UA77765C2 - N3 alkylated derivatives of benzimidazole as mek inhibitors - Google Patents
N3 alkylated derivatives of benzimidazole as mek inhibitors Download PDFInfo
- Publication number
- UA77765C2 UA77765C2 UA20040907722A UA20040907722A UA77765C2 UA 77765 C2 UA77765 C2 UA 77765C2 UA 20040907722 A UA20040907722 A UA 20040907722A UA 20040907722 A UA20040907722 A UA 20040907722A UA 77765 C2 UA77765 C2 UA 77765C2
- Authority
- UA
- Ukraine
- Prior art keywords
- heteroaryl
- aryl
- heterocyclyl
- group
- arylalkyl
- Prior art date
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- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title abstract description 3
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 238000000034 method Methods 0.000 claims abstract description 47
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- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 14
- -1 difluoromethoxyl Chemical group 0.000 claims description 133
- 125000000623 heterocyclic group Chemical group 0.000 claims description 102
- 125000001072 heteroaryl group Chemical group 0.000 claims description 94
- 125000003118 aryl group Chemical group 0.000 claims description 90
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 60
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- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 53
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 52
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 50
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 45
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
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Classifications
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- 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
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- 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
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- 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
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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PCT/US2003/007864 WO2003077914A1 (en) | 2002-03-13 | 2003-03-13 | N3 alkylated benzimidazole derivatives as mek inhibitors |
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Families Citing this family (244)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100984573B1 (ko) * | 2002-03-13 | 2010-09-30 | 어레이 바이오파마 인크. | Mek 억제제로서의 n3 알킬화 벤즈이미다졸 유도체 |
US7235537B2 (en) * | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
EP1581527A4 (en) * | 2002-12-13 | 2006-11-22 | Smithkline Beecham Corp | MIMETICS OF THROMBOPOIETINE |
EP1598079B1 (en) * | 2003-02-26 | 2009-04-22 | Kowa Co., Ltd. | Remedies for allergic contact dermatitis |
BRPI0412851A (pt) | 2003-07-24 | 2006-10-03 | Warner Lambert Co | benzamidazóis de n-metila-substituìdos |
US7144907B2 (en) * | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
US7538120B2 (en) * | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
TWI349664B (en) | 2003-09-22 | 2011-10-01 | S Bio Pte Ltd | Benzimidazole derivatives: preparation and pharmaceutical applications |
AU2004293017B2 (en) * | 2003-11-19 | 2010-08-19 | Array Biopharma Inc. | Bicyclic inhibitors of MEK and methods of use thereof |
US7517994B2 (en) * | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
US7732616B2 (en) * | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
KR101223914B1 (ko) | 2003-11-21 | 2013-01-18 | 어레이 바이오파마 인크. | Akt 단백질 키나제 억제제 |
EP1699477A2 (en) * | 2003-12-11 | 2006-09-13 | Theravance, Inc. | Compositions for use in the treatment of mutant receptor tyrosine kinase driven cellular proliferative diseases |
US7956191B2 (en) | 2004-10-20 | 2011-06-07 | Merck Serono Sa | 3-arylamino pyridine derivatives |
ES2330872T3 (es) * | 2004-12-01 | 2009-12-16 | Merck Serono Sa | Derivados de (1,2,4)triazolo(4,3-a)piridina para el tratamiento de enfermedades hiperproliferativas. |
US7429667B2 (en) * | 2005-01-20 | 2008-09-30 | Ardea Biosciences, Inc. | Phenylamino isothiazole carboxamidines as MEK inhibitors |
ES2378760T3 (es) * | 2005-05-18 | 2012-04-17 | Array Biopharma, Inc. | Inhibidores heterocíclicos de MEK y métodos de uso de los mismos |
CA2612296A1 (en) * | 2005-06-23 | 2007-01-04 | Array Biopharma Inc. | Snar process for preparing benzimidazole compounds |
MY177122A (en) * | 2005-06-23 | 2020-09-07 | Array Biopharma Inc | Process for preparing benzimidazole compounds |
US8101799B2 (en) | 2005-07-21 | 2012-01-24 | Ardea Biosciences | Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK |
AU2013203939B2 (en) * | 2005-10-07 | 2015-08-13 | Exelixis, Inc. | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
AU2012261703B2 (en) * | 2005-10-07 | 2015-08-13 | Exelixis, Inc. | Azetidines as MEK inhibitors for the treatment of proliferative diseases |
CN110668988A (zh) * | 2005-10-07 | 2020-01-10 | 埃克塞利希斯股份有限公司 | 作为用于治疗增生性疾病的mek抑制剂的吖丁啶 |
US7968108B2 (en) * | 2005-10-25 | 2011-06-28 | Metbro Distributing L.P. | Hydrogen cyanamide pesticide formulations |
