ZA200410322B - Inhibitors of tyrosine kinases - Google Patents
Inhibitors of tyrosine kinases Download PDFInfo
- Publication number
- ZA200410322B ZA200410322B ZA200410322A ZA200410322A ZA200410322B ZA 200410322 B ZA200410322 B ZA 200410322B ZA 200410322 A ZA200410322 A ZA 200410322A ZA 200410322 A ZA200410322 A ZA 200410322A ZA 200410322 B ZA200410322 B ZA 200410322B
- Authority
- ZA
- South Africa
- Prior art keywords
- lower alkyl
- phenyl
- mono
- compound
- amino
- Prior art date
Links
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title description 13
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title description 13
- 239000003112 inhibitor Substances 0.000 title description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 253
- -1 benzcycloalkyl Chemical group 0.000 claims description 228
- 150000001875 compounds Chemical class 0.000 claims description 151
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 87
- 150000003839 salts Chemical class 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 56
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 46
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 238000011282 treatment Methods 0.000 claims description 39
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 125000003282 alkyl amino group Chemical group 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
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- 125000004076 pyridyl group Chemical group 0.000 claims description 27
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
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- TZHVYFBSLOMRCU-RXMQYKEDSA-N tert-butyl (2r)-2-aminopropanoate Chemical compound C[C@@H](N)C(=O)OC(C)(C)C TZHVYFBSLOMRCU-RXMQYKEDSA-N 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
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GBGB0215676.8A GB0215676D0 (en) | 2002-07-05 | 2002-07-05 | Organic compounds |
GBGB0229893.3A GB0229893D0 (en) | 2002-07-05 | 2002-12-20 | Organic compounds |
PCT/EP2003/007198 WO2004005281A1 (en) | 2002-07-05 | 2003-07-04 | Inhibitors of tyrosine kinases |
Publications (1)
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ZA200410322B true ZA200410322B (en) | 2006-07-26 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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ZA200410322A ZA200410322B (en) | 2002-07-05 | 2004-12-22 | Inhibitors of tyrosine kinases |
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US (5) | US7169791B2 (he) |
EP (4) | EP2368889A1 (he) |
JP (4) | JP4110140B2 (he) |
KR (2) | KR100733639B1 (he) |
CN (2) | CN101045727A (he) |
AR (1) | AR040390A1 (he) |
AT (1) | ATE414699T1 (he) |
AU (1) | AU2003249962C9 (he) |
BR (1) | BRPI0312464B8 (he) |
CA (3) | CA2677315C (he) |
CO (1) | CO5680432A2 (he) |
CY (1) | CY1108813T1 (he) |
DE (1) | DE60324805D1 (he) |
DK (1) | DK1532138T3 (he) |
EC (1) | ECSP055525A (he) |
ES (2) | ES2318164T3 (he) |
GB (2) | GB0215676D0 (he) |
HK (2) | HK1077811A1 (he) |
IL (2) | IL165977A (he) |
MX (1) | MXPA05000328A (he) |
MY (1) | MY143466A (he) |
NO (1) | NO331166B1 (he) |
NZ (1) | NZ537396A (he) |
PE (1) | PE20040647A1 (he) |
PL (3) | PL219723B1 (he) |
PT (2) | PT2357182E (he) |
RU (2) | RU2348627C2 (he) |
SI (1) | SI1532138T1 (he) |
TW (1) | TWI313603B (he) |
WO (1) | WO2004005281A1 (he) |
ZA (1) | ZA200410322B (he) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0215676D0 (en) * | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
GB0325031D0 (en) | 2003-10-27 | 2003-12-03 | Novartis Ag | Organic compounds |
CN1882344A (zh) * | 2003-11-18 | 2006-12-20 | 诺瓦提斯公司 | Kit突变形式的抑制剂 |
WO2005063720A1 (ja) * | 2003-12-25 | 2005-07-14 | Nippon Shinyaku Co., Ltd. | アミド誘導体及び医薬 |
JP5138362B2 (ja) | 2004-03-23 | 2013-02-06 | ノバルティス アーゲー | 医薬組成物 |
JP5097539B2 (ja) | 2004-05-07 | 2012-12-12 | アムジエン・インコーポレーテツド | タンパク質キナーゼ調節剤および使用方法 |
EP1885352A2 (en) * | 2004-11-24 | 2008-02-13 | Novartis AG | Combinations comprising jak inhibitors and at least one of bcr-abl, flt-3, fak or raf kinase inhibitors |
CN1939910A (zh) | 2004-12-31 | 2007-04-04 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
KR20130100371A (ko) * | 2005-01-28 | 2013-09-10 | 노파르티스 아게 | Tie-2 키나제 활성의 조절에 반응하는 질환의 치료를 위한 피리미딜아미노벤즈아미드의 용도 |
US20080207658A1 (en) * | 2005-02-25 | 2008-08-28 | Manley Paul W | Pharmaceutical Combination of Bcr-Abl and Raf Inhibitors |
WO2006117185A1 (en) * | 2005-05-02 | 2006-11-09 | Novartis Ag | Pyrimidylaminobenzamide derivatives for hypereosinophilic syndrome |
WO2006119154A1 (en) * | 2005-05-02 | 2006-11-09 | Novartis Ag | Use of pyrimidylamimobenzamide derivatives for the treatment of systematic mastocytosis |
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AU2013205820B2 (en) * | 2005-06-09 | 2015-11-26 | Novartis Ag | Process for the synthesis of organic compounds |
MY146795A (en) * | 2005-06-09 | 2012-09-28 | Novartis Ag | Process for the synthesis of organic compounds |
CN101184748B (zh) * | 2005-06-09 | 2011-09-28 | 诺瓦提斯公司 | 合成5-(甲基-1h-咪唑-1-基)-3-(三氟甲基)苯胺的方法 |
SA06270147B1 (ar) * | 2005-06-09 | 2009-12-22 | نوفارتيس ايه جي | عملية لتخليق 5-(مثيل–1h–إيميدازول–1-يل )–3-(ثلاثي فلـورو مثيل)–بنزامـين |
GT200600207A (es) * | 2005-06-09 | 2007-01-15 | Novartis Ag | Proceso para la síntesis de compuestos orgánicos |
US20060281788A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using a flt3 inhibitor and a farnesyl transferase inhibitor |
US8071768B2 (en) | 2005-06-10 | 2011-12-06 | Janssen Pharmaceutica, N.V. | Alkylquinoline and alkylquinazoline kinase modulators |
US7825244B2 (en) | 2005-06-10 | 2010-11-02 | Janssen Pharmaceutica Nv | Intermediates useful in the synthesis of alkylquinoline and alkylquinazoline kinase modulators, and related methods of synthesis |
