JP3878849B2 - インダゾール及びプロテインキナーゼ阻害のためのその使用 - Google Patents
インダゾール及びプロテインキナーゼ阻害のためのその使用 Download PDFInfo
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- JP3878849B2 JP3878849B2 JP2001507809A JP2001507809A JP3878849B2 JP 3878849 B2 JP3878849 B2 JP 3878849B2 JP 2001507809 A JP2001507809 A JP 2001507809A JP 2001507809 A JP2001507809 A JP 2001507809A JP 3878849 B2 JP3878849 B2 JP 3878849B2
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- indazole
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- 108060006633 protein kinase Proteins 0.000 title claims description 30
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 50
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- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 230000000694 effects Effects 0.000 claims description 36
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- 239000002585 base Substances 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
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Classifications
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- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Applications Claiming Priority (3)
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US14213099P | 1999-07-02 | 1999-07-02 | |
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PCT/US2000/018263 WO2001002369A2 (en) | 1999-07-02 | 2000-06-30 | Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use |
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---|---|---|---|---|
RU2262935C2 (ru) | 1999-02-10 | 2005-10-27 | Астразенека Аб | Производные хиназолина в качестве ингибиторов ангиогенеза |
PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
CZ301750B6 (cs) | 1999-12-24 | 2010-06-09 | Aventis Pharma Limited | Bicyklický pyrrolový derivát, jeho použití pri výrobe léciva, farmaceutická kompozice tento derivát obsahující a pro použití pri lécení |
DE60106409T2 (de) | 2000-02-07 | 2006-02-02 | Bristol-Myers Squibb Co. | 3-aminopyrazole als inhibitoren von cyclinabhängigen kinasen |
WO2001068585A1 (fr) * | 2000-03-14 | 2001-09-20 | Fujisawa Pharmaceutical Co., Ltd. | Nouveaux composes amides |
JP2004507455A (ja) | 2000-04-25 | 2004-03-11 | ブリストル−マイヤーズ スクイブ カンパニー | サイクリン依存性キナーゼ阻害剤としての、5−チオ−、スルフィニル−およびスルホニルピラゾロ[3,4−b]−ピリジンの用途 |
CN1252065C (zh) | 2000-08-09 | 2006-04-19 | 阿斯特拉曾尼卡有限公司 | 噌啉化合物 |
AU2001276536B2 (en) | 2000-08-09 | 2007-01-04 | Astrazeneca Ab | Quinoline derivatives having vegf inhibiting activity |
AU2001293233A1 (en) | 2000-09-01 | 2002-03-13 | Chiron Corporation | Aza heterocyclic derivatives and their therapeutic use |
KR100728797B1 (ko) | 2000-09-11 | 2007-06-19 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 티로신 키나제 억제제로서의 퀴놀리논 유도체 |
HU230302B1 (hu) | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
GB0115109D0 (en) | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
EP1401831A1 (en) * | 2001-07-03 | 2004-03-31 | Chiron Corporation | Indazole benzimidazole compounds as tyrosine and serine/threonine kinase inhibitors |
US7642278B2 (en) | 2001-07-03 | 2010-01-05 | Novartis Vaccines And Diagnostics, Inc. | Indazole benzimidazole compounds |
US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
BR0213562A (pt) * | 2001-10-26 | 2004-08-31 | Aventis Pharma Inc | Benzimidazóis e análogos e seu uso como inibidores de cinases de proteìna |
FR2831536A1 (fr) * | 2001-10-26 | 2003-05-02 | Aventis Pharma Sa | Nouveaux derives de benzimidazoles, leur procede de preparation, leur application a titre de medicament, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de kdr |
US6897208B2 (en) * | 2001-10-26 | 2005-05-24 | Aventis Pharmaceuticals Inc. | Benzimidazoles |
FR2831537B1 (fr) * | 2001-10-26 | 2008-02-29 | Aventis Pharma Sa | Nouveaux derives de benzimidazoles, leur procede de preparation, leur application a titre de medicament, compositions pharmaceutiques et nouvelle utilisation |
PT1474420E (pt) | 2002-02-01 | 2012-05-10 | Astrazeneca Ab | Compostos de quinazolina |
US7166293B2 (en) * | 2002-03-29 | 2007-01-23 | Carlsbad Technology, Inc. | Angiogenesis inhibitors |
US20050119278A1 (en) * | 2002-05-16 | 2005-06-02 | Che-Ming Teng | Anti-angiogenesis methods |
BR0313396A (pt) | 2002-08-12 | 2005-06-28 | Sugen Inc | 3-pirrolil-piridopirazóis e 3-pirrolil-indazóis, como inibidores de quinase |
US7470709B2 (en) | 2002-08-23 | 2008-12-30 | Novartis Vaccines And Diagnostics, Inc. | Benzimidazole quinolinones and uses thereof |
JPWO2004050088A1 (ja) * | 2002-12-03 | 2006-03-30 | 協和醗酵工業株式会社 | Jnk阻害剤 |
CN1747950A (zh) | 2002-12-19 | 2006-03-15 | 美国辉瑞有限公司 | 用于治疗眼病的作为蛋白激酶抑制剂的2-(1h-吲唑-6-基氨基)-苯甲酰胺化合物 |
US7192976B2 (en) | 2002-12-21 | 2007-03-20 | Angion Biomedica Corporation | Small molecule modulators of hepatocyte growth factor (scatter factor) activity |
MXPA05009459A (es) | 2003-03-03 | 2006-05-17 | Array Biopharma Inc | Inhibidores de p38 y sus metodos de uso. |
US7135575B2 (en) | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
CA2520932A1 (en) * | 2003-04-03 | 2004-10-14 | Pfizer Inc. | Dosage forms comprising ag013736 |
EP1618133A1 (en) * | 2003-04-17 | 2006-01-25 | Pfizer Inc. | Crystal structure of vegfrkd: ligand complexes and methods of use thereof |
