AU2011343642A1 - Inhibitors of influenza viruses replication - Google Patents
Inhibitors of influenza viruses replication Download PDFInfo
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- AU2011343642A1 AU2011343642A1 AU2011343642A AU2011343642A AU2011343642A1 AU 2011343642 A1 AU2011343642 A1 AU 2011343642A1 AU 2011343642 A AU2011343642 A AU 2011343642A AU 2011343642 A AU2011343642 A AU 2011343642A AU 2011343642 A1 AU2011343642 A1 AU 2011343642A1
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- Prior art date
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- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
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- 239000003549 soybean oil Substances 0.000 description 1
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- 239000008223 sterile water Substances 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
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- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Pulmonology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42394310P | 2010-12-16 | 2010-12-16 | |
| US61/423,943 | 2010-12-16 | ||
| US201161527273P | 2011-08-25 | 2011-08-25 | |
| US61/527,273 | 2011-08-25 | ||
| PCT/US2011/065371 WO2012083117A1 (en) | 2010-12-16 | 2011-12-16 | Inhibitors of influenza viruses replication |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2011343642A1 true AU2011343642A1 (en) | 2013-05-02 |
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| AU2011343642A Abandoned AU2011343642A1 (en) | 2010-12-16 | 2011-12-16 | Inhibitors of influenza viruses replication |
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| Country | Link |
|---|---|
| US (1) | US8871774B2 (enExample) |
| EP (1) | EP2651940A1 (enExample) |
| JP (1) | JP2013545816A (enExample) |
| KR (1) | KR20140014110A (enExample) |
| CN (1) | CN103492381A (enExample) |
| AU (1) | AU2011343642A1 (enExample) |
| CA (1) | CA2822057A1 (enExample) |
| MX (1) | MX2013006836A (enExample) |
| RU (1) | RU2013132681A (enExample) |
| WO (1) | WO2012083117A1 (enExample) |
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| KR101903354B1 (ko) | 2009-06-17 | 2018-10-04 | 버텍스 파마슈티칼스 인코포레이티드 | 인플루엔자 바이러스 복제의 억제제 |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| DK3068776T3 (da) | 2013-11-13 | 2019-07-29 | Vertex Pharma | Inhibitorer af replikation af influenzavira |
| ES2684755T3 (es) | 2013-11-13 | 2018-10-04 | Vertex Pharmaceuticals Incorporated | Métodos para preparar inhibidores de la replicación de virus de la gripe |
| KR102488479B1 (ko) * | 2014-08-08 | 2023-01-12 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 인플루엔자 바이러스 감염에 사용하기 위한 인돌 |
| CN106661036B (zh) * | 2014-09-08 | 2022-03-15 | 爱尔兰詹森科学公司 | 用于在流感病毒感染中使用的吡咯并嘧啶 |
| JP6892433B2 (ja) | 2015-04-03 | 2021-06-23 | ユニバーシティ・オブ・マサチューセッツＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｍａｓｓａｃｈｕｓｅｔｔｓ | 十分に安定化された非対称ｓｉｒｎａ |
| WO2016183120A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| WO2016183116A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
