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)
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- General Chemical & Material Sciences (AREA)
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- 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 (enExample) |
| EP (1) | EP3801499B1 (enExample) |
| JP (1) | JP7478142B2 (enExample) |
| CN (1) | CN112839648B (enExample) |
| ES (1) | ES2988933T3 (enExample) |
| MA (1) | MA52809A (enExample) |
| WO (1) | WO2019236884A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112839647B (zh) | 2018-06-07 | 2025-09-23 | 达萨玛治疗公司 | Sarm1抑制剂 |
| EP3897670A4 (en) | 2018-12-19 | 2022-09-07 | Disarm Therapeutics, Inc. | MRSA1 INHIBITORS IN COMBINATION WITH NEUROPROTECTIVE AGENTS |
| US12595252B2 (en) | 2019-06-14 | 2026-04-07 | Disarm Therapeutics, Inc. | Inhibitors of SARM1 |
| CA3150878A1 (en) | 2019-09-12 | 2021-03-18 | Jonathan Bentley | Inhibitors of sarm1 |
| JP7528212B2 (ja) * | 2019-11-26 | 2024-08-05 | 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 | 神経保護のための方法および組成物 |
| US12435084B2 (en) | 2020-04-09 | 2025-10-07 | Eli Lilly And Company | Indazole derivatives as inhibitors of SARM1 |
| US12606558B2 (en) | 2020-04-09 | 2026-04-21 | Disarm Therapeutics, Inc. | Condensed pyrazole derivatives as inhibitors of SARM1 |
| TWI904906B (zh) | 2020-08-24 | 2025-11-11 | 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 |
| WO2000026211A1 (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 |
| US7109208B2 (en) * | 2001-04-11 | 2006-09-19 | Senju Pharmaceutical Co., Ltd. | Visual function disorder improving agents |
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| CA2462453C (en) | 2001-10-02 | 2009-07-28 | Pharmacia & Upjohn Company | Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease |
| US6849620B2 (en) | 2001-10-26 | 2005-02-01 | Pfizer Inc | N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease |
| WO2003076442A1 (en) | 2002-03-05 | 2003-09-18 | Eli Lilly And Company | Purine derivatives as kinase inhibitors |
| US7429609B2 (en) | 2002-05-31 | 2008-09-30 | Eisai R & D Management Co., Ltd. | Pyrazole compound and medicinal composition containing the same |
| AU2003269413A1 (en) | 2002-11-01 | 2004-05-25 | Pharmacia & Upjohn Company Llc | Nicotinic acetylcholine agonists in the treatment of glaucoma and retinal neuropathy |
| 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 |
| AP2005003336A0 (en) | 2002-12-11 | 2005-06-30 | Pharmacia & Upjohn Co Llc | Combination for the treatment of ADHD |
| PL377777A1 (pl) | 2002-12-11 | 2006-02-20 | Pharmacia & Upjohn Company Llc | Leczenie chorób połączeniami agonistów receptora alfa 7-nikotynowego i innych związków |
| EP1587511A2 (en) | 2003-01-22 | 2005-10-26 | Pharmacia & Upjohn Company LLC | Treatment of diseases with alpha-7 nach receptor full agonists |
| EP1706384A1 (en) | 2004-01-07 | 2006-10-04 | AstraZeneca AB | Therapeutic agents i |
| CA2572047C (en) | 2004-07-21 | 2014-04-08 | Applied Research Systems Ars Holding N.V. | Octahydropyrrolo[2,3,c]pyridine derivatives and pharmaceutical use thereof |
| KR100958829B1 (ko) | 2004-09-03 | 2010-05-25 | 주식회사유한양행 | 피롤로[2,3-ｃ]피리딘 유도체 및 그의 제조방법 |
