CA3021068A1 - Combinations and methods comprising a capsid assembly inhibitor - Google Patents
Combinations and methods comprising a capsid assembly inhibitor Download PDFInfo
- Publication number
- CA3021068A1 CA3021068A1 CA3021068A CA3021068A CA3021068A1 CA 3021068 A1 CA3021068 A1 CA 3021068A1 CA 3021068 A CA3021068 A CA 3021068A CA 3021068 A CA3021068 A CA 3021068A CA 3021068 A1 CA3021068 A1 CA 3021068A1
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- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- reverse transcriptase
- transcriptase inhibitor
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- 239000012096 transfection reagent Substances 0.000 description 1
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Classifications
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- 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
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- A61K31/025—Halogenated hydrocarbons carbocyclic
- A61K31/03—Halogenated hydrocarbons carbocyclic aromatic
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- 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
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- A61K31/52—Purines, e.g. adenine
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- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
- C12N7/04—Inactivation or attenuation; Producing viral sub-units
- C12N7/06—Inactivation or attenuation by chemical treatment
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Virology (AREA)
- Molecular Biology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
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| US201662323251P | 2016-04-15 | 2016-04-15 | |
| US62/323,251 | 2016-04-15 | ||
| US201662421035P | 2016-11-11 | 2016-11-11 | |
| US62/421,035 | 2016-11-11 | ||
| PCT/US2017/027802 WO2017181141A2 (en) | 2016-04-15 | 2017-04-14 | Combinations and methods comprising a capsid assembly inhibitor |
Publications (1)
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| CA3021068A1 true CA3021068A1 (en) | 2017-10-19 |
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| EP (2) | EP3848026A1 (OSRAM) |
| JP (1) | JP2019511542A (OSRAM) |
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| MX (2) | MX2018012557A (OSRAM) |
| SG (2) | SG11201808949SA (OSRAM) |
| WO (1) | WO2017181141A2 (OSRAM) |
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| KR20160128305A (ko) | 2014-02-05 | 2016-11-07 | 노비라 테라퓨틱스, 인코포레이티드 | Hbv 감염의 치료를 위한 병용 요법 |
| JP6845231B2 (ja) * | 2015-09-29 | 2021-03-17 | ノヴィラ・セラピューティクス・インコーポレイテッド | Ｂ型肝炎抗ウイルス薬の結晶形態 |
| KR20180129943A (ko) | 2016-04-15 | 2018-12-05 | 노비라 테라퓨틱스, 인코포레이티드 | 캡시드 조립 억제제를 포함하는 배합물 및 방법 |
| US11335890B2 (en) | 2016-12-19 | 2022-05-17 | Pioneer Corporation | Light-emitting device and light-emitting system |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | ２，４－二胺基喹唑啉衍生物及其醫學用途 |
| EP3765011A1 (en) | 2018-03-14 | 2021-01-20 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
| CN114072142A (zh) * | 2019-04-18 | 2022-02-18 | 杨森制药公司 | 用于治疗乙型肝炎病毒感染的组合疗法 |
| AR119732A1 (es) | 2019-05-06 | 2022-01-05 | Janssen Sciences Ireland Unlimited Co | Derivados de amida útiles en el tratamiento de la infección por vhb o de enfermedades inducidas por vhb |
| WO2020255039A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and quinazoline derivatives |
| US20220305116A1 (en) * | 2019-06-18 | 2022-09-29 | Janssen Sciences lreland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and capsid assembly modulators being sulfonamide derivatives |
| TW202146008A (zh) * | 2020-02-27 | 2021-12-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | Ｈｂｖ的治療 |
| TW202146011A (zh) * | 2020-03-05 | 2021-12-16 | 美商詹森藥物公司 | 治療b型肝炎病毒感染之組合療法 |
| CN115515596A (zh) * | 2020-05-15 | 2022-12-23 | 福建广生中霖生物科技有限公司 | 包含三并环类化合物的组合及其在制备治疗hbv药物中的应用 |
| EP4241770A1 (en) * | 2020-11-05 | 2023-09-13 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Pharmaceutical combination containing capsid protein inhibitor and nucleoside analog |
Family Cites Families (240)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3843662A (en) | 1971-12-09 | 1974-10-22 | Pfizer | 2-halo-5-(substituted piperidino sulfonyl)benzoic acids |
| AU1508183A (en) | 1982-06-04 | 1983-12-08 | Beecham Group Plc | Benzamide and anilide derivatives of 8-azabicyclo-(3.2.1)- -octane |
| EP0135545A1 (en) | 1983-02-19 | 1985-04-03 | Beecham Group Plc | Azabicycloalkyl benzamide and anilide derivatives |
| JPS62142164A (ja) | 1985-12-13 | 1987-06-25 | Ishihara Sangyo Kaisha Ltd | ４，５−ジクロロイミダゾ−ル系化合物及びそれらを含有する有害生物防除剤 |
