ES2318164T3 - Inhibidores de tirosina quinasa. - Google Patents
Inhibidores de tirosina quinasa. Download PDFInfo
- Publication number
- ES2318164T3 ES2318164T3 ES03762632T ES03762632T ES2318164T3 ES 2318164 T3 ES2318164 T3 ES 2318164T3 ES 03762632 T ES03762632 T ES 03762632T ES 03762632 T ES03762632 T ES 03762632T ES 2318164 T3 ES2318164 T3 ES 2318164T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- methyl
- formula
- acid
- trifluoromethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- -1 pyrrolidino, piperidino, piperazino Chemical group 0.000 claims abstract description 137
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 38
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 27
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 20
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 11
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 99
- 239000000203 mixture Substances 0.000 claims description 52
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- 239000007858 starting material Substances 0.000 claims description 11
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- 125000000524 functional group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
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- 239000000460 chlorine Substances 0.000 claims description 5
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 12
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- 239000003480 eluent Substances 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 241000208199 Buxus sempervirens Species 0.000 description 11
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- 102000005962 receptors Human genes 0.000 description 11
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- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 10
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- YFXZSOLFHNJVPW-UHFFFAOYSA-N 2-[3-amino-5-(trifluoromethyl)phenyl]propan-2-ol Chemical compound CC(C)(O)C1=CC(N)=CC(C(F)(F)F)=C1 YFXZSOLFHNJVPW-UHFFFAOYSA-N 0.000 description 9
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- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 6
- LLPKQRMDOFYSGZ-UHFFFAOYSA-N 2,5-dimethyl-1h-imidazole Chemical compound CC1=CN=C(C)N1 LLPKQRMDOFYSGZ-UHFFFAOYSA-N 0.000 description 6
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- 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
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Landscapes
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Families Citing this family (367)
| 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 |
| SI1686997T1 (sl) * | 2003-11-18 | 2009-08-31 | Novartis Ag | Inhibitorji mutantne oblike KIT |
| WO2005063720A1 (ja) * | 2003-12-25 | 2005-07-14 | Nippon Shinyaku Co., Ltd. | アミド誘導体及び医薬 |
| RU2412686C2 (ru) * | 2004-03-23 | 2011-02-27 | Новартис Аг | Фармацевтические композиции |
| CA2564355C (en) * | 2004-05-07 | 2012-07-03 | Amgen Inc. | Protein kinase modulators and method of use |
| JP2008520612A (ja) * | 2004-11-24 | 2008-06-19 | ノバルティス アクチエンゲゼルシャフト | ＪＡＫ阻害剤およびＢｃｒ−Ａｂｌ、Ｆｌｔ−３、ＦＡＫまたはＲＡＦキナーゼ阻害剤のうち少なくとも１個の組合せ |
| 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 |
| CN1972917B (zh) * | 2004-12-31 | 2010-08-25 | 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 |
| MX2007009135A (es) * | 2005-01-28 | 2007-09-06 | Novartis Ag | Uso de pirimidilaminobenzamidas para el tratamiento de enfermedades que responden a la modulacion de la actividad de la cinasa tie-2. |
| CN101160131A (zh) * | 2005-02-25 | 2008-04-09 | 诺瓦提斯公司 | Bcr-abl和raf抑制剂的药物组合产品 |
| JP5129123B2 (ja) | 2005-05-02 | 2013-01-23 | ノバルティス アーゲー | 全身性肥満細胞症の処置のためのピリミジルアミノベンズアミド誘導体の使用 |
| KR20080004564A (ko) | 2005-05-02 | 2008-01-09 | 노파르티스 아게 | 과호산구성 증후군을 위한 피리미딜아미노벤즈아미드유도체 |
| WO2006122150A1 (en) | 2005-05-10 | 2006-11-16 | Incyte Corporation | Modulators of indoleamine 2,3-dioxygenase and methods of using the same |
| HRP20100265T1 (hr) * | 2005-06-03 | 2010-06-30 | Novartis Ag | Smjesa od pirimidilaminobenzamid spojeva i imatiniba za liječenje ili prevenciju proliferativnih bolesti |
| SA06270147B1 (ar) * | 2005-06-09 | 2009-12-22 | نوفارتيس ايه جي | عملية لتخليق 5-(مثيل–1h–إيميدازول–1-يل )–3-(ثلاثي فلـورو مثيل)–بنزامـين |
| ES2356257T3 (es) * | 2005-06-09 | 2011-04-06 | Novartis Ag | Proceso para la síntesis del 5-(metil-1h-imidazol-1-il)-3-(trifluorometil)-bencenoamina. |
| GT200600207A (es) * | 2005-06-09 | 2007-01-15 | Novartis Ag | Proceso para la síntesis de compuestos orgánicos |
| 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 |
| 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 |
| 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 |
| US8071768B2 (en) | 2005-06-10 | 2011-12-06 | Janssen Pharmaceutica, N.V. | Alkylquinoline and alkylquinazoline kinase modulators |
| KR101354114B1 (ko) * | 2005-06-14 | 2014-01-24 | 타이젠 바이오테크놀러지 컴퍼니 리미티드 | 피리미딘 화합물 |
| US8193206B2 (en) | 2005-06-14 | 2012-06-05 | Taigen Biotechnology Co., Ltd. | Pyrimidine compounds |
| 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. | |