| WO2006061212A1 (en) | 2004-12-08 | 2006-06-15 | Johannes Gutenberg-Universität Mainz | 3-(indolyl)-4-arylmaleimide derivatives and their use as angiogenesis inhibitors |
| EP1838706A1 (en) | 2004-12-24 | 2007-10-03 | Prosidion Limited | G-protein coupled receptor agonists |
| US7557103B2 (en) | 2005-04-05 | 2009-07-07 | Eli Lilly And Company | Imidazopyridazine compounds |
| PT1906965E (pt) | 2005-06-22 | 2015-09-03 | Chemocentryx Inc | Compostos de azaindazol e métodos de utilização |
| 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 |
| NZ579892A (en) | 2007-03-30 | 2012-03-30 | Sanofi Aventis | Pyrimidine hydrazide compounds as prostaglandin D synthase inhibitors |
| AU2008241488A1 (en) | 2007-04-16 | 2008-10-30 | Merck Sharp & Dohme Corp. | Bicyclic anilide heterocyclic CGRP receptor antagonists |
| US20100324049A1 (en) | 2007-09-27 | 2010-12-23 | Makoto Ando | Diaryl ketimine derivative having antagonism against melanin-concentrating hormone receptor |
| GB0803018D0 (en) | 2008-02-19 | 2008-03-26 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| WO2009120717A2 (en) | 2008-03-24 | 2009-10-01 | Medivation Technologies, Inc. | Pyrido [3, 4-b] indoles and methods of use |
| CL2009001152A1 (es) | 2008-05-13 | 2009-10-16 | Array Biopharma Inc | Compuestos derivados de n-(4-(cicloalquilo nitrogenado-1-il)-1h-pirrolo[2,3-b]piridin-3-il)amida, inhibidores de cinasa; proceso de preparacion; composicion farmaceutica; y su uso para el tratamiento de una enfermedad proliferativa. |
| US8012992B2 (en) | 2008-06-30 | 2011-09-06 | Allergan, Inc. | Aza-indoles and related compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| BRPI0917540A2 (pt) | 2008-08-05 | 2015-11-17 | Daiichi Sankyo Co Ltd | composto, sal farmacologicamente aceitavél, composição farmacêutica, e, uso de um composto ou sal farmacologicamente aceitável |
| JP5576370B2 (ja) | 2008-08-06 | 2014-08-20 | ファイザー・インク | Ｃｈｋ−１阻害剤としての６置換２−ヘテロシクリルアミノピラジン化合物 |
| US20110183975A1 (en) | 2008-10-07 | 2011-07-28 | Yasuhiro Goto | Novel 6-azaindole aminopyrimidine derivatives having nik inhibitory activity |
| CA2738929A1 (en) | 2008-10-17 | 2010-04-22 | 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 |
| MY153715A (en) | 2008-11-14 | 2015-03-13 | Merial Ltd | Enantiomerically enriched aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof |
| 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 |
| 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 |
| EP2534156A1 (en) | 2010-02-11 | 2012-12-19 | OSI Pharmaceuticals, LLC | 7-aminofuropyridine derivatives |
| GB201017345D0 (en) | 2010-10-14 | 2010-11-24 | Proximagen Ltd | Receptor antagonists |
| WO2012058645A1 (en) | 2010-10-29 | 2012-05-03 | Biogen Idec 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 |
| PT2661433T (pt) | 2011-01-04 | 2017-10-24 | Novartis Ag | Compostos de indole ou seus análogos úteis para o tratamento da degeneração macular relacionada com a idade (amd) |
| DE102011009961A1 (de) | 2011-02-01 | 2012-08-02 | Merck Patent Gmbh | 7-Azaindolderivate |
| AU2012212323A1 (en) | 2011-02-01 | 2013-09-12 | The Board Of Trustees Of The University Of Illinois | HDAC inhibitors and therapeutic methods using the same |
