406B1 (en) 2014-05-01 2023-02-15 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating complement factor b expression
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
TW201620526A (zh) 2014-06-17 2016-06-16 愛羅海德研究公司 用於抑制α－１抗胰蛋白酶基因表現之組合物及方法
WO2016017422A1 (ja) * 2014-07-31 2016-02-04 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
IL234246A0 (en) 2014-08-21 2014-11-30 Omrix Biopharmaceuticals Ltd Stabilized thrombin
EP3188799B1 (en) 2014-09-05 2022-07-06 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting tyr or mmp1
CN107109411B (zh) 2014-10-03 2022-07-01 冷泉港实验室 核基因输出的定向增加
US9816080B2 (en) 2014-10-31 2017-11-14 President And Fellows Of Harvard College Delivery of CAS9 via ARRDC1-mediated microvesicles (ARMMs)
JP2018504380A (ja) 2014-12-18 2018-02-15 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｒｅｖｅｒｓｉｒ（商標）化合物
US9688707B2 (en) 2014-12-30 2017-06-27 Ionis Pharmaceuticals, Inc. Bicyclic morpholino compounds and oligomeric compounds prepared therefrom
WO2016112132A1 (en) 2015-01-06 2016-07-14 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
WO2016167780A1 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
WO2017007825A1 (en) 2015-07-06 2017-01-12 Rxi Pharmaceuticals Corporation Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
JP6983752B2 (ja) 2015-07-06 2021-12-17 フィオ ファーマシューティカルズ コーポレーションPhio Pharmaceuticals Corp. スーパーオキシドディスムターゼ１（ｓｏｄ１）を標的とする核酸分子
AU2016295168B2 (en) 2015-07-17 2021-08-19 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
DK3341479T3 (da) 2015-08-24 2020-02-24 Roche Innovation Ct Copenhagen As LNA-G-Proces
IL308174A (en) 2015-10-09 2024-01-01 Univ Southampton Gene expression modulation and dysregulated protein expression scanning
JP2018531037A (ja) 2015-10-19 2018-10-25 アールエックスアイ ファーマシューティカルズ コーポレーション 長い非コードｒｎａを標的とする減少したサイズの自己送達型核酸化合物
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
WO2017079442A1 (en) 2015-11-04 2017-05-11 Icahn School Of Medicine At Mount Sinai Methods of treating tumors and cancer, and identifying candidate subjects for such treatment
KR102482440B1 (ko) 2015-11-12 2022-12-29 에프. 호프만-라 로슈 아게 부계 ube3a 발현을 유도하기 위한 올리고뉴클레오티드
WO2017096395A1 (en) 2015-12-04 2017-06-08 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
CA3005256A1 (en) 2015-12-14 2017-06-22 Cold Spring Harbor Laboratory Antisense oligomers for treatment of autosomal dominant mental retardation-5 and dravet syndrome
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
JOP20200228A1 (ar) 2015-12-21 2017-06-16 Novartis Ag تركيبات وطرق لخفض تعبير البروتين tau
LT3430141T (lt) 2016-03-14 2021-03-25 F. Hoffmann-La Roche Ag Oligonukleotidai, skirti pd-l1 raiškai sumažinti
CA3013799A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Methods of modulating keap1
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
WO2017178656A1 (en) 2016-04-14 2017-10-19 Roche Innovation Center Copenhagen A/S TRITYL-MONO-GalNAc COMPOUNDS AND THEIR USE
EP3448881B1 (en) 2016-04-26 2023-06-07 Icahn School of Medicine at Mount Sinai Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment
MA45496A (fr) 2016-06-17 2019-04-24 Hoffmann La Roche Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b
AU2017286811A1 (en) 2016-06-17 2018-11-22 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
TW201803990A (zh) 2016-07-01 2018-02-01 赫孚孟拉羅股份公司 用於調節htra1表現之反股寡核苷酸
WO2018009466A1 (en) 2016-07-05 2018-01-11 Aduro Biotech, Inc. Locked nucleic acid cyclic dinucleotide compounds and uses thereof
AU2017296195A1 (en) 2016-07-11 2019-01-24 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
KR102627418B1 (ko) 2016-09-14 2024-01-19 얀센 바이오파마, 인크. 변형된 올리고뉴클레오티드 및 사용 방법
JOP20190065A1 (ar) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن tau
EP3518981A4 (en) 2016-10-03 2020-06-10 President and Fellows of Harvard College DELIVERING THERAPEUTIC RNAS VIA ARRDC1-MEDIATED MICROVESICLES
US20190284621A1 (en) 2016-11-11 2019-09-19 Roche Innovation Center Copenhagen A/S Therapeutic oligonucleotides capture and detection
WO2018102745A1 (en) 2016-12-02 2018-06-07 Cold Spring Harbor Laboratory Modulation of lnc05 expression
CA3047894A1 (en) 2016-12-28 2018-07-05 Daiichi Sankyo Company, Limited Therapeutic drug for alport's syndrome
CA3045045A1 (en) 2017-01-10 2018-07-19 Zhen Li Alpha-1 antitrypsin (aat) rnai agents, compositions including aat rnai agents, and methods of use
US20190345496A1 (en) 2017-01-13 2019-11-14 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
WO2018130583A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
EP3568480A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
US20190338286A1 (en) 2017-01-13 2019-11-07 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
WO2018165564A1 (en) 2017-03-09 2018-09-13 Ionis Pharmaceuticals, Inc. Morpholino modified oligomeric compounds