CA2612227C (en) * | 2005-06-14 | 2014-04-22 | Taigen Biotechnology Co., Ltd. | Pyrimidine compounds |
US8193206B2 (en) | 2005-06-14 | 2012-06-05 | Taigen Biotechnology Co., Ltd. | Pyrimidine compounds |
CN101222925A (zh) * | 2005-07-20 | 2008-07-16 | 诺瓦提斯公司 | 嘧啶基氨基苯甲酰胺和mTOR激酶抑制剂的组合产品 |
AU2012203844B2 (en) * | 2005-07-20 | 2014-12-11 | Novartis Ag | Salts of 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide |
GT200600315A (es) | 2005-07-20 | 2007-03-19 | Formas cristalinas de 4-metilo-n-[3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo]-3-(4-pyridina-3-ilo-pirimidina-2-iloamino)-benzamida | |
JP2009501766A (ja) * | 2005-07-20 | 2009-01-22 | ノバルティス アクチエンゲゼルシャフト | 増殖性疾患の処置のためのピリミジルアミノベンズアミドおよびFlt−3阻害剤を含む組合せ剤 |
GT200600316A (es) * | 2005-07-20 | 2007-04-02 | Sales de 4-metilo-n-(3-(4-metilo-imidazol-1-ilo)-5-trifluorometilo-fenilo)-3-(4-piridina-3-ilo-pirimidina-2-iloamino)- benzamida. | |
KR100674813B1 (ko) * | 2005-08-05 | 2007-01-29 | 일양약품주식회사 | N-페닐-2-피리미딘-아민 유도체 및 그의 제조방법 |
WO2007022042A2 (en) * | 2005-08-11 | 2007-02-22 | Novartis Ag | Combinations comrising a protein kinase inhibitor being a pyrimidylaminobξnzamide compound and a hsp90 inhibitor such as 17-aag |
JP2009504674A (ja) * | 2005-08-11 | 2009-02-05 | ノバルティス アクチエンゲゼルシャフト | 有機化合物の組合せ |
CA2621261C (en) | 2005-09-22 | 2014-05-20 | Incyte Corporation | Azepine inhibitors of janus kinases |
WO2007042465A2 (en) * | 2005-10-07 | 2007-04-19 | Novartis Ag | Combinati0n of nilotinib with farnesyl transferase inhibitors |
NZ595182A (en) | 2005-10-18 | 2012-12-21 | Janssen Pharmaceutica Nv | Pharmaceutical uses of 4-cyano-1H-imidazole-2-carboxylic acid { 2-cyclohex-1-enyl-4-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-phenyl} -amide |
WO2007051862A1 (en) * | 2005-11-07 | 2007-05-10 | Novartis Ag | Combination of organic compounds |
US20090099197A1 (en) * | 2005-11-15 | 2009-04-16 | Bristol-Myers Squibb Company | Methods of Identifying and Treating Individuals Exhibiting MDR-1 Overexpression With Protein Tyrosine Kinase Inhibitors and Combinations Thereof |
KR101498848B1 (ko) * | 2005-12-06 | 2015-03-05 | 노파르티스 아게 | 신경섬유종증의 치료를 위한 피리미딜아미노벤즈아미드 유도체 |
PT3184526T (pt) | 2005-12-13 | 2018-12-19 | Incyte Holdings Corp | Derivados de pirrolo[2,3-d]pirimidina como inibidores da cinase janus |
US20090306094A1 (en) * | 2006-03-17 | 2009-12-10 | Bristol-Myers Squibb Company | Methods Of Identifying And Treating Individuals Exhibiting Mutant Bcr/Abl Kinase Polypeptides |
KR20140020367A (ko) * | 2006-04-05 | 2014-02-18 | 노파르티스 아게 | 암을 치료하기 위한 bcr-abl/c-kit/pdgf-r tk 억제제를 포함하는 조합물 |
AU2011202833B2 (en) * | 2006-04-07 | 2012-05-24 | Novartis Ag | Combination comprising a) a pyrimidylaminobenzamide compound, and b) a Thr315lle kinase inhibitor |
EP2007391B8 (en) * | 2006-04-07 | 2013-05-29 | Novartis AG | Combination comprising a) a pyrimidylaminobenzamide compound, and b) a thr315ile kinase inhibitor |
WO2007124316A1 (en) | 2006-04-20 | 2007-11-01 | Janssen Pharmaceutica N.V. | Heterocyclic compounds as inhibitors of c-fms kinase |
RU2475483C2 (ru) | 2006-04-20 | 2013-02-20 | Янссен Фармацевтика Н.В. | Ингибиторы с-fms киназы |
US8697716B2 (en) | 2006-04-20 | 2014-04-15 | Janssen Pharmaceutica Nv | Method of inhibiting C-KIT kinase |
PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
WO2007137981A1 (en) * | 2006-05-25 | 2007-12-06 | Novartis Ag | Inhibitors of tyrosine kinases |
CA2662977A1 (en) | 2006-09-22 | 2008-03-27 | Novartis Ag | Method of optimizing the treatment of philadelphia-positive leukemia with abl tyrosine kinase inhibitors |
EP1923053A1 (en) | 2006-09-27 | 2008-05-21 | Novartis AG | Pharmaceutical compositions comprising nilotinib or its salt |
JP5528806B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
WO2008044045A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
EP2079729A1 (en) * | 2006-11-03 | 2009-07-22 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
JP5212692B6 (ja) * | 2006-11-13 | 2018-06-27 | 東レ・ファインケミカル株式会社 | 2,2’−ビス(トリフルオロメチル)−4,4’−ジアミノビフェニルの製造方法 |
US8198464B2 (en) * | 2006-12-21 | 2012-06-12 | Astellas Pharma Inc. | Method for producing C-glycoside derivative and intermediate for synthesis thereof |
EP2121692B1 (en) | 2006-12-22 | 2013-04-10 | Incyte Corporation | Substituted heterocycles as janus kinase inhibitors |
EP2152688A1 (en) | 2007-05-04 | 2010-02-17 | Irm Llc | Compounds and compositions as c-kit and pdgfr kinase inhibitors |
KR101122481B1 (ko) * | 2007-05-04 | 2012-02-29 | 아이알엠 엘엘씨 | C-kit 및 pdgfr 키나제 억제제로서의 피리미딘 유도체 및 조성물 |
CA2689989A1 (en) | 2007-06-04 | 2008-12-11 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
EP2166860B1 (en) | 2007-06-07 | 2016-09-21 | Intra-Cellular Therapies, Inc. | Novel heterocycle compounds and uses thereof |
EP2170887A2 (en) | 2007-06-07 | 2010-04-07 | Amgen Inc. | Heterocyclic compounds as raf kinase modulators |
US8367686B2 (en) | 2007-06-07 | 2013-02-05 | Intra-Cellular Therapies, Inc. | Heterocycle compounds and uses thereof |
CL2008001709A1 (es) | 2007-06-13 | 2008-11-03 | Incyte Corp | Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras. |
US20080312259A1 (en) | 2007-06-13 | 2008-12-18 | Incyte Corporation | SALTS OF THE JANUS KINASE INHIBITOR (R)-3-(4-(7H-PYRROLO[2,3-d]PYRIMIDIN-4-YL)-1H-PYRAZOL-1-YL)-3-CYCLOPENTYLPROPANENITRILE |
JP5303557B2 (ja) | 2007-08-22 | 2013-10-02 | アイアールエム・リミテッド・ライアビリティ・カンパニー | キナーゼ阻害剤である2−ヘテロアリールアミノ−ピリミジン誘導体 |
PT2190825E (pt) | 2007-08-22 | 2014-07-16 | Irm Llc | Compostos e composições de 5-(4- (haloalcoxi)fenil)pirimidina-2-amina como inibidores de cinases |