| KR20130087058A (ko) | 2005-07-20 | 2013-08-05 | 노파르티스 아게 | 피리미딜아미노벤즈아미드와 ｍｔｏｒ 키나제 억제제의 조합물 |
| BRPI0613868A2 (pt) * | 2005-07-20 | 2011-02-15 | Novartis Ag | compostos orgánicos |
| 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 | |
| KR100674813B1 (ko) * | 2005-08-05 | 2007-01-29 | 일양약품주식회사 | Ｎ-페닐-2-피리미딘-아민 유도체 및 그의 제조방법 |
| MX2008001971A (es) * | 2005-08-11 | 2008-03-26 | Novartis Ag | Combinacion de compuestos organicos. |
| US20080200488A1 (en) * | 2005-08-11 | 2008-08-21 | Manley Paul W | Combinations Comprising a Protein Kinase Inhibitor Being a Pyrimidylaminobenzamide Compound and a Hsp90 Inhibitor Such as 17-Aag |
| EP1926735A1 (en) | 2005-09-22 | 2008-06-04 | Incyte Corporation | Tetracyclic inhibitors of janus kinases |
| WO2007042465A2 (en) * | 2005-10-07 | 2007-04-19 | Novartis Ag | Combinati0n of nilotinib with farnesyl transferase inhibitors |
| JP2009511628A (ja) | 2005-10-18 | 2009-03-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｆｌｔ３キナーゼの阻害方法 |
| WO2007051862A1 (en) * | 2005-11-07 | 2007-05-10 | Novartis Ag | Combination of organic compounds |
| WO2007059143A2 (en) * | 2005-11-15 | 2007-05-24 | Bristol-Myers Squibb Company | Methods of identifying and treating individuals exhibiting mdr-1 overexpression with protein tyrosine kinase inhibitors and combinations thereof |
| AU2006323992B2 (en) * | 2005-12-06 | 2010-07-08 | Novartis Ag | Pyrimidylaminobenzamide derivatives for the treatment of neurofibromatosis |
| PT1966202E (pt) | 2005-12-13 | 2012-01-03 | Incyte Corp | Pirrolo[2,3-b] pirimidinas e pirrolo[2,3-b]piridinas substituídas com heteroarilo como inibidores de janus quinase |
| US20090306094A1 (en) * | 2006-03-17 | 2009-12-10 | Bristol-Myers Squibb Company | Methods Of Identifying And Treating Individuals Exhibiting Mutant Bcr/Abl Kinase Polypeptides |
| AU2007234382B2 (en) * | 2006-04-05 | 2011-06-09 | Novartis Ag | Combinations comprising BCR-ABL/C-KIT/PDGF-R TK inhibitors for treating cancer |
| JP2009532440A (ja) * | 2006-04-07 | 2009-09-10 | ノバルティス アクチエンゲゼルシャフト | ａ）ピリミジルアミノベンズアミド化合物、およびｂ）Ｔｈｒ３１５Ｉｌｅキナーゼ阻害剤を含む、組合せ剤 |
| AU2011202833B2 (en) * | 2006-04-07 | 2012-05-24 | Novartis Ag | Combination comprising a) a pyrimidylaminobenzamide compound, and b) a Thr315lle kinase inhibitor |
| WO2007124322A1 (en) | 2006-04-20 | 2007-11-01 | Janssen Pharmaceutica N.V. | Inhibitors of c-fms kinase |
| US8697716B2 (en) | 2006-04-20 | 2014-04-15 | Janssen Pharmaceutica Nv | Method of inhibiting C-KIT kinase |
| SI2021335T1 (sl) | 2006-04-20 | 2011-09-30 | Janssen Pharmaceutica Nv | Heterocikliäśne spojine kot zaviralci c-fms kinaze |
| 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 |
| EP2251042A3 (en) | 2006-09-22 | 2012-05-02 | 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 |
| US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
| US8883790B2 (en) | 2006-10-12 | 2014-11-11 | Astex Therapeutics Limited | Pharmaceutical combinations |
| CA2668190A1 (en) * | 2006-11-03 | 2008-05-15 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| US20100036167A1 (en) * | 2006-11-13 | 2010-02-11 | Toray Fine Chemicals Co., Ltd. | Process for production of 2,2'-bis(trifluoromethyl)-4,4'-diaminobiphenyl |
| 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 |
| MX2009011950A (es) * | 2007-05-04 | 2009-12-11 | Irm Llc | Derivados de pirimidina y composiciones como inhibidores de cinasa c-kit y pdgfr. |
| AU2008247442B2 (en) | 2007-05-04 | 2013-01-10 | Irm Llc | Compounds and compositions as c-kit and PDGFR kinase inhibitors |
| US8242271B2 (en) * | 2007-06-04 | 2012-08-14 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| US9062023B2 (en) | 2007-06-07 | 2015-06-23 | Intra-Cellular Therapies, Inc. | Heterocycle compounds and uses thereof |
| US8557830B2 (en) | 2007-06-07 | 2013-10-15 | Amgen Inc. | RAF kinase modulators and methods of use |
| WO2008153959A1 (en) | 2007-06-07 | 2008-12-18 | Intra-Cellular Therapies, Inc. | Novel heterocycle compounds and uses thereof |
| RS53245B2 (sr) | 2007-06-13 | 2022-10-31 | Incyte Holdings Corp | Soli inhibitora janus kinaze (r)-3-(4-(7h-pirolo(2,3-d) pirimidin-4-il)-1h-pirazol-1-il)-3-ciklopentilpropan-nitrila |
| 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. |
| CN101784539A (zh) | 2007-08-22 | 2010-07-21 | Irm责任有限公司 | 作为激酶抑制剂的2-杂芳基氨基嘧啶衍生物 |
| PL2190825T3 (pl) | 2007-08-22 | 2014-09-30 | Novartis Ag | Związki 5-(4-(chlorowcoalkoksy)-fenylo)-pirymidyno-2-aminowe i kompozycje jako inhibitory kinazy |
| EP2200436B1 (en) | 2007-09-04 | 2015-01-21 | 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 |
| WO2009064835A1 (en) | 2007-11-16 | 2009-05-22 | Incyte Corporation | 4-pyrazolyl-n-arylpyrimidin-2-amines and 4-pyrazolyl-n-heteroarylpyrimidin-2-amines as janus kinase inhibitors |
| EP2240172B1 (en) | 2007-12-21 | 2014-03-19 | Novartis AG | Combination of nilotinib and chlorambucil for the treatment of chronic lymphocytic leukemia |
| BRPI0909040B8 (pt) | 2008-03-11 | 2021-05-25 | Incyte Holdings Corp | derivados de azetidina e ciclobutano, seus usos, e composição |