US12030908B2 (en) 2017-03-10 2024-07-09 Lakewood Amedex, Inc. Antimicrobial compounds, compositions, and uses thereof
AU2018230805B2 (en) * 2017-03-10 2020-11-26 Lakewood Amedex, Inc. Antimicrobial compounds, compositions, and uses thereof
US11377468B2 (en) 2017-03-10 2022-07-05 Lakewood Amedex, Inc. Antimicrobial compounds, compositions, and uses thereof
US11795192B2 (en) 2017-03-10 2023-10-24 Lakewood Amedex, Inc. Antimicrobial compounds, compositions, and uses thereof
WO2018164275A1 (ja) 2017-03-10 2018-09-13 国立研究開発法人国立成育医療研究センター アンチセンスオリゴヌクレオチドおよび糖原病Ｉａ型予防または治療用組成物
WO2018169063A1 (ja) 2017-03-17 2018-09-20 国立大学法人千葉大学 構造強化されたＳ－ＴｕＤを用いた新規がん治療法
JP7246729B2 (ja) 2017-05-18 2023-03-28 国立大学法人京都大学 脊髄小脳変性症３６型の予防又は治療用組成物
US20190055564A1 (en) 2017-06-01 2019-02-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
US20200172903A1 (en) 2017-07-05 2020-06-04 Osaka University ENA ANTISENSE OLIGONUCLEOTIDE FOR INHIBITION OF alpha-SYNUCLEIN EXPRESSION
JP7307417B2 (ja) 2017-07-10 2023-07-12 国立大学法人大阪大学 Ｔｄｐ－４３の発現量を調節するアンチセンスオリゴヌクレオチド及びその用途
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
US11197884B2 (en) 2017-08-18 2021-12-14 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
HUE064635T2 (hu) 2017-08-25 2024-04-28 Stoke Therapeutics Inc Antisensz oligomerek állapotok és betegségek kezelésére
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
SG11202002149XA (en) 2017-09-14 2020-04-29 Janssen Biopharma Inc Galnac derivatives
EP3694995A1 (en) 2017-10-13 2020-08-19 Roche Innovation Center Copenhagen A/S Methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides
IL272566B2 (en) 2017-10-16 2024-07-01 Hoffmann La Roche Nucleic acid molecule to reduce papd5 and papd7 mRNA to treat hepatitis b infection
EP3697904A1 (en) 2017-10-17 2020-08-26 INSERM (Institut National de la Santé et de la Recherche Médicale) Combination treatment for cystic fibrosis
WO2019111791A1 (ja) * 2017-12-07 2019-06-13 第一三共株式会社 ジストロフィン遺伝子のイントロンリテンションを解消するアンチセンスオリゴヌクレオチド
EP3724333A2 (en) 2017-12-11 2020-10-21 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating fndc3b expression
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
BR112020012523A2 (pt) 2017-12-21 2020-11-24 F. Hoffmann-La Roche Ag diagnóstico complementar para antagonistas de rna htra1
AU2018386527A1 (en) 2017-12-22 2020-04-30 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
CA3085406A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorodithioate internucleoside linkage
EP4092118A1 (en) 2017-12-22 2022-11-23 Roche Innovation Center Copenhagen A/S Novel thiophosphoramidites
WO2019137883A1 (en) 2018-01-10 2019-07-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating pias4 expression
CA3085964A1 (en) 2018-01-12 2019-07-18 Roche Innovation Center Copenhagen A/S Alpha-synuclein antisense oligonucleotides and uses thereof
CN111556894A (zh) 2018-01-12 2020-08-18 哥本哈根罗氏创新中心 用于调控gsk3b表达的寡核苷酸
AU2019208011A1 (en) 2018-01-12 2020-07-23 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
JP7455746B2 (ja) 2018-01-12 2024-03-26 ブリストル－マイヤーズ スクイブ カンパニー アルファ－シヌクレインを標的とするアンチセンスオリゴヌクレオチドおよびその使用
WO2019141656A1 (en) 2018-01-17 2019-07-25 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
JP2021511029A (ja) 2018-01-18 2021-05-06 ロシュ イノベーション センター コペンハーゲン エーエス Ｓｒｅｂｐ１を標的とするアンチセンスオリゴヌクレオチド
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
RU2020125769A (ru) 2018-02-09 2022-03-10 Дженентек, Инк. Олигонуклеотиды для модуляции экспрессии tmem106b
CN112020559A (zh) 2018-02-21 2020-12-01 百时美施贵宝公司 Camk2d反义寡核苷酸及其用途
KR20210130854A (ko) 2018-03-09 2021-11-01 다이이찌 산쿄 가부시키가이샤 당원병 Ia형 치료약
WO2019175260A2 (en) 2018-03-13 2019-09-19 Janssen Pharmaceutica Nv Modified oligonucleotides and methods of use in tauopathies
AU2019247645A1 (en) 2018-04-05 2020-10-15 Centre Leon Berard Use of FUBP1 inhibitors for treating hepatitis B virus infection
EP3788169A4 (en) 2018-05-04 2022-08-10 Stoke Therapeutics, Inc. METHODS AND COMPOSITIONS FOR TREATING A CHOLESTERYL ESTER STORAGE DISEASE
JP2021522808A (ja) 2018-05-07 2021-09-02 ロシュ イノベーション センター コペンハーゲン エーエス オリゴヌクレオチド治療剤の超並列発見方法
CA3098623A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
EP3790971A1 (en) 2018-05-08 2021-03-17 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating myh7 expression
US20210220387A1 (en) 2018-05-18 2021-07-22 Hoffmann-La Roche, Inc. Pharmaceutical compositions for treatment of microrna related diseases
WO2019224172A1 (en) 2018-05-25 2019-11-28 Roche Innovation Center Copenhagen A/S Novel process for making allofuranose from glucofuranose
JP7379387B2 (ja) 2018-06-05 2023-11-14 エフ． ホフマン－ラ ロシュ アーゲー Ａｔｘｎ２発現を制御するためのオリゴヌクレオチド
US20210207136A1 (en) 2018-06-13 2021-07-08 Daiichi Sankyo Company, Limited Myocardial dysfunction therapeutic agent
