ES2988933T3 - Inhibidores de SARM1 - Google Patents
Inhibidores de SARM1 Download PDFInfo
- Publication number
- ES2988933T3 ES2988933T3 ES19814860T ES19814860T ES2988933T3 ES 2988933 T3 ES2988933 T3 ES 2988933T3 ES 19814860 T ES19814860 T ES 19814860T ES 19814860 T ES19814860 T ES 19814860T ES 2988933 T3 ES2988933 T3 ES 2988933T3
- Authority
- ES
- Spain
- Prior art keywords
- aliphatic
- sarm1
- hydrogen
- optionally substituted
- independently selected
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003112 inhibitor Substances 0.000 title description 2
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- 230000007850 degeneration Effects 0.000 claims abstract description 20
- 125000001931 aliphatic group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862682045P | 2018-06-07 | 2018-06-07 | |
| PCT/US2019/035839 WO2019236884A1 (en) | 2018-06-07 | 2019-06-06 | Inhibitors of sarm1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2988933T3 true ES2988933T3 (es) | 2024-11-22 |
Family
ID=68770684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES19814860T Active ES2988933T3 (es) | 2018-06-07 | 2019-06-06 | Inhibidores de SARM1 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US12448374B2 (https=) |
| EP (1) | EP3801499B1 (https=) |
| JP (1) | JP7478142B2 (https=) |
| CN (1) | CN112839648B (https=) |
| ES (1) | ES2988933T3 (https=) |
| MA (1) | MA52809A (https=) |
| WO (1) | WO2019236884A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES3028093T3 (en) | 2018-06-07 | 2025-06-18 | Disarm Therapeutics Inc | Inhibitors of sarm1 |
| WO2020132045A1 (en) | 2018-12-19 | 2020-06-25 | Disarm Therapeutics, Inc. | Inhibitors of sarm1 in combination with neuroprotective agents |
| CA3141404A1 (en) | 2019-06-14 | 2020-12-17 | Disarm Therapeutics, Inc. | Inhibitors of sarm1 |
| JP7534390B2 (ja) | 2019-09-12 | 2024-08-14 | ディスアーム セラピューティクス， インコーポレイテッド | Ｓａｒｍ１の阻害剤 |
| EP4065714A1 (en) * | 2019-11-26 | 2022-10-05 | Disarm Therapeutics, Inc. | Methods and compositions for neuroprotection |
| US12606558B2 (en) | 2020-04-09 | 2026-04-21 | Disarm Therapeutics, Inc. | Condensed pyrazole derivatives as inhibitors of SARM1 |
| CN115916764B (zh) | 2020-04-09 | 2024-09-20 | 达萨玛治疗公司 | 作为sarm1抑制剂的吲唑衍生物 |
| TW202334117A (zh) * | 2020-08-24 | 2023-09-01 | 美商達薩瑪治療公司 | Ｓａｒｍ１之抑制劑 |
| EP4615448A1 (en) * | 2022-11-12 | 2025-09-17 | Cambridge Enterprise Limited | Sarm1 agents for use in therapy and cosmetics |
| TW202509019A (zh) * | 2023-04-27 | 2025-03-01 | 香港商維泰瑞隆（香港）生物科技有限公司 | Sarm1調節子、其製劑及用途 |
| CN116836162B (zh) * | 2023-05-24 | 2025-09-05 | 南方医科大学 | 吡唑[4,3-c]吡啶类化合物或其药学上可接受的盐及其应用 |
Family Cites Families (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2148289B (en) * | 1983-10-17 | 1987-09-23 | Lilly Co Eli | 3-bicyclicpyridinium-methyl cephalosporins |
