UA61997C2 - Nucleosides with bicyclic sugar constituent, oligonucleotide and antiviral pharmaceutical composition - Google Patents
Nucleosides with bicyclic sugar constituent, oligonucleotide and antiviral pharmaceutical composition Download PDFInfo
- Publication number
- UA61997C2 UA61997C2 UA2000116545A UA2000116545A UA61997C2 UA 61997 C2 UA61997 C2 UA 61997C2 UA 2000116545 A UA2000116545 A UA 2000116545A UA 2000116545 A UA2000116545 A UA 2000116545A UA 61997 C2 UA61997 C2 UA 61997C2
- Authority
- UA
- Ukraine
- Prior art keywords
- nucleosides
- solution
- dioxabicyclo
- pharmaceutical composition
- mmol
- Prior art date
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- 239000002777 nucleoside Substances 0.000 title claims abstract description 44
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 21
- 125000003835 nucleoside group Chemical group 0.000 title claims abstract description 21
- 125000002619 bicyclic group Chemical group 0.000 title claims description 21
- 235000000346 sugar Nutrition 0.000 title claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 title claims 5
- 230000000840 anti-viral effect Effects 0.000 title claims 2
- 239000000470 constituent Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 10
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 239000001226 triphosphate Substances 0.000 claims description 8
- 235000011178 triphosphate Nutrition 0.000 claims description 7
- 229940113082 thymine Drugs 0.000 claims description 5
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 4
- 229940035893 uracil Drugs 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 2
- 229930024421 Adenine Natural products 0.000 claims description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 2
- 229960000643 adenine Drugs 0.000 claims description 2
- 229940104302 cytosine Drugs 0.000 claims description 2
- 239000001177 diphosphate Substances 0.000 claims description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 2
- 235000011180 diphosphates Nutrition 0.000 claims description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 2
- 241000725303 Human immunodeficiency virus Species 0.000 claims 4
- 241000700721 Hepatitis B virus Species 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
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- 238000004587 chromatography analysis Methods 0.000 description 34
- 239000000377 silicon dioxide Substances 0.000 description 33
- 239000000203 mixture Substances 0.000 description 32
- 238000005481 NMR spectroscopy Methods 0.000 description 27
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
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- 238000011282 treatment Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
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- 238000006243 chemical reaction Methods 0.000 description 12
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- 230000005494 condensation Effects 0.000 description 11
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 10
- -1 nucleoside triphosphates Chemical class 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
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Classifications
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- 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
-
- 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
-
- 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
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- 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
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compounds Of Unknown Constitution (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8671998P | 1998-05-26 | 1998-05-26 | |