CA3103663A1 (en) 2018-06-18 2019-12-26 University Of Rochester Inhibition of re1-silencing transcription factor in the treatment of schizophrenia and other neuropsychiatric disorders
KR20210054502A (ko) 2018-06-21 2021-05-13 유니버시티 오브 로체스터 헌팅턴병을 치료하거나 이의 발병을 저해하는 방법
WO2020007700A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting spi1
WO2020007702A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting bcl2l11
WO2020007772A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
AU2019297391B2 (en) 2018-07-03 2023-01-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating Tau expression
EP3819378A4 (en) 2018-07-04 2022-09-14 Aichi Medical University OLIGONUCLEOTIDES FOR CONTROL OF TAU SPLICING AND THEIR USES
WO2020007889A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting stat1
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011653A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
WO2020011743A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mafb
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
WO2020011869A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting tlr2
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
EP3821013A1 (en) 2018-07-13 2021-05-19 F. Hoffmann-La Roche AG Oligonucleotides for modulating rtel1 expression
CN112236439A (zh) 2018-07-31 2021-01-15 罗氏创新中心哥本哈根有限公司 包含三硫代磷酸酯核苷间键的寡核苷酸
WO2020025563A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
US12018087B2 (en) 2018-08-02 2024-06-25 Dyne Therapeutics, Inc. Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject
US11911484B2 (en) 2018-08-02 2024-02-27 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating myotonic dystrophy
WO2020038976A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting usp8
WO2020038968A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Microrna-134 biomarker
WO2020038971A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting vcan
WO2020038973A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting sptlc1
WO2020043750A1 (en) 2018-08-28 2020-03-05 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
EP3620519A1 (en) 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
WO2020069055A1 (en) 2018-09-28 2020-04-02 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2020081839A1 (en) 2018-10-17 2020-04-23 Lakewood Amedex, Inc. Methods and compositions for treating oral mucositis
CN112969709A (zh) 2018-11-01 2021-06-15 豪夫迈·罗氏有限公司 靶向tia1的反义寡核苷酸
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
WO2020102630A1 (en) 2018-11-15 2020-05-22 Ionis Pharmaceuticals, Inc. Modulators of irf5 expression
WO2020104492A1 (en) 2018-11-22 2020-05-28 Roche Innovation Center Copenhagen A/S Pyridinium salts as activators in the synthesis of stereodefined oligonucleotides
WO2020109343A1 (en) 2018-11-29 2020-06-04 F. Hoffmann-La Roche Ag Combination therapy for treatment of macular degeneration
WO2020109344A1 (en) 2018-11-29 2020-06-04 F. Hoffmann-La Roche Ag Occular administration device for antisense oligonucleotides
AU2019396450A1 (en) 2018-12-11 2021-06-24 University Of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
CN113330118A (zh) 2018-12-21 2021-08-31 勃林格殷格翰国际有限公司 靶向card9的反义寡核苷酸
WO2020152303A1 (en) 2019-01-25 2020-07-30 F. Hoffmann-La Roche Ag Lipid vesicle for oral drug delivery
WO2020160453A1 (en) * 2019-01-31 2020-08-06 Ionis Pharmaceuticals, Inc. Modulators of yap1 expression
US20230057355A1 (en) 2019-02-13 2023-02-23 University Of Rochester Gene networks that mediate remyelination of the human brain
BR112021016354A2 (pt) 2019-02-20 2021-10-19 Roche Innovation Center Copenhagen A/S Composto, processo para a fabricação de um composto de fórmula, uso de um composto e invenção
EP3927826A1 (en) 2019-02-20 2021-12-29 Roche Innovation Center Copenhagen A/S Phosphonoacetate gapmer oligonucleotides
JP7503072B2 (ja) 2019-02-26 2024-06-19 ロシュ イノベーション センター コペンハーゲン エーエス オリゴヌクレオチドの製剤化方法
JP7492526B2 (ja) 2019-02-27 2024-05-29 アイオーニス ファーマシューティカルズ， インコーポレーテッド Ｍａｌａｔ１発現のモジュレーター
CN113507942A (zh) 2019-03-05 2021-10-15 豪夫迈·罗氏有限公司 分子的细胞内靶向
CN113747925A (zh) 2019-03-21 2021-12-03 科迪亚克生物科学公司 胞外囊泡缀合物及其用途
JP7413362B2 (ja) 2019-03-29 2024-01-15 シスメックス株式会社 新規人工核酸、その製造方法及び用途
WO2020206115A2 (en) 2019-04-03 2020-10-08 Bristol-Myers Squibb Company Angptl2 antisense oligonucleotides and uses thereof
CN113785060A (zh) 2019-04-04 2021-12-10 豪夫迈·罗氏有限公司 用于调节atxn2表达的寡核苷酸
US11286485B2 (en) 2019-04-04 2022-03-29 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
CN113661168A (zh) 2019-04-16 2021-11-16 罗氏创新中心哥本哈根有限公司 用于制备核苷酸p(v)单体的新方法
EP3962918A1 (en) 2019-04-30 2022-03-09 Roche Innovation Center Copenhagen A/S Novel process for preparing rhenium chelated mag3 oligonucleotides
MX2021013418A (es) 2019-05-03 2021-12-10 Dicerna Pharmaceuticals Inc Moleculas inhibidoras de acido nucleico bicatenario con cadenas de sentido acortadas.