| US5468757A (en) * | 1994-01-31 | 1995-11-21 | Eli Lilly And Company | 6-azaindole thromboxane synthase inhibitors |
| CA2348734A1 (en) * | 1998-10-30 | 2000-05-11 | Merck & Co., Inc. | Thrombin inhibitors |
| US6420382B2 (en) | 2000-02-25 | 2002-07-16 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US6809105B2 (en) | 2000-04-27 | 2004-10-26 | Abbott Laboratories | Diazabicyclic central nervous system active agents |
| CN100411686C (zh) * | 2001-04-11 | 2008-08-20 | 千寿制药株式会社 | 视觉功能障碍改善剂 |
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| HUP0402289A2 (hu) | 2001-10-02 | 2005-02-28 | Pharmacia & Upjohn Company | Gyógyhatású azabiciklusos csoporttal helyettesített kondenzált heteroaril-származékok, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk |
| US6849620B2 (en) | 2001-10-26 | 2005-02-01 | Pfizer Inc | N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease |
| DK1483265T3 (da) | 2002-03-05 | 2007-03-19 | Lilly Co Eli | Purinderivater som kinaseinhibitorer |
| CA2482838A1 (en) | 2002-05-31 | 2003-12-11 | Eisai Co., Ltd. | Pyrazole compounds and pharmaceutical compositions containing the compound |
| WO2004039815A2 (en) | 2002-11-01 | 2004-05-13 | Pharmacia & Upjohn Company Llc | Compounds having both alpha7 nachr agonist and 5ht antagonist activity for treatment of cns diseases |
| WO2004039366A1 (en) | 2002-11-01 | 2004-05-13 | Pharmacia & Upjohn Company Llc | Nicotinic acetylcholine agonists in the treatment of glaucoma and retinal neuropathy |
| CA2509142A1 (en) | 2002-12-11 | 2004-06-24 | Pharmacia & Upjohn Company Llc | Combination for the treatment of adhd |
| KR20050085535A (ko) | 2002-12-11 | 2005-08-29 | 파마시아 앤드 업존 캄파니 엘엘씨 | 알파 7 니코틴성 아세틸콜린 수용체 아고니스트와 다른화합물의 조합물을 사용한 질환의 치료 방법 |
| WO2004064836A2 (en) | 2003-01-22 | 2004-08-05 | Pharmacia & Upjohn Company Llc | Treatment of diseases with alpha-7 nach receptor full agonists |
| JP2007517868A (ja) | 2004-01-07 | 2007-07-05 | アストラゼネカ アクチボラグ | 治療薬ｉ |
| JP5069108B2 (ja) | 2004-07-21 | 2012-11-07 | メルク セローノ ソシエテ アノニム | オクタヒドロピロロ［２，３，ｃ］ピリジン誘導体と、その医薬としての利用法 |
| DK1784404T3 (da) | 2004-09-03 | 2012-02-13 | Yuhan Corp | Pyrrolo[2,3-c]pyridinderivater samt fremgangsmåder til deres fremstilling |
| US8008320B2 (en) | 2004-12-08 | 2011-08-30 | Johannes Gutenberg-Universitatis | 3-(indolyl)-4-arylmaleimide derivatives and their use as angiogenesis inhibitors |
| JP5065908B2 (ja) | 2004-12-24 | 2012-11-07 | プロシディオン・リミテッド | Ｇタンパク質結合受容体作動薬 |
| WO2006107784A1 (en) | 2005-04-05 | 2006-10-12 | Eli Lilly And Company | Imidazopyridazine compounds |
| BRPI0612112A8 (pt) | 2005-06-22 | 2017-12-26 | Chemocentryx Inc | composto, composição farmacêutica, e, método de tratar doenças ou condições mediadas por ccr1. |
| US7777035B2 (en) | 2005-06-22 | 2010-08-17 | Chemocentryx, Inc. | Azaindazole compounds and methods of use |