US7572460B2 (en) * | 2005-10-25 | 2009-08-11 | Rodrigo Rodriguez-Kabana | Hydrogen cyanamide pesticide formulations |
TWI405756B (zh) | 2005-12-21 | 2013-08-21 | Array Biopharma Inc | 新穎硫酸氫鹽 |
WO2007071951A1 (en) * | 2005-12-21 | 2007-06-28 | Astrazeneca Ab | Tosylate salt of 6- (4-br0m0-2-chl0r0phenylamin0) -7-fluoro-n- (2-hydroxyethoxy) -3-methyl-3h-benzimi dazole- 5 - carboxamide , mek inhibitor useful in the treatment of cancer |
CA2534243A1 (fr) | 2006-01-25 | 2007-07-25 | Hydro Quebec | Particules d'oxyde metallique enrobees a faible taux de dissolution, procedes de preparation et utilisation dans les systemes electrochimiques |
GB0601962D0 (en) | 2006-01-31 | 2006-03-15 | Ucb Sa | Therapeutic agents |
US7842836B2 (en) | 2006-04-11 | 2010-11-30 | Ardea Biosciences | N-aryl-N'alkyl sulfamides as MEK inhibitors |
JP5269762B2 (ja) * | 2006-04-18 | 2013-08-21 | アーディア・バイオサイエンシーズ・インコーポレイテッド | Mek阻害剤としてのピリドンスルホンアミドおよびピリドンスルファミド |
CA2656566C (en) | 2006-07-06 | 2014-06-17 | Array Biopharma Inc. | Dihydrofuro pyrimidines as akt protein kinase inhibitors |
US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
RU2481336C2 (ru) * | 2006-07-06 | 2013-05-10 | Эррэй Биофарма Инк. | Циклопента(d)пиримидины в качестве ингибиторов протеинкиназ акт |
EP2054418B1 (en) | 2006-07-06 | 2011-11-09 | Array Biopharma Inc. | Dihydrothieno pyrimidines as akt protein kinase inhibitors |
WO2008016123A1 (fr) * | 2006-08-03 | 2008-02-07 | Takeda Pharmaceutical Company Limited | INHIBITEUR DE LA GSK-3β |
CN101583616B (zh) * | 2006-08-21 | 2012-05-30 | 健泰科生物技术公司 | 氮杂苯并噻吩基化合物及使用方法 |
ES2376771T3 (es) * | 2006-08-21 | 2012-03-16 | Genentech, Inc. | Compuestos aza-benzofuranilo y métodos de utilización |
US7893085B2 (en) * | 2006-08-21 | 2011-02-22 | Genentech, Inc | Aza-benzothiophenyl compounds and methods of use |
AU2007334402B2 (en) | 2006-12-14 | 2014-02-13 | Exelixis, Inc. | Methods of using MEK inhibitors |
JO2985B1 (ar) | 2006-12-20 | 2016-09-05 | Takeda Pharmaceuticals Co | مثبطات كينازmapk/erk |
WO2008125820A1 (en) * | 2007-04-13 | 2008-10-23 | Astrazeneca Ab | Combination therapy comprising azd2171 and azd6244 or mek-inhibitor ii |
US8509487B2 (en) * | 2007-04-19 | 2013-08-13 | Avago Technologies General Ip (Singapore) Pte. Ltd. | System and method for optically measuring a parameter of an object |
WO2008157179A2 (en) | 2007-06-12 | 2008-12-24 | Genentech, Inc. | N-substituted azaindoles and methods of use |
US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
NZ582692A (en) | 2007-07-05 | 2012-05-25 | Array Biopharma Inc | Pyrimidyl cyclopentanes as akt protein kinase inhibitors |
KR101624361B1 (ko) | 2007-07-05 | 2016-05-25 | 어레이 바이오파마 인크. | Akt 단백질 키나제 억제제로서의 피리미딜 시클로펜탄 |
GB0714384D0 (en) | 2007-07-23 | 2007-09-05 | Ucb Pharma Sa | theraputic agents |
EP2217234A2 (en) * | 2007-10-15 | 2010-08-18 | AstraZeneca AB | Combinations of mek inhibitors with mtor inhibitors |
ES2456966T3 (es) | 2007-11-12 | 2014-04-24 | Takeda Pharmaceutical Company Limited | Inhibidores de MAPK/ERK cinasa |
PT2231662E (pt) | 2007-12-19 | 2011-09-12 | Genentech Inc | 8-anilinoimidazopiridinas e o seu uso como agentes anticancerígenos e/ou anti-inflamatórios |
NZ586802A (en) | 2007-12-19 | 2012-03-30 | Genentech Inc | Imidazo[1,5-a]pyridine and imidazo[1,5-a]pyrazine derivatives for the treatment of inflammatory diseases |
EP2234982A1 (en) | 2007-12-20 | 2010-10-06 | F. Hoffmann-La Roche AG | Substituted hydantoins as mek kinase inhibitors |
CA2708176A1 (en) | 2007-12-21 | 2009-07-02 | Genentech, Inc. | Azaindolizines and methods of use |
NZ586720A (en) | 2008-01-09 | 2012-11-30 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentane as akt protein kinase inhibitor |
ES2422733T3 (es) | 2008-01-09 | 2013-09-13 | Array Biopharma Inc | Pirimidilciclopentanos hidroxilados como inhibidores de proteínas cinasas AKT |
WO2009093008A1 (en) | 2008-01-21 | 2009-07-30 | Ucb Pharma S.A. | Thieno-pyridine derivatives as mek inhibitors |
SA109300195B1 (ar) | 2008-03-28 | 2013-04-20 | Astrazeneca Ab | تركيبة صيدلانية جديدة مضادة للسرطان |
GB0811304D0 (en) | 2008-06-19 | 2008-07-30 | Ucb Pharma Sa | Therapeutic agents |
US8559963B2 (en) | 2008-06-23 | 2013-10-15 | Panasonic Corporation | Wireless communication base station apparatus and reference signal allocation method |
US8841462B2 (en) | 2008-07-01 | 2014-09-23 | Robert A. Heald | Bicyclic heterocycles as MEK kinase inhibitors |
CA2727252A1 (en) * | 2008-07-01 | 2010-01-07 | Genentech, Inc. | Isoindolone derivatives as mek kinase inhibitors and methods of use |
ES2560878T3 (es) | 2008-08-04 | 2016-02-23 | Merck Patent Gmbh | Compuestos novedosos de fenilamino-isonicotinamida |
CN101653607B (zh) * | 2008-08-19 | 2013-02-13 | 鼎泓国际投资(香港)有限公司 | 含有肝细胞生长因子受体抑制剂和丝裂原细胞外激酶抑制剂的药物组合物及其用途 |
EP2358202B1 (en) * | 2008-11-03 | 2016-06-15 | Merck Sharp & Dohme Corp. | Benzimidazole and aza-benzimidazole carboxamides |
US8993630B2 (en) | 2008-11-10 | 2015-03-31 | Bayer Intellectual Property Gmbh | Substituted sulphonamido phenoxybenzamides |