CA3138915A1 (en) 2019-05-17 2020-11-26 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
CN113950529A (zh) 2019-06-06 2022-01-18 豪夫迈·罗氏有限公司 靶向atxn3的反义寡核苷酸
EP3988558A4 (en) * 2019-06-19 2022-09-28 Yamasa Corporation CROSSLINKED NUCLEOSIDE INTERMEDIATE CRYSTAL AND METHOD FOR PRODUCTION THEREOF, AND METHOD FOR PRODUCTION OF CROSSLINKED NUCLEOSIDE AMIDITE
JPWO2020262184A1 (es) 2019-06-26 2020-12-30
US20220251567A1 (en) 2019-07-10 2022-08-11 Inserm (Institut National De La Santè Et De La Recherche Médicale) Methods for the treatment of epilepsy
US20220364086A1 (en) 2019-07-12 2022-11-17 Daiichi Sankyo Company, Limited ANTISENSE OLIGONUCLEOTIDE CAPABLE OF ALTERING SPLICING OF DUX4 pre-mRNA
WO2021011936A2 (en) 2019-07-18 2021-01-21 University Of Rochester Cell-type selective immunoprotection of cells
US11786546B2 (en) 2019-07-26 2023-10-17 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating GFAP
EP4013876A1 (en) 2019-08-14 2022-06-22 Codiak BioSciences, Inc. Extracellular vesicle-nlrp3 antagonist
EP4013877A1 (en) 2019-08-14 2022-06-22 Codiak BioSciences, Inc. Extracellular vesicle-aso constructs targeting stat6
CN114641570A (zh) 2019-08-14 2022-06-17 科迪亚克生物科学公司 具有靶向kras的反义寡核苷酸的细胞外囊泡
KR20220078565A (ko) 2019-08-14 2022-06-10 코디악 바이오사이언시즈, 인크. 분자에 연결된 세포외 소포 및 이의 용도
MX2022001769A (es) 2019-08-14 2022-06-09 Codiak Biosciences Inc Construcciones de vesícula extracelular-oligonucleótido antisentido (aso) que se dirigen a la proteína beta de unión al potenciador ccaat (cebp)/beta.
CN114729327A (zh) 2019-08-14 2022-07-08 科迪亚克生物科学公司 具有stat3反义寡核苷酸的细胞外囊泡
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
CA3150715A1 (en) 2019-09-10 2021-03-18 Makoto Koizumi Conjugate of galnac-oligonucleotide for delivery to liver and manufacturing method thereof
EP4034247A1 (en) 2019-09-25 2022-08-03 Codiak BioSciences, Inc. Sting agonist comprising exosomes for treating neuroimmunological disorders
WO2021074657A1 (en) 2019-10-17 2021-04-22 INSERM (Institut National de la Santé et de la Recherche Médicale) Combination treatment for cystic fibrosis
EP4047005A4 (en) * 2019-10-18 2024-03-06 Daiichi Sankyo Company, Limited PROCESS FOR MANUFACTURING BICYCLIC PHOSPHORAMIDITE
CN111109591A (zh) 2019-10-25 2020-05-08 新疆红旗坡农业发展集团有限公司 肠道微生态高效重建型苹果酵素及加工技术
EP4055165A1 (en) 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
MX2022005220A (es) 2019-11-06 2022-08-11 Alnylam Pharmaceuticals Inc Suministro extrahepático.