CA2698511C (en) | 2007-09-04 | 2016-10-11 | The Scripps Research Institute | Substituted pyrimidinyl-amines as protein kinase inhibitors |
JO3240B1 (ar) | 2007-10-17 | 2018-03-08 | Janssen Pharmaceutica Nv | c-fms مثبطات كيناز |
EA020777B1 (ru) | 2007-11-16 | 2015-01-30 | Инсайт Корпорейшн | 4-пиразолил-n-арилпиримидин-2-амины, 4-пиразолил-n-пиразолилпиримидин-2-амины и 4-пиразолил-n-пиридилпиримидин-2-амины в качестве ингибиторов киназ janus |
ES2459877T3 (es) | 2007-12-21 | 2014-05-12 | Novartis Ag | Combinación de nilotinib y clorambucil para el tratamiento de leucemia linfocítica crónica |
TWI444382B (zh) | 2008-03-11 | 2014-07-11 | Incyte Corp | 作為jak抑制劑之氮雜環丁烷及環丁烷衍生物 |
JP2011518836A (ja) | 2008-04-24 | 2011-06-30 | インサイト・コーポレイション | 大環状化合物およびそれらのキナーゼ阻害剤としての使用 |
BRPI0915692B8 (pt) | 2008-07-08 | 2021-05-25 | Incyte Corp | compostos derivados de 1,2,5-oxadiazóis, sua forma sólida, sua composição, bem como seus usos |
EP2305667A3 (en) | 2008-07-17 | 2011-05-11 | Teva Pharmaceutical Industries Ltd. | Nilotinib intermediates and preparation thereof |
UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
NZ590839A (en) * | 2008-08-13 | 2013-02-22 | Novartis Ag | Treatment of pulmonary arterial hypertension |
KR20100021321A (ko) * | 2008-08-14 | 2010-02-24 | 일양약품주식회사 | Ν-페닐-2-피리미딘-아민 유도체의 제조방법 |
PE20110297A1 (es) | 2008-08-15 | 2011-05-26 | Boehringer Ingelheim Int | Inhibidores de dpp-4 para la cicatrizacion de heridas |
CL2009001884A1 (es) | 2008-10-02 | 2010-05-14 | Incyte Holdings Corp | Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco. |
EP2262793B1 (en) * | 2008-11-05 | 2012-10-03 | Teva Pharmaceutical Industries Ltd. | Nilotinib hci crystalline forms |
EP2186514B1 (en) | 2008-11-14 | 2016-06-29 | Kinki University | Treatment of Malignant Peripheral Nerve Sheath Tumors |
WO2010060074A1 (en) * | 2008-11-24 | 2010-05-27 | Teva Pharmaceutical Industries Ltd. | Preparation of nilotinib and intermediates thereof |
JP2012512848A (ja) | 2008-12-23 | 2012-06-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 有機化合物の塩の形態 |
CN101759683B (zh) * | 2008-12-25 | 2011-12-28 | 哈尔滨誉衡药业股份有限公司 | 二氢化茚酰胺化合物制备方法、包含其的药物组合物、及其作为蛋白激酶抑制剂的应用 |
AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
WO2010085597A1 (en) | 2009-01-23 | 2010-07-29 | Incyte Corporation | Macrocyclic compounds and their use as kinase inhibitors |
TWI466672B (zh) | 2009-01-29 | 2015-01-01 | Boehringer Ingelheim Int | 小兒科病人糖尿病之治療 |
NZ594044A (en) | 2009-02-13 | 2014-08-29 | Boehringer Ingelheim Int | Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics |
WO2010096395A1 (en) * | 2009-02-18 | 2010-08-26 | Syntech Solution Llc | Amides as kinase inhibitors |
BRPI1013366A2 (pt) * | 2009-03-06 | 2016-03-29 | Novartis Ag | uso de derivados de pirimidilaminobenzamida para o tratamento de distúrbios mediados pela quinase contendo zíper de leucina e quinase contendo motivo alfa estéril (zak). |
CN106967070A (zh) | 2009-05-22 | 2017-07-21 | 因塞特控股公司 | 作为jak抑制剂的化合物 |
ES2487542T3 (es) | 2009-05-22 | 2014-08-21 | Incyte Corporation | Derivados de N-(hetero)aril-pirrolidina de pirazol-4-il-pirrolo[2,3-d]pirimidinas y pirrol-3-il-pirrolo[2,3-d]pirimidinas como inhibidores de cinasas Janus |
TW201102068A (en) * | 2009-06-02 | 2011-01-16 | Novartis Ag | Treatment of ophthalmologic disorders mediated by alpha-carbonic anhydrase isoforms |
US20110053968A1 (en) | 2009-06-09 | 2011-03-03 | Auspex Pharmaceuticals, Inc. | Aminopyrimidine inhibitors of tyrosine kinase |
KR101763656B1 (ko) | 2009-06-29 | 2017-08-01 | 인사이트 홀딩스 코포레이션 | Pi3k 저해물질로서의 피리미디논 |
WO2011014520A2 (en) | 2009-07-29 | 2011-02-03 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
EP2461673A4 (en) | 2009-08-05 | 2013-08-07 | Intra Cellular Therapies Inc | NEW REGULATOR PROTEINS AND HEMMER |
AR078012A1 (es) | 2009-09-01 | 2011-10-05 | Incyte Corp | Derivados heterociclicos de las pirazol-4-il- pirrolo (2,3-d) pirimidinas como inhibidores de la quinasa janus |
WO2011033307A1 (en) | 2009-09-17 | 2011-03-24 | Generics [Uk] Limited | Nilotinib dihydrochloride salt |
CN102596191B (zh) | 2009-10-02 | 2016-12-21 | 勃林格殷格翰国际有限公司 | 包含bi‑1356和二甲双胍的药物组合物 |
CA2774573A1 (en) | 2009-10-09 | 2011-04-14 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
BR112012008267B1 (pt) | 2009-10-09 | 2022-10-04 | Incyte Holdings Corporation | Derivados hidroxila, ceto e glucuronida de 3-(4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1- il)-3-ciclopentilpropanonitrila |
RU2012120901A (ru) * | 2009-10-23 | 2013-12-10 | Новартис Аг | Способ лечения пролиферативных расстройств и других патологических состояний, опосредованных действием киназ bcr-abl, c-kit, ddr1, ddr2 или pdgf-r |
JO3634B1 (ar) | 2009-11-17 | 2020-08-27 | Novartis Ag | طريقة لعلاج اضطرابات تكاثرية وحالات مرضية أخرى متوسطة بنشاط كيناز bcr-abl، c-kit، ddr1، ddr2، أو pdgf-r |
BR112012012641A2 (pt) | 2009-11-27 | 2020-08-11 | Boehringer Ingelheim International Gmbh | TRATAMENTO DE PACIENTES DIABÉTICOS GENOTIPADOS COM INIBIDORES DE DPP-lVTAL COMO LINAGLIPTINA |
US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
TW201130842A (en) | 2009-12-18 | 2011-09-16 | Incyte Corp | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
WO2011075643A1 (en) | 2009-12-18 | 2011-06-23 | Incyte Corporation | Substituted heteroaryl fused derivatives as pi3k inhibitors |
EP2521782B1 (en) | 2010-01-05 | 2019-04-10 | INSERM - Institut National de la Santé et de la Recherche Médicale | Flt3 receptor antagonists for the treatment or the prevention of pain disorders |
EP2523952B1 (en) | 2010-01-12 | 2015-03-04 | AB Science | Oxazole kinase inhibitors |
WO2011086541A1 (en) | 2010-01-15 | 2011-07-21 | Generics [Uk] Limited | Novel polymorph of nilotinib monohydrochloride monohydrate |