| EP2274288A2 (en) | 2008-04-24 | 2011-01-19 | Incyte Corporation | Macrocyclic compounds and their use as kinase inhibitors |
| MX2011000235A (es) | 2008-07-08 | 2011-02-23 | Incyte Corp | 1,2,5-oxadiazoles como inhibidores de indolamina 2,3-dioxigenasa. |
| 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" |
| EP2315592A1 (en) * | 2008-08-13 | 2011-05-04 | Novartis AG | Treatment of pulmonary arterial hypertension |
| KR20100021321A (ko) * | 2008-08-14 | 2010-02-24 | 일양약품주식회사 | Ν-페닐-2-피리미딘-아민 유도체의 제조방법 |
| KR101657960B1 (ko) | 2008-08-15 | 2016-09-20 | 베링거 인겔하임 인터내셔날 게엠베하 | Ｆａｂ-관련 질환의 치료에 사용하기 위한 푸린 유도체 |
| 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. |
| CN102203084B (zh) * | 2008-11-05 | 2014-10-29 | 特瓦制药工业有限公司 | 盐酸尼洛替尼晶型 |
| 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 |
| CN102256976A (zh) | 2008-12-23 | 2011-11-23 | 贝林格尔.英格海姆国际有限公司 | 有机化合物的盐形式 |
| 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 |
| TW201036975A (en) | 2009-01-07 | 2010-10-16 | Boehringer Ingelheim Int | Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy |
| US8765727B2 (en) | 2009-01-23 | 2014-07-01 | Incyte Corporation | Macrocyclic compounds and their use as kinase inhibitors |
| AR075204A1 (es) | 2009-01-29 | 2011-03-16 | Boehringer Ingelheim Int | Inhibidores de dpp-4 y composiciones farmaceuticas que los comprenden, utiles para tratar enfermedades metabolicas en pacientes pediatricos, particularmente diabetes mellitus tipo 2 |
| 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 |
| EP2403492A1 (en) * | 2009-03-06 | 2012-01-11 | Novartis AG | Use of pyrimidylaminobenzamide derivatives for the treatment of disorders mediated by the leucine zipper- and sterile alpha motif-containing kinase (zak) |
| PL2432472T3 (pl) | 2009-05-22 | 2020-03-31 | Incyte Holdings Corporation | 3-[4-(7H-Pirolo[2,3-d]pirymidyn-4-ylo)-1H-pirazol-1-ilo]oktano- lub heptano-nitryle jako inhibitory JAK |
| TW201100429A (en) | 2009-05-22 | 2011-01-01 | Incyte Corp | N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| 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 |
| ME01838B (me) | 2009-06-29 | 2014-12-20 | Lncyte Holdings Corp | Pirimidinoni kao inhibitori pi3k |
| WO2011014520A2 (en) | 2009-07-29 | 2011-02-03 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
| SG178279A1 (en) | 2009-08-05 | 2012-03-29 | Intra Cellular Therapies Inc | Novel regulatory proteins and inhibitors |
| TW201113285A (en) | 2009-09-01 | 2011-04-16 | Incyte Corp | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| WO2011033307A1 (en) | 2009-09-17 | 2011-03-24 | Generics [Uk] Limited | Nilotinib dihydrochloride salt |
| EA030999B1 (ru) | 2009-10-02 | 2018-10-31 | Бёрингер Ингельхайм Интернациональ Гмбх | Применение фармацевтической композиции, включающей ингибитор дпп-4 и гидрохлорид метформина |
| ES2435491T3 (es) | 2009-10-09 | 2013-12-19 | Incyte Corporation | Derivados de hidroxilo, ceto y glucurónido de 3-(4-(7H-pirrolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopentilpropanonitrilo |
| JP2013507366A (ja) | 2009-10-09 | 2013-03-04 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｇｐｒ１１９活性モジュレーターとしての化合物および組成物 |
| PH12012500797A1 (en) * | 2009-10-23 | 2012-11-26 | Novartis Ag | Method of treating proliferative disorders and other pathological conditions mediated by bcr-abl, c-kit, ddr1, ddr2 or pdgf-r kinase activity |
| 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 |
| EA034869B1 (ru) | 2009-11-27 | 2020-03-31 | Бёрингер Ингельхайм Интернациональ Гмбх | Лечение генотипированных пациентов с диабетом ингибиторами дпп-4, такими как линаглиптин |
| US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
| US8759359B2 (en) | 2009-12-18 | 2014-06-24 | Incyte Corporation | Substituted heteroaryl fused derivatives as PI3K inhibitors |
| TW201130842A (en) | 2009-12-18 | 2011-09-16 | Incyte Corp | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
| WO2011083124A1 (en) | 2010-01-05 | 2011-07-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Flt3 receptor antagonists for the treatment or the prevention of pain disorders |
| ES2539170T3 (es) | 2010-01-12 | 2015-06-26 | Ab Science | Inhibidores de quinasas de oxazol |
| IN2010KO00035A (enExample) | 2010-01-15 | 2016-09-02 | ||
| CN102844317B (zh) | 2010-02-18 | 2015-06-03 | 因西特公司 | 作为Janus激酶抑制剂的环丁烷和甲基环丁烷衍生物 |
| MX354212B (es) | 2010-03-10 | 2018-02-19 | Incyte Corp | Derivados de piperidin-4-il azetidina como inhibidores de janus cinasa 1 (jak1). |
| JP2013522279A (ja) | 2010-03-18 | 2013-06-13 | 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 | 糖尿病及び関連状態の治療で用いるｇｐｒ１１９作動薬とｄｄｐ−ｉｖ阻害薬リナグリプチンの組合せ |
| CA2796311A1 (en) | 2010-04-14 | 2011-10-20 | Incyte Corporation | Fused derivatives as pi3k.delta. inhibitors |
| 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 |
| KR101819609B1 (ko) | 2010-05-05 | 2018-01-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법 |
| EA202091303A3 (ru) | 2010-05-21 | 2021-05-31 | Инсайт Холдингс Корпорейшн | Композиция ингибитора jak для местного применения |
