NO328041B1 - Indazolforbindelser som er nyttige som proteinkinaseinhibitorer, samt anvendelse derav for fremstilling av medikamenter - Google Patents
Indazolforbindelser som er nyttige som proteinkinaseinhibitorer, samt anvendelse derav for fremstilling av medikamenter Download PDFInfo
- Publication number
- NO328041B1 NO328041B1 NO20043531A NO20043531A NO328041B1 NO 328041 B1 NO328041 B1 NO 328041B1 NO 20043531 A NO20043531 A NO 20043531A NO 20043531 A NO20043531 A NO 20043531A NO 328041 B1 NO328041 B1 NO 328041B1
- Authority
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- Norway
- Prior art keywords
- phenyl
- independently selected
- aliphatic group
- compound
- halogen
- Prior art date
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US35159702P | 2002-01-25 | 2002-01-25 | |
PCT/US2003/002096 WO2003064397A1 (en) | 2002-01-25 | 2003-01-23 | Indazole compounds useful as protein kinase inhibitors |
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NO328041B1 true NO328041B1 (no) | 2009-11-16 |
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NO20043531A NO328041B1 (no) | 2002-01-25 | 2004-08-24 | Indazolforbindelser som er nyttige som proteinkinaseinhibitorer, samt anvendelse derav for fremstilling av medikamenter |
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US (1) | US7041687B2 (zh) |
EP (3) | EP2295413A1 (zh) |
JP (2) | JP4718118B2 (zh) |
KR (2) | KR20100119902A (zh) |
CN (1) | CN1812973B (zh) |
AR (1) | AR038202A1 (zh) |
AU (1) | AU2003212833C1 (zh) |
CA (1) | CA2473986C (zh) |
HK (1) | HK1096385A1 (zh) |
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PL (1) | PL371512A1 (zh) |
RU (1) | RU2004125852A (zh) |
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Families Citing this family (144)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003217961B2 (en) * | 2002-03-08 | 2008-02-28 | Signal Pharmaceuticals, Llc | Combination therapy for treating, preventing or managing proliferative disorders and cancers |
TW200406385A (en) * | 2002-05-31 | 2004-05-01 | Eisai Co Ltd | Pyrazole compound and pharmaceutical composition containing the same |
US20050070567A1 (en) * | 2002-08-12 | 2005-03-31 | The Regents Of The University Of Michigan | Diagnosis and treatment of diseases arising from defects in the tuberous sclerosis pathway |
JP2005535332A (ja) * | 2002-08-12 | 2005-11-24 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 結節性硬化症の診断法および治療法 |
AR045134A1 (es) * | 2003-07-29 | 2005-10-19 | Smithkline Beecham Plc | Compuesto de 1h - imidazo [4,5-c] piridin-ilo, composicion farmaceutica que lo comprende, proceso para prepararla, su uso para preparar dicha composicion farmaceutica, combinacion farmaceutica, uso de la combinacion farmaceutica para la preparacion de un medicamento, procedimientos para preparar dic |
WO2005014554A1 (en) * | 2003-08-08 | 2005-02-17 | Astex Therapeutics Limited | 1h-indazole-3-carboxamide compounds as mapkap kinase modulators |
JP2005089457A (ja) | 2003-09-03 | 2005-04-07 | Yung Shin Pharmaceutical Industry Co Ltd | 骨成長を促進するまたは骨吸収を阻害するための薬剤組成物 |