WO2021099394A1 (en) 2019-11-19 2021-05-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Antisense oligonucleotides and their use for the treatment of cancer
WO2021122910A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sbds inhibitors for treating hepatitis b virus infection
JP2023506954A (ja) 2019-12-19 2023-02-20 エフ． ホフマン－ラ ロシュ エージー． Ｂ型肝炎ウイルス感染を処置するためのｓａｒａｆ阻害剤の使用
CN114901821A (zh) 2019-12-19 2022-08-12 豪夫迈·罗氏有限公司 Sept9抑制剂用于治疗乙型肝炎病毒感染的用途
CN115516091A (zh) 2019-12-19 2022-12-23 豪夫迈·罗氏有限公司 Cops3抑制剂用于治疗乙型肝炎病毒感染的用途
JP2023506540A (ja) 2019-12-19 2023-02-16 エフ． ホフマン－ラ ロシュ エージー． Ｂ型肝炎ウイルス感染を処置するためのｓｃａｍｐ３阻害剤の使用
TW202136510A (zh) 2019-12-20 2021-10-01 瑞士商赫孚孟拉羅股份公司 用於抑制ｓｃｎ９ａ表現之增強型寡核苷酸
AU2020415322A1 (en) 2019-12-24 2022-06-16 F. Hoffmann-La Roche Ag Pharmaceutical combination of antiviral agents targeting HBV and/or an immune modulator for treatment of HBV
CA3163490A1 (en) 2019-12-24 2021-07-01 F. Hoffman-La Roche Ag Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv
WO2021158810A1 (en) 2020-02-05 2021-08-12 Bristol-Myers Squibb Company Oligonucleotides for splice modulation of camk2d
EP4110916A1 (en) 2020-02-28 2023-01-04 F. Hoffmann-La Roche AG Oligonucleotides for modulating cd73 exon 7 splicing
JP6953053B1 (ja) 2020-03-11 2021-10-27 隆光 矢野 −１フレームシフトを誘導するための１本鎖核酸分子及び組成物
WO2021184020A1 (en) 2020-03-13 2021-09-16 Codiak Biosciences, Inc. Methods of treating neuroinflammation
WO2021184021A1 (en) 2020-03-13 2021-09-16 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting pmp22
CA3178892A1 (en) 2020-03-31 2021-10-07 Janssen Biopharma, Inc. Synthesis of oligonucleotides and related compounds
EP4149486A1 (en) 2020-05-11 2023-03-22 Genentech, Inc. Complement component c1s inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
WO2021231204A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component 4 inhibitors for treating neurological diseases, and related compositons, systems and methods of using same
JP2023527693A (ja) 2020-05-11 2023-06-30 ジェネンテック， インコーポレイテッド 神経疾患を治療するための補体成分ｃ１ｒ阻害剤、並びに関連する組成物、システム、及びそれを使用する方法
TW202208627A (zh) 2020-05-11 2022-03-01 美商斯托克治療公司 用於病症及疾病之治療的opa1反義寡聚物
JP2023526267A (ja) 2020-05-13 2023-06-21 エフ． ホフマン－ラ ロシュ アーゲー プログラニュリン標的オリゴヌクレオチドアゴニスト
JP2023526096A (ja) 2020-05-22 2023-06-20 エフ． ホフマン－ラ ロシュ アーゲー Ｃａｒｄ９のスプライス調節のためのオリゴヌクレオチド
WO2021249993A1 (en) 2020-06-09 2021-12-16 Roche Innovation Center Copenhagen A/S Guanosine analogues for use in therapeutic polynucleotides
AR122731A1 (es) 2020-06-26 2022-10-05 Hoffmann La Roche Oligonucleótidos mejorados para modular la expresión de fubp1
CA3177613A1 (en) 2020-07-10 2022-04-13 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and compositions for treating epilepsy
WO2022018187A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Oligonucleotides targeting rna binding protein sites
WO2022018155A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Lna oligonucleotides for splice modulation of stmn2
US20230272403A1 (en) 2020-07-28 2023-08-31 Knc Laboratories Co., Ltd. Antisense oligonucleotide inducing exon skipping of angiotensin converting enzyme 2 gene
JP2023538630A (ja) 2020-08-21 2023-09-08 エフ． ホフマン－ラ ロシュ アーゲー Ｂ型肝炎ウイルス感染症を処置するためのａ１ｃｆ阻害剤の使用
WO2022043531A1 (en) * 2020-08-28 2022-03-03 Janssen Sciences Ireland Unlimited Company 7'-substituted 2'-o-4'-c-ethylene-bridged nucleic acid (ena) monomers and uses thereof
JPWO2022065413A1 (es) 2020-09-25 2022-03-31
US20230364127A1 (en) 2020-10-06 2023-11-16 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting stat6
AR124227A1 (es) 2020-12-03 2023-03-01 Hoffmann La Roche Oligonucleótidos antisentido que actúan sobre atxn3
US20220177883A1 (en) 2020-12-03 2022-06-09 Hoffmann-La Roche Inc. Antisense Oligonucleotides Targeting ATXN3
WO2022122613A1 (en) 2020-12-08 2022-06-16 F. Hoffmann-La Roche Ag Novel synthesis of phosphorodithioate oligonucleotides
AR124378A1 (es) 2020-12-18 2023-03-22 Hoffmann La Roche Oligonucleótidos antisentido dirigida a progranulina
WO2022136140A1 (en) 2020-12-22 2022-06-30 F. Hoffmann-La Roche Ag Oligonucleotides targeting xbp1
EP4271695A2 (en) 2020-12-31 2023-11-08 Alnylam Pharmaceuticals, Inc. 2'-modified nucleoside based oligonucleotide prodrugs
US20240117356A1 (en) * 2020-12-31 2024-04-11 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating myotonic dystrophy
AU2021411579A1 (en) 2020-12-31 2023-07-13 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
TW202246500A (zh) 2021-02-02 2022-12-01 瑞士商赫孚孟拉羅股份公司 用於抑制 ｒｔｅｌ１ 表現之增強型寡核苷酸
WO2022178149A2 (en) 2021-02-17 2022-08-25 Codiak Biosciences, Inc. Extracellular vesicle-nlrp3 antagonist
IL305176A (en) 2021-02-17 2023-10-01 Lonza Sales Ag An extracellular vesicle is linked to a biologically active molecule via an optimal linker and an anchored moiety
EP4299743A1 (en) 2021-02-26 2024-01-03 KNC Laboratories Co., Ltd. Nucleic acid medicine expressing splicing variant of myostatin
CA3212944A1 (en) 2021-03-31 2022-10-06 Patrick Dougherty Cyclic cell penetrating peptides
KR20230166101A (ko) 2021-04-01 2023-12-06 론자 세일즈 아게 세포외 소포 조성물
IL308353A (en) 2021-05-10 2024-01-01 Entrada Therapeutics Inc Compositions and methods for modulating tissue distribution of intracellular therapies
JP2024518476A (ja) 2021-05-10 2024-05-01 エントラーダ セラピューティクス，インコーポレイティド ｍＲＮＡスプライシングを調節するための組成物及び方法
WO2022240721A1 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity
EP4352222A1 (en) 2021-06-08 2024-04-17 F. Hoffmann-La Roche AG Oligonucleotide progranulin agonists
MX2023015509A (es) 2021-06-23 2024-01-22 Entrada Therapeutics Inc Compuestos antisentido y metodos para dirigirse a repeticiones cug.
