ES2286093T3 - Compuestos terapeuticos morfolino-sustituidos. - Google Patents
Compuestos terapeuticos morfolino-sustituidos. Download PDFInfo
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- ES2286093T3 ES2286093T3 ES01902568T ES01902568T ES2286093T3 ES 2286093 T3 ES2286093 T3 ES 2286093T3 ES 01902568 T ES01902568 T ES 01902568T ES 01902568 T ES01902568 T ES 01902568T ES 2286093 T3 ES2286093 T3 ES 2286093T3
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- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/64—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with oxygen atoms directly attached in position 8
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Pyrane Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17735100P | 2000-01-24 | 2000-01-24 | |
| US177351P | 2000-01-24 | ||
| US22582600P | 2000-08-17 | 2000-08-17 | |
| US225826P | 2000-08-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2286093T3 true ES2286093T3 (es) | 2007-12-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01902568T Expired - Lifetime ES2286093T3 (es) | 2000-01-24 | 2001-01-24 | Compuestos terapeuticos morfolino-sustituidos. |
Country Status (14)
| Country | Link |
|---|---|
| US (4) | US6977255B2 (https=) |
| EP (2) | EP1857443B1 (https=) |
| JP (1) | JP4820518B2 (https=) |
| CN (3) | CN1891699A (https=) |
| AT (2) | ATE363471T1 (https=) |
| AU (2) | AU2001230426C1 (https=) |
| CA (1) | CA2398163C (https=) |
| CY (1) | CY1108023T1 (https=) |
| DE (1) | DE60128655T2 (https=) |
| DK (1) | DK1257537T3 (https=) |
| ES (1) | ES2286093T3 (https=) |
| NZ (1) | NZ520300A (https=) |
| PT (1) | PT1257537E (https=) |
| WO (1) | WO2001053266A1 (https=) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| ES2788383T3 (es) | 2000-04-25 | 2020-10-21 | Icos Corp | Inhibidores de delta fosfatidilo-inositol 3-quinasa humana |
| GB0119865D0 (en) * | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
| GB0119863D0 (en) | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
| GB2405093B (en) * | 2001-08-14 | 2005-07-06 | Cancer Rec Tech Ltd | DNA-PK inhibitors |
| CN1551766A (zh) * | 2001-09-05 | 2004-12-01 | ������������ʽ���� | 淋巴细胞活化抑制剂和自身免疫性疾病治疗剂 |
| US7049313B2 (en) | 2002-02-25 | 2006-05-23 | Kudos Pharmaceuticals Ltd. | ATM inhibitors |
| TWI314928B (en) | 2002-02-28 | 2009-09-21 | Novartis A | 5-phenylthiazole derivatives and use as pi3 kinase inhibitors |
| EP2311818B1 (en) * | 2002-02-28 | 2013-01-16 | Novartis AG | Combination of a 5-phenylthiazole compound as PI3 kinase inhibitor with an antiinflammatory, bronchodilatory or antihistamine drug |
| JP4646626B2 (ja) * | 2002-08-16 | 2011-03-09 | アストラゼネカ アクチボラグ | ホスホイノシチド３−キナーゼβの阻害 |
| CN101260104A (zh) * | 2002-08-16 | 2008-09-10 | 阿斯利康(瑞典)有限公司 | 抑制磷酸肌醇3-激酶β |
| KR101050700B1 (ko) * | 2002-08-26 | 2011-07-20 | 다케다 야쿠힌 고교 가부시키가이샤 | 칼슘 수용체 조절 화합물 및 이의 용도 |
| CA2508601A1 (en) | 2002-12-06 | 2004-06-24 | Warner-Lambert Company Llc | Benzoxazin-3-ones and derivatives thereof as inhibitors of pi3k |
| GB0305152D0 (en) | 2003-03-06 | 2003-04-09 | Novartis Ag | Organic compounds |
| WO2004092154A1 (en) * | 2003-04-03 | 2004-10-28 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
| KR20070087266A (ko) * | 2003-04-03 | 2007-08-28 | 세마포르 파머슈티컬즈, 아이엔씨. | 피아이-3 키나아제 억제제 프로드러그 |
| EP1636212B1 (en) * | 2003-06-05 | 2007-06-27 | Warner-Lambert Company LLC | Cycloalkylsulfanyl substituted benzo¬b|thiophenes as therapeutic agents |