| PCT/US1999/011442 WO1999060855A1 (en) | 1998-05-26 | 1999-05-24 | Novel nucleosides having bicyclic sugar moiety |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA61997C2 true UA61997C2 (en) | 2003-12-15 |
Family
ID=22200439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2000116545A UA61997C2 (en) | 1998-05-26 | 1999-05-24 | Nucleosides with bicyclic sugar constituent, oligonucleotide and antiviral pharmaceutical composition |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US6403566B1 (sh) |
| EP (1) | EP1082012A4 (sh) |
| JP (1) | JP2002516256A (sh) |
| CN (1) | CN1311630A (sh) |
| AU (1) | AU757724B2 (sh) |
| BR (1) | BR9911596A (sh) |
| CA (1) | CA2333380A1 (sh) |
| HR (1) | HRP20000751A2 (sh) |
| HU (1) | HUP0102152A3 (sh) |
| IL (1) | IL139420A0 (sh) |
| MX (1) | MXPA00011473A (sh) |
| NO (1) | NO20005938L (sh) |
| NZ (1) | NZ507913A (sh) |
| PL (1) | PL344303A1 (sh) |
| RU (1) | RU2211223C2 (sh) |
| SI (1) | SI20474A (sh) |
| SK (1) | SK17432000A3 (sh) |
| UA (1) | UA61997C2 (sh) |
| WO (1) | WO1999060855A1 (sh) |
| YU (1) | YU73600A (sh) |
| ZA (1) | ZA200006315B (sh) |
Families Citing this family (96)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20040033977A1 (en) * | 1990-08-14 | 2004-02-19 | Bennett C. Frank | Oligonucleotide modulation of cell adhesion |
| US7119184B2 (en) * | 1991-08-12 | 2006-10-10 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
| CA2190304A1 (en) * | 1995-12-15 | 1997-06-16 | Elazar Rabbani | Property effecting and/or property exhibiting compositions for therapeutic and diagnostic uses |
| US6833361B2 (en) * | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| US6900186B1 (en) * | 1999-06-21 | 2005-05-31 | Murdock Children's Research Institute | Method for the prophylaxis and/or treatment of medical disorders |
| WO2004044132A2 (en) * | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
| WO2005009418A2 (en) * | 2003-07-25 | 2005-02-03 | Idenix (Cayman) Limited | Purine nucleoside analogues for treating diseases caused by flaviviridae including hepatitis c |
| JP4731324B2 (ja) | 2003-08-28 | 2011-07-20 | 武 今西 | Ｎ−ｏ結合性架橋構造型新規人工核酸 |
| US7480382B2 (en) * | 2003-09-30 | 2009-01-20 | Microsoft Corporation | Image file container |
| US20050182252A1 (en) | 2004-02-13 | 2005-08-18 | Reddy K. R. | Novel 2'-C-methyl nucleoside derivatives |
| WO2007087113A2 (en) * | 2005-12-28 | 2007-08-02 | The Scripps Research Institute | Natural antisense and non-coding rna transcripts as drug targets |
| HUE040417T2 (hu) | 2007-05-04 | 2019-03-28 | Marina Biotech Inc | Aminosavlipidek és alkalmazásuk |
| US20100015708A1 (en) * | 2008-06-18 | 2010-01-21 | Mdrna, Inc. | Ribonucleic acids with non-standard bases and uses thereof |
| MY188457A (en) * | 2008-10-03 | 2021-12-10 | Opko Curna Llc | Treatment of apolipoprotein-a1 related diseases by inhibition of natural antisense transcript to apolipoprotein-a1 |
| AU2009305639B2 (en) | 2008-10-16 | 2016-06-23 | Marina Biotech, Inc. | Processes and compositions for liposomal and efficient delivery of gene silencing therapeutics |
| EP2447274B1 (en) | 2008-10-24 | 2017-10-04 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| CN102317458B (zh) * | 2008-12-04 | 2018-01-02 | 库尔纳公司 | 通过红细胞生成素(epo)天然反义转录物的抑制对epo相关疾病的治疗 |
| EP2370581B1 (en) | 2008-12-04 | 2016-08-03 | CuRNA, Inc. | Treatment of vascular endothelial growth factor (vegf) related diseases by inhibition of natural antisense transcript to vegf |
| KR101866152B1 (ko) | 2008-12-04 | 2018-06-08 | 큐알엔에이, 인크. | 종양 억제 유전자에 대한 천연 안티센스 전사체의 억제에 의해 종양 억제 유전자 관련된 질환의 치료 |