US11633498B2 (en) 2021-07-09 2023-04-25 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating myotonic dystrophy
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
JP2024526890A (ja) 2021-07-21 2024-07-19 アルナイラム ファーマシューティカルズ， インコーポレイテッド 代謝障害関連標的遺伝子ｉｒｎａ組成物およびその使用方法
CA3229305A1 (en) 2021-08-16 2023-02-23 Vib Vzw Oligonucleotides for modulating synaptogyrin-3 expression
EP4389893A1 (en) 2021-08-21 2024-06-26 Takeda Pharmaceutical Company Limited Human transferrin receptor binding peptide-drug conjugate
IL311139A (en) 2021-09-01 2024-04-01 Entrada Therapeutics Inc Compounds and methods for skipping exon 44 in Duchenne muscular dystrophy
CN118019848A (zh) 2021-09-29 2024-05-10 豪夫迈·罗氏有限公司 Rna编辑
CA3234887A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
WO2023078883A1 (en) 2021-11-03 2023-05-11 F. Hoffmann-La Roche Ag Oligonucleotides for modulating apolipoprotein e4 expression
CA3234478A1 (en) 2021-11-11 2023-05-19 Souphalone LUANGSAY Pharmaceutical combinations for treatment of hbv
CN118434858A (zh) 2021-12-07 2024-08-02 豪夫迈·罗氏有限公司 靶向actl6b的反义寡核苷酸
WO2023111210A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Combination of oligonucleotides for modulating rtel1 and fubp1
WO2023111336A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Oligonucleotide gba agonists
CN118434860A (zh) 2021-12-20 2024-08-02 豪夫迈·罗氏有限公司 苏糖核酸反义寡核苷酸及其方法
WO2023122762A1 (en) 2021-12-22 2023-06-29 Camp4 Therapeutics Corporation Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2023127857A1 (ja) 2021-12-27 2023-07-06 株式会社理研ジェネシス 新規人工核酸、その製造方法及び用途
WO2023141507A1 (en) 2022-01-20 2023-07-27 Genentech, Inc. Antisense oligonucleotides for modulating tmem106b expression
WO2023150553A1 (en) 2022-02-01 2023-08-10 University Of Rochester Gpr17 promoter-based targeting and transduction of glial progenitor cells
WO2023152369A1 (en) 2022-02-14 2023-08-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Nucleic acid mir-9 inhibitor for the treatment of cystic fibrosis
US20240167040A1 (en) 2022-02-21 2024-05-23 Hoffmann-La Roche Inc. Antisense oligonucleotide
US11931421B2 (en) 2022-04-15 2024-03-19 Dyne Therapeutics, Inc. Muscle targeting complexes and formulations for treating myotonic dystrophy
WO2023217890A1 (en) 2022-05-10 2023-11-16 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting cfp-elk1 intergene region
WO2023220744A2 (en) 2022-05-13 2023-11-16 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
TW202409276A (zh) 2022-05-18 2024-03-01 瑞士商赫孚孟拉羅股份公司 改良之靶向ｒｎａ結合蛋白位點的寡核苷酸
WO2023240277A2 (en) 2022-06-10 2023-12-14 Camp4 Therapeutics Corporation Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas
WO2023242324A1 (en) 2022-06-17 2023-12-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for targeting progranulin
WO2024006999A2 (en) 2022-06-30 2024-01-04 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2024017990A1 (en) 2022-07-21 2024-01-25 Institut National de la Santé et de la Recherche Médicale Methods and compositions for treating chronic pain disorders
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
WO2024040041A1 (en) 2022-08-15 2024-02-22 Dicerna Pharmaceuticals, Inc. Regulation of activity of rnai molecules
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
EP4332221A1 (en) 2022-08-29 2024-03-06 Roche Innovation Center Copenhagen A/S Threose nucleic acid antisense oligonucleotides and methods thereof
WO2024052403A1 (en) 2022-09-06 2024-03-14 F. Hoffmann-La Roche Ag Double-stranded rna molecule for administration to the eye
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
US20240182561A1 (en) 2022-11-04 2024-06-06 Regeneron Pharmaceuticals, Inc. Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle
WO2024107765A2 (en) 2022-11-14 2024-05-23 Regeneron Pharmaceuticals, Inc. Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes
WO2024119145A1 (en) 2022-12-01 2024-06-06 Camp4 Therapeutics Corporation Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2024126654A1 (en) 2022-12-14 2024-06-20 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b
WO2024146935A1 (en) 2023-01-06 2024-07-11 Institut National de la Santé et de la Recherche Médicale Intravenous administration of antisense oligonucleotides for the treatment of pain
WO2024160756A1 (en) 2023-01-30 2024-08-08 Vib Vzw Suppressors of tauopathies