CA2790070C (en) | 2010-02-18 | 2018-03-06 | Incyte Corporation | Cyclobutane and methylcyclobutane derivatives as janus kinase inhibitors |
TWI766281B (zh) | 2010-03-10 | 2022-06-01 | 美商英塞特控股公司 | 作為jak1抑制劑之哌啶-4-基三亞甲亞胺衍生物 |
WO2011113947A1 (en) | 2010-03-18 | 2011-09-22 | Boehringer Ingelheim International Gmbh | Combination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions |
JP5816678B2 (ja) | 2010-04-14 | 2015-11-18 | インサイト・コーポレイションIncyte Corporation | PI3Kδ阻害剤としての縮合誘導体 |
JP2013525296A (ja) * | 2010-04-16 | 2013-06-20 | ノバルティス アーゲー | 内分泌療法抵抗性乳癌の処置 |
EP2382976A1 (en) | 2010-04-30 | 2011-11-02 | Hiroshima University | Use of pdgf-r inhibitors for the treatment of lymph node metastasis of gastric cancer |
WO2011138421A1 (en) | 2010-05-05 | 2011-11-10 | Boehringer Ingelheim International Gmbh | Combination therapy |
PE20130216A1 (es) | 2010-05-21 | 2013-02-27 | Incyte Corp | Formulacion topica para un inhibidor de jak |
JP5894153B2 (ja) | 2010-06-21 | 2016-03-23 | テバ ファーマシューティカル インダストリーズ リミティド | ニロチニブ塩及びそれらの結晶性形態 |
WO2011163195A1 (en) | 2010-06-21 | 2011-12-29 | Incyte Corporation | Fused pyrrole derivatives as pi3k inhibitors |
EP3366304B1 (en) | 2010-06-24 | 2020-05-13 | Boehringer Ingelheim International GmbH | Diabetes therapy |
US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
WO2012027716A1 (en) | 2010-08-27 | 2012-03-01 | Collabrx, Inc. | Method to treat melanoma in braf inhibitor-resistant subjects |
US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
JP5917544B2 (ja) | 2010-11-19 | 2016-05-18 | インサイト・ホールディングス・コーポレイションIncyte Holdings Corporation | Jak阻害剤としての複素環置換ピロロピリジンおよびピロロピリミジン |
AR083933A1 (es) | 2010-11-19 | 2013-04-10 | Incyte Corp | Derivados de pirrolopiridina y pirrolopirimidina sustituidos con ciclobutilo como inhibidores de jak |
IN2010CH03577A (he) * | 2010-11-26 | 2012-07-20 | Hetero Research Foundation | |
JP5961187B2 (ja) | 2010-12-20 | 2016-08-02 | インサイト・ホールディングス・コーポレイションIncyte Holdings Corporation | Pi3k阻害剤としてのn−(1−(置換フェニル)エチル)−9h−プリン−6−アミン |
WO2012098416A1 (en) | 2011-01-21 | 2012-07-26 | Sun Pharma Advanced Research Company Ltd | Diarylacetylene hydrazide containing tyrosine kinase inhibitors |
US9993480B2 (en) | 2011-02-18 | 2018-06-12 | Novartis Pharma Ag | mTOR/JAK inhibitor combination therapy |
WO2012118599A1 (en) | 2011-02-28 | 2012-09-07 | Emory University | C-abl tyrosine kinase inhibitors useful for inhibiting filovirus replication |
WO2012125629A1 (en) | 2011-03-14 | 2012-09-20 | Incyte Corporation | Substituted diamino-pyrimidine and diamino-pyridine derivatives as pi3k inhibitors |
US9126948B2 (en) | 2011-03-25 | 2015-09-08 | Incyte Holdings Corporation | Pyrimidine-4,6-diamine derivatives as PI3K inhibitors |
EP2717883B1 (en) | 2011-05-02 | 2017-03-22 | Stichting VUmc | Protection against endothelial barrier dysfunction through inhibition of the tyrosine kinase abl-related gene (arg) |
EA201490042A1 (ru) | 2011-06-20 | 2014-10-30 | Инсайт Корпорейшн | Азетидинил-фенил-, пиридил- или пиразинилкарбоксамидные производные как ингибиторы jak |
WO2013010964A1 (en) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions |
WO2013023119A1 (en) | 2011-08-10 | 2013-02-14 | Novartis Pharma Ag | JAK P13K/mTOR COMBINATION THERAPY |
CN102321073A (zh) * | 2011-08-12 | 2012-01-18 | 西安交通大学 | 一种尼罗替尼的制备方法 |
TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為jak抑制劑之環己基氮雜環丁烷衍生物 |
WO2013033569A1 (en) | 2011-09-02 | 2013-03-07 | Incyte Corporation | Heterocyclylamines as pi3k inhibitors |
UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
WO2013063000A1 (en) | 2011-10-28 | 2013-05-02 | Novartis Ag | Method of treating gastrointestinal stromal tumors |
WO2013063003A1 (en) | 2011-10-28 | 2013-05-02 | Novartis Ag | Method of treating gastrointestinal stromal tumors |
GB2496135B (en) | 2011-11-01 | 2015-03-18 | Valirx Plc | Inhibitors of the interaction between a Src family kinase and an androgen receptor or estradiol receptor for treatment of endometriosis |
WO2013068836A1 (en) | 2011-11-07 | 2013-05-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A ddr1 antagonist or an inhibitor of ddr1 gene expression for use in the prevention or treatment of crescentic glomerulonephritis |
AR088844A1 (es) * | 2011-11-14 | 2014-07-10 | Novartis Ag | Formulacion de liberacion inmediata de 4-metil-3-[[4-(3-piridinil)-2-pirimidinil]-amino]-n-[5-(4-metil-1h-imidazol-1-il)-3-(trifluoro-metil)-fenil]-benzamida |
CN103172617A (zh) * | 2011-12-20 | 2013-06-26 | 天津市国际生物医药联合研究院 | 1,5-二取代-1,2,3-三氮唑三氟甲基类化合物的应用 |
US20130172244A1 (en) | 2011-12-29 | 2013-07-04 | Thomas Klein | Subcutaneous therapeutic use of dpp-4 inhibitor |
EP2626355B1 (en) | 2012-02-09 | 2016-02-03 | Natco Pharma Limited | Process for the preparation of nilotinib hydrochloride |
US9061028B2 (en) | 2012-02-15 | 2015-06-23 | Natco Pharma Limited | Process for the preparation of Nilotinib |
SI3321262T1 (sl) * | 2012-03-01 | 2021-04-30 | Array Biopharma, Inc. | Inhibitorji serin/treonin kinaze |
AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
SG11201406860SA (en) | 2012-04-24 | 2014-11-27 | Chugai Pharmaceutical Co Ltd | Quinazolinedione derivative |
BR112014026266A2 (pt) | 2012-04-24 | 2017-06-27 | Chugai Pharmaceutical Co Ltd | derivado de quinazolidinadiona |
US20130303554A1 (en) | 2012-05-14 | 2013-11-14 | Boehringer Ingelheim International Gmbh | Use of a dpp-4 inhibitor in sirs and/or sepsis |
WO2013171167A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
WO2013171641A1 (en) | 2012-05-15 | 2013-11-21 | Novartis Ag | Compounds and compositions for inhibiting the activity of abl1, abl2 and bcr-abl1 |