| HUE026280T2 (en) | 2009-02-12 | 2016-06-28 | Curna Inc | Treatment of brain-derived neurotrophic factor (BDNF) -related diseases by inhibition of natural antisense transcripts associated with BDNF \ t |
| 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 |
| JP5904935B2 (ja) | 2009-03-17 | 2016-04-20 | クルナ・インコーポレーテッド | デルタ様１ホモログ（ｄｌｋ１）に対する天然アンチセンス転写物の抑制によるｄｌｋ１関連疾患の治療 |
| ES2609655T3 (es) | 2009-05-06 | 2017-04-21 | Curna, Inc. | Tratamiento de enfermedades relacionadas con tristetraprolina (TTP) mediante inhibición de transcrito antisentido natural para TTP |
| CA2761152A1 (en) | 2009-05-06 | 2010-11-11 | Opko Curna, Llc | Treatment of lipid transport and metabolism gene related diseases by inhibition of natural antisense transcript to a lipid transport and metabolism gene |
| KR101742334B1 (ko) | 2009-05-08 | 2017-06-01 | 큐알엔에이, 인크. | Ｄｍｄ 패밀리에 대한 천연 안티센스 전사체의 억제에 의한 디스트로핀 패밀리 관련된 질환의 치료 |
| US8957037B2 (en) | 2009-05-18 | 2015-02-17 | Curna, Inc. | Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor |
| CN102549158B (zh) | 2009-05-22 | 2017-09-26 | 库尔纳公司 | 通过抑制针对转录因子e3(tfe3)的天然反义转录物来治疗tfe3和胰岛素受体底物蛋白2(irs2)相关的疾病 |
| EP2435571B1 (en) | 2009-05-28 | 2016-12-14 | CuRNA, Inc. | Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene |
| KR101702689B1 (ko) | 2009-06-16 | 2017-02-06 | 큐알엔에이, 인크. | Ｐｏｎ1에 대한 천연 안티센스 전사체의 억제에 의한 파라옥소나제 1(ｐｏｎ1) 관련된 질환의 치료 |
| CN102695797B (zh) | 2009-06-16 | 2018-05-25 | 库尔纳公司 | 通过抑制针对胶原基因的天然反义转录物来治疗胶原基因相关的疾病 |
| CA2765889A1 (en) | 2009-06-24 | 2010-12-29 | Opko Curna, Llc | Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2 |
| EP2446037B1 (en) | 2009-06-26 | 2016-04-20 | CuRNA, Inc. | Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene |
| CN102712925B (zh) | 2009-07-24 | 2017-10-27 | 库尔纳公司 | 通过抑制sirtuin(sirt)的天然反义转录物来治疗sirtuin(sirt)相关性疾病 |
| CN102762731B (zh) | 2009-08-05 | 2018-06-22 | 库尔纳公司 | 通过抑制针对胰岛素基因(ins)的天然反义转录物来治疗胰岛素基因(ins)相关的疾病 |
| EP2464731B1 (en) | 2009-08-11 | 2016-10-05 | CuRNA, Inc. | Treatment of adiponectin (adipoq) related diseases by inhibition of natural antisense transcript to an adiponectin (adipoq) |
| CA2771228C (en) | 2009-08-21 | 2020-12-29 | Opko Curna, Llc | Treatment of 'c terminus of hsp70-interacting protein' (chip) related diseases by inhibition of natural antisense transcript to chip |
| US9023822B2 (en) | 2009-08-25 | 2015-05-05 | Curna, Inc. | Treatment of 'IQ motif containing GTPase activating protein' (IQGAP) related diseases by inhibition of natural antisense transcript to IQGAP |
| EP2480669B1 (en) | 2009-09-25 | 2017-11-08 | CuRNA, Inc. | Treatment of filaggrin (flg) related diseases by modulation of flg expression and activity |
| CN102596983B (zh) * | 2009-10-29 | 2016-06-15 | 国立大学法人大阪大学 | 交联型人工核苷和核苷酸 |
| CN102712927B (zh) | 2009-12-16 | 2017-12-01 | 库尔纳公司 | 通过抑制膜结合转录因子肽酶，位点1(mbtps1)的天然反义转录物来治疗mbtps1相关疾病 |
| CN102869776B (zh) | 2009-12-23 | 2017-06-23 | 库尔纳公司 | 通过抑制肝细胞生长因子(hgf)的天然反义转录物而治疗hgf相关疾病 |
| CN102781480B (zh) | 2009-12-23 | 2018-07-27 | 库尔纳公司 | 通过抑制解偶联蛋白2(ucp2)的天然反义转录物而治疗ucp2相关疾病 |
| EP2519633B1 (en) | 2009-12-29 | 2017-10-25 | CuRNA, Inc. | Treatment of nuclear respiratory factor 1 (nrf1) related diseases by inhibition of natural antisense transcript to nrf1 |
| CN102770540B (zh) | 2009-12-29 | 2017-06-23 | 库尔纳公司 | 通过抑制肿瘤蛋白63(p63)的天然反义转录物而治疗p63相关疾病 |
| JP6083735B2 (ja) | 2009-12-31 | 2017-02-22 | カッパーアールエヌエー，インコーポレイテッド | インスリン受容体基質２（ｉｒｓ２）および転写因子３（ｔｆｅ３）に対する天然アンチセンス転写物の阻害によるインスリン受容体基質２（ｉｒｓ２）関連疾患の治療 |
| CN102906264B (zh) | 2010-01-04 | 2017-08-04 | 库尔纳公司 | 通过抑制干扰素调节因子8(irf8)的天然反义转录物而治疗irf8相关疾病 |
| CN102822342B (zh) | 2010-01-06 | 2017-05-10 | 库尔纳公司 | 通过抑制胰腺发育基因的天然反义转录物而治疗胰腺发育基因相关疾病 |