| US10633653B2 (en) | 2015-08-14 | 2020-04-28 | University Of Massachusetts | Bioactive conjugates for oligonucleotide delivery |
| CN108290869B (zh) | 2015-11-27 | 2021-05-18 | 爱尔兰詹森科学公司 | 用于在流感病毒感染中使用的杂环吲哚 |
| CN109748915B (zh) | 2015-12-09 | 2021-03-26 | 广东东阳光药业有限公司 | 流感病毒复制抑制剂及其使用方法和用途 |
| HRP20202051T1 (hr) | 2016-01-20 | 2021-02-19 | Janssen Sciences Ireland Unlimited Company | Aril supstituirani pirimidini za uporabu kod infekcije virusom influence |
| JP7749201B6 (ja) | 2016-01-31 | 2025-10-21 | ユニバーシティー オブ マサチューセッツ | 分岐オリゴヌクレオチド |
| WO2017133667A1 (en) * | 2016-02-05 | 2017-08-10 | Savira Pharmaceuticals Gmbh | Pyrimidine and pyridine derivatives and use in treatment, amelioration or prevention of influenza thereof |
| WO2017133670A1 (en) * | 2016-02-05 | 2017-08-10 | Savira Pharmaceuticals Gmbh | Pyridine and pyrimidine derivatives and their use in treatment, amelioration or prevention of influenza |
| WO2017133657A1 (en) * | 2016-02-05 | 2017-08-10 | Savira Pharmaceuticals Gmbh | Pyridine and pyrimidine derivatives and their use in treatment, amelioration or prevention of influenza |
| WO2018033082A1 (en) | 2016-08-16 | 2018-02-22 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication, application methods and uses thereof |
| WO2018041091A1 (en) | 2016-08-30 | 2018-03-08 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication, application methods and uses thereof |
| US11136319B2 (en) * | 2016-09-05 | 2021-10-05 | Guangdong Raynovent Biotech Co., Ltd. | Anti-influenza virus pyrimidine derivative |
| US10987354B2 (en) | 2016-12-15 | 2021-04-27 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication and uses thereof |
| WO2018127096A1 (en) * | 2017-01-05 | 2018-07-12 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication and uses thereof |
| WO2018157830A1 (en) | 2017-03-02 | 2018-09-07 | Sunshine Lake Pharma Co., Ltd. | Inhibitors of influenza virus replication and uses thereof |
| US10844377B2 (en) | 2017-06-23 | 2020-11-24 | University Of Massachusetts | Two-tailed self-delivering siRNA |
| US11535613B2 (en) | 2018-03-05 | 2022-12-27 | Guangdong Raynovent Biotech Co., Ltd. | Crystal form and salt form of pyridoimidazole compound and preparation method therefor |
| CN110590768B (zh) * | 2018-06-13 | 2021-02-26 | 银杏树药业(苏州)有限公司 | 杂环化合物、其组合物及其作为抗流感病毒药物的应用 |
| AU2019311117B2 (en) * | 2018-07-27 | 2025-05-22 | Cocrystal Pharma, Inc. | Pyrrolo(2,3-b)pyridin derivatives as inhibitors of influenza virus replication |
| WO2020041769A1 (en) | 2018-08-23 | 2020-02-27 | University Of Massachusetts | O-methyl rich fully stabilized oligonucleotides |
| WO2020150636A1 (en) | 2019-01-18 | 2020-07-23 | University Of Massachusetts | Dynamic pharmacokinetic-modifying anchors |
| WO2020198509A2 (en) | 2019-03-26 | 2020-10-01 | University Of Massachusetts | Modified oligonucleotides with increased stability |
| CN114127068B (zh) | 2019-07-22 | 2024-05-28 | 广东众生睿创生物科技有限公司 | 嘧啶衍生物的优势盐型及其晶型 |
| MX2022001710A (es) | 2019-08-09 | 2022-05-10 | Univ Massachusetts | Oligonucleótidos modificados químicamente dirigidos a los snp. |