CA2539549A1 (en) | 2003-09-23 | 2005-04-07 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrrole derivatives as protein kinase inhibitors |
RU2006117635A (ru) | 2003-10-24 | 2007-12-10 | Шеринг Акциенгезельшафт (De) | Производные индолинона и их применение для лечения патологических состояний, таких как злокачественное новообразование |
CN1882347A (zh) | 2003-11-21 | 2006-12-20 | 阿雷生物药品公司 | Akt蛋白激酶抑制剂 |
JP4728965B2 (ja) * | 2003-12-17 | 2011-07-20 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | プロテインキナーゼモジュレーターとしての二環ピラゾロ−縮合化合物 |
FR2864084B1 (fr) * | 2003-12-17 | 2006-02-10 | Aventis Pharma Sa | Nouveaux derives organophosphores des indazoles et leur utilisation comme medicaments |
US7994196B2 (en) | 2004-02-12 | 2011-08-09 | Mitsubishi Tanabe Pharma Corporation | Indazole compound and pharmaceutical use thereof |
WO2005082890A1 (en) * | 2004-02-20 | 2005-09-09 | Smithkline Beecham Corporation | Novel compounds |
US7378532B2 (en) | 2004-03-26 | 2008-05-27 | Yung Shin Pharmaceutical Ind. Co., Ltd. | Fused pyrazolyl compound |
DE102004028862A1 (de) * | 2004-06-15 | 2005-12-29 | Merck Patent Gmbh | 3-Aminoindazole |
BRPI0513899A (pt) * | 2004-07-27 | 2008-05-20 | Sgx Pharmaceuticals Inc | moduladores de cinase heterocìclica de anel fundido |
US7626021B2 (en) | 2004-07-27 | 2009-12-01 | Sgx Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
JP4895219B2 (ja) * | 2005-02-16 | 2012-03-14 | アステラス製薬株式会社 | Rock阻害剤を含有する疼痛治療剤 |
US20070155738A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
US7625890B2 (en) | 2005-11-10 | 2009-12-01 | Smithkline Beecham Corp. | Substituted imidazo[4,5-c]pyridine compounds as Akt inhibitors |
WO2007058626A1 (en) * | 2005-11-16 | 2007-05-24 | S*Bio Pte Ltd | Indazole compounds |
SI1951724T1 (sl) | 2005-11-17 | 2011-09-30 | Osi Pharmaceuticals Llc | Kondenzirani biciklični mTOR inhibitorji |
UA95940C2 (uk) | 2006-01-17 | 2011-09-26 | Вертекс Фармасьютикалс Інкорпорейтед | Азаіндоли як інгібітори кіназ януса |
GB0606429D0 (en) * | 2006-03-30 | 2006-05-10 | Novartis Ag | Organic compounds |
TW200808739A (en) | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
US20070286864A1 (en) * | 2006-06-09 | 2007-12-13 | Buck Elizabeth A | Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors |
EP2054418B1 (en) | 2006-07-06 | 2011-11-09 | Array Biopharma Inc. | Dihydrothieno pyrimidines as akt protein kinase inhibitors |
BRPI0713555A2 (pt) | 2006-07-06 | 2012-03-20 | Array Biopharma, Inc. | ciclopenta [d] pirimidinas como inibidores de akt protéina cinase |
UA95641C2 (en) * | 2006-07-06 | 2011-08-25 | Эррей Биофарма Инк. | Hydroxylated cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
US8329701B2 (en) | 2006-07-06 | 2012-12-11 | Array Biopharma Inc. | Dihydrofuro pyrimidines as AKT protein kinase inhibitors |
US8063050B2 (en) * | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
DE102006033140A1 (de) | 2006-07-18 | 2008-01-24 | Merck Patent Gmbh | Aminoindazolharnstoffderivate |