| WO2011163195A1 (en) | 2010-06-21 | 2011-12-29 | Incyte Corporation | Fused pyrrole derivatives as pi3k inhibitors |
| US8937082B2 (en) | 2010-06-21 | 2015-01-20 | Teva Pharmaceutical Industries Ltd. | Nilotinib salts and crystalline forms thereof |
| KR20230051307A (ko) | 2010-06-24 | 2023-04-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 당뇨병 요법 |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| US8426418B2 (en) | 2010-08-27 | 2013-04-23 | CollabRx Inc. | Method to treat melanoma in BRAF inhibitor-resistant subjects |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| WO2012068440A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors |
| CA2818542A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| EP2648519A4 (en) * | 2010-11-26 | 2014-04-30 | Hetero Research Foundation | NEW POLYMORPH OF NILOTINIB HYDROCHLORIDE |
| 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 |
| BR112013018212B1 (pt) | 2011-01-21 | 2021-12-14 | Sun Pharma Advanced Research Company Ltd | Inibidores de tirosino quinase contendo diarilacettleno hidrazida |
| EP2675451B9 (en) | 2011-02-18 | 2017-07-26 | 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 |
| US9290765B2 (en) | 2011-05-02 | 2016-03-22 | Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patiëntenzorg | Protection against endothelial barrier dysfunction through inhibition of the tyrosine kinase abl-related gene (ARG) |
| CN103797010B (zh) | 2011-06-20 | 2016-02-24 | 因塞特控股公司 | 作为jak抑制剂的氮杂环丁烷基苯基、吡啶基或吡嗪基甲酰胺衍生物 |
| MX366629B (es) | 2011-07-15 | 2019-07-17 | Boehringer Ingelheim Int | Quinazolinas sustituidas, su preparación y su uso en composiciones farmacéuticas. |
| HK1198579A1 (en) | 2011-08-10 | 2015-04-30 | 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 |
| SI3513793T1 (sl) | 2011-09-02 | 2021-07-30 | Incyte Holdings Corporation | Heterociklilamini kot zaviralci PI3K |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| WO2013063003A1 (en) | 2011-10-28 | 2013-05-02 | Novartis Ag | Method of treating gastrointestinal stromal tumors |
| EP2770999A1 (en) | 2011-10-28 | 2014-09-03 | 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 |
| CA2855503A1 (en) * | 2011-11-14 | 2013-05-23 | Novartis Ag | Immediate release 4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-n-[5-(4-methyl-1h-imidazol-1-yl)-3-(trifluoromethyl)phenyl] benzamide formulation |
| 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 |
| PT2820009T (pt) * | 2012-03-01 | 2018-04-12 | Array Biopharma Inc | Inibidores de serina/treonina quinases |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| AU2013253541A1 (en) | 2012-04-24 | 2014-11-20 | Chugai Seiyaku Kabushiki Kaisha | Quinazolinedione derivative |
| TW201348187A (zh) | 2012-04-24 | 2013-12-01 | Chugai Pharmaceutical Co Ltd | 苯甲醯胺衍生物 |
| JP6218811B2 (ja) | 2012-05-14 | 2017-10-25 | 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 | Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| EP2849755A1 (en) | 2012-05-14 | 2015-03-25 | Boehringer Ingelheim International GmbH | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
| CN104334529B (zh) | 2012-05-15 | 2017-03-15 | 诺华股份有限公司 | 用于抑制abl1、abl2和bcr‑abl1的活性的化合物和组合物 |
| MY169377A (en) * | 2012-05-15 | 2019-03-26 | Novartis Ag | Benzamide derivatives for inhibiting the activity of abl1, abl2 and bcr-abl1 |
| MX2014013373A (es) | 2012-05-15 | 2015-08-14 | Novartis Ag | Derivados de benzamida para inhibir la actividad de abl1, abl2 y bcr-abl1. |
| EP2861576B1 (en) | 2012-05-15 | 2018-01-10 | Novartis AG | Benzamide derivatives for inhibiting the activity of abl1, abl2 and bcr-abl1 |
| US9193733B2 (en) | 2012-05-18 | 2015-11-24 | Incyte Holdings Corporation | Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors |
| 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 |
| WO2013174768A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of autoimmune diabetes, particularly lada |
| US9056860B2 (en) * | 2012-06-05 | 2015-06-16 | Gilead Pharmasset Llc | Synthesis of antiviral compound |
| SI2861595T1 (sl) | 2012-06-13 | 2017-04-26 | Incyte Holdings Corporation | Substituirane triciklične spojine kot inhibitorji fgfr |
| BR112015000349A2 (pt) | 2012-07-11 | 2017-06-27 | Novartis Ag | método de tratamento de tumores estromais gastrointestinais |
| BR112015001838B1 (pt) | 2012-07-27 | 2022-10-25 | Izumi Technology, Llc | Composição de inibidor de efluxo |
| ES2608628T3 (es) | 2012-08-07 | 2017-04-12 | Janssen Pharmaceutica Nv | Procedimiento para la preparacion de derivados de ester heterociclicos |
| JOP20180012A1 (ar) | 2012-08-07 | 2019-01-30 | Janssen Pharmaceutica Nv | عملية السلفنة باستخدام نونافلوروبوتانيسولفونيل فلوريد |
| KR101738063B1 (ko) | 2012-09-21 | 2017-05-19 | 아로그 파마슈티칼스, 인코퍼레이티드 | 구조적으로 활성인 인산화된 ｆｌｔ３ 키나제의 억제 방법 |
| WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
| BR112015008552A2 (pt) * | 2012-10-19 | 2017-07-04 | Basf Se | material cristalino, composição farmacêutica, e, processo para a preparação de um material cristalino |