| CN114502150B (zh) * | 2019-09-10 | 2023-03-24 | 广东众生睿创生物科技有限公司 | 一种用于治疗病毒性感冒的药物组合物及其制剂 |
| US12365894B2 (en) | 2019-09-16 | 2025-07-22 | University Of Massachusetts | Branched lipid conjugates of siRNA for specific tissue delivery |
| CN110787170B (zh) * | 2019-12-19 | 2022-06-28 | 浙江立恩生物科技有限公司 | 一种治疗流感病毒感染的药物 |
| AU2021244600A1 (en) | 2020-03-26 | 2022-11-03 | University Of Massachusetts | Synthesis of modified oligonucleotides with increased stability |
| CN116323593B (zh) * | 2020-10-29 | 2025-06-03 | 广东众生睿创生物科技有限公司 | 一种嘧啶衍生物的晶型及其制备方法 |
Family Cites Families (127)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3829581A (en) * | 1970-07-23 | 1974-08-13 | Du Pont | Aliphatic polycyclic amidoximes as influenza antiviral agents |
| PT85662B (pt) | 1986-09-10 | 1990-06-29 | Sandoz Sa | Processo para a preparacao de derivados de aza-indol e de indolizina e de composicoes farmaceuticas que os contem |
| WO1990007926A1 (en) | 1989-01-20 | 1990-07-26 | Pfizer Inc. | 3-(1,2,5,6-tetrahydropyridyl)-pyrrolopyridines |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| FR2687402B1 (fr) | 1992-02-14 | 1995-06-30 | Lipha | Nouveaux azaindoles, procedes de preparation et medicaments les contenant. |
| DE4304455A1 (de) | 1993-02-15 | 1994-08-18 | Bayer Ag | Heterocyclisch substituierte Phenyl-cyclohexan-carbonsäurederivate |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| IL129871A (en) | 1994-05-06 | 2003-11-23 | Pharmacia & Upjohn Inc | Process for preparing 4-phenyl-substituted octanoyl-oxazolidin-2-one intermediates that are useful for preparing pyran-2-ones useful for treating retroviral infections |
| US6075037A (en) | 1994-06-09 | 2000-06-13 | Smithkline Beecham Corporation | Endothelin receptor antagonists |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| GB9721437D0 (en) | 1997-10-10 | 1997-12-10 | Glaxo Group Ltd | Heteroaromatic compounds and their use in medicine |
| US6313126B1 (en) | 1999-01-07 | 2001-11-06 | American Home Products Corp | Arylpiperazinyl-cyclohexyl indole derivatives for the treatment of depression |
| AU2494300A (en) | 1999-01-07 | 2000-07-24 | American Home Products Corporation | 3,4-dihydro-2h-benzo(1,4)oxazine derivatives |
| ES2219302T3 (es) | 1999-01-07 | 2004-12-01 | Wyeth | Derivados de arilpiperazinil-ciclohexilindol para el tratamiento de la depresion. |
| US6265403B1 (en) | 1999-01-20 | 2001-07-24 | Merck & Co., Inc. | Angiogenesis inhibitors |
| AR028475A1 (es) | 1999-04-22 | 2003-05-14 | Wyeth Corp | Derivados de azaindol y uso de los mismos para la manufactura de un medicamento para el tratamiento de la depresion. |
| US20030153560A1 (en) | 1999-04-23 | 2003-08-14 | Salituro Francesco G. | Inhibitors of c-Jun N-terminal kinases (JNK) |
| DE60027431T2 (de) | 1999-07-02 | 2007-07-12 | Stuart A. Rancho Santa Fe Lipton | Verwendung von p38 MAPK Inhibitoren in der Behandlung von Augenkrankheiten |
| GB9919843D0 (en) | 1999-08-20 | 1999-10-27 | Smithkline Beecham Plc | Novel compounds |