| IN164880B (OSRAM) | 1986-01-30 | 1989-06-24 | Ishihara Sangyo Kaisha | |
| US5272167A (en) | 1986-12-10 | 1993-12-21 | Schering Corporation | Pharmaceutically active compounds |
| CA1339133C (en) | 1987-03-13 | 1997-07-29 | Rikuo Nasu | Imidazole compounds and biocidal composition comprising the same for controlling harmful organisms |
| US5571821A (en) | 1993-05-20 | 1996-11-05 | Texas Biotechnology Corporation | Sulfonamides and derivatives thereof that modulate the activity of endothelin |
| GB8904174D0 (en) | 1989-02-23 | 1989-04-05 | British Bio Technology | Compounds |
| US4962101A (en) | 1989-08-21 | 1990-10-09 | Merck & Co., Inc. | 2-(Heterocyclylalkyl)phenyl carbapenem antibacterial agents |
| GB9023082D0 (en) | 1990-10-24 | 1990-12-05 | Schering Agrochemicals Ltd | Fungicides |
| GB9109557D0 (en) | 1991-05-02 | 1991-06-26 | Wellcome Found | Chemical compounds |
| US5308826A (en) | 1993-04-22 | 1994-05-03 | Zeneca Limited | Herbicidal 4-substituted pyridyl-3-carbinols |
| GB9405347D0 (en) | 1994-03-18 | 1994-05-04 | Agrevo Uk Ltd | Fungicides |
| US5795907A (en) | 1994-05-27 | 1998-08-18 | James Black Foundation Limited | Gastin and CCK receptor ligands |
| WO1995032949A1 (en) | 1994-05-27 | 1995-12-07 | James Black Foundation Limited | Gastrin and cck antagonists |
| US5763618A (en) | 1995-05-12 | 1998-06-09 | Konica Corporation | Manufacturing method of sulfides |
| US5723411A (en) | 1995-10-31 | 1998-03-03 | E. I. Du Pont De Nemours And Company | Herbicidal pyridazinones |
| DE19540995A1 (de) | 1995-11-03 | 1997-05-07 | Hoechst Ag | Substituierte Sulfonimidamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| GB9612884D0 (en) | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
| WO1997049695A1 (en) | 1996-06-25 | 1997-12-31 | Smithkline Beecham P.L.C. | Sulfonamide derivatives as 5ht7 receptor antagonists |
| AU5127098A (en) | 1996-11-29 | 1998-06-22 | Smithkline Beecham Plc | Use of a combination of penciclovir and alpha-interferon in the manufacture of a medicament for the treatment of hepatitis |
| US5939423A (en) | 1997-04-16 | 1999-08-17 | Sciclone Pharmaceuticals, Inc. | Treatment of hepatitis B infection with thymosin alpha 1 and famciclovir |
| US5919970A (en) | 1997-04-24 | 1999-07-06 | Allergan Sales, Inc. | Substituted diaryl or diheteroaryl methanes, ethers and amines having retinoid agonist, antagonist or inverse agonist type biological activity |
| EP1741424B1 (en) | 1997-08-11 | 2018-10-03 | Pfizer Products Inc. | Solid pharmaceutical dispersions with enhanced bioavailabilty |
| US5994396A (en) | 1997-08-18 | 1999-11-30 | Centaur Pharmaceuticals, Inc. | Furansulfonic acid derivatives and pharmaceutical compositions containing the same |
| AU759255B2 (en) | 1998-01-29 | 2003-04-10 | Amgen, Inc. | PPAR-gamma modulators |
| BR9909666A (pt) | 1998-03-26 | 2001-09-11 | Japan Tobacco Inc | Derivados de amida e antagonistas de nociceptina |
| US6251893B1 (en) | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
| CZ300366B6 (cs) | 1999-01-15 | 2009-05-06 | Nycomed Gmbh | Fenylfenanthridinová sloucenina, farmaceutický prostredek s jejím obsahem a její použití |
| ATE400251T1 (de) | 1999-02-09 | 2008-07-15 | Pfizer Prod Inc | Zusammensetzungen basischer arzneistoffe mit verbesserter bioverfügbarkeit |
| KR20020015376A (ko) | 1999-07-16 | 2002-02-27 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | Ｍｅｋ 억제제를 사용한 만성 통증의 치료 방법 |
| JP2003506406A (ja) | 1999-08-10 | 2003-02-18 | ザ・チャンセラー・マスターズ・アンド・スカラーズ・オブ・ザ・ユニバーシティ・オブ・オックスフォード | 長鎖ｎ−アルキル化合物およびそのオキサ誘導体 |
| CA2385592C (en) | 1999-09-17 | 2011-01-11 | Bing-Yan Zhu | Benzamides and related inhibitors of factor xa |
| PE20010628A1 (es) | 1999-10-01 | 2001-06-18 | Takeda Chemical Industries Ltd | Compuestos de amina ciclica, su produccion y su uso |
| SK8562002A3 (en) | 1999-12-23 | 2003-10-07 | Pfizer Prod Inc | Pharmaceutical compositions providing enhanced drug concentrations |
| AU2018301A (en) | 1999-12-28 | 2001-07-24 | Pfizer Products Inc. | Non-peptidyl inhibitors of vla-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases |
| WO2001055121A1 (en) | 2000-01-28 | 2001-08-02 | Kaken Pharmaceutical Co., Ltd. | Azepine derivatives |
| US6511980B2 (en) | 2000-05-05 | 2003-01-28 | Ortho Mcneil Pharmaceutical, Inc. | Substituted diamine derivatives useful as motilin antagonists |
| EP1193268A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| WO2002051410A2 (en) | 2000-12-22 | 2002-07-04 | Akzo Nobel N.V. | Phenylthiazole and thiazoline derivatives and their use as antiparasitics |