| BR112015009942A2 (pt) | 2012-11-01 | 2017-07-11 | Incyte Corp | derivados de tiofeno fundidos tricíclicos como inibidores de jak |
| NZ708157A (en) | 2012-11-15 | 2019-07-26 | Incyte Holdings 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 |
| TWI634121B (zh) | 2013-03-06 | 2018-09-01 | 英塞特控股公司 | 用於製備ｊａｋ抑制劑之方法及中間物 |
| 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 |
| LT2986610T (lt) | 2013-04-19 | 2018-04-10 | Incyte Holdings Corporation | Bicikliniai heterociklai, kaip fgfr inhibitoriai |
| US9682081B2 (en) | 2013-04-25 | 2017-06-20 | Sun Pharmaceutical Industries Limited | Pharmaceutical gastro-retentive solid oral dosage form of nilotinib |
| GB2513615A (en) | 2013-05-01 | 2014-11-05 | Cancer Rec Tech Ltd | Medical use |
| WO2014186706A1 (en) | 2013-05-17 | 2014-11-20 | Incyte Corporation | Bipyrazole derivatives as jak inhibitors |
| 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 |
| MX394928B (es) | 2013-08-07 | 2025-03-24 | Incyte Holdings Corp | Formas de dosificacion de liberacion prolongada para un inhibidor de jak 1 (cinasa de janus 1). |
| CN105555313A (zh) | 2013-08-20 | 2016-05-04 | 因赛特公司 | 在c-反应蛋白水平较高的实体肿瘤患者中的存活益处 |
| US10570204B2 (en) | 2013-09-26 | 2020-02-25 | The Medical College Of Wisconsin, Inc. | Methods for treating hematologic cancers |
| WO2015060373A1 (ja) | 2013-10-23 | 2015-04-30 | 中外製薬株式会社 | キナゾリノンおよびイソキノリノン誘導体 |
| 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 |
| SG11201607083VA (en) | 2014-02-28 | 2016-09-29 | Incyte Corp | Jak1 inhibitors for the treatment of myelodysplastic syndromes |
| LT3116909T (lt) | 2014-03-14 | 2020-02-10 | Novartis Ag | Antikūno molekulės prieš lag-3 ir jų panaudojimas |
| HRP20201887T1 (hr) | 2014-04-08 | 2021-02-05 | Incyte Corporation | LIJEČENJE B-STANIČNIH MALIGNITETA S KOMBINACIJOM INHIBITORA JAK i PI3K |
| SG11201609016VA (en) | 2014-04-30 | 2016-11-29 | Incyte Corp | Processes of preparing a jak1 inhibitor and new forms thereto |
| 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 |
| US10045987B2 (en) | 2014-08-28 | 2018-08-14 | Codexis, Inc. | Imidazoyl anilide derivatives and methods of use |
| WO2016035023A1 (en) | 2014-09-03 | 2016-03-10 | Novartis Ag | Pharmaceutical combinations and their use |
| BR112017004826A2 (pt) | 2014-09-13 | 2017-12-12 | Novartis Ag | terapias de combinação de inibidores de alk |
| AU2015327868A1 (en) | 2014-10-03 | 2017-04-20 | 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 |
| EP3206711B1 (en) | 2014-10-14 | 2023-05-31 | 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 |
| SG10201913036RA (en) | 2015-02-20 | 2020-02-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| MA41607B1 (fr) | 2015-02-27 | 2021-01-29 | Incyte Corp | Sels d'un inhibiteur de pi3k et procédés de préparation de ces sels |
| 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 |
| PE20171448A1 (es) | 2015-03-10 | 2017-10-02 | Aduro Biotech Inc | Composiciones y metodos para activar la senalizacion dependiente del estimulador del gen de interferon |
| WO2016151304A1 (en) | 2015-03-20 | 2016-09-29 | Cipla Limited | Novel polymorphic form x of nilotinib dihydrochloride hydrate |
| WO2016183063A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Crystalline forms of a pi3k 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 |
| US9732097B2 (en) | 2015-05-11 | 2017-08-15 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase 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 |
| WO2017019897A1 (en) | 2015-07-29 | 2017-02-02 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
| EP3317301B1 (en) | 2015-07-29 | 2021-04-07 | Novartis AG | Combination therapies comprising antibody molecules to lag-3 |
| CN114272371A (zh) | 2015-07-29 | 2022-04-05 | 诺华股份有限公司 | 包含抗pd-1抗体分子的联合疗法 |
| CA3004138A1 (en) | 2015-11-03 | 2017-05-11 | Janssen Biotech, Inc. | Antibodies specifically binding pd-1 and tim-3 and their uses |
| AR106595A1 (es) | 2015-11-06 | 2018-01-31 | Incyte Corp | COMPUESTOS HETEROCÍCLICOS COMO INHIBIDORES DE PI3K-g |
| ES2986067T3 (es) | 2015-12-17 | 2024-11-08 | Novartis Ag | Moléculas de anticuerpos frente 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 |
| EP3792256B1 (en) | 2016-01-05 | 2024-10-23 | Incyte Corporation | Pyridine compounds as pi3k-gamma inhibitors |
| AU2017226004B2 (en) | 2016-03-01 | 2021-07-22 | Propellon Therapeutics Inc. | Inhibitors of WDR5 protein-protein binding |
| EP3423437A4 (en) | 2016-03-01 | 2019-07-24 | 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 |
| US10155000B2 (en) | 2016-06-10 | 2018-12-18 | Boehringer Ingelheim International Gmbh | Medical use of pharmaceutical combination or composition |
| TW201803871A (zh) | 2016-06-24 | 2018-02-01 | 英塞特公司 | 作為ＰＩ３Ｋ-γ抑制劑之雜環化合物 |
| WO2018002958A1 (en) | 2016-06-30 | 2018-01-04 | Sun Pharma Advanced Research Company Limited | Novel hydrazide containing compounds as btk inhibitors |
| WO2018009466A1 (en) | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