| WO2012114252A1 (en) | 2011-02-21 | 2012-08-30 | Actelion Pharmaceuticals Ltd | Novel indole and pyrrolopyridine amides |
| PH12013502020A1 (en) | 2011-04-05 | 2018-04-11 | Pfizer Ltd | Pyrrolo [2,3-d] pyrimidine derivatives as inhibitors of tropomyosin-related kinases |
| WO2012178022A2 (en) | 2011-06-24 | 2012-12-27 | University Of Massachusetts | 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 |
| AR092289A1 (es) | 2011-11-14 | 2015-04-15 | Sunshine Lake Pharma Co Ltd | Derivados de aminoquinazolina y sus sales y metodos de uso |
| 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 |
| CA2882724A1 (en) | 2012-07-12 | 2014-01-16 | Novartis Ag | Complement pathway modulators and uses thereof |
| KR101916443B1 (ko) | 2012-07-26 | 2018-11-08 | 글락소 그룹 리미티드 | Pad4 억제제로서의 2-(아자인돌-2-일) 벤즈이미다졸 |
| BR112015022643A2 (pt) | 2013-03-12 | 2017-07-18 | Abbvie Inc | inibidores diidro-pirrolpiridinona |
| TWI663166B (zh) | 2013-04-24 | 2019-06-21 | 健生藥品公司 | 新化合物 |
| EA027936B1 (ru) | 2013-05-02 | 2017-09-29 | Пфайзер Инк. | Производные имидазотриазина в качестве ингибиторов фосфодиэстеразы 10 (pde10) |
| 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 |
| US9732103B2 (en) * | 2014-02-25 | 2017-08-15 | Achillion Pharmaceuticals, Inc. | Carbamate, ester, and ketone compounds for treatment of complement mediated disorders |
| ES2774923T3 (es) | 2014-04-28 | 2020-07-23 | China Resources Pharmaceutical Holdings Company Ltd | Derivados de isoquinolinsulfonilo como inhibidores de RHO quinasa |
| WO2015191403A1 (en) | 2014-06-13 | 2015-12-17 | Bristol-Myers Squibb Company | Tricyclic compounds as alpha-7 nicotinic acetylcholine receptor ligands |
| WO2015188368A1 (en) | 2014-06-13 | 2015-12-17 | Merck Sharp & Dohme Corp. | Pyrrolo[2,3-c]pyridines as imaging agents for neurofibrilary tangles |
| ES2708965T3 (es) | 2014-06-13 | 2019-04-12 | Bristol Myers Squibb Co | Compuestos tricíclicos como ligandos del receptor de alfa-7 nicotínico de acetilcolina |
| CN111253424B (zh) | 2014-08-06 | 2023-06-20 | 加州理工学院 | 芳族杂环通过地球丰富的无过渡金属的催化剂的甲硅烷基化 |
| CA2960336C (en) | 2014-10-23 | 2023-03-07 | Janssen Pharmaceutica Nv | Compounds as nik inhibitors |
| KR102523405B1 (ko) | 2014-10-23 | 2023-04-18 | 얀센 파마슈티카 엔.브이. | Ｎｉｋ 억제제로서의 신규 피라졸로피리미딘 유도체 |
| 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 |
| WO2016100157A2 (en) | 2014-12-19 | 2016-06-23 | 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 |
| CA2979302A1 (en) | 2015-05-13 | 2016-11-17 | Selvita S.A. | Substituted quinoxaline derivatives |
| BR112017028269A2 (pt) | 2015-07-13 | 2018-09-04 | Arvinas Inc | composto, composição farmacêutica, uso de uma quantidade efetiva de um composto, estado ou condição de doença, e, método para identificar um composto. |
| ES2821896T3 (es) | 2015-08-05 | 2021-04-28 | Indivior Uk Ltd | Antagonistas del receptor de dopamina D3 que tienen una unidad estructural biciclo |
| 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 |
| EP3389664A4 (en) | 2015-12-14 | 2020-01-08 | Raze Therapeutics Inc. | MTHFD2 CAFFEIN INHIBITORS AND USES THEREOF |