| DE19948417A1 (de) | 1999-10-07 | 2001-04-19 | Morphochem Ag | Imidazol-Derivate und ihre Verwendung als Arzneimittel |
| JP2003519143A (ja) | 1999-12-28 | 2003-06-17 | ファーマコピーア，インコーポレーティッド | ピリミジン及びトリアジン系キナーゼ阻害剤 |
| CA2400447C (en) | 2000-02-17 | 2008-04-22 | Amgen Inc. | Kinase inhibitors |
| US7041277B2 (en) | 2000-03-10 | 2006-05-09 | Cadbury Adams Usa Llc | Chewing gum and confectionery compositions with encapsulated stain removing agent compositions, and methods of making and using the same |
| CA2308994A1 (en) | 2000-05-19 | 2001-11-19 | Aegera Therapeutics Inc. | Neuroprotective compounds |
| HK1052705B (en) | 2000-08-14 | 2006-09-29 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted pyrazole |
| AU2001288714A1 (en) | 2000-09-06 | 2002-03-22 | Ortho-Mcneil Pharmaceutical, Inc. | A method for treating allergies |
| ES2309088T3 (es) | 2000-09-06 | 2008-12-16 | Ortho-Mcneil Pharmaceutical, Inc. | Uso de pirazoles sustituidos para el tratamiento de alergias. |
| EP1322652A1 (en) | 2000-09-22 | 2003-07-02 | Eli Lilly And Company | Stereoselective process for preparing cyclohexyl amine derivatives |
| KR20030062442A (ko) | 2000-12-22 | 2003-07-25 | 와이어쓰 | 5-하이드록시트립타민-6-리간드로서의 헤테로사이클인다졸및 아자인다졸 화합물 |
| EP1364212B1 (en) | 2001-03-02 | 2011-02-02 | GPC Biotech AG | Three hybrid assay system |
| EP1392697B1 (en) | 2001-03-14 | 2004-11-03 | Wyeth | Antidepressant azaheterocyclymethyl derivatives of 2,3-dihydro-1,4-dioxino 2,3-f]quinoline |
| AU2002258971A1 (en) | 2001-04-24 | 2002-11-05 | Wyeth | Antidepressant azaheterocyclylmethyl derivatives of 2,3-dihydro-1,4-benzodioxan |
| US6656950B2 (en) | 2001-04-25 | 2003-12-02 | Wyeth | Antidepressant azaheterocyclylmethyl derivatives of 1,4-dioxino[2,3-b]pyridine |
| DE60201590T2 (de) | 2001-04-26 | 2005-02-17 | Wyeth | Antidepressiv wirksame azaheterocyclymethyl-derivative von oxaheterocycyl-anellierten (1,4)-benzodioxanen |
| US6593350B2 (en) | 2001-04-26 | 2003-07-15 | Wyeth | Antidepressant indoletetrahydropyridine derivatives of 2,3-dihydro-7H-[1,4]dioxino[2,3-e]indole |
| MXPA03009828A (es) | 2001-04-26 | 2005-03-07 | Wyeth Corp | Sssri) azaheterociclilmetil derivados de 7,8-dihidro-3h-t,9-dioxa-1,3-diazaciclopenta[a]naftaleno como agentes antidepresivos. |
| MXPA03009826A (es) | 2001-04-26 | 2005-03-07 | Wyeth Corp | Azaheterociclilmetil derivados de 2,3-dihidro-1,4-dioxino[2,3-f]quinoxalina como agentes antidepresivos. |
| EP1381612A1 (en) | 2001-04-26 | 2004-01-21 | Wyeth | Antidepressant aza-heterocyclylmethyl derivatives of 2,3-dihydro-1,4-dioxino[2,3-f]quinazoline |
| US6555560B2 (en) | 2001-04-30 | 2003-04-29 | Wyeth | Antidepressant azaheterocyclylmethyl derivatives of 1,4,5-trioxa-phenanthrene |
| TR200402753T4 (tr) | 2001-04-30 | 2004-11-22 | Wyeth | 7,8-Dihidro-1,6,9-trioksa-3-aza-siklopenta[a]naftalen'in antidepresan azaheterosiklmetil türevleri. |
| GB0111186D0 (en) | 2001-05-08 | 2001-06-27 | Smithkline Beecham Plc | Novel compounds |