WO2024168010A2 (en) 2023-02-09 2024-08-15 Alnylam Pharmaceuticals, Inc. Reversir molecules and methods of use thereof
WO2024175588A1 (en) 2023-02-21 2024-08-29 Vib Vzw Oligonucleotides for modulating synaptogyrin-3 expression
WO2024175586A2 (en) 2023-02-21 2024-08-29 Vib Vzw Inhibitors of synaptogyrin-3 expression
CN117510564B (zh) * 2024-01-08 2024-03-08 苏州诺维康生物科技有限公司 一种医药中间体N2-Ac-5'-O-DMT-2'-O-炔丙基鸟苷的合成方法

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
NZ209840A (en) 1983-10-17 1988-11-29 Kaji Akira A method of inhibiting viral propagation by hybridising dna with the viral rna thus blocking its action
US5194428A (en) 1986-05-23 1993-03-16 Worcester Foundation For Experimental Biology Inhibition of influenza virus replication by oligonucleotide phosphorothioates
US4806463A (en) 1986-05-23 1989-02-21 Worcester Foundation For Experimental Biology Inhibition of HTLV-III by exogenous oligonucleotides
US5004810A (en) 1988-09-30 1991-04-02 Schering Corporation Antiviral oligomers
US5457189A (en) 1989-12-04 1995-10-10 Isis Pharmaceuticals Antisense oligonucleotide inhibition of papillomavirus
US5591623A (en) 1990-08-14 1997-01-07 Isis Pharmaceuticals, Inc. Oligonucleotide modulation of cell adhesion
US5514788A (en) 1993-05-17 1996-05-07 Isis Pharmaceuticals, Inc. Oligonucleotide modulation of cell adhesion
US5620963A (en) 1991-10-15 1997-04-15 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating protein kinase C having phosphorothioate linkages of high chiral purity
US5514577A (en) 1990-02-26 1996-05-07 Isis Pharmaceuticals, Inc. Oligonucleotide therapies for modulating the effects of herpes viruses
US5248670A (en) 1990-02-26 1993-09-28 Isis Pharmaceuticals, Inc. Antisense oligonucleotides for inhibiting herpesviruses
US5166195A (en) 1990-05-11 1992-11-24 Isis Pharmaceuticals, Inc. Antisense inhibitors of the human immunodeficiency virus phosphorothioate oligonucleotides
JPH06501843A (ja) 1990-08-14 1994-03-03 アイシス・ファーマシューティカルス・インコーポレーテッド アンチセンスオリゴヌクレオチドによるインフルエンザａ型ウイルス，アン・アーバｈ２ｎ２株の阻害
US6111094A (en) 1990-08-14 2000-08-29 Isis Pharmaceuticals Inc. Enhanced antisense modulation of ICAM-1
US5442049A (en) 1992-11-19 1995-08-15 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating the effects of cytomegalovirus infections
US5691461A (en) 1990-08-16 1997-11-25 Isis Pharmaceuticals, Inc. Oligonucleotides inhibiting candida germ tube formation
JP2708960B2 (ja) 1990-08-16 1998-02-04 アイシス・ファーマシューティカルス・インコーポレーテッド サイトメガウイルス感染の作用を変調するオリゴヌクレオチド
JP2515230Y2 (ja) * 1990-08-31 1996-10-30 徹 松井 道糸通し糸付き浮子
US5242906A (en) 1991-04-22 1993-09-07 University Of North Carolina At Chapel Hill Antisense oligonucleotides against Epstein-Barr virus
WO1994008003A1 (en) 1991-06-14 1994-04-14 Isis Pharmaceuticals, Inc. ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE
US5582986A (en) 1991-06-14 1996-12-10 Isis Pharmaceuticals, Inc. Antisense oligonucleotide inhibition of the ras gene
ATE186072T1 (de) 1991-06-14 1999-11-15 Isis Pharmaceuticals Inc Antisense-oligonukleotid-inhibition des ras-gen
US5661134A (en) 1991-10-15 1997-08-26 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity
US5607923A (en) 1991-10-15 1997-03-04 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity
US5681747A (en) 1992-03-16 1997-10-28 Isis Pharmaceuticals, Inc. Nucleic acid sequences encoding protein kinase C and antisense inhibition of expression thereof
US5523389A (en) 1992-09-29 1996-06-04 Isis Pharmaceuticals, Inc. Inhibitors of human immunodeficiency virus
US5985558A (en) 1997-04-14 1999-11-16 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the inibition of c-Jun and c-Fos
US6033784A (en) 1995-04-07 2000-03-07 Jacobsen; Mogens Havsteen Method of photochemical immobilization of ligands using quinones
US6127533A (en) 1997-02-14 2000-10-03 Isis Pharmaceuticals, Inc. 2'-O-aminooxy-modified oligonucleotides
BR9808838A (pt) * 1997-03-07 2000-07-04 Kvaerner Oilfield Prod As Terminação de um elemento de tensão para uso como um tendão para uma plataforma de perna de tensão
JP3756313B2 (ja) * 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US5877309A (en) 1997-08-13 1999-03-02 Isis Pharmaceuticals, Inc. Antisense oligonucleotides against JNK
JP4236812B2 (ja) * 1997-09-12 2009-03-11 エクシコン エ／エス オリゴヌクレオチド類似体