| JP6027893B2 (ja) | 2010-01-11 | 2016-11-16 | カッパーアールエヌエー，インコーポレイテッド | 性ホルモン結合グロブリン（ｓｈｂｇ）に対する天然アンチセンス転写物の阻害による性ホルモン結合グロブリン（ｓｈｂｇ）関連疾患の治療 |
| NO2529015T3 (sh) | 2010-01-25 | 2018-04-14 | ||
| US8962586B2 (en) | 2010-02-22 | 2015-02-24 | Curna, Inc. | Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related diseases by inhibition of natural antisense transcript to PYCR1 |
| WO2011115818A1 (en) | 2010-03-17 | 2011-09-22 | Isis Pharmaceuticals, Inc. | 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom |
| EP2553098B1 (en) | 2010-04-02 | 2017-10-11 | CuRNA, Inc. | Treatment of colony-stimulating factor 3 (csf3) related diseases by inhibition of natural antisense transcript to csf3 |
| KR101900962B1 (ko) | 2010-04-09 | 2018-09-20 | 큐알엔에이, 인크. | 섬유아세포 성장 인자 21 (ｆｇｆ21)에 대한 자연 안티센스 전사체의 저해에 의한 섬유아세포 성장 인자 21 (ｆｇｆ21) 관련된 질환의 치료 |
| EP2563922A1 (en) | 2010-04-26 | 2013-03-06 | Marina Biotech, Inc. | Nucleic acid compounds with conformationally restricted monomers and uses thereof |
| CN103154014B (zh) | 2010-04-28 | 2015-03-25 | Isis制药公司 | 修饰核苷、其类似物以及由它们制备的寡聚化合物 |
| US9127033B2 (en) | 2010-04-28 | 2015-09-08 | Isis Pharmaceuticals, Inc. | 5′ modified nucleosides and oligomeric compounds prepared therefrom |
| CA2798218A1 (en) | 2010-05-03 | 2011-11-10 | Curna, Inc. | Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (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 |
| NO2576783T3 (sh) | 2010-05-26 | 2018-04-28 | ||
| US8980858B2 (en) | 2010-05-26 | 2015-03-17 | Curna, Inc. | Treatment of methionine sulfoxide reductase a (MSRA) related diseases by inhibition of natural antisense transcript to MSRA |
| WO2011163499A2 (en) | 2010-06-23 | 2011-12-29 | Opko Curna, Llc | Treatment of sodium channel, voltage-gated, alpha subunit (scna) related diseases by inhibition of natural antisense transcript to scna |
| ES2663598T3 (es) | 2010-07-14 | 2018-04-16 | Curna, Inc. | Tratamiento de enfermedades relacionadas con el homólogo de discos grandes (dlg) mediante la inhibición del transcrito antisentido natural a dlg |
| KR101886457B1 (ko) | 2010-10-06 | 2018-08-07 | 큐알엔에이, 인크. | 시알리다아제 4 (neu4)에 대한 자연 안티센스 전사체의 저해에 의한 neu4 관련된 질환의 치료 |
| EP2630241B1 (en) | 2010-10-22 | 2018-10-17 | CuRNA, Inc. | Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua |
| US9416360B2 (en) | 2010-11-05 | 2016-08-16 | MiRagen Therapeutics, Inc. | Base modified oligonucleotides |
| WO2012068340A2 (en) | 2010-11-18 | 2012-05-24 | Opko Curna Llc | Antagonat compositions and methods of use |
| KR102010598B1 (ko) | 2010-11-23 | 2019-08-13 | 큐알엔에이, 인크. | Nanog에 대한 자연 안티센스 전사체의 저해에 의한 nanog 관련된 질환의 치료 |
| SG190355A1 (en) | 2010-12-15 | 2013-07-31 | Miragen Therapeutics | Microrna inhibitors comprising locked nucleotides |
| EP2697374A2 (en) | 2011-04-12 | 2014-02-19 | Beth Israel Deaconess Medical Center, Inc. | Micro-rna inhibitors and their uses in disease |
| KR20140037868A (ko) | 2011-05-09 | 2014-03-27 | 더 유니버시티 코트 오브 더 유니버시티 오브 글래스고우 | 폐동맥 고혈압의 치료에서 마이크로rna를 조절하는 방법 |
| US9593330B2 (en) | 2011-06-09 | 2017-03-14 | Curna, Inc. | Treatment of frataxin (FXN) related diseases by inhibition of natural antisense transcript to FXN |
| WO2013036403A1 (en) | 2011-09-06 | 2013-03-14 | Curna, Inc. | TREATMENT OF DISEASES RELATED TO ALPHA SUBUNITS OF SODIUM CHANNELS, VOLTAGE-GATED (SCNxA) WITH SMALL MOLECULES |
| CA2863253A1 (en) * | 2011-09-07 | 2013-03-14 | Marina Biotech, Inc. | Synthesis and uses of nucleic acid compounds with conformationally restricted monomers |
| EP2806878A1 (en) * | 2012-01-23 | 2014-12-03 | Can-Fite Biopharma Ltd. | Treatment of liver conditions |