| MXPA03010524A (es) | 2001-05-17 | 2005-03-07 | Wyeth Corp | Proceso para la sintesis de derivados de la 2,3-dihidro-1,4-dioxino-[2,3-f]-quinolina. |
| EP1399440B1 (en) * | 2001-06-15 | 2009-06-03 | Vertex Pharmaceuticals Incorporated | 5-(2-aminopyrimidin-4-yl)benzisoxazoles as protein kinase inhibitors |
| GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| AR035083A1 (es) | 2001-07-25 | 2004-04-14 | Wyeth Corp | Derivados azaheterociclilmetilicos de 7,8-dihidro-6h-5-oxa-1-aza-fenantreno, composiciones farmaceuticas, el uso de dichos derivados para la preparacion de un medicamento antidepresivo e intermediarios |
| EP1417967A4 (en) | 2001-08-14 | 2007-03-28 | Toyama Chemical Co Ltd | NEW VIRUS PROTECTION INHIBITION, VIRCIDIDIC PROCEDURE AND NEW PYRADIN NUCLEOTIDE / PYRADIN NUCLEOSIDE ANALOGON |
| US6667322B2 (en) | 2001-10-05 | 2003-12-23 | Wyeth | Antidepressant chroman and chromene derivatives of 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole |
| US7361671B2 (en) | 2001-11-15 | 2008-04-22 | The Institute For Pharmaceutical Discovery, Inc. | Substituted heteroarylalkanoic acids |
| TW200306819A (en) | 2002-01-25 | 2003-12-01 | Vertex Pharma | Indazole compounds useful as protein kinase inhibitors |
| EP1506189A1 (en) | 2002-04-26 | 2005-02-16 | Vertex Pharmaceuticals Incorporated | Pyrrole derivatives as inhibitors of erk2 and uses thereof |
| IL164209A0 (en) | 2002-05-31 | 2005-12-18 | Eisai Co Ltd | Pyrazole derivatives and pharmaceutical compositions containing the same |
| UA78999C2 (en) | 2002-06-04 | 2007-05-10 | Wyeth Corp | 1-(aminoalkyl)-3-sulfonylazaindoles as ligands of 5-hydroxytryptamine-6 |
| ATE339419T1 (de) | 2002-08-02 | 2006-10-15 | Vertex Pharma | Pyrazolenthaltende zusammensetzungen und ihre verwendung als gsk-3 inhibitoren |
| AU2002368154A1 (en) | 2002-08-08 | 2004-02-25 | Ribapharm Inc. | Improved synthesis for hydroxyalkylated heterocyclic bases |
| SE0202463D0 (sv) | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | Novel compounds |
| WO2004037814A1 (en) | 2002-10-25 | 2004-05-06 | Vertex Pharmaceuticals Incorporated | Indazolinone compositions useful as kinase inhibitors |
| DK1599478T3 (da) | 2003-02-26 | 2007-09-17 | Boehringer Ingelheim Pharma | Dihydropteridinoner, fremgangsmåde til fremstilling af disse og anvendelse af disse som lægemiddel |
| JP4787150B2 (ja) | 2003-03-06 | 2011-10-05 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | Ｊｎｋ阻害剤 |
| US7169801B2 (en) | 2003-03-17 | 2007-01-30 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| GB0308466D0 (en) | 2003-04-11 | 2003-05-21 | Novartis Ag | Organic compounds |
| WO2005000813A1 (en) | 2003-05-30 | 2005-01-06 | Imclone Systems Incorporated | Heteroarylamino-phenylketone derivatives and their use as kinase inhibitors |
| WO2004106298A1 (en) | 2003-05-30 | 2004-12-09 | Janssen Pharmaceutica N.V. | Indole derivatives with an improved antipsychotic activity |
| TWI339206B (en) | 2003-09-04 | 2011-03-21 | Vertex Pharma | Compositions useful as inhibitors of protein kinases |