MY169377A (en) * | 2012-05-15 | 2019-03-26 | Novartis Ag | Benzamide derivatives for inhibiting the activity of abl1, abl2 and bcr-abl1 |
AU2013261128B2 (en) * | 2012-05-15 | 2015-11-12 | Novartis Ag | Benzamide derivatives for inhibiting the activity of ABL1, ABL2 and BCR-ABL1 |
EP2861576B1 (en) | 2012-05-15 | 2018-01-10 | Novartis AG | Benzamide derivatives for inhibiting the activity of abl1, abl2 and bcr-abl1 |
AR091079A1 (es) | 2012-05-18 | 2014-12-30 | Incyte Corp | Derivados de pirrolopirimidina y pirrolopiridina sustituida con piperidinilciclobutilo como inhibidores de jak |
EP2854812A1 (en) | 2012-05-24 | 2015-04-08 | Boehringer Ingelheim International GmbH | A xanthine derivative as dpp -4 inhibitor for use in the treatment of autoimmune diabetes, particularly lada |
WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
US9056860B2 (en) * | 2012-06-05 | 2015-06-16 | Gilead Pharmasset Llc | Synthesis of antiviral compound |
PT3495367T (pt) | 2012-06-13 | 2020-11-12 | Incyte Holdings Corp | Compostos tricíclicos substituídos como inibidores de fgfr |
IN2014DN10801A (he) | 2012-07-11 | 2015-09-04 | Novartis Ag | |
MX2015001194A (es) | 2012-07-27 | 2015-11-23 | Izumi Technology Llc | Composiciones inhibidoras de eflujo y metodos de tratamiento que usan las mismas. |
IN2015DN00659A (he) | 2012-08-07 | 2015-06-26 | Janssen Pharmaceutica Nv | |
JOP20180012A1 (ar) | 2012-08-07 | 2019-01-30 | Janssen Pharmaceutica Nv | عملية السلفنة باستخدام نونافلوروبوتانيسولفونيل فلوريد |
TWI569799B (zh) | 2012-09-21 | 2017-02-11 | 安羅格製藥股份有限公司 | 抑制組成型活性磷酸化flt3激酶的方法 |
WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
AU2013333953B2 (en) * | 2012-10-19 | 2017-08-31 | Basf Se | Multicomponent crystalline system comprising nilotinib and selected co-crystal formers |
CN107936039A (zh) | 2012-11-01 | 2018-04-20 | 因赛特公司 | 作为jak抑制剂的三环稠合噻吩衍生物 |
SG11201503695XA (en) | 2012-11-15 | 2015-06-29 | Incyte Corp | Sustained-release dosage forms of ruxolitinib |
BR112015016282A2 (pt) | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals Inc | crenolanibe para tratamento de distúrbios proliferativos de flt3 mutado |
CN103910714A (zh) * | 2013-01-09 | 2014-07-09 | 天津泰瑞倍药研科技有限公司 | 氟代环丁烷基咪唑类化合物 |
WO2014124860A1 (en) | 2013-02-14 | 2014-08-21 | Boehringer Ingelheim International Gmbh | Specific pde4b-inhibitors for the treatment of diabetes mellitus |
TWI687220B (zh) | 2013-03-01 | 2020-03-11 | 美商英塞特控股公司 | 吡唑并嘧啶衍生物治療PI3Kδ相關病症之用途 |
HUE057262T2 (hu) | 2013-03-06 | 2022-04-28 | Incyte Holdings Corp | Eljárás és köztitermékek JAK inhibitor elõállítására |
CN110075098A (zh) | 2013-03-15 | 2019-08-02 | 勃林格殷格翰国际有限公司 | 利格列汀在心脏和肾脏保护性抗糖尿病治疗中的用途 |
TWI715901B (zh) | 2013-04-19 | 2021-01-11 | 美商英塞特控股公司 | 作為fgfr抑制劑之雙環雜環 |
WO2014174496A1 (en) | 2013-04-25 | 2014-10-30 | Ranbaxy Laboratories Limited | Pharmaceutical gastro-retentive solid oral dosage form of nilotinib |
GB2513615A (en) | 2013-05-01 | 2014-11-05 | Cancer Rec Tech Ltd | Medical use |
PL3786162T3 (pl) | 2013-05-17 | 2024-04-08 | Incyte Holdings Corporation | Pochodne bipirazolu jako inhibitory jak |
CN103288804A (zh) * | 2013-05-24 | 2013-09-11 | 苏州明锐医药科技有限公司 | 一种尼洛替尼的制备方法 |
US9655854B2 (en) | 2013-08-07 | 2017-05-23 | Incyte Corporation | Sustained release dosage forms for a JAK1 inhibitor |
US20150065447A1 (en) | 2013-08-20 | 2015-03-05 | Incyte Corporation | Survival benefit in patients with solid tumors with elevated c-reactive protein levels |
US10570204B2 (en) | 2013-09-26 | 2020-02-25 | The Medical College Of Wisconsin, Inc. | Methods for treating hematologic cancers |
AU2014338070A1 (en) | 2013-10-23 | 2016-05-05 | Chugai Seiyaku Kabushiki Kaisha | Quinazolinone and isoquinolinone derivative |
US10463658B2 (en) | 2013-10-25 | 2019-11-05 | Videra Pharmaceuticals, Llc | Method of inhibiting FLT3 kinase |
WO2015092624A1 (en) | 2013-12-16 | 2015-06-25 | Ranbaxy Laboratories Limited | Nilotinib mono-oxalate and its crystalline form |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
PE20161388A1 (es) | 2014-02-28 | 2016-12-28 | Incyte Corp | Inhibidores de la jak1 para el tratamiento de sindromes mielodisplasicos |
EP3116909B1 (en) | 2014-03-14 | 2019-11-13 | Novartis Ag | Antibody molecules to lag-3 and uses thereof |
CN106413716B (zh) | 2014-04-08 | 2020-03-27 | 因赛特公司 | 通过jak和pi3k抑制剂组合治疗b细胞恶性肿瘤 |
MA39987A (fr) | 2014-04-30 | 2017-03-08 | Incyte Corp | Procédés de préparation d'un inhibiteur de jak1 et nouvelles formes associées |
US9498467B2 (en) | 2014-05-30 | 2016-11-22 | Incyte Corporation | Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1 |
WO2015191677A1 (en) | 2014-06-11 | 2015-12-17 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors |
US10065937B2 (en) | 2014-07-31 | 2018-09-04 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | FLT3 receptor antagonists |
WO2016033304A1 (en) | 2014-08-28 | 2016-03-03 | Codexis, Inc. | Imidazoyl anilide derivatives and methods of use |
WO2016035023A1 (en) | 2014-09-03 | 2016-03-10 | Novartis Ag | Pharmaceutical combinations and their use |
EP3925622A1 (en) | 2014-09-13 | 2021-12-22 | Novartis AG | Combination therapies |
CA2963281A1 (en) | 2014-10-03 | 2016-04-07 | Novartis Ag | Combination therapies |
MA41044A (fr) | 2014-10-08 | 2017-08-15 | Novartis Ag | Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer |
EP4245376A3 (en) | 2014-10-14 | 2023-12-13 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
WO2016059220A1 (en) | 2014-10-16 | 2016-04-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Tcr-activating agents for use in the treatment of t-all |
CN104592122B (zh) * | 2014-12-09 | 2018-01-23 | 凯莱英医药集团(天津)股份有限公司 | 3‑(4‑甲基‑1h‑咪唑‑1‑基)‑5‑(三氟甲基)苯胺的制备方法 |
US9586949B2 (en) | 2015-02-09 | 2017-03-07 | Incyte Corporation | Aza-heteroaryl compounds as PI3K-gamma inhibitors |
MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
CN113004278B (zh) | 2015-02-20 | 2023-07-21 | 因赛特控股公司 | 作为fgfr抑制剂的双环杂环 |
NZ734993A (en) | 2015-02-27 | 2024-03-22 | Incyte Holdings Corp | Salts of pi3k inhibitor and processes for their preparation |
CN105985293B (zh) * | 2015-03-04 | 2018-04-03 | 埃斯特维华义制药有限公司 | 尼洛替尼中间体的制备方法 |
JO3746B1 (ar) | 2015-03-10 | 2021-01-31 | Aduro Biotech Inc | تركيبات وطرق لتنشيط الإشارات المعتمدة على "منبه أو تحفيز جين انترفيرون" |
EP3271351A1 (en) | 2015-03-20 | 2018-01-24 | Cipla Limited | Novel polymorphic form x of nilotinib dihydrochloride hydrate |
US9732097B2 (en) | 2015-05-11 | 2017-08-15 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
WO2016183062A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Salts of (s)-7-(1-(9h-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5h-thiazolo[3,2-a]pyrimidin-5-one |
US9988401B2 (en) | 2015-05-11 | 2018-06-05 | Incyte Corporation | Crystalline forms of a PI3K inhibitor |
EP3095782A1 (en) | 2015-05-18 | 2016-11-23 | Esteve Química, S.A. | New method for preparing 3-(4-methyl-1h-imidazol-1-yl)-5-(trifluoromethyl)benzenamine |
CN104860929B (zh) * | 2015-05-26 | 2017-10-31 | 凯莱英医药集团(天津)股份有限公司 | 尼洛替尼的制备方法 |
US20180207273A1 (en) | 2015-07-29 | 2018-07-26 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
EP3328418A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
LT3317301T (lt) | 2015-07-29 | 2021-07-26 | Novartis Ag | Kombinuotos terapijos, apimančios antikūno molekules prieš lag-3 |
MA43186B1 (fr) | 2015-11-03 | 2022-03-31 | Janssen Biotech Inc | Anticorps se liant spécifiquement à pd-1 et leurs utilisations |
AR106595A1 (es) | 2015-11-06 | 2018-01-31 | Incyte Corp | COMPUESTOS HETEROCÍCLICOS COMO INHIBIDORES DE PI3K-g |
MX2018007423A (es) | 2015-12-17 | 2018-11-09 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-1 y usos de las mismas. |
CN106905298A (zh) * | 2015-12-22 | 2017-06-30 | 江苏先声药业有限公司 | 盐酸尼洛替尼杂质的制备方法 |
US20170190689A1 (en) | 2016-01-05 | 2017-07-06 | Incyte Corporation | Pyridine and pyridimine compounds as pi3k-gamma inhibitors |
AU2017226005A1 (en) | 2016-03-01 | 2018-09-06 | Propellon Therapeutics Inc. | Inhibitors of WDR5 protein-protein binding |
EP3423451B1 (en) | 2016-03-01 | 2022-08-17 | Propellon Therapeutics Inc. | Inhibitors of wdr5 protein-protein binding |
CN105801559B (zh) * | 2016-04-28 | 2019-03-01 | 北京化工大学 | 4-甲基-3-[[4-(3-吡啶基)-2-嘧啶基]氨基]苯甲酸乙酯的制备方法 |
EP3254698A1 (en) | 2016-06-08 | 2017-12-13 | Universite De Montpellier | Flt3 receptor inhibitor at low dosage for the treatment of neuropathic pain |
EP3468562A1 (en) | 2016-06-10 | 2019-04-17 | Boehringer Ingelheim International GmbH | Combinations of linagliptin and metformin |
US10138248B2 (en) | 2016-06-24 | 2018-11-27 | Incyte Corporation | Substituted imidazo[2,1-f][1,2,4]triazines, substituted imidazo[1,2-a]pyridines, substituted imidazo[1,2-b]pyridazines and substituted imidazo[1,2-a]pyrazines as PI3K-γ inhibitors |
WO2018002958A1 (en) | 2016-06-30 | 2018-01-04 | Sun Pharma Advanced Research Company Limited | Novel hydrazide containing compounds as btk inhibitors |
EP3507367A4 (en) | 2016-07-05 | 2020-03-25 | Aduro BioTech, Inc. | CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF |
US11078541B2 (en) | 2016-11-02 | 2021-08-03 | Arog Pharmaceuticals, Inc. | Crenolanib for treating FLT3 mutated proliferative disorders associated mutations |
WO2018148533A1 (en) | 2017-02-09 | 2018-08-16 | Georgetown University | Compositions and methods for treating lysosomal storage disorders |
EP3609882B1 (en) | 2017-03-17 | 2022-07-13 | Cardio Therapeutics Pty Ltd | Heterocyclic inhibitors of pcsk9 |
UY37695A (es) | 2017-04-28 | 2018-11-30 | Novartis Ag | Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo |
EP3404025B1 (en) | 2017-05-16 | 2019-12-04 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Process for the preparation of pure nilotinib and its salt |
WO2018211018A1 (en) | 2017-05-17 | 2018-11-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Flt3 inhibitors for improving pain treatments by opioids |
AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
CN107188887A (zh) * | 2017-06-15 | 2017-09-22 | 苏州立新制药有限公司 | 一种尼洛替尼氧化降解杂质及其制备方法 |
EP3642240A1 (en) | 2017-06-22 | 2020-04-29 | Novartis AG | Antibody molecules to cd73 and uses thereof |
WO2019057649A1 (en) | 2017-09-19 | 2019-03-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA |
AU2018350980B2 (en) | 2017-10-18 | 2023-02-23 | Incyte Corporation | Condensed imidazole derivatives substituted by tertiary hydroxy groups as pi3k-y gamma inhibitors |
AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
CZ2017821A3 (cs) | 2017-12-20 | 2019-07-03 | Zentiva, K.S. | Léková forma obsahující krystalický nilotinib |
US11306079B2 (en) | 2017-12-21 | 2022-04-19 | Incyte Corporation | 3-(5-amino-pyrazin-2-yl)-benzenesulfonamide derivatives and related compounds as PI3K-gamma kinase inhibitors |
CN112105608B (zh) | 2018-01-30 | 2023-07-14 | 因赛特公司 | 制备(1-(3-氟-2-(三氟甲基)异烟碱基)哌啶-4-酮)的方法 |
EP3752146A1 (en) | 2018-02-16 | 2020-12-23 | Incyte Corporation | Jak1 pathway inhibitors for the treatment of cytokine-related disorders |
CN112384515A (zh) | 2018-02-27 | 2021-02-19 | 因赛特公司 | 作为a2a/a2b抑制剂的咪唑并嘧啶和三唑并嘧啶 |
HUE057970T2 (hu) | 2018-03-08 | 2022-06-28 | Incyte Corp | Aminopirazindiol-vegyületek mint PI3K-Y inhibitorok |
AU2019245420A1 (en) | 2018-03-30 | 2020-11-12 | Incyte Corporation | Treatment of hidradenitis suppurativa using JAK inhibitors |
US11220510B2 (en) | 2018-04-09 | 2022-01-11 | Incyte Corporation | Pyrrole tricyclic compounds as A2A / A2B inhibitors |