FR2854159B1 (fr) * | 2003-04-25 | 2008-01-11 | Aventis Pharma Sa | Nouveaux derives de l'indole, leur preparation a titre de medicaments, compositions pharmaceutiques et notamment comme inhibiteurs de kdr |
TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
WO2005012256A1 (en) | 2003-07-22 | 2005-02-10 | Astex Therapeutics Limited | 3, 4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
AU2004259012C1 (en) | 2003-07-23 | 2012-08-02 | Exelixis, Inc. | Anaplastic lymphoma kinase modulators and methods of use |
JP4363530B2 (ja) * | 2003-07-30 | 2009-11-11 | 協和発酵キリン株式会社 | タンパク質キナーゼ阻害剤 |
MXPA05011420A (es) * | 2003-07-30 | 2005-12-12 | Kyowa Hakko Kogyo Kk | Derivados de indazol. |
CA2537430A1 (en) * | 2003-09-04 | 2005-03-24 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
US20050164300A1 (en) * | 2003-09-15 | 2005-07-28 | Plexxikon, Inc. | Molecular scaffolds for kinase ligand development |
WO2005039564A1 (en) * | 2003-10-02 | 2005-05-06 | Vertex Pharmaceuticals Incorporated | Phthalimide compounds useful as protein kinase inhibitors |
EP1699421B1 (en) | 2003-11-07 | 2014-05-21 | Novartis Vaccines and Diagnostics, Inc. | Lactate salts of quinolinone compounds and their pharmaceutical use |
US7683172B2 (en) | 2003-11-11 | 2010-03-23 | Eisai R&D Management Co., Ltd. | Urea derivative and process for preparing the same |
CA2546493A1 (en) * | 2003-11-19 | 2005-06-09 | Signal Pharmaceuticals, Llc | Indazole compounds and methods of use thereof as protein kinase inhibitors |
GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
EP1747202A1 (en) | 2004-02-27 | 2007-01-31 | F.Hoffmann-La Roche Ag | Indazole derivatives and pharmaceutical compositions containing them |
EP1720855A4 (en) * | 2004-03-02 | 2008-12-17 | Smithkline Beecham Corp | HEMMER OF ACT ACTIVITY |
WO2005094823A1 (ja) * | 2004-03-30 | 2005-10-13 | Kyowa Hakko Kogyo Co., Ltd. | Flt-3阻害剤 |
WO2005108370A1 (ja) * | 2004-04-16 | 2005-11-17 | Ajinomoto Co., Inc. | ベンゼン化合物 |
US7585859B2 (en) | 2004-05-06 | 2009-09-08 | Plexxikon, Inc. | PDE4B inhibitors and uses therefor |
RU2007101509A (ru) | 2004-06-17 | 2008-07-27 | Уайт (Us) | Способ получения антагонистов рецепторов гормона, высвобождающего гонадотропин |
MXPA06014798A (es) * | 2004-06-17 | 2007-06-22 | Wyeth Corp | Antagonistas del receptor de hormona para liberar gonadotropina. |
EP1786777A1 (en) * | 2004-08-26 | 2007-05-23 | Pfizer, Inc. | Aminoheteroaryl compounds as protein tyrosine kinase inhibitors |
CN101048407A (zh) | 2004-09-03 | 2007-10-03 | 普莱希科公司 | 双环杂芳基pde4b抑制剂 |
ATE428421T1 (de) | 2004-09-17 | 2009-05-15 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
EP1647549A1 (en) * | 2004-10-14 | 2006-04-19 | Laboratoire Theramex | Indazoles, benzisoxazoles and benzisothiazoles as estrogenic agents |
EP1809625A1 (en) * | 2004-11-02 | 2007-07-25 | Pfizer, Inc. | Methods for preparing indazole compounds |
CA2591313A1 (en) * | 2004-11-02 | 2006-05-11 | Pfizer Inc. | Methods for preparing indazole compounds |
KR20070060145A (ko) * | 2004-11-02 | 2007-06-12 | 화이자 인코포레이티드 | 6-[2-(메틸카바모일)페닐설파닐]-3-e-[2-(피리딘-2-일)에테닐]인다졸의 다형체 형태 |
WO2006068760A2 (en) | 2004-11-19 | 2006-06-29 | The Regents Of The University Of California | Anti-inflammatory pyrazolopyrimidines |
FR2878442B1 (fr) * | 2004-11-29 | 2008-10-24 | Aventis Pharma Sa | THIENO(2,3-c)PYRAZOLES SUBSTITUES, PROCEDE DE PREPARATION, COMPOSITIONS LES CONTENANT ET UTILISATION |
US20060142247A1 (en) * | 2004-12-17 | 2006-06-29 | Guy Georges | Tricyclic heterocycles |
US8110573B2 (en) | 2004-12-30 | 2012-02-07 | Astex Therapeutics Limited | Pyrazole compounds that modulate the activity of CDK, GSK and aurora kinases |
US7622583B2 (en) | 2005-01-14 | 2009-11-24 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2 |
MX2007008781A (es) | 2005-01-21 | 2007-09-11 | Astex Therapeutics Ltd | Compuestos farmaceuticos. |
AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
BRPI0606480A (pt) | 2005-01-21 | 2008-03-11 | Astex Therapeutics Ltd | compostos farmacêuticos |
US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
WO2006081230A2 (en) * | 2005-01-26 | 2006-08-03 | Schering Corporation | 3-(indazol-5-yl)-(1,2, 4) triazine derivatives and related compounds as protein kinase inhibitors for the treatment of cancer |
AU2006209712B2 (en) * | 2005-01-27 | 2011-06-09 | Kyowa Hakko Kirin Co., Ltd. | IGF-1R inhibitor |
US7538113B2 (en) | 2005-02-18 | 2009-05-26 | Wyeth | 4-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
US7534796B2 (en) | 2005-02-18 | 2009-05-19 | Wyeth | Imidazo[4,5-b]pyridine antagonists of gonadotropin releasing hormone receptor |
US7582634B2 (en) | 2005-02-18 | 2009-09-01 | Wyeth | 7-substituted imidazo[4,5-c]pyridine antagonists of gonadotropin releasing hormone receptor |
ATE530533T1 (de) | 2005-05-17 | 2011-11-15 | Novartis Ag | Verfahren zur synthese heterocyclischer verbindungen |
US7531542B2 (en) | 2005-05-18 | 2009-05-12 | Wyeth | Benzooxazole and benzothiazole antagonists of gonadotropin releasing hormone receptor |
CA2608952A1 (en) * | 2005-05-19 | 2006-11-23 | Dwayne Thomas Friesen | Pharmaceutical compostions comprising an amorphous form of a vegf-r inhibitor |
US8921376B2 (en) * | 2005-05-20 | 2014-12-30 | Vertex Pharmaceuticals Incorporated | Pyrrolopyridines useful as inhibitors of protein kinase |