| DE60115501T2 (de) | 2000-12-27 | 2006-07-13 | Dainippon Sumitomo Pharma Co., Ltd. | Neue Carbapenemverbindungen, Arzneimittel und antibakterielles Mittel, das diese enthält, und deren Verwendungen |
| AU2002248418A1 (en) | 2001-02-09 | 2002-08-28 | Massachusetts Institute Of Technology | Methods of identifying agents that mediate polypeptide aggregation |
| US6650463B2 (en) | 2001-03-13 | 2003-11-18 | Seiko Epson Corporation | Electrophoretic display device |
| JP3795458B2 (ja) | 2001-04-19 | 2006-07-12 | エーザイ株式会社 | ２−イミノピロリジン誘導体 |
| HUP0400263A2 (hu) | 2001-06-21 | 2005-03-29 | Pfizer Products Inc. | Koleszteril-észter transzfer protein inhibitort tartalmazó önemulgeáló készítmény |
| EP1269994A3 (en) | 2001-06-22 | 2003-02-12 | Pfizer Products Inc. | Pharmaceutical compositions comprising drug and concentration-enhancing polymers |
| SE0102315D0 (sv) | 2001-06-28 | 2001-06-28 | Astrazeneca Ab | Compounds |
| KR100713137B1 (ko) | 2001-06-28 | 2007-05-02 | 동화약품공업주식회사 | 신규의 2,4-디플루오로벤즈아미드 유도체 |
| WO2003007955A2 (en) | 2001-07-20 | 2003-01-30 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| DE10136043A1 (de) | 2001-07-25 | 2003-02-13 | Degussa | Verfahren zur Herstellung von modifiziertem Ruß |
| US6956035B2 (en) | 2001-08-31 | 2005-10-18 | Inotek Pharmaceuticals Corporation | Isoquinoline derivatives and methods of use thereof |
| EP1448560B1 (en) | 2001-11-20 | 2005-06-15 | Eli Lilly And Company | 3-SUBSTITUTED OXINDOLE beta 3 AGONISTS |
| RU2004123621A (ru) | 2002-02-01 | 2005-04-10 | Пфайзер Продактс Инк. (Us) | Лекарственные формы с немедленным высвобождением, содержащие твердые дисперсии лекарств |
| EP1469830A2 (en) | 2002-02-01 | 2004-10-27 | Pfizer Products Inc. | Method for making homogeneous spray-dried solid amorphous drug dispersions using pressure nozzles |
| KR100664822B1 (ko) | 2002-02-01 | 2007-01-04 | 화이자 프로덕츠 인코포레이티드 | 변형된 분무-건조 장치를 이용한 균질한 분무-건조된 고체비결정성 약물 분산액의 제조 방법 |
| SE0201635D0 (sv) | 2002-05-30 | 2002-05-30 | Astrazeneca Ab | Novel compounds |
| CN1658849A (zh) | 2002-06-05 | 2005-08-24 | 株式会社医药分子设计研究所 | Ap－1和nfat活化抑制剂 |
| RU2340605C2 (ru) | 2002-06-27 | 2008-12-10 | Ново Нордиск А/С | Арилкарбонильные производные в качестве терапевтических средств |
| EP1531815B1 (en) | 2002-06-27 | 2014-09-24 | Novo Nordisk A/S | Glucokinase activators |
| WO2004010943A2 (en) | 2002-07-31 | 2004-02-05 | Smithkline Beecham Corporation | Substituted benzanilides as modulators of the ccr5 receptor |
| WO2004011427A2 (en) | 2002-07-31 | 2004-02-05 | Smithkline Beecham Corporation | Substituted benzanilides as modulators of the ccr5 receptor |
| US7186735B2 (en) | 2002-08-07 | 2007-03-06 | Sanofi-Aventis Deutschland Gmbh | Acylated arylcycloalkylamines and their use as pharmaceuticals |
| US7338956B2 (en) | 2002-08-07 | 2008-03-04 | Sanofi-Aventis Deutschland Gmbh | Acylamino-substituted heteroaromatic compounds and their use as pharmaceuticals |
| JP4399862B2 (ja) | 2002-08-09 | 2010-01-20 | 味の素株式会社 | 腸疾患および内臓痛の治療薬 |
| US20040110802A1 (en) | 2002-08-23 | 2004-06-10 | Atli Thorarensen | Antibacterial benzoic acid derivatives |
| CN1694704A (zh) | 2002-09-06 | 2005-11-09 | 詹森药业有限公司 | （1h－苯并咪唑－2－基）－（哌嗪基）－甲酮衍生物及其相关化合物作为组胺h4受体拮抗剂用于治疗炎性和过敏性疾病 |
| SE0202838D0 (sv) | 2002-09-24 | 2002-09-24 | Astrazeneca Ab | Chemical compounds |
| US7378525B2 (en) | 2002-12-23 | 2008-05-27 | Millennium Pharmaceuticals, Inc. | CCR8 inhibitors |
| US7320989B2 (en) | 2003-02-28 | 2008-01-22 | Encysive Pharmaceuticals, Inc. | Pyridine, pyrimidine, quinoline, quinazoline, and naphthalene urotensin-II receptor antagonists |
| US7595322B2 (en) | 2003-03-27 | 2009-09-29 | Cytokinetics, Inc. | Heterocyclic sulfonamides as modulators of cardiac sarcomeres |
| WO2004099192A2 (en) | 2003-04-30 | 2004-11-18 | The Institutes Of Pharmaceutical Discovery, Llc | Heterocycle substituted carboxylic acids as inhibitors of protein tyrosine phosphatase-1b |
| EP1620094A4 (en) | 2003-05-06 | 2010-04-28 | Glaxosmithkline Llc | NEW CHEMICAL COMPOUNDS |
| US7368457B2 (en) | 2003-05-13 | 2008-05-06 | Schering Corporation | Bridged N-arylsulfonylpiperidines as gamma-secretase inhibitors |
| WO2005007621A2 (en) | 2003-05-30 | 2005-01-27 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
| US20110275630A1 (en) | 2003-06-02 | 2011-11-10 | Abbott Laboratories | Isoindolinone kinase inhibitors |
| EP1631559A4 (en) | 2003-06-06 | 2008-08-27 | Smithkline Beecham Corp | IL-8 SB / SB RECEPTOR ANTAGONISTS |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| GB0319151D0 (en) | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Novel compounds |