| WO2005044181A2 (en) | 2003-09-09 | 2005-05-19 | Temple University-Of The Commonwealth System Of Higher Education | Protection of tissues and cells from cytotoxic effects of ionizing radiation by abl inhibitors |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| US20070066641A1 (en) | 2003-12-19 | 2007-03-22 | Prabha Ibrahim | Compounds and methods for development of RET modulators |
| US7504509B2 (en) | 2003-12-19 | 2009-03-17 | Plexxikon, Inc. | Compounds and methods for development of Ret modulators |
| GB0405055D0 (en) | 2004-03-05 | 2004-04-07 | Eisai London Res Lab Ltd | JNK inhibitors |
| SI2332940T1 (sl) * | 2004-03-30 | 2013-03-29 | Vertex Pharmaceuticals Incorporated | Azaindoli, uporabni kot inhibitorji jak in drugih protein-kinaz |
| EP2332940B1 (en) | 2004-03-30 | 2012-10-31 | Vertex Pharmaceuticals Incorporated | Azaindoles useful as inhibitors of JAK and other protein kinases |
| AU2005236002A1 (en) | 2004-04-02 | 2005-11-03 | Vertex Pharmaceuticals Incorporated | Azaindoles useful as inhibitors of rock and other protein kinases |
| ITMI20040874A1 (it) | 2004-04-30 | 2004-07-30 | Ist Naz Stud Cura Dei Tumori | Derivati indolici ed azaindolici con azione antitumorale |
| KR100476851B1 (ko) | 2004-05-18 | 2005-03-17 | (주)성신엔지니어링 | 중력식 섬유여과기 |
| DE102004029784A1 (de) | 2004-06-21 | 2006-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel |
| US20060122213A1 (en) | 2004-06-30 | 2006-06-08 | Francoise Pierard | Azaindoles useful as inhibitors of protein kinases |
| EP1781654A1 (en) | 2004-07-27 | 2007-05-09 | SGX Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| JP5002460B2 (ja) | 2004-10-04 | 2012-08-15 | ミレニアム ファーマシューティカルズ， インコーポレイテッド | タンパク質キナーゼインヒビターとして有用なラクタム化合物 |
| WO2006038001A1 (en) | 2004-10-06 | 2006-04-13 | Celltech R & D Limited | Aminopyrimidine derivatives as jnk inhibitors |
| WO2006050076A1 (en) | 2004-10-29 | 2006-05-11 | Janssen Pharmaceutica, N.V. | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
| DK1812440T3 (da) * | 2004-11-04 | 2011-01-31 | Vertex Pharma | Pyrazolo[1,5-a]pyrimidiner, der kan anvendes som inhibistorer af proteinkinaser |
| CN101098872B (zh) | 2004-11-22 | 2012-09-05 | 沃泰克斯药物股份有限公司 | 可用作蛋白激酶抑制剂的吡咯并吡嗪和吡唑并吡嗪 |
| JP4954086B2 (ja) | 2004-12-08 | 2012-06-13 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | １ｈ−ピロロ［２，３−ｂ］ピリジン |
| RU2423351C2 (ru) | 2004-12-16 | 2011-07-10 | Вертекс Фармасьютикалз Инкорпорейтед | Пирид-2-оны, применимые как ингибиторы протеинкиназ семейства тес для лечения воспалительных, пролиферативных и иммунологически-опосредованных заболеваний |
| US20060161001A1 (en) | 2004-12-20 | 2006-07-20 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| KR20070104641A (ko) | 2005-02-03 | 2007-10-26 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제의 억제제로 유용한 피롤로피리미딘 |
| ES2345629T3 (es) | 2005-05-16 | 2010-09-28 | Irm Llc | Derivados de pirrolopiridina como inhibidores de proteina quinasas. |
| NZ564065A (en) | 2005-05-20 | 2011-03-31 | Vertex Pharma | Pyrrolopyridines useful as inhibitors of protein kinase |
| TWI473808B (zh) | 2005-06-22 | 2015-02-21 | Plexxikon Inc | 用於激酶調節的化合物及方法及其適應症 |