US20080207671A1 (en) * | 2006-07-31 | 2008-08-28 | The Regents Of The University Of Michigan | Diagnosis and treatment of diseases arising from defects in the tuberous sclerosis pathway |
EP2526948A1 (en) | 2006-09-20 | 2012-11-28 | Aerie Pharmaceuticals, Inc. | RHO kinase inhibitors |
WO2008061109A2 (en) * | 2006-11-15 | 2008-05-22 | Forest Laboratories Holdings Limited | Indazole derivatives useful as melanin concentrating receptor ligands |
WO2008070823A2 (en) | 2006-12-07 | 2008-06-12 | University Of South Florida | Substrate-mimetic akt inhibitor |
US8247421B2 (en) | 2006-12-21 | 2012-08-21 | Vertex Pharmaceuticals Incorporated | 5-cyano-4-(pyrrolo [2,3B] pyridine-3-yl)-pyrimidine derivatives useful as protein kinase inhibitors |
US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
DE102007002717A1 (de) | 2007-01-18 | 2008-07-24 | Merck Patent Gmbh | Heterocyclische Indazolderivate |
WO2008089307A2 (en) * | 2007-01-18 | 2008-07-24 | Lexicon Pharmaceuticals, Inc. | Delta 5 desaturase inhibitors for the treatment of pain, inflammation and cancer |
WO2008094181A2 (en) * | 2007-02-01 | 2008-08-07 | The Regents Of The University Of Michigan | Compositions and methods for detecting, preventing and treating seizures and seizure related disorders |
UY30892A1 (es) * | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
US8338434B2 (en) * | 2007-03-29 | 2012-12-25 | Glaxosmithkline Llc | Inhibitors of Akt activity |
DE102007022565A1 (de) | 2007-05-14 | 2008-11-20 | Merck Patent Gmbh | Heterocyclische Indazolderivate |
AU2008272830B8 (en) * | 2007-07-05 | 2013-12-12 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
CA2692506C (en) | 2007-07-05 | 2015-11-24 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as akt protein kinase inhibitors |
US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
WO2009008992A2 (en) * | 2007-07-06 | 2009-01-15 | Osi Pharmaceuticals Inc. | Combination anti-cancer therapy comprising an inhibitor of both mtorc1 and mt0rc2 |
US8436038B2 (en) * | 2007-08-17 | 2013-05-07 | Lg Life Sciences Ltd. | Indole and indazole compounds as an inhibitor of cellular necrosis |
MX354184B (es) * | 2007-10-05 | 2018-02-16 | Acucela Inc | Compuestos alcoxi para el tratamiento de enfermedades. |
NZ586346A (en) * | 2008-01-09 | 2012-02-24 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors |
MX2010007546A (es) * | 2008-01-09 | 2010-09-30 | Array Biopharma Inc | Pirimidil ciclopentanos hidroxilados en forma de inhibidores de akt proteína quinasa. |
WO2009145814A2 (en) * | 2008-03-10 | 2009-12-03 | Vertex Pharmaceuticals Incorporated | Pyrimidines and pyridines useful as inhibitors of protein kinases |
JP5657524B2 (ja) | 2008-04-24 | 2015-01-21 | エフツージー リミテッド | ピロール抗真菌剤 |
US8158656B2 (en) * | 2008-05-16 | 2012-04-17 | Shenzhen Chipscreen Biosciences Ltd. | 2-indolinone derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors |
WO2009147187A1 (en) * | 2008-06-05 | 2009-12-10 | Glaxo Group Limited | 4-carboxamide indazole derivatives useful as inhibitors of p13-kinases |