| KR101142363B1 (ko) | 2005-06-27 | 2012-05-21 | 주식회사유한양행 | 피롤로피리딘 유도체를 포함하는 항암제 조성물 |
| CN101003537A (zh) | 2006-01-17 | 2007-07-25 | 上海恒瑞医药有限公司 | 吡咯并哒嗪类衍生物及其制备方法和用途 |
| GB0705803D0 (en) | 2007-03-28 | 2007-05-02 | Glaxo Group Ltd | Novel compounds |
| DK2142516T3 (da) | 2007-03-30 | 2013-04-15 | Sanofi Sa | Pyrimidinhydrazidforbindelser i ders egenskab af pgds-inhibitorer |
| AU2008241488A1 (en) | 2007-04-16 | 2008-10-30 | Merck Sharp & Dohme Corp. | Bicyclic anilide heterocyclic CGRP receptor antagonists |
| WO2009041567A1 (ja) | 2007-09-27 | 2009-04-02 | Banyu Pharmaceutical Co., Ltd. | メラニン凝集ホルモン受容体拮抗作用を有するジアリールケチミン誘導体 |
| GB0803018D0 (en) | 2008-02-19 | 2008-03-26 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| TWI443098B (zh) | 2008-03-24 | 2014-07-01 | Medivation Technologies Inc | 吡啶并〔３，４－ｂ〕吲哚及使用方法 |
| AR071717A1 (es) | 2008-05-13 | 2010-07-07 | Array Biopharma Inc | Pirrolo[2,3-b]piridinas inhibidoras de quinasas chk1 y chk2,composiciones farmaceuticas que las contienen,proceso para prepararlas y uso de las mismas en el tratamiento y prevencion del cancer. |
| US8012992B2 (en) | 2008-06-30 | 2011-09-06 | Allergan, Inc. | Aza-indoles and related compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| NZ590688A (en) | 2008-08-05 | 2012-09-28 | Daiichi Sankyo Co Ltd | imidazo[4,5-b]pyridin-2-one derivatives |
| ES2378513T3 (es) | 2008-08-06 | 2012-04-13 | Pfizer Inc. | Compuestos 2-heterociclilamino piracinas sustituidas en posición 6 como inhibidores de CHK-1 |
| WO2010042337A1 (en) | 2008-10-07 | 2010-04-15 | Merck Sharp & Dohme Corp. | Novel 6-azaindole aminopyrimidine derivatives having nik inhibitory activity |
| US8785489B2 (en) | 2008-10-17 | 2014-07-22 | Boehringer Ingelheim International Gmbh | Heteroaryl substituted indole compounds useful as MMP-13 inhibitors |
| WO2010046780A2 (en) | 2008-10-22 | 2010-04-29 | Institut Pasteur Korea | Anti viral compounds |
| CN101723936B (zh) | 2008-10-27 | 2014-01-15 | 上海睿星基因技术有限公司 | 激酶抑制剂及其在药学中的用途 |
| AR074024A1 (es) | 2008-11-14 | 2010-12-15 | Merial Ltd | Compuesto de arilazol-2-il-cianoetilamino enantiomericamente enriquecidos, composicion plaguicida y su uso para prevenir la infeccion parasitaria |
| WO2011096490A1 (ja) | 2010-02-04 | 2011-08-11 | 第一三共株式会社 | イミダゾピリジン－２－オン誘導体 |
| JP2011178779A (ja) | 2010-02-04 | 2011-09-15 | Daiichi Sankyo Co Ltd | イミダゾピリジン−２−オン誘導体 |
| WO2011100502A1 (en) | 2010-02-11 | 2011-08-18 | OSI Pharmaceuticals, LLC | 7-aminofuropyridine derivatives |
| GB201017345D0 (en) | 2010-10-14 | 2010-11-24 | Proximagen Ltd | Receptor antagonists |
| US9273028B2 (en) | 2010-10-29 | 2016-03-01 | Biogen Ma Inc. | Heterocyclic tyrosine kinase inhibitors |
| CN102464654B (zh) | 2010-11-12 | 2016-01-13 | 上海泓博智源医药技术有限公司 | 抗病毒化合物 |