US7582636B2 (en) | 2005-05-26 | 2009-09-01 | Wyeth | Piperazinylimidazopyridine and piperazinyltriazolopyridine antagonists of Gonadotropin Releasing Hormone receptor |
WO2006130673A1 (en) | 2005-05-31 | 2006-12-07 | Janssen Pharmaceutica, N.V. | 3-benzoimidazolyl-pyrazolopyridines useful in treating kinase disorders |
US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
EP1925676A4 (en) | 2005-08-02 | 2010-11-10 | Eisai R&D Man Co Ltd | TEST METHOD FOR THE EFFECT OF A VASCULARIZATION INHIBITOR |
NZ567550A (en) | 2005-11-29 | 2011-08-26 | Novartis Ag | Formulations of lactic acid salts of 4-amino-5-fluoro-3-[6-(4-methyl-piperazin-1-yl)-1 H-benzimidazol-2-yl]1H-quinolin-2-one |
TW200732305A (en) * | 2005-12-23 | 2007-09-01 | Yung Shin Pharmaceutical Ind | Cancer chemotherapy |
JP5131990B2 (ja) | 2006-01-31 | 2013-01-30 | アレイ バイオファーマ、インコーポレイテッド | キナーゼ阻害剤およびその使用方法 |
AU2007228940A1 (en) * | 2006-03-23 | 2007-09-27 | F. Hoffmann-La Roche Ag | Substituted indazole derivatives, their manufacture and use as pharmaceutical agents |
PT2004654E (pt) | 2006-04-04 | 2013-08-27 | Univ California | Derivados de pirazolopirimidina para utilização como antagonistas da quinase |
ES2556173T3 (es) | 2006-05-18 | 2016-01-13 | Eisai R&D Management Co., Ltd. | Agente antitumoral para un cáncer de tiroides |
JPWO2008001886A1 (ja) | 2006-06-30 | 2009-11-26 | 協和発酵キリン株式会社 | オーロラ(Aurora)阻害剤 |
JPWO2008001885A1 (ja) | 2006-06-30 | 2009-11-26 | 協和発酵キリン株式会社 | Ablキナーゼ阻害剤 |
US8519135B2 (en) | 2006-07-14 | 2013-08-27 | Chemocentryx, Inc. | Heteroaryl sulfonamides and CCR2/CCR9 |
JPWO2008020606A1 (ja) * | 2006-08-16 | 2010-01-07 | 協和発酵キリン株式会社 | 血管新生阻害剤 |
US8865737B2 (en) | 2006-08-28 | 2014-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for undifferentiated gastric cancer |
CL2007002617A1 (es) | 2006-09-11 | 2008-05-16 | Sanofi Aventis | Compuestos derivados de pirrolo[2,3-b]pirazin-6-ilo; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar inflamacion de las articulaciones, artritis reumatoide, tumores, linfoma de las celulas del manto. |
WO2008093855A1 (ja) | 2007-01-29 | 2008-08-07 | Eisai R & D Management Co., Ltd. | 未分化型胃癌治療用組成物 |
TW200901975A (en) | 2007-03-05 | 2009-01-16 | Kyowa Hakko Kogyo Kk | Pharmaceutical composition |
CN101730703B (zh) * | 2007-03-16 | 2012-12-26 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | 具有抗增殖活性的苯甲酰胺类衍生物及其药用制剂 |
FI2134702T4 (fi) * | 2007-04-05 | 2023-09-12 | 6-[2-(metyylikarbamoyyli)fenyylisulfanyyli]-3-E-[2-(pyridiini-2-yyli)etenyyli]indatsolin kidemuotoja jotka soveltuvat nisäkkäiden poikkeavan solukasvun hoitamiseen | |
EP2002836B1 (en) | 2007-05-31 | 2010-10-20 | Nerviano Medical Sciences S.r.l. | Cyclocondensed azaindoles active as kinase inhibitors |
KR101969689B1 (ko) | 2007-07-12 | 2019-04-16 | 케모센트릭스, 인크. | 염증의 치료를 위한 ccr2 조절물질로서 융합된 헤테로아릴 피리딜과 페닐 벤젠술폰아마이드 |
GB2467670B (en) | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
JP5562859B2 (ja) * | 2007-10-11 | 2014-07-30 | 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 | 電位開口型ナトリウムチャネルの阻害剤として有用なアリールアミド |
JP5444239B2 (ja) | 2007-11-02 | 2014-03-19 | 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 | タンパク質キナーゼC−θとしての[1H−ピラゾロ[3,4−B]ピリジン−4−イル]−フェニレンまたは−ピリジン−2−イル誘導体 |
CN101848895B (zh) | 2007-11-09 | 2013-10-23 | 卫材R&D管理有限公司 | 血管新生抑制物质和抗肿瘤性铂络合物的组合使用 |
US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
ES2647163T3 (es) | 2008-01-04 | 2017-12-19 | Intellikine, Inc. | Derivados de isoquinolinona sustituidos con una purina útiles como inhibidores de la PI3K |
US8993580B2 (en) | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
EP2252293B1 (en) | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
WO2009133831A1 (ja) | 2008-04-28 | 2009-11-05 | 旭化成ファーマ株式会社 | フェニルプロピオン酸誘導体及びその用途 |
KR20110039326A (ko) | 2008-07-08 | 2011-04-15 | 인텔리카인, 인크. | 키나제 억제제 및 사용 방법 |
WO2010006072A2 (en) | 2008-07-08 | 2010-01-14 | The Regents Of The University Of California | Mtor modulators and uses thereof |
CN102149379A (zh) | 2008-07-10 | 2011-08-10 | 安吉翁生物医药有限公司 | 调节肝细胞生长因子(分散因子)活性的方法和肝细胞生长因子(分散因子)活性的小分子调节剂组合物 |
CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
JP5819195B2 (ja) | 2008-10-16 | 2015-11-18 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 融合環ヘテロアリールキナーゼ阻害剤 |
US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
CN104030987B (zh) | 2009-04-02 | 2017-04-12 | 默克雪兰诺有限公司 | 二氢乳清酸脱氢酶抑制剂 |
EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
DK2987487T3 (da) | 2009-08-10 | 2020-12-07 | Samumed Llc | Indazolinhibitorer af wnt-signalvejen og terapeutiske anvendelser deraf |
US8980899B2 (en) | 2009-10-16 | 2015-03-17 | The Regents Of The University Of California | Methods of inhibiting Ire1 |
WO2011073521A1 (en) | 2009-12-15 | 2011-06-23 | Petri Salven | Methods for enriching adult-derived endothelial progenitor cells and uses thereof |
ES2550820T3 (es) | 2009-12-21 | 2015-11-12 | Samumed, Llc | 1H-pirazol[3,4-beta]piridinas y usos terapéuticos de las mismas |
WO2011090738A2 (en) | 2009-12-29 | 2011-07-28 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
UY33236A (es) | 2010-02-25 | 2011-09-30 | Novartis Ag | Inhibidores dimericos de las iap |
CN103080093A (zh) * | 2010-03-16 | 2013-05-01 | 达纳-法伯癌症研究所公司 | 吲唑化合物及其应用 |
AU2011255218B2 (en) | 2010-05-21 | 2015-03-12 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