EP2280959B1 (en) | 2008-06-05 | 2012-04-04 | Glaxo Group Limited | 4-amino-indazoles |
WO2009147189A1 (en) | 2008-06-05 | 2009-12-10 | Glaxo Group Limited | Novel compounds |
ES2445199T3 (es) | 2008-06-05 | 2014-02-28 | Glaxo Group Limited | Derivados de benzpirazol como inhibidores de PI3-quinasas |
US20110129455A1 (en) * | 2008-06-26 | 2011-06-02 | Hong Lin | Inhibitors of akt activity |
US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
US8455477B2 (en) * | 2008-08-05 | 2013-06-04 | Merck Sharp & Dohme Corp. | Therapeutic compounds |
DE102008038222A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Indazol-5-carbonsäurehydrazid-derivate |
DE102008038220A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Oxadiazolderivate |
DE102008038221A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | 7-Azaindolderivate |
JP5743897B2 (ja) * | 2008-11-20 | 2015-07-01 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーGlaxoSmithKline LLC | 化合物 |
EP4242206A1 (en) * | 2009-01-30 | 2023-09-13 | Novartis AG | Crystalline n-{(1-s)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1h-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride |
AU2010214095B2 (en) | 2009-02-11 | 2015-12-24 | Merck Patent Gmbh | Novel amino azaheterocyclic carboxamides |
JP5656880B2 (ja) | 2009-03-09 | 2015-01-21 | グラクソ グループ リミテッドGlaxo Group Limited | Pi3キナーゼの阻害剤としての4−オキサジアゾール−2−イル−インダゾール |
WO2010120854A1 (en) * | 2009-04-15 | 2010-10-21 | Glaxosmithkline Llc | Chemical compounds |
PL2899191T3 (pl) | 2009-04-30 | 2018-01-31 | Glaxo Group Ltd | Indazole podstawione oksazolem jako inhibitory kinazy PI3 |
CA2929545C (en) | 2009-05-01 | 2019-04-09 | Aerie Pharmaceuticals, Inc. | Dual mechanism inhibitors for the treatment of disease |
US8211901B2 (en) | 2009-05-22 | 2012-07-03 | Shenzhen Chipscreen Biosciences Ltd. | Naphthamide derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors |
CN101906076B (zh) | 2009-06-04 | 2013-03-13 | 深圳微芯生物科技有限责任公司 | 作为蛋白激酶抑制剂和组蛋白去乙酰化酶抑制剂的萘酰胺衍生物、其制备方法及应用 |
WO2010148197A1 (en) | 2009-06-17 | 2010-12-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
BR112012002336A2 (pt) | 2009-08-07 | 2016-05-31 | Merck Patent Gmbh | compostos aza-heterocíclicos |
WO2011019780A1 (en) | 2009-08-11 | 2011-02-17 | Bristol-Myers Squibb Company | Azaindazoles as btk kinase modulators and use thereof |
US8487102B2 (en) * | 2010-04-20 | 2013-07-16 | Hoffmann-La Roche Inc. | Pyrrazolopyridine compounds as dual NK1/NK3 receptor antagonists |
UA110113C2 (xx) | 2010-07-29 | 2015-11-25 | Біциклічні азагетероциклічні карбоксаміди | |
WO2012016001A1 (en) | 2010-07-29 | 2012-02-02 | Merck Patent Gmbh | Cyclic amine azaheterocyclic carboxamides |
WO2012033525A2 (en) * | 2010-09-08 | 2012-03-15 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | P53-mdm2 antagonists |
GB201018124D0 (en) | 2010-10-27 | 2010-12-08 | Glaxo Group Ltd | Polymorphs and salts |
JP6076258B2 (ja) | 2010-11-12 | 2017-02-08 | ジョージタウン ユニヴァーシティ | 上皮細胞の不死化および使用法 |