| US8084457B2 (en) | 2003-09-15 | 2011-12-27 | Lead Discovery Center Gmbh | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| US7498050B2 (en) | 2003-12-15 | 2009-03-03 | Kraft Foods Global Brands Llc | Edible spread composition and packaged product |
| DE102004009238A1 (de) | 2004-02-26 | 2005-09-08 | Merck Patent Gmbh | Arylamid-Derivate |
| WO2005087217A1 (en) | 2004-03-05 | 2005-09-22 | The General Hospital Corporation | Compositions and methods for modulating interaction between polypeptides |
| WO2005105785A2 (en) | 2004-05-04 | 2005-11-10 | Novo Nordisk A/S | Indole derivatives for treatment of obesity |
| ATE409462T1 (de) | 2004-05-28 | 2008-10-15 | Pfizer Prod Inc | Pharmazeutische zusammensetzungen mit verbesserter leistung enthaltend ein hpmca polymer |
| US20090105218A1 (en) | 2004-05-29 | 2009-04-23 | 7Tm Pharma A/S | CRTH2 Receptor Ligands For Therapeutic Use |
| WO2006002133A1 (en) | 2004-06-22 | 2006-01-05 | Schering Corporation | Cannabinoid receptor ligands |
| SG155188A1 (en) | 2004-07-30 | 2009-09-30 | Exelixis Inc | Pyrrole derivatives as pharmaceutical agents |
| AU2005278959A1 (en) | 2004-08-31 | 2006-03-09 | Astrazeneca Ab | Quinazolinone derivatives and their use as B-Raf inhibitors |
| DE102004042441A1 (de) | 2004-08-31 | 2006-04-06 | Sanofi-Aventis Deutschland Gmbh | Mit Aminosäuren substituierte Hexahydro-pyrazino(1,2-a)pyrimidin-4,7-dionderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| TW200626559A (en) | 2004-10-13 | 2006-08-01 | Wyeth Corp | Anilino-pyrimidine analogs |
| WO2006049835A2 (en) | 2004-10-19 | 2006-05-11 | Novartis Vaccines And Diagnostics Inc. | Indole and benzimidazole derivatives |
| TW200628463A (en) | 2004-11-10 | 2006-08-16 | Synta Pharmaceuticals Corp | Heteroaryl compounds |
| US20060122236A1 (en) | 2004-12-06 | 2006-06-08 | Wood Michael R | Substituted biaryl-carboxylate derivatives |
| EP1831198B1 (en) | 2004-12-22 | 2009-04-08 | AstraZeneca AB | Pyridine carboxamide derivatives for use as anticancer agents |
| AR053992A1 (es) | 2004-12-22 | 2007-05-30 | Astrazeneca Ab | Compuestos quimicos con actividad anticancerosa, un procedimiento para su preparacion, su uso en la preparacion de medicamentos y composicion farmaceutica. |
| FI117653B (fi) | 2005-02-21 | 2006-12-29 | Eigenor Oy | Menetelmä ja laitteisto liikkuvien kohteiden havaitsemiseksi tutkalla |
| WO2006107593A2 (en) | 2005-04-06 | 2006-10-12 | Mallinckrodt Inc. | Matrix-based pulse release pharmaceutical formulation |
| GB0510141D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B3 |
| WO2006128129A2 (en) | 2005-05-26 | 2006-11-30 | Synta Pharmaceuticals Corp. | Method for treating cancer |
| US20070032493A1 (en) | 2005-05-26 | 2007-02-08 | Synta Pharmaceuticals Corp. | Method for treating B cell regulated autoimmune disorders |
| US7790726B2 (en) | 2005-08-16 | 2010-09-07 | Chemocentryx, Inc. | Monocyclic and bicyclic compounds and methods of use |
| AU2006290442B2 (en) | 2005-09-16 | 2010-07-29 | Arrow Therapeutics Limited | Biphenyl derivatives and their use in treating hepatitis C |
| AU2006326494A1 (en) | 2005-12-12 | 2007-06-21 | Genelabs Technologies, Inc. | N-(6-membered aromatic ring)-amido anti-viral compounds |
| AU2006331770A1 (en) | 2005-12-21 | 2007-07-05 | Schering Corporation | Treatment of nonalcoholic fatty liver disease using cholesterol lowering agents and H3 receptor antagonist/inverse agonist |
| US20090018118A1 (en) | 2005-12-29 | 2009-01-15 | Uros Urleb | Heterocyclic compounds |
| EP2019830A4 (en) | 2006-05-04 | 2011-01-19 | Inst Hepatitis & Virus Res | INHIBITORS OF THE SECRETION OF HEPATITIS B VIRUS ANTIGENS FOR THE TREATMENT OF A CHRONIC HEPATITIS VIRUS |
| US20080021063A1 (en) | 2006-07-18 | 2008-01-24 | Kazantsev Aleksey G | Compositions and methods for modulating sirtuin activity |
| US8153803B2 (en) | 2006-07-18 | 2012-04-10 | The General Hospital Corporation | Compositions and methods for modulating sirtuin activity |
| FR2903985B1 (fr) | 2006-07-24 | 2008-09-05 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| FR2904316B1 (fr) | 2006-07-31 | 2008-09-05 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique. |
| WO2008022171A1 (en) | 2006-08-17 | 2008-02-21 | Boehringer Ingelheim International Gmbh | Methods of using aryl sulfonyl compounds effective as soluble epoxide hydrolase inhibitors |
| WO2008054605A2 (en) | 2006-10-06 | 2008-05-08 | Merck & Co., Inc. | Non-nucleoside reverse transcriptase inhibitors |