US8242260B2 (en) | 2009-08-28 | 2012-08-14 | Novartis Ag | Compounds and compositions as protein kinase inhibitors |
JO3002B1 (ar) | 2009-08-28 | 2016-09-05 | Irm Llc | مركبات و تركيبات كمثبطات كيناز بروتين |
JP2013508320A (ja) | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたハロフェノキシベンズアミド誘導体 |
JP2013508318A (ja) | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたベンゾスルホンアミド誘導体 |
EP2491016A1 (en) | 2009-10-21 | 2012-08-29 | Bayer Pharma Aktiengesellschaft | Substituted benzosulphonamides |
WO2011095807A1 (en) | 2010-02-07 | 2011-08-11 | Astrazeneca Ab | Combinations of mek and hh inhibitors |
WO2011133520A1 (en) | 2010-04-19 | 2011-10-27 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a hsp90 inhibitory compounds and a egfr inhibitor |
EP2560953B1 (en) | 2010-04-21 | 2016-01-06 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
US20130096149A1 (en) | 2010-06-25 | 2013-04-18 | Novartis Ag | Heteroaryl compounds and compositions as protein kinase inhibitors |
ES2575995T3 (es) | 2010-08-05 | 2016-07-04 | Case Western Reserve University | Inhibidores de ERK para trastornos del desarrollo de la conectividad neuronal |
BR112013008259A2 (pt) | 2010-10-06 | 2017-12-12 | Glaxosmithkline Llc | composto, composição farmacêutica, e, uso de um composto |
JP2013542214A (ja) | 2010-10-29 | 2013-11-21 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 置換フェノキシピリジン類 |
CN102020651B (zh) | 2010-11-02 | 2012-07-18 | 北京赛林泰医药技术有限公司 | 6-芳基氨基吡啶酮甲酰胺mek抑制剂 |
JP6182456B2 (ja) | 2010-12-22 | 2017-08-23 | フェイト セラピューティクス,インコーポレイテッド | 単細胞選別のための細胞培養プラットホームおよびiPSCの再プログラミングの増強 |
ES2531465T3 (es) | 2010-12-23 | 2015-03-16 | Sanofi | Derivados de pirimidinona, su preparación y su utilización farmacéutica |
BR112013025353A8 (pt) | 2011-04-01 | 2018-01-02 | Genentech Inc | combinação de a) um composto de fórmula ia, composto de fórmula ia ou um sal farmaceuticamente aceitável do mesmo, método para tratamento de um distúrbio hiperproliferativo em um mamífero, uso de um composto de fórmula ia ou um sal farmaceuticamente aceitável do mesmo, kit e produto |
CN110433165A (zh) | 2011-04-01 | 2019-11-12 | 基因泰克公司 | Akt和mek抑制剂化合物的组合及其使用方法 |
WO2012145503A1 (en) | 2011-04-21 | 2012-10-26 | Novartis Ag | Pharmaceutical combinations |
WO2012162293A1 (en) * | 2011-05-23 | 2012-11-29 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitory compounds with mek inhibitors |
CA2836364C (en) | 2011-05-25 | 2021-01-26 | Universite Paris Descartes | Erk inhibitors for use in treating spinal muscular atrophy |
PL3409278T3 (pl) | 2011-07-21 | 2021-02-22 | Sumitomo Pharma Oncology, Inc. | Heterocykliczne inhibitory kinazy białkowej |
SG10201606284UA (en) | 2011-08-01 | 2016-09-29 | Genentech Inc | Methods Of Treating Cancer Using Pd-1 Axis Binding Antagonists And Mek Inhibitors |
US10813630B2 (en) | 2011-08-09 | 2020-10-27 | Corquest Medical, Inc. | Closure system for atrial wall |
US10314594B2 (en) | 2012-12-14 | 2019-06-11 | Corquest Medical, Inc. | Assembly and method for left atrial appendage occlusion |
US10307167B2 (en) | 2012-12-14 | 2019-06-04 | Corquest Medical, Inc. | Assembly and method for left atrial appendage occlusion |
KR20140072028A (ko) * | 2011-08-31 | 2014-06-12 | 노파르티스 아게 | Pi3k- 및 mek-억제제의 상승작용적 조합물 |
EP2750672A1 (en) | 2011-09-01 | 2014-07-09 | Novartis AG | Use of organic compound for the treatment of noonan syndrome |
EP2570127A1 (en) | 2011-09-16 | 2013-03-20 | Sanofi | Compositions and methods for treating cancer using PI3KB beta inhibitor and MAPK pathway inhibitor, including MEK and RAF inhibitors |
UA116875C2 (uk) | 2011-10-14 | 2018-05-25 | Еррей Біофарма Інк. | Поліморфи arry-380 селективного інгібітору erbb2 і фармацевтичні композиції, що їх містять |
AU2012332421A1 (en) | 2011-11-02 | 2014-06-05 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of Hsp90 inhibitors with topoisomerase I inhibitors |
EP2776025A1 (en) | 2011-11-02 | 2014-09-17 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with platinum-containing agents |
EP2780010A1 (en) | 2011-11-14 | 2014-09-24 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with braf inhibitors |
DK2797957T3 (da) | 2011-11-23 | 2019-09-23 | Medimmune Llc | Bindingsmolekyler specifikke for her3 og anvendelser deraf |
WO2013082511A1 (en) | 2011-12-02 | 2013-06-06 | Genentech, Inc. | Methods for overcoming tumor resistance to vegf antagonists |
US10023862B2 (en) | 2012-01-09 | 2018-07-17 | Arrowhead Pharmaceuticals, Inc. | Organic compositions to treat beta-catenin-related diseases |
WO2013109142A1 (en) | 2012-01-16 | 2013-07-25 | Stichting Het Nederlands Kanker Instituut | Combined pdk and mapk/erk pathway inhibition in neoplasia |
CN103204825B (zh) | 2012-01-17 | 2015-03-04 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噻唑化合物及其制备方法和用途 |
GB201201332D0 (en) | 2012-01-26 | 2012-03-14 | Imp Innovations Ltd | Method |
AU2013235596B9 (en) * | 2012-03-20 | 2017-12-14 | Amgen Inc. | Combination therapy of a MEK inhibitor and IGF1R inhibitor |
WO2013152425A1 (en) | 2012-04-09 | 2013-10-17 | Switch Materials , Inc. | Switching materials, and compositions and methods for making same |