| TWI726968B (zh) | 2016-01-07 | 2021-05-11 | 開曼群島商Ｃｓ醫藥技術公司 | Egfr酪胺酸激酶之臨床重要突變體之選擇性抑制劑 |
| TWI747873B (zh) | 2016-02-01 | 2021-12-01 | 美商百歐克斯製藥公司 | 苯并吡唑化合物及其類似物 |
| WO2017202748A1 (en) | 2016-05-24 | 2017-11-30 | Merck Patent Gmbh | Tricyclic heterocylic derivatives |
| 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 |
| WO2018035204A1 (en) | 2016-08-16 | 2018-02-22 | Henry Ford Health System | Compositions for the treatment of neuropathic pain and sensitization of tumors to chemotherapies |
| CN115819417A (zh) | 2016-09-09 | 2023-03-21 | 因赛特公司 | 作为hpk1调节剂的吡唑并吡啶衍生物及其用于治疗癌症的用途 |
| JP7044789B2 (ja) | 2016-09-24 | 2022-03-30 | ワシントン・ユニバーシティ | Ｓａｒｍ１ ｎａｄアーゼ活性の阻害剤およびその使用 |
| US10323036B2 (en) | 2016-10-14 | 2019-06-18 | Nimbus Lakshmi, Inc. | TYK2 inhibitors and uses thereof |
| MX385576B (es) | 2016-11-02 | 2025-03-18 | Janssen Pharmaceutica Nv | Derivados de [1,2,4]triazol[1,5-a]pirimidina como inhibidores de pde2 |
| WO2018149986A1 (en) | 2017-02-16 | 2018-08-23 | Oryzon Genomics, S.A. | 2-(bicyclo-heteroaryl)-isonicotinic derivatives as histone demethylase inhibitors |
| WO2018170173A1 (en) | 2017-03-15 | 2018-09-20 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| IL269068B (en) | 2017-03-15 | 2022-09-01 | Metacrine Inc | Paranoid x receptor agonists and uses thereof |
| WO2018170165A1 (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 |
| WO2019034890A1 (en) | 2017-08-18 | 2019-02-21 | Cancer Research Technology Limited | PYRROLO [2,3-B] PYRIDINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER |
| WO2019106087A1 (en) | 2017-11-29 | 2019-06-06 | Syddansk Universitet | Ampk inhibitors |
| CA3118400A1 (en) | 2017-12-01 | 2019-06-06 | The Board Of Trustees Of The University Of Illinois | Pyridinone-based epigenetic modifiers and uses thereof |
| SG11202005254RA (en) | 2017-12-05 | 2020-07-29 | Oryzon Genomics Sa | 1,2,4-oxadiazole derivatives as histone deacetylase 6 inhibitors |
| MX2020008265A (es) | 2018-02-16 | 2020-09-21 | UCB Biopharma SRL | Derivados farmaceuticos del anillo heterobiciclico 6,5. |
| AR117398A1 (es) | 2018-03-12 | 2021-08-04 | Abbvie Inc | Inhibidores de la señalización mediada por tirosina cinasa 2 |
| MX2020009957A (es) | 2018-03-27 | 2021-01-15 | Ptc Therapeutics Inc | Compuestos para el tratamiento de enfermedad de hungtinton. |
| 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 |
| EP3774775B8 (en) | 2018-04-11 | 2023-11-15 | 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 |
| TW201946624A (zh) | 2018-05-09 | 2019-12-16 | 新旭生技股份有限公司 | 雜芳基化合物及其用途 |
| CN112839647B (zh) | 2018-06-07 | 2025-09-23 | 达萨玛治疗公司 | Sarm1抑制剂 |
| CA3108669A1 (en) | 2018-06-07 | 2019-12-12 | Disarm Therapeutics, Inc. | Inhibitors of sarm1 |
| AU2019319907B2 (en) | 2018-08-09 | 2024-09-05 | Valo Health, Inc. | Carboxamides as ubiquitin-specific protease inhibitors |
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| US20220194933A1 (en) | 2022-06-23 |
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| WO2019236884A1 (en) | 2019-12-12 |
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| CA3102598A1 (en) | 2019-12-12 |
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