| EP2101741B1 (en) | 2006-10-17 | 2010-08-11 | Bend Research, Inc. | Solid dispersion comprising a poorly water soluble drug |
| WO2008076270A2 (en) | 2006-12-13 | 2008-06-26 | Temple University-Of The Commonwealth System Of Higher Education | Sulfide, sulfoxide and sulfone chalcone analogues, derivatives thereof and therapeutic uses thereof |
| US8071779B2 (en) | 2006-12-18 | 2011-12-06 | Inspire Pharmaceuticals, Inc. | Cytoskeletal active rho kinase inhibitor compounds, composition and use |
| US20100022517A1 (en) | 2006-12-18 | 2010-01-28 | Richards Lori A | Ophthalmic formulation of rho kinase inhibitor compound |
| FR2910473B1 (fr) | 2006-12-26 | 2009-02-13 | Sanofi Aventis Sa | Derives de n-(amino-heteroaryl)-1h-pyrrolopyridine-2- carboxamides, leur preparation et leur application en therapeutique. |
| JP2008179621A (ja) | 2006-12-28 | 2008-08-07 | Taisho Pharmaceutical Co Ltd | 含窒素飽和複素環化合物 |
| JP2008184403A (ja) | 2007-01-29 | 2008-08-14 | Japan Health Science Foundation | 新規ｃ型肝炎ウイルス阻害剤 |
| AU2008225766B2 (en) | 2007-03-15 | 2012-06-07 | Novartis Ag | Organic compounds and their uses |
| US8097728B2 (en) | 2007-04-30 | 2012-01-17 | Philadelphia Health & Education Corporation | Iminosugar compounds with antiflavirus activity |
| JP5160637B2 (ja) | 2007-05-04 | 2013-03-13 | アイアールエム・リミテッド・ライアビリティ・カンパニー | ｃ−ｋｉｔおよびＰＤＧＦＲキナーゼインヒビターとしての化合物および組成物 |
| WO2008154819A1 (fr) | 2007-06-18 | 2008-12-24 | Zhang, Zhongneng | Thiazolyl-dihydropyrimidines à substitution carbéthoxy |
| WO2009018219A2 (en) | 2007-07-28 | 2009-02-05 | University Of Chicago | Methods and compositions for modulating rad51 and homologous recombination |
| EP2182935A1 (en) | 2007-08-02 | 2010-05-12 | F. Hoffmann-Roche AG | The use of benzamide derivatives for the treatment of cns disorders |
| CN101429166B (zh) | 2007-11-07 | 2013-08-21 | 上海特化医药科技有限公司 | 喹唑啉酮衍生物及其制备方法和用途 |
| CA2704645A1 (en) | 2007-11-09 | 2009-05-14 | The Salk Institute For Biological Studies | Non-nucleoside reverse transcriptase inhibitors |
| JP2011507910A (ja) | 2007-12-21 | 2011-03-10 | ユニバーシティー オブ ロチェスター | 真核生物の寿命を変更するための方法 |
| FR2926556B1 (fr) | 2008-01-22 | 2010-02-19 | Sanofi Aventis | Derives de carboxamides n-azabicycliques, leur preparation et leur application en therapeutique |
| FR2926554B1 (fr) | 2008-01-22 | 2010-03-12 | Sanofi Aventis | Derives de carboxamides azabicycliques, leur preparation et leur application en therapeutique |
| FR2926555B1 (fr) | 2008-01-22 | 2010-02-19 | Sanofi Aventis | Derives bicycliques de carboxamides azabicycliques, leur preparation et leur application en therapeutique |
| FR2926553B1 (fr) | 2008-01-23 | 2010-02-19 | Sanofi Aventis | Derives d'indole-2-carboxamides et d'azaindole-2- carboxamides substitues par un groupe silanyle, leur preparation et leur application en therapeutique |
| CU20080028A6 (es) | 2008-02-29 | 2011-02-24 | Ct Ingenieria Genetica Biotech | Compuestos químicos obtenidos in silico para la preparación de composiciones farmacéuticas para atenuar o inhibir la infección por virus dengue y otros flavivirus |
| WO2009146013A1 (en) | 2008-03-31 | 2009-12-03 | Georgetown University | Myosin light chain phosphatase inhibitors |
| CN102015638A (zh) | 2008-04-24 | 2011-04-13 | 万有制药株式会社 | 以芳基磺酰基衍生物作为有效成分的长链脂肪酸延长酶抑制剂 |
| US8299096B2 (en) | 2008-06-26 | 2012-10-30 | Inspire Pharmaceuticals, Inc. | Method for treating pulmonary diseases using rho kinase inhibitor compounds |
| US20100008968A1 (en) | 2008-06-26 | 2010-01-14 | Lampe John W | Method for treating cardiovascular diseases using rho kinase inhibitor compounds |
| US20090325960A1 (en) | 2008-06-26 | 2009-12-31 | Fulcher Emilee H | Method for treating inflammatory diseases using rho kinase inhibitor compounds |
| US8207195B2 (en) | 2008-06-26 | 2012-06-26 | Inspire Pharmaceuticals, Inc. | Method for treating neurological and neuropathic diseases using rho kinase inhibitor compounds |
| US8410147B2 (en) | 2008-06-26 | 2013-04-02 | Inspire Pharmaceuticals, Inc. | Method for treating diseases associated with alterations in cellular integrity using Rho kinase inhibitor compounds |
| US20090325959A1 (en) | 2008-06-26 | 2009-12-31 | Vittitow Jason L | Method for treating ophthalmic diseases using rho kinase inhibitor compounds |
| CA2735392A1 (en) | 2008-08-15 | 2010-02-18 | F. Hoffmann-La Roche Ag | Bi-aryl aminotetralines |
| US9040488B2 (en) | 2008-09-02 | 2015-05-26 | Baruch S. Blumberg Institute | Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity |
| US8143269B2 (en) | 2008-10-03 | 2012-03-27 | Calcimedica, Inc. | Inhibitors of store operated calcium release |
| WO2010043592A1 (en) | 2008-10-15 | 2010-04-22 | Revotar Biopharmaceuticals Ag | Lipase inhibitors for use for the treatment of obesity |
| WO2010059658A1 (en) | 2008-11-20 | 2010-05-27 | Glaxosmithkline Llc | Chemical compounds |
| EP2400969A4 (en) | 2008-12-04 | 2012-05-16 | Inspire Pharmaceuticals Inc | METHOD FOR TREATING PULMONARY DISEASES USING RHO KINASE INHIBITORY COMPOUNDS |
| CA2748174A1 (en) | 2008-12-30 | 2010-07-08 | Arqule, Inc. | Substituted 1h-pyrazolo[3,4-d]pyrimidine-6-amine compounds |
| WO2010088000A2 (en) | 2009-02-02 | 2010-08-05 | Angion Biomedica Corp. | Antifibrotic compounds and uses thereof |
| WO2010123139A1 (ja) | 2009-04-24 | 2010-10-28 | 持田製薬株式会社 | スルファモイル基を有するアリールカルボキサミド誘導体 |
| WO2010133336A1 (en) | 2009-05-19 | 2010-11-25 | Bayer Cropscience Ag | Insecticidal arylpyrrolines |
| CN102480957A (zh) | 2009-05-27 | 2012-05-30 | Ptc医疗公司 | 治疗癌症及非肿瘤病症的方法 |
| CN102469788A (zh) | 2009-06-30 | 2012-05-23 | 西佳技术公司 | 登革病毒感染的治疗和预防 |
| US8703938B2 (en) | 2009-09-11 | 2014-04-22 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| US8822700B2 (en) | 2009-09-11 | 2014-09-02 | Enanta Pharmaceuticals, Inc. | Hepatitis C virus inhibitors |
| WO2011035143A2 (en) | 2009-09-17 | 2011-03-24 | The Regents Of The University Of Michigan | Methods and compositions for inhibiting rho-mediated diseases and conditions |
| WO2011058766A1 (en) | 2009-11-16 | 2011-05-19 | Raqualia Pharma Inc. | Aryl carboxamide derivatives as ttx-s blockers |
| CN102093320B (zh) | 2009-12-09 | 2013-08-28 | 扬子江药业集团上海海尼药业有限公司 | 一种可溶性环氧化物水解酶抑制剂 |
| WO2011088015A1 (en) | 2010-01-15 | 2011-07-21 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| WO2011088561A1 (en) | 2010-01-20 | 2011-07-28 | University Of Manitoba | Anti-viral compounds and compositions |
| KR101791266B1 (ko) | 2010-02-12 | 2017-10-30 | 엘지전자 주식회사 | 무선 통신 시스템에서 데이터 전송 방법 및 장치 |
| WO2011109237A2 (en) | 2010-03-02 | 2011-09-09 | Emory University | Uses of noscapine and derivatives in subjects diagnosed with fap |
| JP2013522192A (ja) | 2010-03-11 | 2013-06-13 | ブリストル−マイヤーズ スクイブ カンパニー | Ｃ型肝炎の処置のための化合物 |
| CN102206172B (zh) | 2010-03-30 | 2015-02-25 | 中国医学科学院医药生物技术研究所 | 一组取代双芳基化合物及其制备方法和抗病毒应用 |
| JP2013523766A (ja) | 2010-03-31 | 2013-06-17 | グラクソ グループ リミテッド | キナーゼ阻害剤としてのイミダゾリル‐イミダゾール |
| PH12012502194A1 (en) | 2010-05-07 | 2014-09-05 | Glaxosmithkline Llc | Indoles |
| WO2011155898A1 (en) | 2010-06-11 | 2011-12-15 | Wadell Goeran | New antiviral compounds |
| KR101807338B1 (ko) | 2010-06-14 | 2018-01-10 | 다우 글로벌 테크놀로지스 엘엘씨 | 아세테이트 및 석신에이트 치환이 향상된 하이드록시프로필 메틸 셀룰로즈 아세테이트 석신에이트 |
| US20130142827A1 (en) | 2010-06-25 | 2013-06-06 | Philadelphia Health & Education Corporation D/B/A | Induction of immune response |
| WO2012012282A1 (en) | 2010-07-19 | 2012-01-26 | Inspire Pharmaceuticals, Inc. | Bifunctional rho kinase inhibitor compounds, composition and use |
| JP2013536178A (ja) | 2010-07-26 | 2013-09-19 | ニューロセラピューティクス ファーマ， インコーポレイテッド | アリールスルホンアミド誘導体、組成物、および使用方法 |
| BR112013001015A2 (pt) | 2010-07-27 | 2016-05-24 | Inspire Pharmaceuticals Inc | método por tratar doenças oftálmicas que usam compostos de inibidor de cinase em formas de prodrug |
| WO2012016133A2 (en) | 2010-07-29 | 2012-02-02 | President And Fellows Of Harvard College | Ros1 kinase inhibitors for the treatment of glioblastoma and other p53-deficient cancers |
| WO2012033956A1 (en) | 2010-09-08 | 2012-03-15 | Mithridion, Inc. | Cognition enhancing compounds and compositions, methods of making, and methods of treating |
| WO2012047856A2 (en) | 2010-10-04 | 2012-04-12 | Institute For Hepatitis And Virus Research | Novel inhibitors of secretion of hepatitis b virus antigens |
| GB201017345D0 (en) | 2010-10-14 | 2010-11-24 | Proximagen Ltd | Receptor antagonists |
| EP2646439B1 (en) | 2010-12-02 | 2016-05-25 | Bristol-Myers Squibb Company | Alkyl amides as hiv attachment inhibitors |
| WO2012080050A1 (en) | 2010-12-14 | 2012-06-21 | F. Hoffmann-La Roche Ag | Solid forms of a phenoxybenzenesulfonyl compound |
| GB201103419D0 (OSRAM) | 2011-02-28 | 2011-04-13 | Univ Aberdeen | |
| PH12013502033A1 (en) | 2011-04-08 | 2014-01-06 | Janssen Sciences Ireland Uc | Pyrimidine derivatives for the treatment of viral infections |
| US8889716B2 (en) | 2011-05-10 | 2014-11-18 | Chdi Foundation, Inc. | Transglutaminase TG2 inhibitors, pharmaceutical compositions, and methods of use thereof |
| EP2726459B1 (en) | 2011-07-01 | 2019-09-11 | Baruch S. Blumberg Institute | Sulfamoylbenzamide derivatives as antiviral agents against hbv infection |