| TWI501967B (zh) | 2010-12-16 | 2015-10-01 | Janssen R&D Ireland | 作為呼吸道融合病毒抗病毒劑之氮雜吲哚類 |
| EP2661433B1 (en) | 2011-01-04 | 2017-08-16 | Novartis AG | Indole compounds or analogues thereof useful for the treatment of age-related macular degeneration (amd) |
| WO2012106343A2 (en) | 2011-02-01 | 2012-08-09 | The Board Of Trustees Of The University Of Illinois | Hdac inhibitors and therapeutic methods using the same |
| DE102011009961A1 (de) | 2011-02-01 | 2012-08-02 | Merck Patent Gmbh | 7-Azaindolderivate |
| WO2012114252A1 (en) | 2011-02-21 | 2012-08-30 | Actelion Pharmaceuticals Ltd | Novel indole and pyrrolopyridine amides |
| ES2581848T3 (es) | 2011-04-05 | 2016-09-07 | Pfizer Limited | Derivados de pirrolo[2,3-d]pirimidina como inhibidores de quinasas relacionadas con tropomiosina |
| US20120328629A1 (en) | 2011-06-24 | 2012-12-27 | University Of Miami | Therapeutic Applications Targeting SARM1 |
| UA111756C2 (uk) | 2011-11-03 | 2016-06-10 | Ф. Хоффманн-Ля Рош Аг | Сполуки гетероарилпіридону та азапіридону як інгібітори тирозинкінази брутона |
| TWI577671B (zh) | 2011-11-14 | 2017-04-11 | Sunshine Lake Pharma Co Ltd | Aminoquinazoline derivatives and salts thereof and methods of use thereof |
| CN102532027A (zh) | 2012-03-01 | 2012-07-04 | 常州协丰医药研发有限公司 | 一种通过羟胺活化来形成吲唑衍生物的合成方法 |
| CN102675310B (zh) | 2012-05-09 | 2014-12-24 | 林辉 | 制备吡唑并芳杂环化合物的方法 |
| EP2855477A4 (en) | 2012-05-29 | 2015-11-18 | Merck Sharp & Dohme | ISOTOPICALLY MARKED BIARYL UREA COMPOUNDS |
| CN104379579B (zh) | 2012-06-28 | 2017-03-08 | 诺华股份有限公司 | 吡咯烷衍生物及其作为补体途径调节剂的用途 |
| ES2644700T3 (es) | 2012-06-28 | 2017-11-30 | Novartis Ag | Derivados de pirrolidina y su uso como moduladores de la ruta del complemento |
| WO2014009833A2 (en) | 2012-07-12 | 2014-01-16 | Novartis Ag | Complement pathway modulators and uses thereof |
| RS55684B1 (sr) | 2012-07-26 | 2017-07-31 | Glaxo Group Ltd | 2-(azaindol-2-il)benzimidazoli kao pad4 inhibitori |
| US9321764B2 (en) | 2013-03-12 | 2016-04-26 | Abbvie Inc. | Dihydro-pyrrolopyridinone inhibitors |
| TWI663166B (zh) | 2013-04-24 | 2019-06-21 | 健生藥品公司 | 新化合物 |
| AU2014261070A1 (en) | 2013-05-02 | 2015-10-29 | Pfizer Inc. | Imidazo-triazine derivatives as PDE10 inhibitors |
| GB201310460D0 (en) * | 2013-06-12 | 2013-07-24 | Lytix Biopharma As | Compounds |
| FR3008975A1 (fr) | 2013-07-23 | 2015-01-30 | Servier Lab | Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| HRP20200182T1 (hr) * | 2014-02-25 | 2020-05-01 | Achillion Pharmaceuticals, Inc. | Aril, heteroaril i heterociklični spojevi za liječenje komplementom posredovanih poremećaja |
| US9856264B2 (en) | 2014-04-28 | 2018-01-02 | Medshine Discovery Inc. | Isoquinolinesulfonyl derivative as RHO kinase inhibitor |
| WO2015188368A1 (en) | 2014-06-13 | 2015-12-17 | Merck Sharp & Dohme Corp. | Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles |
| WO2015191403A1 (en) | 2014-06-13 | 2015-12-17 | Bristol-Myers Squibb Company | Tricyclic compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| WO2015191401A1 (en) | 2014-06-13 | 2015-12-17 | Bristol-Myers Squibb Company | Tricyclic compounds as alpha- 7 nicotinic acetylcholine receptor ligands |
| EP3705482B1 (en) | 2014-08-06 | 2023-02-22 | California Institute of Technology | Silylation of aromatic heterocycles by earth abundant transition-metal-free catalysts |
| AU2015334917B2 (en) | 2014-10-23 | 2019-08-29 | Janssen Pharmaceutica Nv | New compounds as NIK inhibitors |
| JP6616412B2 (ja) | 2014-10-23 | 2019-12-04 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｎｉｋ阻害剤としての新規のピラゾロピリミジン誘導体 |
| WO2016095088A1 (en) | 2014-12-15 | 2016-06-23 | Merck Sharp & Dohme Corp. | Erk inhibitors |
| WO2016095089A1 (en) | 2014-12-15 | 2016-06-23 | Merck Sharp & Dohme Corp. | Erk inhibitors |
| US9938276B2 (en) | 2014-12-19 | 2018-04-10 | Merck Sharp & Dohme Corp. | 6,5-bicyclic octahydropyrrolopyridine orexin receptor antagonists |
| WO2016161571A1 (en) | 2015-04-08 | 2016-10-13 | Merck Sharp & Dohme Corp. | Indazole and azaindazole btk inhibitors |
| JP2018515612A (ja) | 2015-05-13 | 2018-06-14 | セルビタ スプウカ アクツィーナ | 置換キノキサリン誘導体 |
| CA2988436A1 (en) | 2015-07-13 | 2017-01-19 | Arvinas, Inc. | Alanine-based modulators of proteolysis and associated methods of use |
| HK1250029A1 (zh) | 2015-08-05 | 2018-11-23 | Indivior Uk Limited | 具有双环结构的多巴胺d3受体拮抗剂 |
| WO2017035408A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Compounds for treatment of immune and inflammatory disorders |
| AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
| AR105809A1 (es) | 2015-08-26 | 2017-11-08 | Achillion Pharmaceuticals Inc | Compuestos para el tratamiento de trastornos médicos |
| US11370792B2 (en) | 2015-12-14 | 2022-06-28 | Raze Therapeutics, Inc. | Caffeine inhibitors of MTHFD2 and uses thereof |
| EP3399968B8 (en) | 2016-01-07 | 2021-12-01 | Xuanzhu Biopharmaceutical Co., Ltd. | Selective inhibitors of clinically important mutants of the egfr tyrosine kinase |
| TWI854164B (zh) | 2016-02-01 | 2024-09-01 | 美商百歐克斯製藥公司 | 苯并吡唑化合物及其類似物 |
| CN109071565B (zh) | 2016-05-24 | 2022-05-10 | 默克专利股份公司 | 三环杂环衍生物 |
| US20170355708A1 (en) | 2016-06-09 | 2017-12-14 | Cadent Therapeutics, Inc. | Potassium channel modulators |
| CN110022875A (zh) | 2016-07-11 | 2019-07-16 | 莱福斯希医药公司 | 治疗性抑制化合物 |
| EP3500285B1 (en) | 2016-08-16 | 2022-04-20 | Henry Ford Health System | Compositions for the treatment of chemotherapy-induced neuropathic pain |
| UA125650C2 (uk) | 2016-09-09 | 2022-05-11 | Інсайт Корпорейшн | Регулятори нрk1 на основі похідних піразолопіридину та їх застосування для лікування раку |
| WO2018057989A1 (en) | 2016-09-24 | 2018-03-29 | Washington University | INHIBITORS OF SARM1 NADase ACTIVITY AND USES THEREOF |