US9588358B2 (en) | 2012-05-29 | 2017-03-07 | Switch Materials, Inc. | Optical filter comprising a variable transmittance layer |
EA201401353A1 (ru) | 2012-05-31 | 2015-05-29 | Байер Фарма Акциенгезельшафт | Биомаркеры для определения эффективной ответной реакции на лечение пациентов с гепатоцеллюлярной карциномой (гцк) |
AR091876A1 (es) * | 2012-07-26 | 2015-03-04 | Novartis Ag | Combinaciones farmaceuticas para el tratamiento de enfermedades proliferativas |
SG10201708494QA (en) | 2012-08-17 | 2017-11-29 | Hoffmann La Roche | Combination therapies for melanoma comprising administering cobimetinib and vemurafinib |
MD20150043A2 (ro) | 2012-10-02 | 2015-08-31 | Epitherapeutics Aps | Inhibitori ai histon-demetilazelor |
NZ706723A (en) | 2012-10-12 | 2018-07-27 | Exelixis Inc | Novel process for making compounds for use in the treatment of cancer |
WO2014062838A2 (en) | 2012-10-16 | 2014-04-24 | Tolero Pharmaceuticals, Inc. | Pkm2 modulators and methods for their use |
US9238627B2 (en) | 2012-10-19 | 2016-01-19 | Array Biopharma, Inc. | Preparation of and formulation comprising a MEK inhibitor |
US20140142689A1 (en) | 2012-11-21 | 2014-05-22 | Didier De Canniere | Device and method of treating heart valve malfunction |
ES2669248T3 (es) * | 2012-11-29 | 2018-05-24 | Novartis Ag | Combinaciones farmacéuticas |
ES2676177T3 (es) | 2012-12-20 | 2018-07-17 | Novartis Ag | Una combinación farmacéutica que comprende binimetinib |
EP2752191A1 (en) | 2013-01-07 | 2014-07-09 | Sanofi | Compositions and methods using hdm2 antagonist and mek inhibitor |
CN105229144A (zh) | 2013-02-22 | 2016-01-06 | 细胞动力学国际有限公司 | 通过组合的遗传工程和化学工程经由正向编程产生肝细胞 |
ES2670864T3 (es) | 2013-02-27 | 2018-06-01 | Gilead Sciences, Inc. | Inhibidores de histonas desmetilasas |
ES2703208T3 (es) | 2013-02-27 | 2019-03-07 | Daiichi Sankyo Co Ltd | Método de predicción de la sensibilidad a un compuesto que inhibe la vía de transducción de señales de MAPK |
PL2970205T3 (pl) | 2013-03-14 | 2019-10-31 | Tolero Pharmaceuticals Inc | Inhibitory jak2 i alk2 oraz sposoby ich zastosowania |
PL2976106T3 (pl) * | 2013-03-21 | 2021-10-25 | Array Biopharma Inc. | Terapia kombinowana obejmująca inhibitor B-Raf i drugi inhibitor |
AR097617A1 (es) | 2013-09-13 | 2016-04-06 | Actelion Pharmaceuticals Ltd | Derivados antibacterianos del 2h-indazol |
US9629851B2 (en) | 2013-09-20 | 2017-04-25 | Stitching Het Nederlands Kanker Institut—Antoni Van Leeuwenhoek Ziekenhuis | ROCK in combination with MAPK pathway |
WO2015041534A1 (en) | 2013-09-20 | 2015-03-26 | Stichting Het Nederlands Kanker Instituut | P90rsk in combination with raf/erk/mek |
US10570204B2 (en) | 2013-09-26 | 2020-02-25 | The Medical College Of Wisconsin, Inc. | Methods for treating hematologic cancers |
US9566443B2 (en) | 2013-11-26 | 2017-02-14 | Corquest Medical, Inc. | System for treating heart valve malfunction including mitral regurgitation |
SG11201605014YA (en) | 2013-12-19 | 2016-07-28 | Actelion Pharmaceuticals Ltd | Antibacterial 1h-indazole and 1h-indole derivatives |
CA2935804A1 (en) | 2014-01-14 | 2015-07-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of melanoma using pd-l1 isoforms |
CN104788365B (zh) * | 2014-01-16 | 2018-08-10 | 上海艾力斯医药科技有限公司 | 异烟酰胺衍生物、其制备方法及应用 |
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 |
AR099612A1 (es) | 2014-03-04 | 2016-08-03 | Actelion Pharmaceuticals Ltd | Derivados antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona |
ES2966757T3 (es) | 2014-03-04 | 2024-04-24 | Fate Therapeutics Inc | Métodos de reprogramación mejorados y plataformas de cultivo celular |
AU2015229103C9 (en) | 2014-03-14 | 2020-11-26 | Immutep S.A.S | Antibody molecules to LAG-3 and uses thereof |
AR099890A1 (es) | 2014-03-31 | 2016-08-24 | Epitherapeutics Aps | Inhibidores de histona demetilasas |
US20170107486A1 (en) | 2014-04-21 | 2017-04-20 | Cellular Dynamics International, Inc. | Hepatocyte production via forward programming by combined genetic and chemical engineering |
JP2017515906A (ja) | 2014-05-16 | 2017-06-15 | アクテリオン ファーマシューティカルズ リミテッドActelion Pharmaceuticals Ltd | 抗菌性キナゾロン−4(3h)−オン誘導体 |
US10023879B2 (en) | 2014-06-04 | 2018-07-17 | Fate Therapeutics, Inc. | Minimal volume reprogramming of mononuclear cells |
EP3563870A1 (en) | 2014-07-15 | 2019-11-06 | F. Hoffmann-La Roche AG | Methods of treating cancer using pd-1 axis binding antagonists and mek inhibitors |
WO2016033169A1 (en) | 2014-08-27 | 2016-03-03 | Epitherapeutics Aps | Compounds and methods for inhibiting histone demethylases |
US11344620B2 (en) | 2014-09-13 | 2022-05-31 | Novartis Ag | Combination therapies |
CN107106687A (zh) | 2014-10-03 | 2017-08-29 | 诺华股份有限公司 | 组合治疗 |
WO2016057367A1 (en) | 2014-10-06 | 2016-04-14 | Dana-Farber Cancer Institute, Inc. | Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response |
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 |
MA40035A (fr) | 2014-10-14 | 2016-04-21 | Dana Farber Cancer Inst Inc | Molécules d'anticorps de pd-l1 et leurs utilisations |