| CN106957282B (zh) | 2011-12-21 | 2019-08-30 | 诺维拉治疗公司 | B型肝炎抗病毒剂 |
| ES2581489T3 (es) | 2012-01-06 | 2016-09-06 | Janssen Sciences Ireland Uc | 1,4-dihidropirimidinas 4,4-disustituidas y el uso de las mismas como medicamentos para el tratamiento de la hepatitis B |
| JP6134338B2 (ja) | 2012-02-29 | 2017-05-24 | バルーク エス．ブルームバーグ インスティテュート | Ｂ型肝炎ウイルス共有結合閉環状ｄｎａ形成の阻害剤およびそれらの使用方法 |
| US20130267517A1 (en) | 2012-03-31 | 2013-10-10 | Hoffmann-La Roche Inc. | Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| CA2865259A1 (en) | 2012-03-31 | 2013-10-03 | F. Hoffmann-La Roche Ag | Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| PL2861611T3 (pl) | 2012-05-25 | 2017-08-31 | Janssen Sciences Ireland Uc | Nukleozydy uracylowe spirooksetanu |
| WO2013181584A2 (en) | 2012-06-01 | 2013-12-05 | Guo, Ju-Tao | Modulation of hepatitis b virus cccdna transcription |
| JO3300B1 (ar) | 2012-06-06 | 2018-09-16 | Novartis Ag | مركبات وتركيبات لتعديل نشاط egfr |
| TW201408652A (zh) | 2012-07-11 | 2014-03-01 | Hoffmann La Roche | 作爲ＲＯＲｃ調節劑之芳基磺內醯胺衍生物 |
| AR092270A1 (es) | 2012-08-28 | 2015-04-08 | Janssen R&D Ireland | Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b |
| UA115069C2 (uk) | 2012-08-28 | 2017-09-11 | ЯНССЕН САЙЄНСІЗ АЙРЛЕНД ЮСі | Конденсовані біциклічні похідні сульфамоїлу та їх застосування як лікарських препаратів для лікування гепатиту b |
| EP2892893B2 (en) | 2012-09-10 | 2019-10-16 | F.Hoffmann-La Roche Ag | 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| SG11201504740UA (en) * | 2012-12-27 | 2015-07-30 | Univ Drexel | Novel antiviral agents against hbv infection |
| WO2014126969A1 (en) | 2013-02-12 | 2014-08-21 | Bend Research, Inc. | Solid dispersions of low-water solubility actives |
| BR112015020545A2 (pt) | 2013-02-28 | 2017-07-18 | Eisai R&D Man Co Ltd | derivado de tetraidroimidazo[1,5-d][1,4]oxazepina |
| ES2628953T3 (es) | 2013-02-28 | 2017-08-04 | Janssen Sciences Ireland Uc | Sulfamoilarilamidas y el uso de las mismas como medicamentos para el tratamiento de la hepatitis B |
| WO2014137777A1 (en) | 2013-03-07 | 2014-09-12 | Dow Global Technologies Llc | Novel esterified cellulose ethers of low viscosity |
| WO2014165128A2 (en) | 2013-03-12 | 2014-10-09 | Novira Therapeutics, Inc. | Hepatitis b antiviral agents |
| US9944658B2 (en) | 2013-03-14 | 2018-04-17 | VenatoRx Pharmaceuticals, Inc. | Beta-lactamase inhibitors |
| MX353412B (es) | 2013-04-03 | 2018-01-10 | Janssen Sciences Ireland Uc | Derivados de n-fenil-carboxamida y su uso como medicamentos para el tratamiento de la hepatitis b. |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| JP6441315B2 (ja) | 2013-05-17 | 2018-12-19 | ヤンセン・サイエンシズ・アイルランド・ユーシー | スルファモイルチオフェンアミド誘導体およびｂ型肝炎を治療するための医薬品としてのその使用 |
| MX2015015692A (es) | 2013-05-17 | 2016-03-04 | Hoffmann La Roche | Novedosas heteroarildihidropirimidinas, unidas por puentes en 6 para el tratamiento y la profilaxis de infeccion por el virus de hepatitis b. |
| LT3004090T (lt) | 2013-05-28 | 2018-01-10 | Astrazeneca Ab | Cheminiai junginiai |
| US9688681B2 (en) | 2013-05-28 | 2017-06-27 | Bayer Cropscience Aktiengesellschaft | Heterocyclic compounds as pest control agents |
| WO2014198880A1 (en) | 2013-06-14 | 2014-12-18 | Ferrer Internacional, S.A. | 2-(2-aminophenoxy)-3-chloronaphthalene-1,4-dione compounds having orexin 2 receptor agonist activity |
| PL3024819T3 (pl) | 2013-07-25 | 2018-08-31 | Janssen Sciences Ireland Uc | Pochodne piroloamidowe podstawione glioksamidem i ich zastosowanie jako leków do leczenia wirusowego zapalenia wątroby typu B |
| WO2015055764A1 (en) | 2013-10-18 | 2015-04-23 | Syngenta Participations Ag | 3-methanimidamid-pyridine derivatives as fungicides |
| WO2015057945A1 (en) | 2013-10-18 | 2015-04-23 | Indiana University Research And Technology Corporation | Hepatitis b viral assembly effectors |
| SG11201602748XA (en) | 2013-10-23 | 2016-05-30 | Janssen Sciences Ireland Uc | Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b |
| US9115113B2 (en) | 2013-11-14 | 2015-08-25 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| JO3466B1 (ar) | 2013-12-20 | 2020-07-05 | Takeda Pharmaceuticals Co | مواد ضابطة لتترا هيدرو بيريدوبيرازينات من gpr6 |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9181288B2 (en) | 2014-01-16 | 2015-11-10 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| DK3099296T3 (en) | 2014-01-31 | 2019-04-15 | Cognition Therapeutics Inc | ISO-INDOLINE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE |
| KR20160128305A (ko) | 2014-02-05 | 2016-11-07 | 노비라 테라퓨틱스, 인코포레이티드 | Hbv 감염의 치료를 위한 병용 요법 |
| ES2705401T3 (es) | 2014-02-06 | 2019-03-25 | Janssen Sciences Ireland Uc | Derivados de sulfamoilpirrolamida y su uso como medicamentos para el tratamiento de la Hepatitis B |
| HUE041734T2 (hu) | 2014-03-07 | 2019-05-28 | Hoffmann La Roche | Új, 6-tagú gyûrûvel kondenzált heteroarildihidropirimidinek hepatitisz B vírusfertõzés kezelésére és megelõzésére |
| PT3116316T (pt) | 2014-03-13 | 2019-09-30 | Assembly Biosciences Inc | Moduladores alostéricos da proteína do núcleo da hepatite b |
| US9400280B2 (en) * | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
| KR20160133563A (ko) | 2014-03-28 | 2016-11-22 | 선샤인 레이크 파르마 컴퍼니 리미티드 | 다이하이드로피리미딘 화합물 및 이의 약제학적 용도 |
| CA2950807C (en) | 2014-05-30 | 2022-05-31 | Medshine Discovery Inc. | Dihydropyrimido fused ring derivative as hbv inhibitor |
| WO2016089990A1 (en) | 2014-12-02 | 2016-06-09 | Novira Therapeutics, Inc. | Sulfide alkyl and pyridyl reverse sulfonamide compounds for hbv treatment |
| US9550779B2 (en) | 2014-12-30 | 2017-01-24 | Novira Therapeutics, Inc. | Derivatives and methods of treating hepatitis B infections |
| MA41338B1 (fr) | 2015-01-16 | 2019-07-31 | Hoffmann La Roche | Composés de pyrazine pour le traitement de maladies infectieuses |
| EP3271019A1 (en) | 2015-03-19 | 2018-01-24 | Novira Therapeutics Inc. | Azocane and azonane derivatives and methods of treating hepatitis b infections |
| WO2016161268A1 (en) | 2015-04-01 | 2016-10-06 | Enanta Pharmaceuticals, Inc. | Hepatitis b antviral agents |
| US10273228B2 (en) | 2015-04-17 | 2019-04-30 | Indiana University Research And Technology Corporation | Hepatitis B viral assembly effectors |
| US10738035B2 (en) | 2015-05-13 | 2020-08-11 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| JP6845231B2 (ja) | 2015-09-29 | 2021-03-17 | ノヴィラ・セラピューティクス・インコーポレイテッド | Ｂ型肝炎抗ウイルス薬の結晶形態 |
| KR20180129943A (ko) | 2016-04-15 | 2018-12-05 | 노비라 테라퓨틱스, 인코포레이티드 | 캡시드 조립 억제제를 포함하는 배합물 및 방법 |
| WO2018016563A1 (en) | 2016-07-20 | 2018-01-25 | Eisai R&D Management Co., Ltd. | Use of eribulin and histone deacetylase inhibitors in the treatment of cancer |
| CN109251212A (zh) | 2017-07-14 | 2019-01-22 | 上海长森药业有限公司 | 内环硫醚酰胺-芳基酰胺类化合物及其治疗乙型肝炎的用途 |
| EP3765011A1 (en) | 2018-03-14 | 2021-01-20 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
| CR20210481A (es) | 2019-03-13 | 2021-10-25 | Janssen Sciences Ireland Unlimited Co | Formulación sólida del modulador de ensamblaje de la cápside |
-
2017
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- 2017-04-14 EP EP20211452.6A patent/EP3848026A1/en not_active Withdrawn
- 2017-04-14 WO PCT/US2017/027802 patent/WO2017181141A2/en not_active Ceased
- 2017-04-14 JP JP2018553947A patent/JP2019511542A/ja not_active Withdrawn
- 2017-04-14 AU AU2017248828A patent/AU2017248828A1/en not_active Withdrawn
- 2017-04-14 MA MA044671A patent/MA44671A/fr unknown
- 2017-04-14 EP EP17737399.0A patent/EP3442524A2/en not_active Withdrawn
- 2017-04-14 SG SG11201808949SA patent/SG11201808949SA/en unknown
- 2017-04-14 CA CA3021068A patent/CA3021068A1/en not_active Withdrawn
- 2017-04-14 SG SG10202011827YA patent/SG10202011827YA/en unknown
- 2017-04-14 US US15/488,368 patent/US10441589B2/en not_active Expired - Fee Related
- 2017-04-14 MX MX2018012557A patent/MX2018012557A/es unknown
- 2017-04-14 BR BR112018071048-2A patent/BR112018071048A2/pt not_active Application Discontinuation
- 2017-04-14 CN CN201780037419.6A patent/CN109640980A/zh not_active Withdrawn
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2018
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- 2018-10-15 IL IL262378A patent/IL262378A/en unknown
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2019
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| MX2020011808A (es) | 2020-12-07 |
| AU2017248828A1 (en) | 2018-11-01 |
| MA44671A (fr) | 2019-02-20 |
| US11129834B2 (en) | 2021-09-28 |
| CN109640980A (zh) | 2019-04-16 |
| MX2018012557A (es) | 2019-07-04 |
| US20170340642A1 (en) | 2017-11-30 |
| BR112018071048A2 (pt) | 2019-05-07 |
| WO2017181141A2 (en) | 2017-10-19 |
| EP3442524A2 (en) | 2019-02-20 |
| US10441589B2 (en) | 2019-10-15 |
| US20190365767A1 (en) | 2019-12-05 |
| JP2019511542A (ja) | 2019-04-25 |
| SG10202011827YA (en) | 2021-01-28 |
| WO2017181141A3 (en) | 2018-01-11 |
| KR20180129943A (ko) | 2018-12-05 |
| EP3848026A1 (en) | 2021-07-14 |
| SG11201808949SA (en) | 2018-11-29 |
| IL262378A (en) | 2018-11-29 |
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