| US20040259926A1 (en) * | 2003-06-05 | 2004-12-23 | Bruendl Michelle M. | 3-Aryloxy and 3-heteroaryloxy substituted benzo[b]thiophenes as therapeutic agents |
| MXPA05012894A (es) * | 2003-06-05 | 2006-02-22 | Warner Lambert Co | Benzofuranos 3-sustituidos como agentes terapeuticos. |
| EP1654257B1 (en) | 2003-08-13 | 2010-03-17 | Kudos Pharmaceuticals Limited | Aminopyrones and their use as atm inhibitors |
| JP2007504209A (ja) * | 2003-09-04 | 2007-03-01 | ワーナー−ランバート カンパニー リミティド ライアビリティー カンパニー | ＰＩ３Ｋ阻害活性を有する治療薬としてのハロゲン置換ベンゾ（ｂ）チオフェン類 |
| ES2285517T3 (es) * | 2003-10-31 | 2007-11-16 | Warner-Lambert Company Llc | Pirimidinas como inhibidores de fosfoinositida-3-cinasas(pi3k). |
| US7855214B2 (en) * | 2004-01-26 | 2010-12-21 | Vertex Pharmaceuticals Incorporated | Fused cyclic systems useful as inhibitors of TEC family protein kinases |
| SI2612862T1 (sl) | 2004-05-13 | 2017-04-26 | Icos Corporation | Kinazolini kot inhibitorji humane fosfatidilinozitol 3-kinaze delta |
| CN1300163C (zh) * | 2004-06-23 | 2007-02-14 | 南京大学 | 3－羟基色原酮糖苷及其制法和用途 |
| TW200616986A (en) | 2004-09-20 | 2006-06-01 | Kudos Pharm Ltd | DNA-pk inhibitors |
| JP2008529995A (ja) | 2005-02-09 | 2008-08-07 | クドス ファーマシューティカルズ リミテッド | Ａｔｍ阻害剤 |
| AR054438A1 (es) | 2005-04-15 | 2007-06-27 | Kudos Pharm Ltd | Inhibidores de adn -pk |
| US7691858B2 (en) | 2006-04-25 | 2010-04-06 | Targegen, Inc. | Kinase inhibitors and methods of use thereof |
| CA2656825C (en) * | 2006-06-22 | 2013-12-10 | Prana Biotechnology Limited | Method of treatment and agents useful for same |
| US8106071B2 (en) * | 2007-02-21 | 2012-01-31 | Biobud Co., Ltd. | Compositions for treating hyperproliferative vascular disorders and cancers |
| WO2008126920A1 (ja) | 2007-04-11 | 2008-10-23 | Ajinomoto Co., Inc. | 糖尿病治療薬 |
| WO2008150827A1 (en) * | 2007-05-29 | 2008-12-11 | Smithkline Beecham Corporation | Naphthyridine, derivatives as p13 kinase inhibitors |
| US20100130597A1 (en) * | 2007-07-06 | 2010-05-27 | The United State Of America, As Represented By The Secretary Of The Dept Of Health And Human Service | Dna-pkcs modulates energy regulation and brain function |
| KR20100118977A (ko) * | 2008-01-25 | 2010-11-08 | 아스트라제네카 아베 | 거울상이성질체적으로 순수한 (-) 2-[1-(7-메틸-2-(모르폴린-4-일)-4-옥소-4Ｈ-피리도[1,2-α]피리미딘-9-일)에틸아미노]벤조산, 의학 치료에서의 이의 용도 및 이를 포함하는 약학 조성물-026 |
| EP2262366A4 (en) * | 2008-04-18 | 2012-02-22 | Shenogen Pharma Group Ltd | COMPOUNDS AND METHODS FOR TREATING STROGEN RECEPTOR-RELATED DISEASES |
| US9326986B2 (en) | 2008-09-29 | 2016-05-03 | Glaxosmithkline Llc | Quinazolinone, quinolone and related analogs as sirtuin modulators |
| US8110578B2 (en) * | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
| CN102271683B (zh) | 2008-11-13 | 2014-07-09 | 吉里德卡利斯托加公司 | 恶性血液病的治疗 |
| JP5680639B2 (ja) | 2009-07-02 | 2015-03-04 | サノフイ | 新規６−モルホリン−４−イル−ピリミジン−４−（３ｈ）−オン誘導体、およびａｋｔ（ｐｋｂ）リン酸化阻害剤としてのこの医薬調製物 |
| AR077364A1 (es) | 2009-07-02 | 2011-08-24 | Sanofi Aventis | Derivados de 6-oxo-1,6- dihidro -pirimidin-2-il-) amida, su preparacion y su utilizacion farmaceutica como inhibidores de fosforilacion de akt (pkb) |
| BRPI1015943A8 (pt) | 2009-07-02 | 2018-01-09 | Sanofi Sa | derivados de 1,2,3,4-tetra - hidro - pirimido {1,2-a} pirimidin-6-ona, o respectivo preparo e a respectiva utilização farmacêutica. |
| ES2627428T3 (es) | 2009-07-02 | 2017-07-28 | Sanofi | Nuevos derivados de 2,3-dihidro-1H-imidazo{1,2-a}pirimidin-5-ona, su preparación y su utilización farmacéutica |
| EA201270184A1 (ru) | 2009-07-21 | 2012-08-30 | ГИЛИЭД КАЛИСТОГА ЭлЭлСи | Лечение расстройств печени ингибиторами pi3k |