US10842626B2 (en) | 2014-12-09 | 2020-11-24 | Didier De Canniere | Intracardiac device to correct mitral regurgitation |
EP3233918A1 (en) | 2014-12-19 | 2017-10-25 | Novartis AG | Combination therapies |
EP3237418B1 (en) | 2014-12-23 | 2019-01-30 | Novartis AG | Triazolopyrimidine compounds and uses thereof |
US10626372B1 (en) | 2015-01-26 | 2020-04-21 | Fate Therapeutics, Inc. | Methods and compositions for inducing hematopoietic cell differentiation |
CN105566225A (zh) * | 2015-02-16 | 2016-05-11 | 苏州晶云药物科技有限公司 | 一种口服丝裂原活化蛋白激酶抑制剂的晶型及其制备方法 |
JP2016155776A (ja) * | 2015-02-24 | 2016-09-01 | 学校法人兵庫医科大学 | 抗腫瘍効果増強剤および抗腫瘍剤 |
US10449211B2 (en) | 2015-03-10 | 2019-10-22 | Aduro Biotech, Inc. | Compositions and methods for activating “stimulator of interferon gene”—dependent signalling |
CN107667092B (zh) | 2015-03-25 | 2021-05-28 | 诺华股份有限公司 | 作为fgfr4抑制剂的甲酰化n-杂环衍生物 |
MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
US20180207273A1 (en) | 2015-07-29 | 2018-07-26 | Novartis Ag | Combination therapies comprising antibody molecules to tim-3 |
EP3964528A1 (en) | 2015-07-29 | 2022-03-09 | Novartis AG | Combination therapies comprising antibody molecules to lag-3 |
EP3328418A1 (en) | 2015-07-29 | 2018-06-06 | Novartis AG | Combination therapies comprising antibody molecules to pd-1 |
AR105646A1 (es) | 2015-08-11 | 2017-10-25 | Actelion Pharmaceuticals Ltd | Agentes antibacterianos de 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituida |
US20190008859A1 (en) | 2015-08-21 | 2019-01-10 | Acerta Pharma B.V. | Therapeutic Combinations of a MEK Inhibitor and a BTK Inhibitor |
CA2992221C (en) | 2015-08-28 | 2023-06-27 | Novartis Ag | Mdm2 inhibitors and combinations thereof |
AR105889A1 (es) | 2015-09-03 | 2017-11-22 | Actelion Pharmaceuticals Ltd | Compuestos antibacterianos 1,2-dihidro-3h-pirrolo[1,2-c]imidazol-3-ona sustituidos |
KR20180055918A (ko) | 2015-10-16 | 2018-05-25 | 페이트 세러퓨틱스, 인코포레이티드 | 기저 상태 다능성의 유도 및 유지를 위한 플랫폼 |
BR112018008867A8 (pt) | 2015-11-03 | 2019-02-26 | Janssen Biotech Inc | anticorpos que se ligam especificamente a pd-1 e seus usos |
JP7534070B2 (ja) | 2015-11-04 | 2024-08-14 | フェイト セラピューティクス,インコーポレイテッド | 造血細胞分化を誘導するための方法および組成物 |
EP3371314B1 (en) | 2015-11-04 | 2023-07-05 | Fate Therapeutics, Inc. | Genomic engineering of pluripotent cells |
AU2016369537B2 (en) | 2015-12-17 | 2024-03-14 | Novartis Ag | Antibody molecules to PD-1 and uses thereof |
CA3010236A1 (en) | 2016-01-20 | 2017-07-27 | Fate Therapeutics, Inc. | Compositions and methods for immune cell modulation in adoptive immunotherapies |
WO2017127755A1 (en) | 2016-01-20 | 2017-07-27 | Fate Therapeutics, Inc. | Compositions and methods for immune cell modulation in adoptive immunotherapies |
US11883404B2 (en) | 2016-03-04 | 2024-01-30 | Taiho Pharmaceuticals Co., Ltd. | Preparation and composition for treatment of malignant tumors |
EP3424505A4 (en) | 2016-03-04 | 2019-10-16 | Taiho Pharmaceutical Co., Ltd. | PREPARATION AND COMPOSITION FOR TREATING MALIGNANT TUMORS |
AR108257A1 (es) | 2016-05-02 | 2018-08-01 | Mei Pharma Inc | Formas polimórficas de 3-[2-butil-1-(2-dietilamino-etil)-1h-bencimidazol-5-il]-n-hidroxi-acrilamida y usos de las mismas |
JP6805336B2 (ja) | 2016-06-03 | 2020-12-23 | アレイ バイオファーマ、インコーポレイテッド | 薬学的組み合わせ |
WO2017221092A1 (en) | 2016-06-20 | 2017-12-28 | Novartis Ag | Triazolopyridine compounds and uses thereof |
CN109790166A (zh) | 2016-06-20 | 2019-05-21 | 诺华股份有限公司 | 咪唑并吡啶化合物用于治疗癌症 |
CA3027246A1 (en) | 2016-06-20 | 2017-12-28 | Novartis Ag | Crystalline forms of triazolopyrimidine compound |
WO2018009466A1 (en) | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
WO2018065924A1 (en) * | 2016-10-04 | 2018-04-12 | Sun Pharmaceutical Industries Limited | Intermediates of mitogen-activated protein kinase kinase (map2k or mek) inhibitors and process for their preparation |
WO2018092064A1 (en) | 2016-11-18 | 2018-05-24 | Novartis Ag | Combinations of mdm2 inhibitors and bcl-xl inhibitors |
CN108084078B (zh) * | 2016-11-24 | 2021-07-30 | 中山大学 | 一种治疗银屑病性关节炎疾病的药物阿普斯特的合成方法 |
US11932870B2 (en) | 2016-12-05 | 2024-03-19 | Fate Therapeutics, Inc. | Compositions and methods for immune cell modulation in adoptive immunotherapies |
EP3372624A1 (en) | 2017-03-06 | 2018-09-12 | Henkel AG & Co. KGaA | One component composition based on compounds with at least two exo-vinylene cyclic carbonate units |
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 |
WO2019096112A1 (zh) * | 2017-11-14 | 2019-05-23 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的苯并咪唑化合物及包含该化合物的组合物 |
KR20200089286A (ko) | 2017-11-16 | 2020-07-24 | 노파르티스 아게 | 조합 요법 |
TW201938165A (zh) | 2017-12-18 | 2019-10-01 | 美商輝瑞股份有限公司 | 治療癌症的方法及組合療法 |
AU2019239404B2 (en) | 2018-03-19 | 2021-12-23 | Taiho Pharmaceutical Co., Ltd. | Pharmaceutical composition including sodium alkyl sulfate |
WO2019195753A1 (en) | 2018-04-05 | 2019-10-10 | Tolero Pharmaceuticals, Inc. | Axl kinase inhibitors and use of the same |
US11746157B2 (en) | 2018-05-24 | 2023-09-05 | Janssen Biotech, Inc. | PSMA binding agents and uses thereof |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