MX2012014776A (es) | 2010-06-25 | 2013-01-29 | Eisai R&D Man Co Ltd | Agente antitumoral que emplea compuestos con efecto inhibidor de cinasas combinados. |
US20130177500A1 (en) | 2010-07-23 | 2013-07-11 | Trustee Of Boston University | Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery |
EP2637669A4 (en) | 2010-11-10 | 2014-04-02 | Infinity Pharmaceuticals Inc | Heterocyclic compounds and their use |
WO2012080260A1 (en) | 2010-12-13 | 2012-06-21 | Novartis Ag | Dimeric iap inhibitors |
UY33794A (es) | 2010-12-13 | 2012-07-31 | Novartis Ag | Inhibidores diméricos de las iap |
WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
CA2824197C (en) | 2011-01-10 | 2020-02-25 | Michael Martin | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
EP2694060A4 (en) * | 2011-04-01 | 2014-09-10 | Univ Utah Res Found | SUBSTITUTED 3- (1H-BENZO [D] IMIDAZOL-2-YL) -1H-INDAZOLE ANALOGUES AS INHIBITORS OF PDK1 KINASE |
RU2580609C2 (ru) | 2011-04-18 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое терапевтическое средство |
ES2705950T3 (es) | 2011-06-03 | 2019-03-27 | Eisai R&D Man Co Ltd | Biomarcadores para predecir y valorar la capacidad de respuesta de sujetos con cáncer de tiroides y de riñón a compuestos de lenvatinib |
JP6027611B2 (ja) | 2011-07-19 | 2016-11-16 | インフィニティー ファーマシューティカルズ, インコーポレイテッド | 複素環式化合物及びその使用 |
AU2012284088B2 (en) | 2011-07-19 | 2015-10-08 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
US8575336B2 (en) | 2011-07-27 | 2013-11-05 | Pfizer Limited | Indazoles |
CA2846431A1 (en) | 2011-08-29 | 2013-03-07 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
JP6342805B2 (ja) | 2011-09-02 | 2018-06-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 置換ピラゾロ[3,4−d]ピリミジンおよびその用途 |
CN102432595B (zh) * | 2011-09-14 | 2013-09-25 | 湖南有色凯铂生物药业有限公司 | N-吲哚-1-酰胺类化合物及作为抗癌药物的应用 |
MX362494B (es) | 2011-09-14 | 2019-01-21 | Samumed Llc | Indazol-3-carboxamidas y su uso como inhibidores de la trayectoria de señalizacion de wnt/b-catenina. |
GEP20166432B (en) | 2011-09-27 | 2016-02-10 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
US9382239B2 (en) | 2011-11-17 | 2016-07-05 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-Jun-N-terminal kinase (JNK) |
CA2856824A1 (en) | 2011-12-05 | 2013-06-13 | Novartis Ag | Cyclic urea derivatives as androgen receptor antagonists |
FR2985257B1 (fr) * | 2011-12-28 | 2014-02-14 | Sanofi Sa | Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique |
US10023862B2 (en) | 2012-01-09 | 2018-07-17 | Arrowhead Pharmaceuticals, Inc. | Organic compositions to treat beta-catenin-related diseases |
UY34591A (es) | 2012-01-26 | 2013-09-02 | Novartis Ag | Compuestos de imidazopirrolidinona |
PH12017500997A1 (en) | 2012-04-04 | 2018-02-19 | Samumed Llc | Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof |
US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
CN107417707A (zh) | 2012-05-04 | 2017-12-01 | 萨穆梅德有限公司 | 1H‑吡唑并[3,4‑b]吡啶及其治疗应用 |
WO2014007951A2 (en) | 2012-06-13 | 2014-01-09 | Incyte Corporation | Substituted tricyclic compounds as fgfr inhibitors |
JP6231262B2 (ja) * | 2012-06-20 | 2017-11-15 | 大日本印刷株式会社 | ピタバスタチンカルシウムの前駆体の製造法 |
US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
MX2015003874A (es) | 2012-09-26 | 2015-12-16 | Univ California | Modulacion de ire1. |
EP2909194A1 (en) | 2012-10-18 | 2015-08-26 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
USRE48175E1 (en) | 2012-10-19 | 2020-08-25 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
WO2014063054A1 (en) | 2012-10-19 | 2014-04-24 | Dana-Farber Cancer Institute, Inc. | Bone marrow on x chromosome kinase (bmx) inhibitors and uses thereof |
CN103804349A (zh) * | 2012-11-01 | 2014-05-21 | 杨子娇 | 一类治疗青光眼的化合物及其用途 |
US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
JPWO2014098176A1 (ja) | 2012-12-21 | 2017-01-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キノリン誘導体のアモルファス及びその製造方法 |
WO2014110086A2 (en) | 2013-01-08 | 2014-07-17 | Samumed, Llc | 3-(benzoimidazol-2-yl)-indazole inhibitors of the wnt signaling pathway and therapeutic uses thereof |
CN104370889A (zh) * | 2013-01-24 | 2015-02-25 | 韩冰 | 一类降低眼压的化合物及其制备方法和用途 |
PT2952510T (pt) * | 2013-02-02 | 2019-04-16 | Centaurus Biopharma Co Ltd | Inibidor de proteína-cinase de 2-aminopiridina substituída |
AU2014219283C1 (en) | 2013-02-19 | 2016-10-27 | Novartis Ag | Benzothiophene derivatives and compositions thereof as selective estrogen receptor degraders |
CA2903979A1 (en) | 2013-03-14 | 2014-09-18 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
AU2014229283B2 (en) | 2013-03-14 | 2016-07-28 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH |
US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
WO2014147586A1 (en) | 2013-03-22 | 2014-09-25 | Novartis Ag | 1-(2-(ethylamino)pyrimidin-4-yl)pyrrolidin-2-ones as inhibitors of mutant idh |
DK2986610T5 (en) | 2013-04-19 | 2018-12-10 | Incyte Holdings Corp | BICYCLIC HETEROCYCLES AS FGFR INHIBITORS |
KR102204279B1 (ko) | 2013-05-14 | 2021-01-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 자궁내막암 대상의 렌바티닙 화합물에 대한 반응성을 예측 및 평가하기 위한 생체표지 |
US20150018376A1 (en) | 2013-05-17 | 2015-01-15 | Novartis Ag | Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof |
CN103387565B (zh) * | 2013-07-29 | 2014-10-29 | 苏州明锐医药科技有限公司 | 阿西替尼的制备方法 |
US9359365B2 (en) | 2013-10-04 | 2016-06-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
WO2015058140A1 (en) | 2013-10-18 | 2015-04-23 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7) |
WO2015058126A1 (en) | 2013-10-18 | 2015-04-23 | Syros Pharmaceuticals, Inc. | Heteroaromatic compounds useful for the treatment of prolferative diseases |
CN103570696B (zh) * | 2013-11-06 | 2016-02-24 | 湖南欧亚生物有限公司 | 一种阿西替尼中间体的制备方法以及在制备阿西替尼中的应用 |
WO2015067224A1 (en) | 2013-11-08 | 2015-05-14 | Zentiva, K.S. | Salts of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-e-[2-(pyridin-2-yl)ethanyl] indazole |
WO2015092634A1 (en) | 2013-12-16 | 2015-06-25 | Novartis Ag | 1,2,3,4-tetrahydroisoquinoline compounds and compositions as selective estrogen receptor antagonists and degraders |
JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
WO2015107493A1 (en) | 2014-01-17 | 2015-07-23 | Novartis Ag | 1 -pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and and compositions thereof for inhibiting the activity of shp2 |
EP3094629B1 (en) | 2014-01-17 | 2018-08-22 | Novartis AG | 1-(triazin-3-yl/pyridazin-3-yl)-piper(-azine)idine derivatives and compositions thereof for inhibiting the activity of shp2 |
CA2943075C (en) | 2014-03-19 | 2023-02-28 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
US9617222B1 (en) | 2014-03-31 | 2017-04-11 | Senju Pharmaceutical Co., Ltd. | Alkynyl indazole derivative and use thereof |
WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
US9862688B2 (en) | 2014-04-23 | 2018-01-09 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged janus kinase inhibitors and uses thereof |
US10017477B2 (en) | 2014-04-23 | 2018-07-10 | Dana-Farber Cancer Institute, Inc. | Janus kinase inhibitors and uses thereof |
KR20170005492A (ko) | 2014-05-28 | 2017-01-13 | 아이데닉스 파마슈티칼스 엘엘씨 | 암의 치료를 위한 뉴클레오시드 유도체 |
CN104072484B (zh) * | 2014-07-07 | 2016-07-06 | 渤海大学 | 氮-(4-(芳巯基)-1氢-吲唑-3-基)-1-(芳杂环取代)甲基亚胺类化合物及其药学上可接受的盐及其制备方法和应用 |
AR101196A1 (es) | 2014-07-16 | 2016-11-30 | Gruenenthal Gmbh | Compuestos de pirimidina sustituidos |
AR101198A1 (es) | 2014-07-16 | 2016-11-30 | Gruenenthal Gmbh | Pirimidinas 2,5-sustituidas como inhibidores de pde4b |
EP3825305A1 (en) | 2014-08-28 | 2021-05-26 | Eisai R&D Management Co., Ltd. | Process for preparing lenvatinib |
WO2016040193A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
WO2016040184A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040180A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040182A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-1h-imidazo[4,5-c]pyridine and therapeutic uses thereof |
WO2016040185A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof |
WO2016040190A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
WO2016040181A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
WO2016040188A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
JP6723663B2 (ja) | 2014-09-17 | 2020-07-15 | セルジーン クオンティセル リサーチ,インク. | ヒストンデメチラーゼ阻害剤 |
US9708348B2 (en) | 2014-10-03 | 2017-07-18 | Infinity Pharmaceuticals, Inc. | Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof |
US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
US10442819B2 (en) | 2014-12-05 | 2019-10-15 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
WO2016089833A1 (en) | 2014-12-05 | 2016-06-09 | Merck Sharp & Dohme Corp. | Novel tricyclic compounds as inhibitors of mutant idh enzymes |
EP3226689B1 (en) | 2014-12-05 | 2020-01-15 | Merck Sharp & Dohme Corp. | Novel tricyclic compounds as inhibitors of mutant idh enzymes |
MA41140A (fr) | 2014-12-12 | 2017-10-17 | Cancer Research Tech Ltd | Dérivés de 2,4-dioxo-quinazoline-6-sulfonamide en tant qu'inhibiteurs de la parg |
MA41179A (fr) | 2014-12-19 | 2017-10-24 | Cancer Research Tech Ltd | Composés inhibiteurs de parg |
CA2972239A1 (en) | 2014-12-23 | 2016-06-30 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (cdk7) |
SG11201705767PA (en) | 2015-01-13 | 2017-08-30 | Univ Kyoto | Agent for preventing and/or treating amyotrophic lateral sclerosis |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
NZ773116A (en) | 2015-02-20 | 2024-05-31 | Incyte Holdings Corp | Bicyclic heterocycles as fgfr inhibitors |
US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
WO2016136745A1 (ja) | 2015-02-25 | 2016-09-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キノリン誘導体の苦味抑制方法 |
AU2015384801B2 (en) | 2015-03-04 | 2022-01-06 | Eisai R&D Management Co., Ltd. | Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer |
EP3273966B1 (en) | 2015-03-27 | 2023-05-03 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
US9580406B2 (en) | 2015-04-28 | 2017-02-28 | Signa S.A. De C.V. | Processes for the preparation of axitinib |
WO2016189055A1 (en) | 2015-05-27 | 2016-12-01 | Idenix Pharmaceuticals Llc | Nucleotides for the treatment of cancer |
AU2016276963C1 (en) | 2015-06-12 | 2021-08-05 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
BR112017027227B1 (pt) | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
JP6718889B2 (ja) | 2015-06-19 | 2020-07-08 | ノバルティス アーゲー | Shp2の活性を阻害するための化合物および組成物 |
US10975080B2 (en) | 2015-06-19 | 2021-04-13 | Novartis Ag | Compounds and compositions for inhibiting the activity of SHP2 |