EA023821B1 (ru) | 2010-11-24 | 2016-07-29 | Мерк Патент Гмбх | Хиназолинкарбоксамидазетидины, их применение в лечении гиперпролиферативных заболеваний и содержащие их композиции |
CN103492381A (zh) | 2010-12-16 | 2014-01-01 | 沃泰克斯药物股份有限公司 | 流感病毒复制的抑制剂 |
HUE036513T2 (hu) | 2011-04-01 | 2018-07-30 | Genentech Inc | AKT inhibitor vegyület és abirateron kombinációja terápiás kezelésekben való alkalmazásra |
CN103841976A (zh) | 2011-04-01 | 2014-06-04 | 基因泰克公司 | Akt和mek抑制剂化合物的组合及其使用方法 |
UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
JP5964974B2 (ja) | 2011-09-12 | 2016-08-03 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung | キナーゼ活性のモジュレーターとしての新規イミダゾールアミン |
CN103930407B (zh) | 2011-09-12 | 2019-02-26 | 默克专利有限公司 | 用作激酶活性调节剂的氨基嘧啶衍生物 |
EP2766352B1 (en) * | 2011-10-12 | 2018-06-06 | University Health Network (UHN) | Indazole compounds as kinase inhibitors and method of treating cancer with same |
ES2614232T3 (es) | 2011-12-22 | 2017-05-30 | Merck Patent Gmbh | Carboxamidas heterocíclicas novedosas como moduladores de la actividad cinasa |
AR089701A1 (es) * | 2012-01-13 | 2014-09-10 | Medeia Therapeutics Ltd | Derivados de arilamida que tienen propiedades antiandrogenicas |
US8980934B2 (en) | 2012-06-22 | 2015-03-17 | University Health Network | Kinase inhibitors and method of treating cancer with same |
TW201427970A (zh) * | 2012-10-12 | 2014-07-16 | Univ Health Network | 激酶抑制劑及使用其治療癌症的方法 |
US9580443B2 (en) | 2012-11-16 | 2017-02-28 | Merck Patent Gmbh | Heterocyclic derivatives as modulators of kinase activity |
EP2920154B1 (en) | 2012-11-16 | 2017-10-11 | Merck Patent GmbH | Novel imidazol-piperidinyl derivatives as modulators of kinase activity |
ES2821102T3 (es) | 2012-11-29 | 2021-04-23 | Merck Patent Gmbh | Derivados de azaquinazolincarboxamida |
SG10201900954SA (en) | 2013-03-11 | 2019-02-27 | Merck Patent Gmbh | Heterocycles as Modulators of Kinase Activity |
EP4335507A3 (en) | 2013-03-15 | 2024-06-05 | Aerie Pharmaceuticals, Inc. | Combination therapy |
WO2015013579A1 (en) | 2013-07-26 | 2015-01-29 | Update Pharma Inc. | Compositions to improve the therapeutic benefit of bisantrene |
CN103570624B (zh) * | 2013-08-06 | 2016-07-06 | 安徽世华化工有限公司 | 3-溴-5-硝基-1h-吲唑的合成工艺 |
WO2015041533A1 (en) | 2013-09-20 | 2015-03-26 | Stichting Het Nederlands Kanker Instituut | Rock in combination with mapk-pathway |
JP6615755B2 (ja) | 2013-11-13 | 2019-12-04 | バーテックス ファーマシューティカルズ インコーポレイテッド | インフルエンザウイルスの複製の阻害剤 |
SG10201804021TA (en) | 2013-11-13 | 2018-07-30 | Vertex Pharma | Methods of preparing inhibitors of influenza viruses replication |
SG11201608189WA (en) | 2014-04-03 | 2016-10-28 | Merck Patent Gmbh | Combinations of cancer therapeutics |
CA2953524A1 (en) | 2014-06-27 | 2015-12-30 | The Regents Of The University Of California | Cultured mammalian limbal stem cells, methods for generating the same, and uses thereof |
KR101731624B1 (ko) * | 2014-07-01 | 2017-05-04 | 광주과학기술원 | 세포 리프로그래밍 유도용 조성물 |
JP6681894B2 (ja) | 2014-11-21 | 2020-04-15 | エフツージー リミテッド | 抗真菌剤 |