| AU2017353925A1 (en) | 2016-11-02 | 2018-09-27 | Arog Pharmaceuticals, Inc. | Crenolanib for treating FLT3 mutated proliferative disorders associated mutations |
| US11426406B2 (en) | 2017-02-09 | 2022-08-30 | 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 |
| US20200172628A1 (en) | 2017-06-22 | 2020-06-04 | 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 |
| MX2020003862A (es) | 2017-10-18 | 2020-08-13 | Incyte Corp | Derivados condensados de imidazol sustituidos por grupos hidroxi terciarios como inhibidores de fosfoinositido 3-cinasas gamma (pi3k-gamma). |
| 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 |
| US12398209B2 (en) | 2018-01-22 | 2025-08-26 | Janssen Biotech, Inc. | Methods of treating cancers with antagonistic anti-PD-1 antibodies |
| WO2019152374A1 (en) | 2018-01-30 | 2019-08-08 | Incyte Corporation | Processes for preparing (1 -(3-fluoro-2-(trifluoromethyl)isonicotinyl)piperidine-4-one) |
| WO2019161098A1 (en) | 2018-02-16 | 2019-08-22 | Incyte Corporation | Jak1 pathway inhibitors for the treatment of cytokine-related disorders |
| AU2019227607C1 (en) | 2018-02-27 | 2023-07-20 | Incyte Corporation | Imidazopyrimidines and triazolopyrimidines as A2A / A2B inhibitors |
| WO2019226213A2 (en) | 2018-03-08 | 2019-11-28 | Incyte Corporation | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| HUE067471T2 (hu) | 2018-03-30 | 2024-10-28 | Incyte Corp | Gennyes verejtékmirigy-gyulladás kezelése jak inhibitorok alkalmazásával |
| 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 |
| KR20210018264A (ko) | 2018-05-04 | 2021-02-17 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| PL3788047T3 (pl) | 2018-05-04 | 2025-04-14 | Incyte Corporation | Stałe postacie inhibitora fgfr i sposoby ich otrzymywania |
| MA52940A (fr) | 2018-05-18 | 2021-04-28 | Incyte Corp | Dérivés de pyrimidine fusionnés utilisés en tant qu'inhibiteurs de a2a/a2b |
| ES2929415T3 (es) | 2018-05-25 | 2022-11-29 | Incyte Corp | Compuestos heterocíclicos tricíclicos como activadores de STING |
| UY38247A (es) | 2018-05-30 | 2019-12-31 | Novartis Ag | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación |
| BR112020024427A2 (pt) | 2018-06-01 | 2021-03-23 | Incyte Corporation | regime de dosagem para o tratamento de distúrbios relacionados a pi3k |
| CN113292537B (zh) | 2018-06-15 | 2024-04-05 | 汉达癌症医药责任有限公司 | 激酶抑制剂的盐类及其组合物 |
| 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 |
| WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | 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 |
| CA3105721A1 (en) | 2018-07-05 | 2020-01-09 | Incyte Corporation | Fused pyrazine derivatives as a2a / a2b inhibitors |
| CA3103735A1 (en) | 2018-07-17 | 2020-01-23 | Boehringer Ingelheim International Gmbh | Cardio- and renosafe antidiabetic therapy |
| EP3823624A1 (en) | 2018-07-17 | 2021-05-26 | Boehringer Ingelheim International GmbH | Cardiosafe antidiabetic therapy |
| US10875872B2 (en) | 2018-07-31 | 2020-12-29 | Incyte Corporation | Heteroaryl amide compounds as sting activators |
| WO2020028565A1 (en) | 2018-07-31 | 2020-02-06 | Incyte Corporation | Tricyclic heteraryl compounds as sting activators |
| CR20250050A (es) | 2018-09-05 | 2025-03-19 | Incyte Corp | Formas cristalinas de un inhibidor de fosfoinositida 3–quinasa (pi3k) (divisional 2021-0165) |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| US11078204B2 (en) | 2018-11-13 | 2021-08-03 | Incyte Corporation | Heterocyclic derivatives as PI3K inhibitors |
| WO2020102150A1 (en) | 2018-11-13 | 2020-05-22 | Incyte Corporation | Heterocyclic derivatives as pi3k inhibitors |
| WO2020102216A1 (en) | 2018-11-13 | 2020-05-22 | Incyte Corporation | Substituted heterocyclic derivatives as pi3k inhibitors |
| US11596692B1 (en) | 2018-11-21 | 2023-03-07 | Incyte Corporation | PD-L1/STING conjugates and methods of use |
| JP2022513967A (ja) | 2018-12-20 | 2022-02-09 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| CA3123042A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
| US12441736B2 (en) | 2018-12-20 | 2025-10-14 | Amgen Inc. | KIF18A inhibitors |
| KR20210107069A (ko) | 2018-12-21 | 2021-08-31 | 다이이찌 산쿄 가부시키가이샤 | 항체-약물 컨쥬게이트와 키나아제 저해제의 조합 |
| US12129267B2 (en) | 2019-01-07 | 2024-10-29 | 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 |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| EP3923949A1 (en) | 2019-02-15 | 2021-12-22 | Incyte Corporation | Cyclin-dependent kinase 2 biomarkers and uses thereof |
| TW202100520A (zh) | 2019-03-05 | 2021-01-01 | 美商英塞特公司 | 作為cdk2 抑制劑之吡唑基嘧啶基胺化合物 |
| JP2022523562A (ja) * | 2019-03-05 | 2022-04-25 | ホンイー アンド アソシエイツ エルエルシー | 神経変性疾患および癌の治療のための化合物 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| US11919904B2 (en) | 2019-03-29 | 2024-03-05 | Incyte Corporation | Sulfonylamide compounds as CDK2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| TWI853027B (zh) | 2019-05-16 | 2024-08-21 | 瑞士商諾華公司 | N-[4-(氯二氟甲氧基)苯基]-6-[(3r)-3-羥基吡咯啶-1-基]-5-(1h-吡唑-5-基)吡啶-3-甲醯胺之結晶形狀 |