US10308660B2 (en) | 2015-06-19 | 2019-06-04 | Novartis Ag | Compounds and compositions for inhibiting the activity of SHP2 |
GB201511382D0 (en) | 2015-06-29 | 2015-08-12 | Imp Innovations Ltd | Novel compounds and their use in therapy |
GB201511790D0 (en) | 2015-07-06 | 2015-08-19 | Iomet Pharma Ltd | Pharmaceutical compound |
WO2017024026A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-indol-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
US10383861B2 (en) | 2015-08-03 | 2019-08-20 | Sammumed, LLC | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
WO2017023984A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
US10226448B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-yl)-1H-pyrazolo[3,4-B]pyridines and therapeutic uses thereof |
US10604512B2 (en) | 2015-08-03 | 2020-03-31 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-indazoles and therapeutic uses thereof |
US10519169B2 (en) | 2015-08-03 | 2019-12-31 | Samumed, Llc | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
US10350199B2 (en) | 2015-08-03 | 2019-07-16 | Samumed, Llc | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
US10463651B2 (en) | 2015-08-03 | 2019-11-05 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-indazoles and therapeutic uses thereof |
US10206909B2 (en) | 2015-08-03 | 2019-02-19 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017023980A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
US10329309B2 (en) | 2015-08-03 | 2019-06-25 | Samumed, Llc | 3-(3H-imidazo[4,5-B]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
US10392383B2 (en) | 2015-08-03 | 2019-08-27 | Samumed, Llc | 3-(1H-benzo[d]imidazol-2-yl)-1H-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
WO2017023996A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridines and therapeutic uses thereof |
US10195185B2 (en) | 2015-08-03 | 2019-02-05 | Samumed, Llc | 3-(1H-imidazo[4,5-C]pyridin-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017023988A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
US10226453B2 (en) | 2015-08-03 | 2019-03-12 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
WO2017024003A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc | 3-(1h-pyrrolo[3,2-c]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
UA123701C2 (uk) | 2015-08-13 | 2021-05-19 | Мерк Шарп І Доум Корп. | Циклічні динуклеотидні сполуки як агоністи sting |
US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
EP4019515A1 (en) | 2015-09-09 | 2022-06-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
NZ740616A (en) | 2015-09-14 | 2023-05-26 | Infinity Pharmaceuticals Inc | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
US10736885B2 (en) * | 2015-10-07 | 2020-08-11 | Aiviva Biopharma, Inc. | Compositions and methods of treating dermal fibrotic disorders |
US20180305331A1 (en) * | 2015-10-22 | 2018-10-25 | Selvita S.A. | Pyridone derivatives and their use as kinase inhibitors |
EP3371187A4 (en) | 2015-11-06 | 2019-09-04 | Samumed, LLC | 2- (1H-INDAZOLE-3-YL) -3H-IMIDAZO [4,5-C] PYRIDINE AND ITS USE AS AN INHIBITOR OF INHIBITOR |
US10538497B2 (en) | 2015-12-15 | 2020-01-21 | Merck Sharp & Dohme Corp. | Compounds as indoleamine 2,3-dioxygenase inhibitors |
WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
US10577362B2 (en) | 2016-05-04 | 2020-03-03 | Genoscience Pharma | Substituted 2, 4-diamino-quinoline derivatives for use in the treatment of proliferative diseases |
JP7010851B2 (ja) | 2016-06-01 | 2022-02-10 | バイオスプライス セラピューティクス インコーポレイテッド | N-(5-(3-(7-(3-フルオロフェニル)-3H-イミダゾ[4,5-c]ピリジン-2-イル)-1H-インダゾール-5-イル)ピリジン-3-イル)-3-メチルブタンアミドを調製するための方法 |
US10919914B2 (en) | 2016-06-08 | 2021-02-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
WO2017216706A1 (en) | 2016-06-14 | 2017-12-21 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
MX2018016227A (es) | 2016-06-24 | 2019-07-08 | Infinity Pharmaceuticals Inc | Terapias de combinacion. |
HUE056502T2 (hu) | 2016-10-04 | 2022-02-28 | Merck Sharp & Dohme | Benzo[b]tiofén vegyületek mint STING agonisták |
MX2019004616A (es) | 2016-10-21 | 2019-11-21 | Samumed Llc | Métodos de uso de indazol-3-carboxamidas y su uso como inhibidores de la ruta de señalización de wnt/b-catenina. |
US10758523B2 (en) | 2016-11-07 | 2020-09-01 | Samumed, Llc | Single-dose, ready-to-use injectable formulations |
WO2018091542A1 (en) | 2016-11-21 | 2018-05-24 | Idenix Pharmaceuticals Llc | Cyclic phosphate substituted nucleoside derivatives for the treatment of liver diseases |
KR20240130832A (ko) | 2016-11-23 | 2024-08-29 | 케모센트릭스, 인크. | 국소 분절 사구체경화증의 치료 방법 |
JP7275031B2 (ja) | 2017-01-27 | 2023-05-17 | ヤンセン バイオテツク,インコーポレーテツド | Stingアゴニストとしての環状ジヌクレオチド |
US11021511B2 (en) | 2017-01-27 | 2021-06-01 | Janssen Biotech, Inc. | Cyclic dinucleotides as sting agonists |
EP3584241B1 (en) * | 2017-02-14 | 2023-04-26 | FUJIFILM Corporation | Method for producing indazole compound, and indazole compound |
US11466047B2 (en) | 2017-05-12 | 2022-10-11 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
CN108947961B (zh) * | 2017-05-18 | 2021-06-04 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
CA3071537A1 (en) | 2017-08-04 | 2019-02-07 | Merck Sharp & Dohme Corp. | Combinations of pd-1 antagonists and benzo[b]thiophene sting agonists for cancer treatment |