CN108530364B (zh) | 2018-04-10 | 2020-01-21 | 江苏创诺制药有限公司 | 一种3-(4-甲基-1h-咪唑-1-基)-5-三氟甲基苯胺单盐酸盐的晶型及其应用 |
CR20200591A (es) | 2018-05-04 | 2021-03-31 | Incyte Corp | Sales de un inhibidor de fgfr |
WO2019213544A2 (en) | 2018-05-04 | 2019-11-07 | Incyte Corporation | Solid forms of an fgfr inhibitor and processes for preparing the same |
US11168089B2 (en) | 2018-05-18 | 2021-11-09 | Incyte Corporation | Fused pyrimidine derivatives as A2A / A2B inhibitors |
JP2021525706A (ja) | 2018-05-25 | 2021-09-27 | インサイト・コーポレイションIncyte Corporation | Sting活性化剤としての三環式複素環式化合物 |
TW202015726A (zh) | 2018-05-30 | 2020-05-01 | 瑞士商諾華公司 | Entpd2抗體、組合療法、及使用該等抗體和組合療法之方法 |
AU2019285066B2 (en) | 2018-06-15 | 2024-06-13 | Handa Pharmaceuticals, Inc. | Kinase inhibitor salts and compositions thereof |
JP2020002108A (ja) * | 2018-06-29 | 2020-01-09 | 住友化学株式会社 | 安息香酸化合物の製造方法 |
US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
JP2020007240A (ja) * | 2018-07-04 | 2020-01-16 | 住友化学株式会社 | ベンズアミド化合物の製造方法 |
GEP20237548B (en) | 2018-07-05 | 2023-10-10 | Incyte Corp | Fused pyrazine derivatives as a2a /a2b inhibitors |
AU2019306036A1 (en) | 2018-07-17 | 2020-12-17 | Boehringer Ingelheim International Gmbh | Cardio- and renosafe antidiabetic therapy |
KR20210032468A (ko) | 2018-07-17 | 2021-03-24 | 베링거 인겔하임 인터내셔날 게엠베하 | 심장에 안전한 항당뇨병 요법 |
WO2020028565A1 (en) | 2018-07-31 | 2020-02-06 | Incyte Corporation | Tricyclic heteraryl compounds as sting activators |
US10875872B2 (en) | 2018-07-31 | 2020-12-29 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
LT3847175T (lt) | 2018-09-05 | 2024-03-25 | Incyte Corporation | Fosfoinozitido 3-kinazės (pi3k) inhibitoriaus kristalinės formos |
US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
US11396502B2 (en) | 2018-11-13 | 2022-07-26 | Incyte Corporation | Substituted heterocyclic derivatives as PI3K inhibitors |
WO2020102198A1 (en) | 2018-11-13 | 2020-05-22 | Incyte Corporation | Heterocyclic derivatives as pi3k inhibitors |
US11161838B2 (en) | 2018-11-13 | 2021-11-02 | Incyte Corporation | Heterocyclic derivatives as PI3K inhibitors |
US11596692B1 (en) | 2018-11-21 | 2023-03-07 | Incyte Corporation | PD-L1/STING conjugates and methods of use |
US20220040324A1 (en) | 2018-12-21 | 2022-02-10 | Daiichi Sankyo Company, Limited | Combination of antibody-drug conjugate and kinase inhibitor |
US20220056049A1 (en) | 2019-01-07 | 2022-02-24 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
TWI829857B (zh) | 2019-01-29 | 2024-01-21 | 美商英塞特公司 | 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶 |
US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
US20200316064A1 (en) | 2019-02-15 | 2020-10-08 | Incyte Corporation | Cyclin-dependent kinase 2 biomarkers and uses thereof |
WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
US20200405627A1 (en) | 2019-06-10 | 2020-12-31 | Incyte Corporation | Topical treatment of vitiligo by a jak inhibitor |
WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
EP4007602A1 (en) | 2019-08-01 | 2022-06-08 | Incyte Corporation | A dosing regimen for an ido inhibitor |
AR119765A1 (es) | 2019-08-14 | 2022-01-12 | Incyte Corp | Compuestos de imidazolil pirimidinilamina como inhibidores de cdk2 |
MX2022002219A (es) | 2019-08-26 | 2022-06-14 | Incyte Corp | Triazolopirimidinas como inhibidores de a2a/a2b. |
CN114502590A (zh) | 2019-09-18 | 2022-05-13 | 诺华股份有限公司 | Entpd2抗体、组合疗法、以及使用这些抗体和组合疗法的方法 |
MX2022004390A (es) | 2019-10-11 | 2022-08-08 | Incyte Corp | Aminas biciclicas como inhibidores de la cinasa dependiente de ciclina 2 (cdk2). |
SG10201909596RA (en) * | 2019-10-14 | 2021-05-28 | Esco Aster Pte Ltd | Synthesis of Tyrosine Kinase Inhibitors |
TW202128685A (zh) | 2019-10-14 | 2021-08-01 | 美商英塞特公司 | 作為fgfr抑制劑之雙環雜環 |
US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
US11992490B2 (en) | 2019-10-16 | 2024-05-28 | Incyte Corporation | Use of JAK1 inhibitors for the treatment of cutaneous lupus erythematosus and Lichen planus (LP) |
JP2023506118A (ja) | 2019-10-16 | 2023-02-15 | インサイト・コーポレイション | 皮膚エリテマトーデス及び扁平苔癬(lp)の治療のためのjak1阻害剤の使用 |
CA3162010A1 (en) | 2019-12-04 | 2021-06-10 | Incyte Corporation | Derivatives of an fgfr inhibitor |
EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
IL295007A (he) | 2020-01-31 | 2022-09-01 | Nanocopoeia Llc | מיקרוחלקיקים אמורפיים של nilotinib ושימושים בהם |
EP4103560A1 (en) | 2020-02-15 | 2022-12-21 | Cipla Limited | Novel salts of nilotinib and polymorphic forms thereof |
WO2021178779A1 (en) | 2020-03-06 | 2021-09-10 | Incyte Corporation | Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors |
CR20220584A (es) | 2020-04-16 | 2023-02-15 | Incyte Corp | Inhibidores de kras tricíclicos fusionados |
EP3904342A1 (en) | 2020-04-28 | 2021-11-03 | Grindeks, A Joint Stock Company | Process for the preparation of 3-(trifluoromethyl)-5-(4-methyl-1h-imidazole-1-yl)-benzeneamine hydrochloride |
WO2021222739A1 (en) | 2020-04-30 | 2021-11-04 | Nanocopoeia, Llc | Orally disintegrating tablet comprising amorphous solid dispersion of nilotinib |
WO2021228983A1 (en) | 2020-05-13 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A pharmaceutical composition comprising an arsenic compound, an inductor of type-1 ifn and a protein kinase inhibitor for treating cancer |
US11739102B2 (en) | 2020-05-13 | 2023-08-29 | Incyte Corporation | Fused pyrimidine compounds as KRAS inhibitors |
PE20231102A1 (es) | 2020-06-02 | 2023-07-19 | Incyte Corp | Procesos para preparar un inhibidor de jak1 |
US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
US11713310B2 (en) | 2020-07-20 | 2023-08-01 | Arog Pharmaceuticals, Inc. | Crystal forms of crenolanib and methods of use thereof |
WO2022047093A1 (en) | 2020-08-28 | 2022-03-03 | Incyte Corporation | Vinyl imidazole compounds as inhibitors of kras |