| GB0516156D0 (en) | 2005-08-05 | 2005-09-14 | Eisai London Res Lab Ltd | JNK inhibitors |
| CN101801971A (zh) | 2005-09-30 | 2010-08-11 | 沃泰克斯药物股份有限公司 | 可用作janus激酶抑制剂的脱氮嘌呤 |
| CN102532134A (zh) * | 2006-01-17 | 2012-07-04 | 沃泰克斯药物股份有限公司 | 适用作詹纳斯激酶抑制剂的吖吲哚类 |
| AU2007215161A1 (en) | 2006-02-14 | 2007-08-23 | Vertex Pharmaceuticals Incorporated | Pyrrolo(3,2-C) pyridines useful as inhibitors of protein kinases |
| TW200804389A (en) | 2006-02-14 | 2008-01-16 | Vertex Pharma | Dihydrodiazepines useful as inhibitors of protein kinases |
| DE102006012617A1 (de) | 2006-03-20 | 2007-09-27 | Merck Patent Gmbh | 4-(Pyrrolopyridinyl)-pyrimidinyl-2-amin-derivate |
| CA2648250A1 (en) | 2006-04-05 | 2007-10-18 | Vertex Pharmaceuticals Incorporated | Deazapurines useful as inhibitors of janus kinases |
| WO2007129195A2 (en) * | 2006-05-04 | 2007-11-15 | Pfizer Products Inc. | 4-pyrimidine-5-amino-pyrazole compounds |
| US20090017444A1 (en) | 2006-06-09 | 2009-01-15 | Wisconsin Alumni Research Foundation | Screening method for modulators of viral transcription or replication |
| JP5642963B2 (ja) | 2006-06-30 | 2014-12-17 | スネシス ファーマシューティカルズ，インコーポレイティド | ピリジノニルｐｄｋ１阻害剤 |
| TW200808325A (en) | 2006-07-06 | 2008-02-16 | Astrazeneca Ab | Novel compounds |
| MX2009006345A (es) | 2006-12-14 | 2009-06-23 | Vertex Pharma | Compuestos utiles como inhibidores de proteina cinasa. |
| EP2124951B1 (en) | 2006-12-21 | 2014-05-21 | Vertex Pharmaceuticals Inc. | 5-cyan0-4- (pyrrolo[2, 3b]pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors |
| CN101663295B (zh) | 2007-03-09 | 2014-11-05 | 沃泰克斯药物股份有限公司 | 可用作蛋白激酶抑制剂的氨基嘧啶类化合物 |
| AU2008226466B2 (en) | 2007-03-09 | 2013-06-13 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as inhibitors of protein kinases |
| AU2008226461A1 (en) | 2007-03-09 | 2008-09-18 | Vertex Pharmaceuticals Incorporated | Aminopyridines useful as inhibitors of protein kinases |
| CA2680757A1 (en) | 2007-03-22 | 2008-09-25 | F. Hoffmann-La Roche Ag | Substituted pyrimidodiazepines useful as plk1 inhibitors |
| AU2008287339A1 (en) | 2007-08-15 | 2009-02-19 | Vertex Pharmaceuticals Incorporated | 4-(9-(3, 3-difluorocyclopentyl) -5, 7, 7-trimethyl-6-oxo-6, 7, 8, 9-tetrahydro-5H-pyrimido [4, 5-b][1, 4] diazepin-2-ylamino)-3-methoxybenzamide Derivatives as Inhibitors of the Human Protein Kinases PLK1 to PLK4 for the Treatment of Proliferative Diseases |
| CA2700979C (en) | 2007-09-28 | 2017-06-20 | Cyclacel Limited | Pyrimidine derivatives as protein kinase inhibitors |
| WO2009046983A1 (en) | 2007-10-09 | 2009-04-16 | European Molecular Biology Laboratory (Embl) | Soluble fragments of influenza virus pb2 protein capable of binding rna-cap |
| EP2215089B1 (en) | 2007-11-02 | 2012-06-27 | Vertex Pharmaceuticals Incorporated | [1h- pyrazolo [3, 4-b]pyridine-4-yl]-phenyle or -pyridin-2-yle derivatives as protein kinase c-theta |
| WO2009145814A2 (en) | 2008-03-10 | 2009-12-03 | Vertex Pharmaceuticals Incorporated | Pyrimidines and pyridines useful as inhibitors of protein kinases |