US10100285B2 (en) | 2015-04-03 | 2018-10-16 | Propagenix Inc. | Ex vivo proliferation of epithelial cells |
EP3822339A1 (en) | 2015-04-03 | 2021-05-19 | Propagenix Inc. | Ex vivo proliferation of epithelial cells |
WO2016183116A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
MA42422A (fr) | 2015-05-13 | 2018-05-23 | Vertex Pharma | Inhibiteurs de la réplication des virus de la grippe |
GB201511382D0 (en) | 2015-06-29 | 2015-08-12 | Imp Innovations Ltd | Novel compounds and their use in therapy |
CA2992945A1 (en) | 2015-07-17 | 2017-01-26 | Memorial Sloan-Kettering Cancer Center | Combination therapy using pdk1 and pi3k inhibitors |
EP3347450B1 (en) | 2015-09-11 | 2021-03-17 | Propagenix Inc. | Ex vivo proliferation of epithelial cells |
AU2015414743B2 (en) | 2015-11-17 | 2019-07-18 | Alcon Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
US9643927B1 (en) | 2015-11-17 | 2017-05-09 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
GB201609222D0 (en) | 2016-05-25 | 2016-07-06 | F2G Ltd | Pharmaceutical formulation |
MX2019002396A (es) | 2016-08-31 | 2019-07-08 | Aerie Pharmaceuticals Inc | Composiciones oftalmicas. |
MX2019011784A (es) | 2017-03-31 | 2019-11-18 | Aerie Pharmaceuticals Inc | Compuestos de aril ciclopropil-amino-isoquinolinil amida. |
KR102575246B1 (ko) * | 2017-04-18 | 2023-09-06 | 일라이 릴리 앤드 캄파니 | 페닐-2-히드록시-아세틸아미노-2-메틸-페닐 화합물 |
WO2018234354A1 (en) * | 2017-06-20 | 2018-12-27 | Grünenthal GmbH | NOVEL SUBSTITUTED 3-INDOLE AND 3-INDAZOLE COMPOUNDS AS PHOSPHODIESTERASE INHIBITORS |
CN110869360B (zh) * | 2017-07-12 | 2023-12-15 | 百时美施贵宝公司 | 作为rock抑制剂的苯乙酰胺类 |
EA202090304A1 (ru) * | 2017-07-21 | 2020-06-25 | Кадмон Корпорейшн, Ллк | ИНГИБИТОРЫ Rho-АССОЦИИРОВАННОЙ, СОДЕРЖАЩЕЙ СУПЕРСПИРАЛЬ ПРОТЕИНКИНАЗЫ |
WO2019018855A1 (en) * | 2017-07-21 | 2019-01-24 | Kadmon Corporation, Llc | ALPHA PROPELLER PROTEIN KINASE INHIBITORS ("COILED-COIL") ASSOCIATED WITH RHO |
WO2019161157A1 (en) | 2018-02-16 | 2019-08-22 | Constellation Pharmceuticals, Inc. | P300/cbp hat inhibitors |
CN112218857B (zh) * | 2018-02-16 | 2023-11-21 | 星座制药公司 | P300/cbp hat抑制剂及其使用方法 |
CA3107502A1 (en) | 2018-08-20 | 2020-02-27 | Chengkang ZHANG | Epithelial cell spheroids |
WO2020047229A1 (en) | 2018-08-29 | 2020-03-05 | University Of Massachusetts | Inhibition of protein kinases to treat friedreich ataxia |
CA3112391A1 (en) | 2018-09-14 | 2020-03-19 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
UY38427A (es) | 2018-10-26 | 2020-05-29 | Novartis Ag | Métodos y composiciones para terapia con células oculares |
US11819503B2 (en) | 2019-04-23 | 2023-11-21 | F2G Ltd | Method of treating coccidioides infection |
WO2021021893A1 (en) * | 2019-07-29 | 2021-02-04 | Constellation Pharmaceuticals, Inc. | Compounds for use in treating neurological disorders |
US11608319B2 (en) * | 2019-12-31 | 2023-03-21 | Industrial Technology Research Institute | Beta-amino acid derivative, kinase inhibitor and pharmaceutical composition containing the same, and method for performing an in vivo related application that benefits from the inhibition of a kinase |