| MA56215A (fr) | 2019-06-10 | 2022-04-20 | Incyte Corp | Traitement topique du vitiligo par un inhibiteur de jak |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4007602A1 (en) | 2019-08-01 | 2022-06-08 | Incyte Corporation | A dosing regimen for an ido inhibitor |
| WO2021026098A1 (en) * | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| JP7699100B2 (ja) | 2019-08-02 | 2025-06-26 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤 |
| PH12022550361A1 (en) | 2019-08-14 | 2023-02-27 | Incyte Corp | Imidazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| TW202115082A (zh) | 2019-08-26 | 2021-04-16 | 美商英塞特公司 | 作為ａ２ａ／ａ２ｂ抑制劑之三唑并嘧啶 |
| EP4031578A1 (en) | 2019-09-18 | 2022-07-27 | Novartis AG | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| JP7693656B2 (ja) | 2019-10-11 | 2025-06-17 | インサイト・コーポレイション | Ｃｄｋ２阻害剤としての二環式アミン |
| CR20220169A (es) | 2019-10-14 | 2022-10-27 | Incyte Corp | Heterociclos bicíclicos como inhibidores de fgfr |
| SG10201909596RA (en) * | 2019-10-14 | 2021-05-28 | Esco Aster Pte Ltd | Synthesis of Tyrosine Kinase Inhibitors |
| JP7518900B2 (ja) | 2019-10-16 | 2024-07-18 | 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 |
| 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) |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | 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 |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EP4096791A1 (en) | 2020-01-31 | 2022-12-07 | Nanocopoeia LLC | Amorphous nilotinib microparticles and uses thereof |
| WO2021161347A1 (en) | 2020-02-15 | 2021-08-19 | Cipla Limited | Novel salts of nilotinib and polymorphic forms thereof |
| AU2021230385A1 (en) | 2020-03-06 | 2022-09-22 | Incyte Corporation | Combination therapy comprising AXL/MER and PD-1/PD-L1 inhibitors |
| PH12022552739A1 (en) | 2020-04-16 | 2024-03-25 | Incyte Corp | Fused tricyclic kras inhibitors |
| 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 |
| IL297776A (en) | 2020-04-30 | 2022-12-01 | Nanocopoeia Llc | Orally disintegrating tablets containing an amorphous solid dispersion of nalotinib |
| US11739102B2 (en) | 2020-05-13 | 2023-08-29 | Incyte Corporation | Fused pyrimidine compounds as KRAS inhibitors |
| 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 |
| JP2023528868A (ja) | 2020-06-02 | 2023-07-06 | インサイト・コーポレイション | Ｊａｋ１阻害剤の調製プロセス |
| 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 |
| US20230364095A1 (en) | 2020-09-16 | 2023-11-16 | Incyte Corporation | Topical treatment of vitiligo |
| MX2023003556A (es) | 2020-09-29 | 2023-06-13 | Shenzhen Pharmacin Co Ltd | Composiciones farmaceuticas. |
| WO2022072783A1 (en) | 2020-10-02 | 2022-04-07 | Incyte Corporation | Bicyclic dione compounds as inhibitors of kras |
| WO2022090547A1 (en) | 2020-10-30 | 2022-05-05 | Dsm Ip Assets B.V. | Production of carotenoids by fermentation |
| 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 |
| JP2023552452A (ja) | 2020-12-08 | 2023-12-15 | インサイト・コーポレイション | 白斑治療用のｊａｋ１経路阻害薬 |
| 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 |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含ｆｇｆｒ抑制劑及ｎｅｃｔｉｎ－４靶向劑之組合療法 |
| US12268667B2 (en) | 2021-05-03 | 2025-04-08 | Incyte Corporation | JAK1 pathway inhibitors for the treatment of prurigo nodularis |
| EP4352060A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US11939331B2 (en) | 2021-06-09 | 2024-03-26 | Incyte Corporation | Tricyclic heterocycles as FGFR inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| WO2023283213A1 (en) | 2021-07-07 | 2023-01-12 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
| US20230114765A1 (en) | 2021-07-14 | 2023-04-13 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
| US12441742B2 (en) | 2021-08-31 | 2025-10-14 | 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 |
| US12030883B2 (en) | 2021-09-21 | 2024-07-09 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of KRAS |
| JP2024537824A (ja) | 2021-10-01 | 2024-10-16 | インサイト・コーポレイション | ピラゾロキノリンｋｒａｓ阻害剤 |
| MX2024004444A (es) | 2021-10-14 | 2024-05-08 | Incyte Corp | Compuestos de quinolina como inhibidores de la proteina del virus de sarcoma de rata kirsten (kras). |
| JP2024540411A (ja) | 2021-11-08 | 2024-10-31 | プロジェントス・セラピューティクス・インコーポレイテッド | 血小板由来成長因子受容体（ｐｄｇｆｒ）アルファ阻害剤及びその使用 |
| US20230226040A1 (en) | 2021-11-22 | 2023-07-20 | 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 |
| TW202341982A (zh) | 2021-12-24 | 2023-11-01 | 大陸商上海齊魯銳格醫藥研發有限公司 | Ｃｄｋ２抑制劑及其用途 |
| WO2023168686A1 (en) | 2022-03-11 | 2023-09-14 | Qilu Regor Therapeutics Inc. | Substituted cyclopentanes as cdk2 inhibitors |
| 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 |
| EP4540252A1 (en) | 2022-06-14 | 2025-04-23 | Incyte Corporation | Solid forms of a jak inhibitor and process of preparing the same |
| US20250353842A1 (en) | 2022-06-22 | 2025-11-20 | 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 |
| WO2024142002A1 (en) | 2022-12-29 | 2024-07-04 | Renata Pharmaceuticals (Ireland) Limited | Pharmaceutical suspension of nilotinib |
| US20240368156A1 (en) | 2023-04-18 | 2024-11-07 | Incyte Corporation | 2-azabicyclo[2.2.1]heptane kras inhibitors |