BR112021001148A2 (pt) | 2018-07-25 | 2021-04-20 | Advanced Accelerator Applications S.A. | soluções estáveis de complexo de radionuclídeo concentrado |
WO2020021465A1 (en) | 2018-07-25 | 2020-01-30 | Advanced Accelerator Applications (Italy) S.R.L. | Method of treatment of neuroendocrine tumors |
EP3826684A4 (en) | 2018-07-26 | 2022-04-06 | Sumitomo Dainippon Pharma Oncology, Inc. | METHODS FOR TREATING DISEASES ASSOCIATED WITH ABNORMAL ACVR1 EXPRESSION AND ACVR1 INHIBITORS FOR USE THEREOF |
KR20210047313A (ko) | 2018-08-17 | 2021-04-29 | 노파르티스 아게 | Smarca2/brm atp분해효소 저해제로서의 우레아 화합물 및 조성물 |
EP3856262A1 (en) | 2018-09-25 | 2021-08-04 | Advanced Accelerator Applications (Italy) Srl | Combination therapy |
MA55141A (fr) | 2018-11-20 | 2021-09-29 | Nflection Therapeutics Inc | Composés cyanoaryl-aniline pour le traitement d'affections de la peau |
BR112021011874A2 (pt) | 2018-12-20 | 2021-09-08 | Novartis Ag | Regime de dosagem e combinação farmacêutica compreendendo derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona |
WO2020130125A1 (ja) | 2018-12-21 | 2020-06-25 | 第一三共株式会社 | 抗体-薬物コンジュゲートとキナーゼ阻害剤の組み合わせ |
CN113412262A (zh) | 2019-02-12 | 2021-09-17 | 大日本住友制药肿瘤公司 | 包含杂环蛋白激酶抑制剂的制剂 |
US20220144807A1 (en) | 2019-02-15 | 2022-05-12 | Novartis Ag | 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof |
JP7488826B2 (ja) | 2019-02-15 | 2024-05-22 | ノバルティス アーゲー | 置換3-(1-オキソイソインドリン-2-イル)ピペリジン-2,6-ジオン誘導体及びその使用 |
EA202192575A1 (ru) | 2019-03-21 | 2022-01-14 | Онксео | Соединения dbait в сочетании с ингибиторами киназ для лечения рака |
WO2020198077A1 (en) | 2019-03-22 | 2020-10-01 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
WO2020212832A1 (en) * | 2019-04-16 | 2020-10-22 | Alembic Pharmaceuticals Limited | Process of preparation of benzimidazole compounds |
AR118720A1 (es) | 2019-04-19 | 2021-10-27 | Janssen Biotech Inc | Métodos para tratar el cáncer de próstata con un anticuerpo anti-psma / cd3 |
TWI817018B (zh) | 2019-06-28 | 2023-10-01 | 美商艾瑞生藥股份有限公司 | 用於治療braf相關的疾病和失調症之化合物 |
AU2020300619A1 (en) | 2019-07-03 | 2022-01-27 | Sumitomo Pharma Oncology, Inc. | Tyrosine kinase non-receptor 1 (TNK1) inhibitors and uses thereof |
US20220280509A1 (en) | 2019-09-26 | 2022-09-08 | Novartis Ag | Aza-quinoline compounds and uses thereof |
JP2023500906A (ja) | 2019-11-08 | 2023-01-11 | インサーム(インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル) | キナーゼ阻害剤に対する獲得抵抗性を有するがんの処置方法 |
WO2021116901A1 (en) * | 2019-12-09 | 2021-06-17 | Biocon Limited | Forms of binimetinib and process for preparation thereof |
IL293889A (en) | 2019-12-20 | 2022-08-01 | Novartis Ag | Uses of antitgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
EP4122925A4 (en) * | 2020-03-17 | 2024-04-17 | Medshine Discovery Inc. | PROTEOLYSIS REGULATOR AND METHOD OF USE |
TW202200146A (zh) | 2020-04-10 | 2022-01-01 | 日商大鵬藥品工業股份有限公司 | 使用有3,5-二取代苯炔基化合物與mek抑制劑之癌症治療法 |
BR112022024597A2 (pt) | 2020-06-09 | 2022-12-27 | Array Biopharma Inc | Compostos de 4-oxo-3,4-di-hidroquinazolinona para o tratamento de doenças e distúrbios associados com braf |
MX2022015852A (es) | 2020-06-23 | 2023-01-24 | Novartis Ag | Regimen de dosificacion que comprende derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona. |
AR123185A1 (es) | 2020-08-10 | 2022-11-09 | Novartis Ag | Compuestos y composiciones para inhibir ezh2 |
WO2022043556A1 (en) | 2020-08-31 | 2022-03-03 | Novartis Ag | Stable radiopharmaceutical composition |
WO2022043557A1 (en) | 2020-08-31 | 2022-03-03 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
US20230338587A1 (en) | 2020-08-31 | 2023-10-26 | Advanced Accelerator Applications International Sa | Method of treating psma-expressing cancers |
WO2022074011A1 (en) | 2020-10-05 | 2022-04-14 | Pierre Fabre Medicament | Combination of encorafenib and binimetinib as adjuvant treatment for resected stage ii melanoma |
TW202237119A (zh) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Alk﹘5抑制劑和彼之用途 |
CN112679438A (zh) * | 2020-12-31 | 2021-04-20 | 武汉九州钰民医药科技有限公司 | 制备司美替尼的方法 |
CN112759552A (zh) * | 2020-12-31 | 2021-05-07 | 武汉九州钰民医药科技有限公司 | 司美替尼的合成方法 |
WO2022159600A1 (en) * | 2021-01-21 | 2022-07-28 | Nflection Therapeutics, Inc. | Processes for preparing pyrrolopyridine-aniline compounds |
JP2024504758A (ja) | 2021-01-28 | 2024-02-01 | ヤンセン バイオテツク,インコーポレーテツド | Psma結合タンパク質及びその使用 |
US20240182464A1 (en) | 2021-02-02 | 2024-06-06 | Les Laboratoirens Serviece | Selective bcl-xl protac compounds and methods of use |
JP2024511373A (ja) | 2021-03-18 | 2024-03-13 | ノバルティス アーゲー | がんのためのバイオマーカーおよびその使用 |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
MX2023012060A (es) | 2021-04-13 | 2024-01-22 | Nuvalent Inc | Heterociclos con sustitucion amino para tratar canceres con mutaciones de egfr. |
US20240207257A1 (en) * | 2021-04-15 | 2024-06-27 | Ideaya Biosciences, Inc. | Combination therapy comprising a pkc inhibitor and a mek inhibitor |
AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