CA3071538A1 (en) | 2017-08-04 | 2019-02-07 | Merck Sharp & Dohme Corp. | Benzo[b]thiophene sting agonists for cancer treatment |
RS65380B1 (sr) | 2017-08-24 | 2024-04-30 | Novo Nordisk As | Glp-1 kompozicije i njihova upotreba |
CA3074304A1 (en) | 2017-09-11 | 2019-03-14 | Krouzon Pharmaceuticals, Inc. | Octahydrocyclopenta[c]pyrrole allosteric inhibitors of shp2 |
WO2019067332A1 (en) | 2017-09-27 | 2019-04-04 | Merck Sharp & Dohme Corp. | COMPOSITIONS AND METHODS FOR TREATING CANCER THROUGH A COMBINATION OF PROGRAMMED DEATH ANTIBODY ANTIBODIES (PD-1) AND A CXCR2 ANTAGONIST |
EP3694504A4 (en) | 2017-10-11 | 2021-07-14 | ChemoCentryx, Inc. | TREATMENT OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS WITH CRC2 ANTAGONISTS |
US20210179607A1 (en) | 2017-11-01 | 2021-06-17 | Merck Sharp & Dohme Corp. | Novel substituted tetrahydroquinolin compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
WO2019099294A1 (en) | 2017-11-14 | 2019-05-23 | Merck Sharp & Dohme Corp. | Novel substituted biaryl compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
CA3082108A1 (en) | 2017-11-14 | 2019-05-23 | Merck Sharp & Dohme Corp. | Novel substituted biaryl compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
MX2020006290A (es) | 2017-12-15 | 2020-12-03 | Janssen Biotech Inc | Dinucleotidos ciclicos como agonistas de sting. |
WO2019125974A1 (en) | 2017-12-20 | 2019-06-27 | Merck Sharp & Dohme Corp. | Cyclic di-nucleotide compounds as sting agonists |
MX2020010407A (es) | 2018-04-03 | 2020-10-22 | Merck Sharp & Dohme | Benzotiofenos y compuestos relacionados como agonistas de sting. |
WO2019195063A1 (en) | 2018-04-03 | 2019-10-10 | Merck Sharp & Dohme Corp. | Aza-benzothiophene compounds as sting agonists |
SG11202010636VA (en) | 2018-05-04 | 2020-11-27 | Incyte Corp | Solid forms of an fgfr inhibitor and processes for preparing the same |
BR112020022373A2 (pt) | 2018-05-04 | 2021-02-02 | Incyte Corporation | sais de um inibidor de fgfr |
CN110452176A (zh) * | 2018-05-07 | 2019-11-15 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
EP3810116B1 (en) | 2018-05-31 | 2023-11-15 | Merck Sharp & Dohme LLC | Novel substituted [1.1.1] bicyclo compounds as indoleamine 2,3-dioxygenase inhibitors |
JP7542538B2 (ja) | 2018-09-18 | 2024-08-30 | ニカング セラピューティクス, インコーポレイテッド | Srcホモロジー-2ホスファターゼ阻害剤としての縮合三環式環誘導体 |
CA3113241A1 (en) | 2018-09-25 | 2020-04-02 | Black Diamond Therapeutics, Inc. | Quinazoline derivatives as tyrosine kinase inhibitor, compositions, methods of making them and their use |
JP2022502496A (ja) | 2018-09-25 | 2022-01-11 | ブラック ダイアモンド セラピューティクス,インコーポレイティド | チロシンキナーゼ阻害剤組成物、作製方法、および使用方法 |
EP3856345A1 (en) | 2018-09-29 | 2021-08-04 | Novartis AG | Process of manufacture of a compound for inhibiting the activity of shp2 |
EP3873464A4 (en) | 2018-11-01 | 2022-06-08 | Merck Sharp & Dohme Corp. | NOVEL SUBSTITUTED PYRAZOLE COMPOUNDS AS INDOLAMINE-2,3-DIOXYGENASE INHIBITORS |
EP3877366A4 (en) | 2018-11-06 | 2022-08-24 | Merck Sharp & Dohme Corp. | NOVEL SUBSTITUTED TRICYCLIC COMPOUNDS AS INDOLAMINE-2,3-DIOXYGENASE INHIBITORS |
CN111205227A (zh) * | 2018-11-22 | 2020-05-29 | 四川大学 | 3-乙烯基吲唑类衍生物及其制备方法和用途 |
EP3886845B1 (en) | 2018-11-28 | 2024-09-04 | Merck Sharp & Dohme LLC | Novel substituted piperazine amide compounds as indoleamine 2, 3-dioxygenase (ido) inhibitors |
WO2020160151A1 (en) * | 2019-01-31 | 2020-08-06 | Kyorin Pharmaceutical Co., Ltd. | 15-pgdh inhibitors |
US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
WO2020205688A1 (en) | 2019-04-04 | 2020-10-08 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
WO2020210657A1 (en) | 2019-04-11 | 2020-10-15 | Angion Biomedica Corp. | Solid forms of (e)-3-[2-(2-thienyl)vinyl]-1h-pyrazole |
EP3956321B1 (en) | 2019-04-18 | 2024-03-20 | Synthon B.V. | Process for preparing axitinib, process for purifying the intermediate 2-((3-iodo-1h-indazol-6-yl)thio)-n-methylbenzamide, process for purifying axitinib via the axitinib hcl salt, solid form of the axitinib hcl salt |
US20220226246A1 (en) | 2019-05-09 | 2022-07-21 | Synthon B.V. | Pharmaceutical composition comprising axitinib |
EP3990635A1 (en) | 2019-06-27 | 2022-05-04 | Rigontec GmbH | Design method for optimized rig-i ligands |
WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
MX2022001407A (es) | 2019-08-02 | 2022-04-27 | Mersana Therapeutics Inc | Compuestos derivados y relacionados de bis-[n-((5-carbamoil)-1h be nzo[d]imidazol-2-yl)-pyrazol-5-carboxamida] como agonistas de sting (estimulador de genes de interferón) para el tratamiento de cáncer. |
CA3150701A1 (en) | 2019-08-15 | 2021-02-18 | Black Diamond Therapeutics, Inc. | Alkynyl quinazoline compounds |
CN112442011B (zh) * | 2019-08-30 | 2023-11-14 | 润佳(苏州)医药科技有限公司 | 一种前药化合物及其在治疗癌症方面的应用 |
CN112442010B (zh) * | 2019-08-30 | 2023-10-03 | 润佳(苏州)医药科技有限公司 | 一类前药化合物及其在治疗癌症方面的应用 |
AU2020338490A1 (en) * | 2019-08-30 | 2022-03-17 | Risen (Suzhou) Pharma Tech Co., Ltd. | Prodrugs of the tyrosine kinase inhibitor for treating cancer |
WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
BR112022007163A2 (pt) | 2019-10-14 | 2022-08-23 | Incyte Corp | Heterociclos bicíclicos como inibidores de fgfr |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN112694474B (zh) * | 2019-10-23 | 2022-03-18 | 四川大学 | 吲唑类衍生物及其制备方法和用途 |
JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
US11407750B2 (en) | 2019-12-04 | 2022-08-09 | Incyte Corporation | Derivatives of an FGFR inhibitor |
WO2021113679A1 (en) | 2019-12-06 | 2021-06-10 | Mersana Therapeutics, Inc. | Dimeric compounds as sting agonists |
US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
CN111829859B (zh) * | 2020-01-20 | 2024-01-05 | 北京林业大学 | 一种高效杨树种子透明染色及其三维成像的方法 |
CA3168543A1 (en) | 2020-01-29 | 2021-08-05 | Gilead Sciences, Inc. | Glp-1r modulating compounds |
US20230093542A1 (en) | 2020-02-18 | 2023-03-23 | Novo Nordisk A/S | Glp-1 compositions and uses thereof |
BR102020005423A2 (pt) * | 2020-03-18 | 2021-09-28 | Faculdades Catolicas | Compostos n-acil-hidrazônicos, uso no tratamento de agregopatias degenerativas amiloides e não-amiloides, e composição farmacêutica |
WO2021195206A1 (en) | 2020-03-24 | 2021-09-30 | Black Diamond Therapeutics, Inc. | Polymorphic forms and related uses |
CA3177442A1 (en) | 2020-05-06 | 2021-11-11 | Brandon D. Cash | Il4i1 inhibitors and methods of use |
WO2021232367A1 (zh) * | 2020-05-21 | 2021-11-25 | 四川大学 | 3-乙烯基吲唑类衍生物及其制备方法和用途 |
CN113943271B (zh) * | 2020-07-15 | 2023-11-14 | 鲁南制药集团股份有限公司 | 一种阿昔替尼晶型及其制备方法 |
CN112028831A (zh) * | 2020-09-24 | 2020-12-04 | 山东大学 | 一种苯并吡唑类化合物、其制备方法及作为抗肿瘤药物的应用 |
EP4267575A1 (en) | 2020-12-22 | 2023-11-01 | Nikang Therapeutics, Inc. | Compounds for degrading cyclin-dependent kinase 2 via ubiquitin proteosome pathway |
CA3208313A1 (en) | 2021-01-13 | 2022-07-21 | Monte Rosa Therapeutics Ag | Isoindolinone compounds |
WO2022170052A1 (en) | 2021-02-05 | 2022-08-11 | Black Diamond Therapeutics, Inc. | Quinazoline derivatives, pyridopyrimidine derivatives, pyrimidopyrimidine derivatives, and uses thereof |
WO2022221170A1 (en) | 2021-04-12 | 2022-10-20 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent |
WO2022219412A1 (en) | 2021-04-14 | 2022-10-20 | Monte Rosa Therapeutics Ag | Isoindolinone amide compounds useful to treat diseases associated with gspt1 |
EP4323350A1 (en) | 2021-04-14 | 2024-02-21 | Monte Rosa Therapeutics AG | Isoindolinone compounds |
WO2022227015A1 (en) | 2021-04-30 | 2022-11-03 | Merck Sharp & Dohme Corp. | Il4i1 inhibitors and methods of use |
EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
EP4370522A1 (en) | 2021-07-14 | 2024-05-22 | Nikang Therapeutics, Inc. | Alkylidene derivatives as kras inhibitors |
CN115701423A (zh) * | 2021-08-02 | 2023-02-10 | 沈阳化工大学 | 三氟乙基硫醚(亚砜)取代苯类化合物的制备方法及其中间体 |
TW202346292A (zh) | 2022-03-28 | 2023-12-01 | 美商尼坎醫療公司 | 作為週期蛋白依賴性激酶2抑制劑的磺醯胺基衍生物 |
EP4282415A1 (en) | 2022-05-26 | 2023-11-29 | Genepharm S.A. | A stable tablet composition of axitinib |
WO2023240024A1 (en) | 2022-06-08 | 2023-12-14 | Nikang Therapeutics, Inc. | Sulfamide derivatives as cyclin-dependent kinase 2 inhibitors |
WO2024032584A1 (zh) * | 2022-08-08 | 2024-02-15 | 苏州必扬医药科技有限公司 | 一种蛋白酪氨酸激酶抑制剂及其医疗用途 |
WO2024102849A1 (en) | 2022-11-11 | 2024-05-16 | Nikang Therapeutics, Inc. | Bifunctional compounds containing 2,5-substituted pyrimidine derivatives for degrading cyclin-dependent kinase 2 via ubiquitin proteasome pathway |
WO2024206357A1 (en) | 2023-03-29 | 2024-10-03 | Merck Sharp & Dohme Llc | Il4i1 inhibitors and methods of use |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5625031A (en) * | 1994-02-08 | 1997-04-29 | Bristol-Myers Squibb Company | Peptide inhibitors of the p33cdk2 and p34cdc2 cell cycle regulatory kinases and human papillomavirus E7 oncoprotein |
US5631156A (en) * | 1994-06-21 | 1997-05-20 | The University Of Michigan | DNA encoding and 18 KD CDK6 inhibiting protein |
JPH10509708A (ja) * | 1994-11-10 | 1998-09-22 | コア セラピューティクス,インコーポレイティド | プロテイン・キナーゼのインヒビターとして有用な医薬ピラゾール組成物 |
ZA951822B (en) * | 1994-12-23 | 1996-09-26 | Glaxo Group Ltd | Chemical compounds |
US5710173A (en) * | 1995-06-07 | 1998-01-20 | Sugen, Inc. | Thienyl compounds for inhibition of cell proliferative disorders |
US5733920A (en) * | 1995-10-31 | 1998-03-31 | Mitotix, Inc. | Inhibitors of cyclin dependent kinases |
US5760028A (en) * | 1995-12-22 | 1998-06-02 | The Dupont Merck Pharmaceutical Company | Integrin receptor antagonists |
AU2103097A (en) * | 1996-03-15 | 1997-10-10 | Zeneca Limited | Cinnoline derivatives and use as medicine |
JP4373497B2 (ja) * | 1996-06-19 | 2009-11-25 | ローン−プーラン・ロレ・リミテツド | 置換されたアザビシクロ化合物、ならびにtnfおよびサイクリックampホスホジエステラーゼ産生の阻害剤としてのそれらの使用 |
EA002113B1 (ru) * | 1996-09-04 | 2001-12-24 | Пфайзер Инк. | Производные индазола и их использование в качестве ингибиторов фосфодиэстеразы (фдэ) типа iv и продуцирования фактора некроза опухоли (фно) |
GEP20032896B (en) * | 1997-10-27 | 2003-02-25 | Agouron Pharma | 4-Aminothiazole Derivatives, Containing Them Pharmaceutical Compositions Inhibiting Cyclin-Dependent Kinases and Methods for Treatment |
AU754734B2 (en) * | 1997-11-04 | 2002-11-21 | Pfizer Products Inc. | Indazole bioisostere replacement of catechol in therapeutically active compounds |
HUP0100330A3 (en) * | 1997-11-04 | 2002-03-28 | Pfizer Prod Inc | Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors, compositions containing them and their use |
PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
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