| CA2728729C (en) | 2008-06-23 | 2016-09-27 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors |
| MX2011000021A (es) | 2008-06-23 | 2011-02-24 | Vertex Pharma | Inhibidores de proteina cinasas. |
| WO2010003133A2 (en) * | 2008-07-03 | 2010-01-07 | Exelixis Inc. | Cdk modulators |
| US8569337B2 (en) | 2008-07-23 | 2013-10-29 | Vertex Pharmaceuticals Incorporated | Tri-cyclic pyrazolopyridine kinase inhibitors |
| AU2009274023A1 (en) | 2008-07-23 | 2010-01-28 | Vertex Pharmaceuticals Incorporated | Tri-cyclic pyrazolopyridine kinase inhibitors |
| EP2321318A1 (en) | 2008-07-23 | 2011-05-18 | Vertex Pharmaceuticals Incorporated | Pyrazolopyridine kinase inhibitors |
| KR20110039563A (ko) | 2008-07-23 | 2011-04-19 | 버텍스 파마슈티칼스 인코포레이티드 | 피라졸로피리딘 키나제 억제제 |
| JP2011529066A (ja) | 2008-07-23 | 2011-12-01 | バーテックス ファーマシューティカルズ インコーポレイテッド | 三環式ピラゾロピリジンキナーゼ阻害剤 |
| EP2427464A1 (en) | 2009-05-06 | 2012-03-14 | Vertex Pharmaceuticals Incorporated | Pyrazolopyridines |
| KR101903354B1 (ko) * | 2009-06-17 | 2018-10-04 | 버텍스 파마슈티칼스 인코포레이티드 | 인플루엔자 바이러스 복제의 억제제 |
| WO2011000566A2 (en) | 2009-06-30 | 2011-01-06 | Savira Pharmaceuticals Gmbh | Compounds and pharmaceutical compositions for the treatment of negative-sense ssrna virus infections |
| EP2454257B1 (en) | 2009-07-15 | 2013-08-21 | AbbVie Inc. | Pyrrolopyridine inhibitors of kinases |
| UA109131C2 (ru) | 2010-04-14 | 2015-07-27 | Еррей Біофарма Інк. | 5,7-ЗАМЕЩЕННЫЕ ИМИДАЗО[1,2-c]ПИРИМИДИНЫ КАК ИНГИБИТОРЫ JAK-КИНАЗ |
| WO2011137022A1 (en) | 2010-04-27 | 2011-11-03 | Merck Sharp & Dohme Corp. | Azaindoles as janus kinase inhibitors |
| KR20130128435A (ko) | 2010-12-16 | 2013-11-26 | 버텍스 파마슈티칼스 인코포레이티드 | 인플루엔자 바이러스 복제의 억제제 |
| WO2012083121A1 (en) | 2010-12-16 | 2012-06-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
-
2011
- 2011-12-16 EP EP11808474.8A patent/EP2651940A1/en not_active Withdrawn
- 2011-12-16 RU RU2013132681/04A patent/RU2013132681A/ru not_active Application Discontinuation
- 2011-12-16 WO PCT/US2011/065371 patent/WO2012083117A1/en not_active Ceased
- 2011-12-16 AU AU2011343642A patent/AU2011343642A1/en not_active Abandoned
- 2011-12-16 CA CA2822057A patent/CA2822057A1/en not_active Abandoned
- 2011-12-16 CN CN201180066550.8A patent/CN103492381A/zh active Pending
- 2011-12-16 MX MX2013006836A patent/MX2013006836A/es not_active Application Discontinuation
- 2011-12-16 JP JP2013544808A patent/JP2013545816A/ja active Pending
- 2011-12-16 KR KR1020137018521A patent/KR20140014110A/ko not_active Withdrawn
-
2013
- 2013-06-14 US US13/918,048 patent/US8871774B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR20140014110A (ko) | 2014-02-05 |
| US8871774B2 (en) | 2014-10-28 |
| CA2822057A1 (en) | 2012-06-21 |
| CN103492381A (zh) | 2014-01-01 |
| US20140005192A1 (en) | 2014-01-02 |
| JP2013545816A (ja) | 2013-12-26 |
| MX2013006836A (es) | 2013-09-26 |
| RU2013132681A (ru) | 2015-01-27 |
| WO2012083117A1 (en) | 2012-06-21 |
| EP2651940A1 (en) | 2013-10-23 |
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