CN116261447A (zh) | 2020-09-16 | 2023-06-13 | 因赛特公司 | 局部治疗白癜风 |
US11767320B2 (en) | 2020-10-02 | 2023-09-26 | Incyte Corporation | Bicyclic dione compounds as inhibitors of KRAS |
US11969420B2 (en) | 2020-10-30 | 2024-04-30 | Arog Pharmaceuticals, Inc. | Combination therapy of crenolanib and apoptosis pathway agents for the treatment of proliferative disorders |
MX2023006542A (es) | 2020-12-08 | 2023-08-25 | Incyte Corp | Inhibidores de la vía cinasa jano 1 (jak1) para el tratamiento del vitiligo. |
CN112745300A (zh) * | 2021-01-21 | 2021-05-04 | 杭州浙中医药科技有限公司 | 一种制备n-(5-羧基-2-甲基苯基)-4-(3-吡啶)-2-嘧啶胺的方法 |
WO2022155941A1 (en) | 2021-01-25 | 2022-07-28 | Qilu Regor Therapeutics Inc. | Cdk2 inhibitors |
WO2022206888A1 (en) | 2021-03-31 | 2022-10-06 | Qilu Regor Therapeutics Inc. | Cdk2 inhibitors and use thereof |
JP2024513575A (ja) | 2021-04-12 | 2024-03-26 | インサイト・コーポレイション | Fgfr阻害剤及びネクチン-4標的化剤を含む併用療法 |
CA3220274A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
AR126101A1 (es) | 2021-06-09 | 2023-09-13 | Incyte Corp | Heterociclos tricíclicos como inhibidores de fgfr |
US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
KR20240032915A (ko) | 2021-07-07 | 2024-03-12 | 인사이트 코포레이션 | Kras의 저해제로서의 삼환식 화합물 |
US20230114765A1 (en) | 2021-07-14 | 2023-04-13 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
US20230174555A1 (en) | 2021-08-31 | 2023-06-08 | Incyte Corporation | Naphthyridine compounds as inhibitors of kras |
CN113717152B (zh) * | 2021-09-08 | 2022-06-17 | 上海皓鸿生物医药科技有限公司 | 一种特异性mrk小分子抑制剂的制备方法 |
WO2023049697A1 (en) | 2021-09-21 | 2023-03-30 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of kras |
CA3234375A1 (en) | 2021-10-01 | 2023-04-06 | Incyte Corporation | Pyrazoloquinoline kras inhibitors |
WO2023064857A1 (en) | 2021-10-14 | 2023-04-20 | Incyte Corporation | Quinoline compounds as inhibitors of kras |
WO2023081923A1 (en) | 2021-11-08 | 2023-05-11 | Frequency Therapeutics, Inc. | Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof |
AU2022389961A1 (en) | 2021-11-22 | 2024-06-06 | Incyte Corporation | Combination therapy comprising an fgfr inhibitor and a kras inhibitor |
TW202329937A (zh) | 2021-12-03 | 2023-08-01 | 美商英塞特公司 | 雙環胺ck12抑制劑 |
US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
WO2023107705A1 (en) | 2021-12-10 | 2023-06-15 | Incyte Corporation | Bicyclic amines as cdk12 inhibitors |
US20230192722A1 (en) | 2021-12-22 | 2023-06-22 | Incyte Corporation | Salts and solid forms of an fgfr inhibitor and processes of preparing thereof |
WO2023168686A1 (en) | 2022-03-11 | 2023-09-14 | Qilu Regor Therapeutics Inc. | Substituted cyclopentanes as cdk2 inhibitors |
WO2023116884A1 (en) | 2021-12-24 | 2023-06-29 | Qilu Regor Therapeutics Inc. | Cdk2 inhibitors and use thereof |
US20230279004A1 (en) | 2022-03-07 | 2023-09-07 | Incyte Corporation | Solid forms, salts, and processes of preparation of a cdk2 inhibitor |
EP4260848A1 (en) | 2022-04-11 | 2023-10-18 | Lotus Pharmaceutical Co., Ltd. | Pharmaceutical composition for solid dosage form containing nilotinib and process for its preparation |
US20230399331A1 (en) | 2022-06-14 | 2023-12-14 | Incyte Corporation | Solid forms of jak inhibitor and process of preparing the same |
WO2023250430A1 (en) | 2022-06-22 | 2023-12-28 | Incyte Corporation | Bicyclic amine cdk12 inhibitors |
WO2024015731A1 (en) | 2022-07-11 | 2024-01-18 | Incyte Corporation | Fused tricyclic compounds as inhibitors of kras g12v mutants |
US20240058343A1 (en) | 2022-08-05 | 2024-02-22 | Incyte Corporation | Treatment of urticaria using jak inhibitors |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3524519A1 (de) | 1984-07-11 | 1986-01-16 | Mitsubishi Chemical Industries Ltd., Tokio/Tokyo | Farbstoffe fuer die waermeempfindliche sublimations-transferaufzeichnung |
US4788195A (en) * | 1986-01-13 | 1988-11-29 | American Cyanamid Company | 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines |
US4871372A (en) | 1987-07-17 | 1989-10-03 | Kao Corporation | Dye composition for keratinous fiber |
TW225528B (he) * | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
US5521184A (en) | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
US5516775A (en) | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
DE69434974T2 (de) * | 1993-03-29 | 2008-02-07 | Kyowa Hakko Kogyo K.K. | alpha-2,8 SIALYLTRANSFERASE |
EP0672041B1 (en) * | 1993-10-01 | 2001-11-14 | Novartis AG | Pharmacologically active pyridine derivatives and processes for the preparation thereof |
JPH10182459A (ja) | 1996-12-26 | 1998-07-07 | Otsuka Pharmaceut Co Ltd | cGMP分解酵素阻害剤 |
JP2002179651A (ja) | 1998-06-19 | 2002-06-26 | Wakamoto Pharmaceut Co Ltd | ベンズアニリド誘導体及び医薬組成物 |
MXPA01010292A (es) | 1999-04-15 | 2002-10-23 | Squibb Bristol Myers Co | Inhibidores ciclicos de la proteina tirosina cinasa. |
AU780846B2 (en) | 1999-09-16 | 2005-04-21 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
CA2397575A1 (en) | 2000-01-13 | 2001-07-19 | Tularik Inc. | Antibacterial agents |
HN2001000008A (es) | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
US7122544B2 (en) | 2000-12-06 | 2006-10-17 | Signal Pharmaceuticals, Llc | Anilinopyrimidine derivatives as IKK inhibitors and compositions and methods related thereto |
US7129242B2 (en) | 2000-12-06 | 2006-10-31 | Signal Pharmaceuticals, Llc | Anilinopyrimidine derivatives as JNK pathway inhibitors and compositions and methods related thereto |
ATE447560T1 (de) | 2002-06-28 | 2009-11-15 | Nippon Shinyaku Co Ltd | Amidderivat |
GB0215676D0 (en) * | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
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