| US8399460B2 (en) | 2009-10-27 | 2013-03-19 | Astrazeneca Ab | Chromenone derivatives |
| IT1403156B1 (it) | 2010-12-01 | 2013-10-04 | Università Degli Studi Di Torino | Inibitori di fosfatidilinositol 3-chinasi, relative composizioni ed usi. |
| FR2969613B1 (fr) * | 2010-12-23 | 2013-02-08 | Sanofi Aventis | Nouveaux derives de 1,2,3,4-tetrahydro-pyrimido{1,2-a}pyrimidin-6-one, leur preparation et leur utilisation pharmaceutique |
| FR2969612B1 (fr) * | 2010-12-23 | 2013-02-08 | Sanofi Aventis | Nouveaux derives de 2,3-dihydro-1h-imidazo{1,2-a}pyrimidin-5-one, leur preparation et leur utilisation pharmaceutique |
| DK2655375T3 (en) | 2010-12-23 | 2015-03-09 | Sanofi Sa | PYRIMIDINON DERIVATIVES, PREPARATION AND PHARMACEUTICAL USE THEREOF |
| PL2658844T3 (pl) | 2010-12-28 | 2017-04-28 | Sanofi | Nowe pochodne pirymidyn, ich wytwarzanie i ich zastosowanie farmaceutyczne jako inhibitorów fosforylacji AKT(pkb) |
| EP2808322B1 (en) * | 2012-01-26 | 2017-08-23 | Daiichi Sankyo Company, Limited | Chromone derivative having osteogenesis promoting effect |
| EP2812004B1 (en) * | 2012-02-10 | 2018-06-27 | PTC Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| CA2865957C (en) | 2012-03-01 | 2020-02-11 | F. Hoffmann-La Roche Ag | Compounds for treating spinal muscular atrophy |
| SI2834241T1 (sl) | 2012-03-05 | 2021-06-30 | Gilead Calistoga Llc | Polimorfne oblike (S)-2-(1-(9H-purin-6-ilamino)propil)-5-fluoro-3-fenilkinazolin-4(3H)-ONA |
| CA2868026C (en) | 2012-03-23 | 2021-02-16 | Ptc Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| ITMI20120514A1 (it) * | 2012-03-29 | 2013-09-30 | Cnr Consiglio Naz Delle Ric Erche | Agente terapeutico per il trattamento dei vasi sanguigni |
| FR2992314B1 (fr) | 2012-06-22 | 2015-10-16 | Sanofi Sa | Nouveaux derives de 2,3-dihydro-1h-imidazo{1,2-a}pyrimidin-5-one et 1,2,3,4-tetrahydro-pyrimido{1,2-a}pyrimidin-6-one comportant une morpholine substituee, leur preparation et leur utilisation pharmaceutique |
| US10195202B2 (en) | 2013-12-19 | 2019-02-05 | Ptc Therapeutics, Inc. | Methods for modulating the amount of RNA transcripts |
| US9708327B2 (en) | 2013-12-20 | 2017-07-18 | Gilead Calistoga Llc | Polymorphic forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one |
| WO2015095601A1 (en) | 2013-12-20 | 2015-06-25 | Gilead Calistoga Llc | Process methods for phosphatidylinositol 3-kinase inhibitors |
| EP3154960A1 (en) | 2014-06-13 | 2017-04-19 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
| CN107635999B (zh) * | 2015-05-20 | 2020-09-25 | 豪夫迈·罗氏有限公司 | 用于治疗脊髓性肌萎缩的化合物 |
| US10668171B2 (en) | 2015-05-30 | 2020-06-02 | Ptc Therapeutics, Inc. | Methods for modulating RNA splicing |
| EA201800367A1 (ru) | 2015-12-10 | 2019-02-28 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы лечения болезни хантингтона |
| US11129824B2 (en) | 2015-12-17 | 2021-09-28 | Biokine Therapeutics Ltd. | Small molecules for inhibiting chemokine activity and/or cancer cells growth |
| WO2017103931A1 (en) | 2015-12-17 | 2017-06-22 | Biokine Therapeutics Ltd. | Small molecules against cancer |
| WO2018031987A1 (en) | 2016-08-12 | 2018-02-15 | Nanjing Gator Meditech Company, Ltd. | Protein kinase regulators |
| JP2019535789A (ja) | 2016-11-28 | 2019-12-12 | ピーティーシー セラピューティクス，インコーポレーテッド | Ｒｎａスプライシングを調節する方法 |
| EP3573619A4 (en) | 2017-01-27 | 2020-10-28 | SignalRX Pharmaceuticals, Inc. | THIENOPYRANONES AND FURANOPYRANONES AS KINASE, BROMODOMAIN AND CHECKPOINT INHIBITORS |