AU2022288118A1 (en) | 2021-06-09 | 2023-11-30 | Chugai Seiyaku Kabushiki Kaisha | Combination therapy for cancer treatment |
WO2022262699A1 (zh) * | 2021-06-17 | 2022-12-22 | 深圳市塔吉瑞生物医药有限公司 | 取代的苯并咪唑类化合物及包含该化合物的组合物及其用途 |
JP2024529298A (ja) | 2021-07-09 | 2024-08-06 | プレキシウム インコーポレイテッド | Ikzf2を調節するアリール化合物及び医薬組成物 |
CN118201615A (zh) | 2021-11-04 | 2024-06-14 | 豪夫迈·罗氏有限公司 | 喹唑啉酮化合物用于治疗癌症的新用途 |
WO2023084489A1 (en) | 2021-11-15 | 2023-05-19 | Pfizer Inc. | Methods of treating coronavirus disease 2019 |
TW202342018A (zh) | 2022-03-04 | 2023-11-01 | 美商奇奈特生物製藥公司 | Mek激酶抑制劑 |
AR129382A1 (es) | 2022-05-20 | 2024-08-21 | Novartis Ag | Conjugados de anticuerpo-fármaco inhibidores de bcl-xl y met y sus métodos de uso |
WO2023225320A1 (en) | 2022-05-20 | 2023-11-23 | Novartis Ag | Epha2 bcl-xl inhibitor antibody-drug conjugates and methods of use thereof |
WO2023238000A1 (en) * | 2022-06-06 | 2023-12-14 | Glenmark Life Sciences Limited | Process for preparation of selumetinib and salts thereof |
WO2024105144A1 (en) | 2022-11-18 | 2024-05-23 | F. Hoffmann-La Roche Ag | Quinazolinone compound as braf inhibitor for the treatment of advanced solid cancer or metastases |
Family Cites Families (76)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1980001113A1 (en) | 1978-11-20 | 1980-05-29 | Braun Ag | Time-keeper in particular quartz controlled clock |
GB8607683D0 (en) | 1986-03-27 | 1986-04-30 | Ici Plc | Anti-tumor agents |
GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
IL95975A (en) | 1989-10-24 | 1997-06-10 | Takeda Chemical Industries Ltd | N-benzyl- 2-alkylbenzimidazole derivatives, their production and pharmaceutical compositions containing them |
US5250554A (en) * | 1989-10-24 | 1993-10-05 | Takeda Chemical Industries, Ltd. | Benzimidazole derivatives useful as angiotensin II inhibitors |
US5218356A (en) * | 1991-05-31 | 1993-06-08 | Guenther Knapp | Wireless indoor data relay system |
US5216003A (en) * | 1992-01-02 | 1993-06-01 | G. D. Searle & Co. | Diacid-containing benzimidazole compounds for treatment of neurotoxic injury |
US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
US5750545A (en) | 1993-07-23 | 1998-05-12 | The Green Cross Corporation | Triazole derivative and pharmaceutical use thereof |
EP0639573A1 (de) | 1993-08-03 | 1995-02-22 | Hoechst Aktiengesellschaft | Benzokondensierte 5-Ringheterocyclen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, ihre Verwendung als Diagnostikum, sowie sie enthaltendes Medikament |
CZ104795A3 (en) | 1994-04-29 | 1996-02-14 | Lilly Co Eli | Benzimidazole derivative, process of its preparation, its use for preparing a pharmaceutical preparation and the pharmaceutical composition containing thereof |
US5520187A (en) * | 1994-11-25 | 1996-05-28 | General Electric Company | Ultrasonic probe with programmable multiplexer for imaging systems with different channel counts |
US5525625A (en) | 1995-01-24 | 1996-06-11 | Warner-Lambert Company | 2-(2-Amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran for treating proliferative disorders |
US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
DK0821671T3 (da) | 1995-04-20 | 2001-04-23 | Pfizer | Arylsulfonylhydroxamsyrederivater som MMP- og TNF-inhibitorer |
US5972980A (en) * | 1995-10-05 | 1999-10-26 | Warner-Lambert Company | Method for treating and preventing inflammation and atherosclerosis |
DE69624081T2 (de) | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
GB9600344D0 (en) * | 1996-01-09 | 1996-03-13 | Lilly Co Eli | Benzimidzolyl neuropeptide y receptor antagonists |
YU1899A (sh) | 1996-07-18 | 2000-03-21 | Pfizer Inc. | Inhibitori matričnih metaloproteaza na bazi fosfinata |
EA199900139A1 (ru) | 1996-08-23 | 1999-08-26 | Пфайзер, Инк. | Производные арилсульфониламиногидроксамовой кислоты |
PT950059E (pt) | 1997-01-06 | 2004-10-29 | Pfizer | Derivados de sulfona ciclicos |
AU721748B2 (en) | 1997-02-03 | 2000-07-13 | Pfizer Products Inc. | Arylsulfonylamino hydroxamic acid derivatives |
AU5493598A (en) | 1997-02-07 | 1998-08-26 | Pfizer Inc. | N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases |
EA002546B1 (ru) | 1997-02-11 | 2002-06-27 | Пфайзер Инк. | Производные арилсульфонилгидроксамовой кислоты |
UA73073C2 (uk) | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
ES2229515T3 (es) | 1997-07-01 | 2005-04-16 | Warner-Lambert Company Llc | Derivados 4-bromo o 4-yodo del acido fenilamino benzhidroxamico y su uso como inhibidores de la mek. |
US6506798B1 (en) * | 1997-07-01 | 2003-01-14 | Warner-Lambert Company | 4-Arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective MEK inhibitors |
US6821963B2 (en) * | 1997-07-01 | 2004-11-23 | Warner-Lambert Company | 4-Bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as MEK inhibitors |
ATE344791T1 (de) | 1997-07-01 | 2006-11-15 | Warner Lambert Co | 2-(4-brom or 4-iod phenylamino)benzoesäurederivate und ihre anwendung als mek-inhibitoren |
US6310060B1 (en) * | 1998-06-24 | 2001-10-30 | Warner-Lambert Company | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as MEK inhibitors |
GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