CN111217834B (zh) * | 2020-02-21 | 2021-10-26 | 维眸生物科技(上海)有限公司 | Rock激酶抑制剂的硝基氧衍生物 |
US20230348852A1 (en) | 2020-04-27 | 2023-11-02 | Novartis Ag | Methods and compositions for ocular cell therapy |
JP2023551408A (ja) | 2020-11-16 | 2023-12-08 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | がん処置のためのキナーゼインヒビター組み合わせ |
CN118159645A (zh) | 2021-10-18 | 2024-06-07 | 埃维亚生命科学有限公司 | 组合物及使用其治疗肝纤维化的方法 |
CA3235862A1 (en) | 2021-10-22 | 2023-04-27 | Takahiro Ochiya | Methods for making extracellular vesicles, and compositions and methods of use thereof |
CN114605329B (zh) * | 2022-03-28 | 2024-01-26 | 河南中医药大学 | 取代的吲唑甲酰胺或取代的氮杂吲唑甲酰胺类flt3抑制剂及其用途 |
CN116891460A (zh) * | 2023-07-12 | 2023-10-17 | 浙江大学 | 一种吲唑类衍生物或其药用盐及应用 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5640715B2 (zh) | 1974-04-01 | 1981-09-22 | ||
DE68929303T2 (de) | 1988-09-15 | 2002-05-02 | Pharmacia & Upjohn Co., Kalamazoo | 3-(Stickstoff substituierte)phenyl-5-beta-amidomethyloxazoliden-2-one |
US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
US5994341A (en) | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
AU5041300A (en) | 1999-05-24 | 2000-12-12 | Cor Therapeutics, Inc. | Inhibitors of factor xa |
EP1192132B1 (en) | 1999-06-14 | 2005-09-07 | Eli Lilly And Company | Serine protease inhibitors |
US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
DE10023486C1 (de) | 2000-05-09 | 2002-03-14 | Schering Ag | Ortho substituierte Anthranilsäureamide und deren Verwendung als Arzneimittel |
US6897231B2 (en) * | 2000-07-31 | 2005-05-24 | Signal Pharmaceuticals, Inc. | Indazole derivatives as JNK inhibitors and compositions and methods related thereto |
US6982274B2 (en) * | 2001-04-16 | 2006-01-03 | Eisai Co., Ltd. | 1H-indazole compound |
JPWO2002100833A1 (ja) * | 2001-06-12 | 2004-09-24 | 住友製薬株式会社 | Rhoキナーゼ阻害剤 |
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- 2003-01-23 EP EP10181668A patent/EP2295413A1/en not_active Withdrawn
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- 2003-01-23 CN CN038056127A patent/CN1812973B/zh not_active Expired - Fee Related
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CN1812973B (zh) | 2010-12-22 |
CA2473986C (en) | 2012-01-17 |
JP2005524631A (ja) | 2005-08-18 |
TW200306819A (en) | 2003-12-01 |
WO2003064397A1 (en) | 2003-08-07 |
KR20040078676A (ko) | 2004-09-10 |
HK1096385A1 (en) | 2007-06-01 |
JP2006176530A (ja) | 2006-07-06 |
EP2295413A1 (en) | 2011-03-16 |
CN1812973A (zh) | 2006-08-02 |
PL371512A1 (en) | 2005-06-27 |
AR038202A1 (es) | 2005-01-05 |
MXPA04007126A (es) | 2005-03-31 |
IL163117A (en) | 2010-05-31 |
RU2004125852A (ru) | 2006-01-20 |
CA2473986A1 (en) | 2003-08-07 |
EP1467972A1 (en) | 2004-10-20 |
US20040009968A1 (en) | 2004-01-15 |
AU2003212833B2 (en) | 2008-02-21 |
KR20100119902A (ko) | 2010-11-11 |
NO20043531L (no) | 2004-10-25 |
US7041687B2 (en) | 2006-05-09 |
JP4718118B2 (ja) | 2011-07-06 |
AU2003212833C1 (en) | 2010-12-23 |
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