| EP3848370B1 (en) | 2016-10-14 | 2025-05-07 | Takeda Pharmaceutical Company Limited | Tyk2 inhibitors and uses thereof |
| MY193511A (en) | 2016-11-02 | 2022-10-17 | Janssen Pharmaceutica Nv | [1,2,4]triazolo[1,5-a]pyrimidine derivatives as pde2 inhibitors |
| WO2018149986A1 (en) | 2017-02-16 | 2018-08-23 | Oryzon Genomics, S.A. | 2-(bicyclo-heteroaryl)-isonicotinic derivatives as histone demethylase inhibitors |
| US20200131129A1 (en) | 2017-03-15 | 2020-04-30 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| WO2018170165A1 (en) | 2017-03-15 | 2018-09-20 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| CA3055990A1 (en) | 2017-03-15 | 2018-09-20 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| WO2018210229A1 (zh) | 2017-05-18 | 2018-11-22 | 南京明德新药研发股份有限公司 | α-7尼古丁乙酰胆碱受体激动剂及应用 |
| CN111278840B (zh) | 2017-08-18 | 2023-11-17 | 癌症研究科技有限公司 | 吡咯并[2，3-b]吡啶化合物及其治疗癌症的用途 |
| WO2019106087A1 (en) | 2017-11-29 | 2019-06-06 | Syddansk Universitet | Ampk inhibitors |
| CN111727189B (zh) | 2017-12-01 | 2023-10-03 | 伊利诺伊大学董事会 | 基于吡啶酮的表观遗传修饰剂及其用途 |
| SG11202005254RA (en) | 2017-12-05 | 2020-07-29 | Oryzon Genomics Sa | 1,2,4-oxadiazole derivatives as histone deacetylase 6 inhibitors |
| WO2019158731A1 (en) | 2018-02-16 | 2019-08-22 | Ucb Biopharma Sprl | Pharmaceutical 6,5 heterobicyclic ring derivatives |
| AU2019234574A1 (en) | 2018-03-12 | 2020-09-03 | Abbvie Inc. | Inhibitors of tyrosine kinase 2 mediated signaling |
| EA202092001A1 (ru) | 2018-03-27 | 2021-01-29 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения болезни гентингтона |
| JP2019182784A (ja) | 2018-04-10 | 2019-10-24 | 大日本住友製薬株式会社 | ジヒドロピラゾロピラジノン誘導体 |
| WO2019198024A1 (en) | 2018-04-11 | 2019-10-17 | VIIV Healthcare UK (No.5) Limited | 4-oxo-3,4-dihydroquinazoline compounds as inhibitors of human immunodeficiency virus replication |
| US11882759B2 (en) | 2018-04-13 | 2024-01-23 | Universal Display Corporation | Organic electroluminescent materials and devices |
| JP7293343B2 (ja) | 2018-05-09 | 2023-06-19 | アプリノイア セラピューティクス リミテッド | ヘテロアリール化合物及びその使用 |
| ES3028093T3 (en) | 2018-06-07 | 2025-06-18 | Disarm Therapeutics Inc | Inhibitors of sarm1 |
| JP7481329B2 (ja) | 2018-06-07 | 2024-05-10 | ディスアーム セラピューティクス， インコーポレイテッド | Ｓａｒｍ１阻害剤 |
| JP2021534123A (ja) | 2018-08-09 | 2021-12-09 | ヴァロ アーリー ディスカバリー， インコーポレイテッド | ユビキチン特異的プロテアーゼ阻害剤としてのカルボキサミド |
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| CA3102598A1 (en) | 2019-12-12 |
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| EP3801499B1 (en) | 2024-02-28 |
| EP3801499A4 (en) | 2022-01-12 |
| MA52809A (fr) | 2021-04-14 |
| CN112839648A (zh) | 2021-05-25 |
| JP7478142B2 (ja) | 2024-05-02 |
| US12448374B2 (en) | 2025-10-21 |
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