US6794499B2 (en) * 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US7572582B2 (en) * 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
US5955443A (en) 1998-03-19 1999-09-21 Isis Pharmaceuticals Inc. Antisense modulation of PECAM-1
US7084125B2 (en) * 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
CN1349541A (zh) * 1999-05-04 2002-05-15 埃克西库恩公司 L－核糖－lna类似物
JP4151751B2 (ja) 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
PT1210357E (pt) 1999-09-10 2008-06-11 Geron Corp Oligonucleótido-tiofosforamidatos n3'→p5': sua síntese e utilização
WO2005116207A1 (ja) * 2004-05-28 2005-12-08 Sankyo Company, Limited テロメラーゼ阻害ｅｎａオリゴヌクレオチド

Also Published As

Publication number Publication date
HU228398B1 (en) 2013-03-28
ID30093A (id) 2001-11-01
PT1152009E (pt) 2005-03-31
ZA200106544B (en) 2002-11-08
NO20013899D0 (no) 2001-08-10
PL208245B1 (pl) 2011-04-29
ES2234563T3 (es) 2005-07-01
HUP0105367A3 (en) 2005-10-28
TR200604211T1 (tr) 2007-02-21
CA2361318A1 (en) 2000-08-17
AU758956B2 (en) 2003-04-03
NZ513402A (en) 2003-06-30
DK1152009T3 (da) 2005-03-07
US7314923B2 (en) 2008-01-01
EP1152009A4 (en) 2002-06-05
HK1040084A1 (en) 2002-05-24
BRPI0008131B1 (pt) 2016-12-27
CA2361318C (en) 2008-11-25
BRPI0008131B8 (pt) 2021-05-25
NO320441B1 (no) 2005-12-05
DK1152009T4 (en) 2017-12-11
AU2459800A (en) 2000-08-29
US20030207841A1 (en) 2003-11-06
TR200102328T2 (tr) 2002-01-21
IL144338A (en) 2013-11-28
US20020147332A1 (en) 2002-10-10
DE60017711T2 (de) 2005-11-17
KR20020013498A (ko) 2002-02-20
CN1347418A (zh) 2002-05-01
CZ296576B6 (cs) 2006-04-12
TW513438B (en) 2002-12-11
EP1152009B1 (en) 2005-01-26
US20110009471A1 (en) 2011-01-13
ATE287897T2 (de) 2005-02-15
DE60017711D1 (de) 2005-03-03
WO2000047599A1 (fr) 2000-08-17
JP3420984B2 (ja) 2003-06-30
BR0008131A (pt) 2002-04-09
EP1152009B2 (en) 2017-09-06
RU2233844C2 (ru) 2004-08-10
DE60017711T3 (de) 2018-01-11
US8957201B2 (en) 2015-02-17
US7816333B2 (en) 2010-10-19
HK1040084B (zh) 2005-04-22
IL144338A0 (en) 2002-05-23
KR100573231B1 (ko) 2006-04-24
HUP0105367A2 (hu) 2002-05-29
CZ20012574A3 (cs) 2002-02-13
NO20013899L (no) 2001-10-10
CN1273478C (zh) 2006-09-06
US7335765B2 (en) 2008-02-26
EP1152009A1 (en) 2001-11-07
JP2000297097A (ja) 2000-10-24
US20090149404A1 (en) 2009-06-11

Similar Documents

Publication Publication Date Title
ES2234563T5 (es) Nuevos análogos de nucleósidos y oligonucleótidos
ES2880354T3 (es) Procesos para la síntesis de compuestos de diariltiohidantoína y diarilhidantoína
KR950003274A (ko) 복합약 내성 역전제로서 신규한 비시클릭아민 화합물
EP3611171B1 (en) Method for synthesis of eliglustat and intermediate compounds thereof
AU2006287696A1 (en) A process for preparing oxazolidine protected aminodiol compounds useful as intermediates to Florfenicol
JP2008540414A (ja) 場合により２−置換されていてもよい１，６−ジヒドロ−６−オキソ−４−ピリミジンカルボン酸の製造方法
BR112013000877B1 (pt) processo para a preparação de um ácido bifenil-2-il carbâmico
SE460540B (sv) Nya 2-oxopiperazinfoereningar samt foerfarande foer framstaellning daerav
WO2003101917A2 (en) A process for the preparation of phenylcarbamates
ES2211613T3 (es) Derivados de 4-hidroxibifenilhidrazida.
RU2011101972A (ru) Кристаллические формы спирокетальных производных и способ получения спирокетальных производных
EP3109246A1 (en) Thiopyranose compound and method for producing same
BR112015015229B1 (pt) processo para a preparação de um composto da fórmula, e, composto
KR920021519A (ko) 고순도 1-(3-클로로페닐)-4-메틸-7,8-디메톡시-5h-2,3-벤조디아제핀의 제조방법
BR0115785B1 (pt) Processo para preparação de iopamidol e intermediários do mesmo
HU203358B (en) Process for producing optically active borane complexes
RU2512591C2 (ru) Способ получения плевромутилинов
Smirnov et al. Reactions of chloromethoxy-substituted 3-(2-acetoxyethyl)-1-hydroxytriaz-1-ene 2-oxides with 1-alkoxy-3-(2-hydroxyethyl) triaz-1-ene 2-oxide alkali salts
CA2162761C (en) Antineoplastic cyclolignan derivatives
EP3573615B1 (en) A process for preparing 5-phenoxy-1(3h)isobenzofuranone
DE69722949D1 (de) Verfahren zur herstellung acylierter hexaazaisowurtzitan-derivate
FR2526019A1 (fr) Nouveaux derives de la pleuromutiline, leur preparation et leur utilisation comme medicaments
CZ314696A3 (en) Process for preparing carbazates
EP0149201B1 (de) Neue Carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
ES2212331T3 (es) Procedimiento para la preparacion de derivados del acido 2-alquiltiobenzoico.