US6534503B1 (en) * | 1998-04-28 | 2003-03-18 | Lion Bioscience Ag | Melanocortin receptor-3 ligands to treat sexual dysfunction |
AUPP616498A0 (en) | 1998-09-25 | 1998-10-15 | University Of Queensland, The | Synthesis of cyclic peptides |
IL144103A0 (en) | 1999-01-07 | 2002-05-23 | Warner Lambert Co | Antiviral method using mek inhibitors |
JP2002534380A (ja) | 1999-01-07 | 2002-10-15 | ワーナー−ランバート・カンパニー | Mek阻害剤による喘息の治療 |
BR9916894A (pt) | 1999-01-13 | 2001-11-20 | Warner Lambert Co | ácidos sulfohidroxâmicos e sulfohidroxamatos eseu uso como inibidores de mek |
OA11746A (en) * | 1999-01-13 | 2005-05-13 | Warner Lambert Co | Benzoheterocycles and their use as MEK inhibitors. |
ATE309205T1 (de) * | 1999-01-13 | 2005-11-15 | Warner Lambert Co | Benzenesulfonamid-derivative und ihre verwendung als mek-inhibitoren |
CA2349180A1 (en) | 1999-01-13 | 2000-07-20 | Stephen Douglas Barrett | Anthranilic acid derivatives |
JP2000204077A (ja) | 1999-01-13 | 2000-07-25 | Warner Lambert Co | ジアリ―ルアミン |
CA2348236A1 (en) | 1999-01-13 | 2000-07-20 | Stephen Douglas Barrett | 4-arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective mek inhibitors |
WO2000042029A1 (en) | 1999-01-13 | 2000-07-20 | Warner-Lambert Company | 1-heterocycle substituted diarylamines |
GB9910577D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9912961D0 (en) | 1999-06-03 | 1999-08-04 | Pfizer Ltd | Metalloprotease inhibitors |
US7030119B1 (en) * | 1999-07-16 | 2006-04-18 | Warner-Lambert Company | Method for treating chronic pain using MEK inhibitors |
WO2001005391A2 (en) | 1999-07-16 | 2001-01-25 | Warner-Lambert Company | Method for treating chronic pain using mek inhibitors |
KR20020015376A (ko) * | 1999-07-16 | 2002-02-27 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | Mek 억제제를 사용한 만성 통증의 치료 방법 |
DE60005688T2 (de) | 1999-07-16 | 2004-04-29 | Warner-Lambert Co. Llc | Verfahren zur behandlung von chronischem schmerz durch verabreichung von einem mek hemmer |
AU5786000A (en) | 1999-07-16 | 2001-02-05 | Warner-Lambert Company | Method for treating chronic pain using mek inhibitors |
EP1214330A1 (en) | 1999-09-21 | 2002-06-19 | LION Bioscience AG | Benzimidazole derivatives and combinatorial libraries thereof |
CA2403017A1 (en) | 2000-03-15 | 2001-09-20 | Warner-Lambert Company | 5-amide substituted diarylamines as mex inhibitors |
EP1339702A1 (en) | 2000-03-15 | 2003-09-03 | Warner-Lambert Company | 5-amide substituted diarylamines as mek inhibitors |
DZ3401A1 (fr) | 2000-07-19 | 2002-01-24 | Warner Lambert Co | Esters oxygenes d'acides 4-iodophenylamino benzhydroxamiques |
JP2004507518A (ja) | 2000-08-25 | 2004-03-11 | ワーナー−ランバート・カンパニー・エルエルシー | N−アリール−アントラニル酸及びその誘導体の製造法 |
JP2004514718A (ja) | 2000-11-02 | 2004-05-20 | アストラゼネカ アクチボラグ | 抗癌剤としての置換キノリン類 |
WO2002046168A1 (en) * | 2000-12-07 | 2002-06-13 | Astrazeneca Ab | Therapeutic benzimidazole compounds |
US7102009B2 (en) * | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
CA2440438C (en) * | 2001-03-09 | 2011-05-03 | Ortho-Mcneil Pharmaceutical, Inc. | Heterocyclic compounds |
US20040039208A1 (en) | 2001-07-20 | 2004-02-26 | Chen Michael Huai Gu | Process for making n-aryl-anthranilic acids and their derivatives |
WO2003024899A2 (en) * | 2001-09-17 | 2003-03-27 | Bristol-Myers Squibb Company | CYCLIC HYDROXAMIC ACIDS AS INHIBITORS OF MATRIX METALLOPROTEINASES AND/OR TNF-α CONVERTING ENZYME (TACE) |
WO2003054180A1 (en) | 2001-12-21 | 2003-07-03 | Warner-Lambert Company Llc | Modified mek1 and mek2, crystal of a peptide: ligand: cofactor complex containing such modified mek1 or mek2, and methods of use thereof |
JP2005515253A (ja) | 2002-01-23 | 2005-05-26 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | N−(4−置換フェニル)−アントラニル酸ヒドロキサメートエステル |
US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
KR100984573B1 (ko) | 2002-03-13 | 2010-09-30 | 어레이 바이오파마 인크. | Mek 억제제로서의 n3 알킬화 벤즈이미다졸 유도체 |
PA8569201A1 (es) * | 2002-03-13 | 2004-05-21 | Array Biopharma Inc | "derivados de bencimidazol n3 alquilado como inhibidores de mek" "n3 alkylated benzimimidazole derivatives as mek inhibitors" |
DE10238002A1 (de) * | 2002-08-20 | 2004-03-04 | Merck Patent Gmbh | Benzimidazolderivate |
US7504426B2 (en) * | 2002-09-06 | 2009-03-17 | Janssen Pharmaceutica N.V. | Heterocyclic compounds |
US20040127395A1 (en) * | 2002-09-06 | 2004-07-01 | Desai Pragnya J. | Use of histamine H4 receptor modulators for the treatment of allergy and asthma |
US7582635B2 (en) * | 2002-12-24 | 2009-09-01 | Purdue Pharma, L.P. | Therapeutic agents useful for treating pain |
BRPI0412851A (pt) | 2003-07-24 | 2006-10-03 | Warner Lambert Co | benzamidazóis de n-metila-substituìdos |
DE102005032379A1 (de) | 2005-07-08 | 2007-01-11 | Conti Temic Microelectronic Gmbh | Zugangskontrollsystem für ein Kraftfahrzeug |
TWI405756B (zh) | 2005-12-21 | 2013-08-21 | Array Biopharma Inc | 新穎硫酸氫鹽 |
ES2676177T3 (es) | 2012-12-20 | 2018-07-17 | Novartis Ag | Una combinación farmacéutica que comprende binimetinib |
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