| WO2024220532A1 (en) | 2023-04-18 | 2024-10-24 | Incyte Corporation | Pyrrolidine kras inhibitors |
| WO2024254245A1 (en) | 2023-06-09 | 2024-12-12 | Incyte Corporation | Bicyclic amines as cdk2 inhibitors |
| US20250163079A1 (en) | 2023-11-01 | 2025-05-22 | Incyte Corporation | Kras inhibitors |
| WO2025129002A1 (en) | 2023-12-13 | 2025-06-19 | Incyte Corporation | Bicyclooctane kras 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 (enExample) * | 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 |
| EP0654529B1 (en) * | 1993-03-29 | 2007-05-23 | Kyowa Hakko Kogyo Kabushiki Kaisha | alpha-2,8-SIALYLTRANSFERASE |
| ES2167377T3 (es) * | 1993-10-01 | 2002-05-16 | Novartis Ag | Derivados de piridina farmacologicamente activos y procedimientos para la preparacion de los mismos. |
| 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 |
| EP1169038B9 (en) | 1999-04-15 | 2013-07-10 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| CA2385736C (en) | 1999-09-16 | 2011-11-15 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| ES2293980T3 (es) | 2000-01-13 | 2008-04-01 | Amgen Inc. | Agentes antibacterianos. |
| 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 |
| AU2003246100A1 (en) | 2002-06-28 | 2004-01-19 | Nippon Shinyaku Co., Ltd. | Amide derivative |
| GB0215676D0 (en) * | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
-
2002
- 2002-07-05 GB GBGB0215676.8A patent/GB0215676D0/en not_active Ceased
- 2002-12-20 GB GBGB0229893.3A patent/GB0229893D0/en not_active Ceased
-
2003
- 2003-07-03 PE PE2003000676A patent/PE20040647A1/es active IP Right Grant
- 2003-07-03 TW TW092118223A patent/TWI313603B/zh not_active IP Right Cessation
- 2003-07-03 AR ARP030102415A patent/AR040390A1/es active IP Right Grant
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- 2003-07-04 PL PL406680A patent/PL406680A1/pl not_active Application Discontinuation
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- 2003-07-04 ES ES03762632T patent/ES2318164T3/es not_active Expired - Lifetime
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- 2003-07-04 EP EP10174608.9A patent/EP2357182B1/en not_active Expired - Lifetime
- 2003-07-04 KR KR1020057000159A patent/KR100733639B1/ko not_active Expired - Lifetime
- 2003-07-04 ES ES10174608.9T patent/ES2475066T3/es not_active Expired - Lifetime
- 2003-07-04 US US10/520,359 patent/US7169791B2/en not_active Expired - Lifetime
- 2003-07-04 AT AT03762632T patent/ATE414699T1/de active
- 2003-07-04 PL PL374583A patent/PL219723B1/pl not_active IP Right Cessation
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- 2003-07-04 PL PL395096A patent/PL395096A1/pl not_active Application Discontinuation
- 2003-07-04 WO PCT/EP2003/007198 patent/WO2004005281A1/en not_active Ceased
- 2003-07-04 CA CA002491632A patent/CA2491632C/en not_active Expired - Lifetime
- 2003-07-04 EP EP20080161965 patent/EP2100891A1/en not_active Withdrawn
- 2003-07-04 MY MYPI20032514A patent/MY143466A/en unknown
- 2003-07-04 RU RU2005102917/04A patent/RU2348627C2/ru active
- 2003-07-04 AU AU2003249962A patent/AU2003249962C9/en not_active Expired
- 2003-07-04 PT PT101746089T patent/PT2357182E/pt unknown
- 2003-07-04 CN CNB038187280A patent/CN1324022C/zh not_active Expired - Lifetime
- 2003-07-04 NZ NZ537396A patent/NZ537396A/en not_active IP Right Cessation
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- 2003-07-04 BR BRPI0312464A patent/BRPI0312464B8/pt active IP Right Grant
- 2003-07-04 EP EP10174830A patent/EP2368889A1/en not_active Withdrawn
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2004
- 2004-12-22 ZA ZA200410322A patent/ZA200410322B/en unknown
- 2004-12-23 IL IL165977A patent/IL165977A/en unknown
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2005
- 2005-01-05 EC EC2005005525A patent/ECSP055525A/es unknown
- 2005-01-12 CO CO05001801A patent/CO5680432A2/es active IP Right Grant
- 2005-02-04 NO NO20050636A patent/NO331166B1/no not_active IP Right Cessation
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2006
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2007
- 2007-10-31 JP JP2007283773A patent/JP4895976B2/ja not_active Expired - Lifetime
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2008
- 2008-04-02 US US12/061,334 patent/US7569566B2/en not_active Expired - Lifetime
- 2008-09-24 RU RU2008137927/04A patent/RU2445309C2/ru active
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2009
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- 2009-05-27 IL IL198996A patent/IL198996A/en active IP Right Grant
- 2009-06-22 US US12/489,049 patent/US7956053B2/en not_active Expired - Lifetime
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2011
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- 2011-07-11 JP JP2011153046A patent/JP2011219495A/ja active Pending
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2013
- 2013-08-15 JP JP2013168882A patent/JP2013227358A/ja active Pending
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