| HUE040179T2 (hu) | 2012-03-15 | 2019-02-28 | Curna Inc | Agyi eredetû neutrotróf faktorral (Brain-derived neurotrophic factor, BDNF) összefüggõ betegségek kezelése a BDNF-fel kapcsolatos természetes antiszensz transzkriptumok gátlása révén |
| EP3354734B1 (en) | 2012-06-21 | 2020-06-10 | Miragen Therapeutics, Inc. | Oligonucleotide-based inhibitors comprising locked nucleic acid motif |
| EP2957567B1 (en) * | 2013-02-18 | 2019-06-05 | Shionogi & Co., Ltd. | Nucleoside and nucleotide, having nitrogen-containing hetercycle structure |
| WO2014151835A1 (en) | 2013-03-15 | 2014-09-25 | Miragen Therapeutics, Inc | Locked nucleic acid inhibitor of mir-145 and uses thereof |
| CA2902571A1 (en) | 2013-03-15 | 2014-09-18 | MiRagen Therapeutics, Inc. | Bridged bicyclic nucleosides |
| EP3105238A4 (en) | 2014-02-13 | 2017-11-08 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
| JP2017512774A (ja) * | 2014-03-16 | 2017-05-25 | ミラゲン セラピューティクス， インコーポレイテッド | 二環式ヌクレオシドの合成 |
| WO2016003812A1 (en) | 2014-07-02 | 2016-01-07 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and uses therof |
| KR20170042625A (ko) | 2014-08-04 | 2017-04-19 | 미라젠 세러퓨틱스 인코포레이티드 | Myh7b의 억제제 및 이의 용도 |
| EP3247716A4 (en) | 2015-01-20 | 2018-10-17 | Miragen Therapeutics, Inc. | Mir-92 inhibitors and uses thereof |
| EP3256591A4 (en) | 2015-02-13 | 2018-08-08 | Translate Bio Ma, Inc. | Hybrid oligonucleotides and uses thereof |
| RU2718534C2 (ru) | 2015-06-05 | 2020-04-08 | Мираджен Терапьютикс, Инк. | Ингибиторы mir-155 для лечения кожной t-клеточной лимфомы (ctcl) |
| EP3415524A4 (en) * | 2016-01-07 | 2019-09-04 | Osaka University | INHIBITOR OF EXPRESSION OF α-SYNUCLEIN |
| WO2018009466A1 (en) | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
| WO2019009298A1 (ja) * | 2017-07-05 | 2019-01-10 | 国立大学法人大阪大学 | α－シヌクレイン発現抑制剤 |
| CN111788196A (zh) | 2018-01-09 | 2020-10-16 | 配体药物公司 | 缩醛化合物及其治疗用途 |
| US11447775B2 (en) | 2018-01-12 | 2022-09-20 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
| KR20200131287A (ko) | 2018-03-14 | 2020-11-23 | 베스 이스라엘 데코니스 메디칼 센터 | 마이크로-rna 22의 억제제 |
| EP3833762A4 (en) | 2018-08-09 | 2022-09-28 | Verseau Therapeutics, Inc. | OLIGONUCLEOTIDE COMPOSITIONS FOR TARGETING CCR2 AND CSF1R AND THEIR USES |
| EP4269586A1 (en) | 2022-04-29 | 2023-11-01 | Johann-Wolfgang-Goethe-Universität Frankfurt am Main | Targeting micro rna for treatment of heart failure with preserved ejection fraction (hfpef) |
| EP4353823A1 (en) | 2022-10-12 | 2024-04-17 | Resalis Therapeutics S.r.l. | Inhibitors of micro-rna 22 |
Family Cites Families (2)
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| DE59208572D1 (de) * | 1991-10-17 | 1997-07-10 | Ciba Geigy Ag | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| ES2242291T5 (es) | 1997-09-12 | 2016-03-11 | Exiqon A/S | Análogos de nucleósidos bicíclicos y tricíclicos, nucleótidos y oligonucleótidos |
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- 1999-05-24 HU HU0102152A patent/HUP0102152A3/hu unknown
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| RU2211223C2 (ru) | 2003-08-27 |
| IL139420A0 (en) | 2001-11-25 |
| PL344303A1 (en) | 2001-10-22 |
| SI20474A (sl) | 2001-08-31 |
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| EP1082012A1 (en) | 2001-03-14 |
| ZA200006315B (en) | 2002-02-04 |
| AU4010099A (en) | 1999-12-13 |
| WO1999060855A1 (en) | 1999-12-02 |
| CA2333380A1 (en) | 1999-12-02 |
| EP1082012A4 (en) | 2002-01-16 |
| NO20005938D0 (no) | 2000-11-24 |
| MXPA00011473A (es) | 2002-04-24 |
| HRP20000751A2 (en) | 2001-12-31 |
| NO20005938L (no) | 2001-01-16 |
| US6403566B1 (en) | 2002-06-11 |
| HUP0102152A3 (en) | 2002-04-29 |
| YU73600A (sh) | 2003-08-29 |
| SK17432000A3 (sk) | 2001-07-10 |
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