| EP3634953B1 (en) | 2017-06-05 | 2024-01-03 | PTC Therapeutics, Inc. | Compounds for treating huntington's disease |
| JP2020523365A (ja) | 2017-06-14 | 2020-08-06 | ピーティーシー セラピューティクス，インコーポレーテッド | Ｒｎａスプライシングを改変する方法 |
| CN111182898B (zh) | 2017-06-28 | 2024-04-16 | Ptc医疗公司 | 用于治疗亨廷顿氏病的方法 |
| MX2019015580A (es) | 2017-06-28 | 2020-07-28 | Ptc Therapeutics Inc | Metodos para tratar la enfermedad de huntington. |
| EA202092001A1 (ru) | 2018-03-27 | 2021-01-29 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения болезни гентингтона |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| EP3814360B8 (en) | 2018-06-27 | 2024-11-06 | PTC Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| HRP20240935T1 (hr) | 2018-06-27 | 2024-11-22 | Ptc Therapeutics, Inc. | Heterociklični i heteroaril spojevi za liječenje huntingtonove bolesti |
| CN109748914B (zh) * | 2018-12-29 | 2021-05-25 | 上海珂臻医药科技有限公司 | 吡啶并嘧啶类化合物及其应用 |
| JP7649257B2 (ja) | 2019-05-13 | 2025-03-19 | ピーティーシー セラピューティクス， インコーポレイテッド | ハンチントン病を処置するための化合物 |
| AU2020276793A1 (en) | 2019-05-15 | 2022-01-20 | Alonbio Ltd. | Small molecules for treating cancer, inhibiting chemokine activity and/or inducing cell death |
| AR121719A1 (es) | 2020-04-03 | 2022-06-29 | Petra Pharma Corp | Inhibidores alostéricos de cromenona del fosfoinosítido 3-quinasa (pi3k) para el tratamiento de enfermedades |
| CN111533721B (zh) * | 2020-05-15 | 2022-04-26 | 浙江大学 | 苯并吡喃酮或喹啉酮类化合物及其应用 |
| EP4161926A4 (en) * | 2020-06-03 | 2024-06-19 | Yumanity Therapeutics, Inc. | PYRIDOPYRIMIDINES AND THEIR METHODS OF USE |
| US20240166617A1 (en) * | 2021-02-01 | 2024-05-23 | Geode Therapeutics Inc. | Phosphoinositide 3 kinase beta inhibitors and compositions and methods thereof |
| IL307950A (en) | 2021-05-03 | 2023-12-01 | Petra Pharma Corp | Allosteric chromanone inhibitors of PHOSPHOINOSITIDE 3-KINASE (PI3K) for the treatment of diseases |
| MX2023013987A (es) | 2021-05-27 | 2024-02-12 | Petra Pharma Corp | Inhibidores alostéricos de cromenona de la fosfoinosítido 3-quinasa (pi3k) para el tratamiento contra el cáncer. |
| TW202329930A (zh) | 2021-09-30 | 2023-08-01 | 美商佩特拉製藥公司 | 用於治療疾病之磷酸肌醇3-激酶(pi3k)之異位色烯酮抑制劑 |
| US20250084048A1 (en) * | 2021-10-07 | 2025-03-13 | Relay Therapeutics, Inc. | Pi3k-alpha inhibitors and methods of use thereof |
| WO2025136936A1 (en) * | 2023-12-19 | 2025-06-26 | Merck Sharp & Dohme Llc | Agonists of trem2 activity |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS604170A (ja) * | 1983-06-21 | 1985-01-10 | Nippon Shinyaku Co Ltd | キノロン誘導体 |
| US5703075A (en) * | 1988-12-21 | 1997-12-30 | Pharmacia & Upjohn Company | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones |
| WO1990006921A1 (en) | 1988-12-21 | 1990-06-28 | The Upjohn Company | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones |
| JPH05509302A (ja) | 1990-06-20 | 1993-12-22 | ジ・アップジョン・カンパニー | 抗アテローム性動脈硬化性および抗血栓性１―ベンゾピラン―４―オン類および２―アミノ―１，３―ベンゾオキサジン―４―オン類 |
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2001
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- 2001-01-24 AU AU2001230426A patent/AU2001230426C1/en not_active Ceased
- 2001-01-24 CN CNA2006100847155A patent/CN1891699A/zh active Pending
- 2001-01-24 PT PT01902568T patent/PT1257537E/pt unknown
- 2001-01-24 CN CNA200610084723XA patent/CN1891693A/zh active Pending
- 2001-01-24 AU AU3042601A patent/AU3042601A/xx active Pending
- 2001-01-24 DK DK01902568T patent/DK1257537T3/da active
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