HRP20010524A2 - Benzoheterocycles and their use as mek inhibitors - Google Patents

Benzoheterocycles and their use as mek inhibitors Download PDF

Info

Publication number: HRP20010524A2
Authority: HR; Croatia
Prior art keywords: methyl; compound; alkyl; phenylamino; phenyl
Prior art date: 1999-01-13

Application number

HR20010524A

Other languages

English (en)

Croatian (hr)

Inventor

Stephen Douglas Barrett

Alexander James Bridges

Haile Tecle

Original Assignee

Warner Lambert Co

Priority date (The priority date 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 date listed.)

1999-01-13

Filing date

2001-07-12

Publication date

2002-08-31

2001-07-12 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2002-08-31 Publication of HRP20010524A2 publication Critical patent/HRP20010524A2/hr

Links

239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title description 4
-1 heterocyclic radical Chemical class 0.000 claims description 271
150000001875 compounds Chemical class 0.000 claims description 120
238000002360 preparation method Methods 0.000 claims description 99
238000000034 method Methods 0.000 claims description 57
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
125000000217 alkyl group Chemical group 0.000 claims description 38
125000003342 alkenyl group Chemical group 0.000 claims description 30
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
125000000304 alkynyl group Chemical group 0.000 claims description 24
238000011282 treatment Methods 0.000 claims description 24
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 23
150000002148 esters Chemical class 0.000 claims description 19
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
229910052731 fluorine Inorganic materials 0.000 claims description 17
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
239000011737 fluorine Substances 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
239000000460 chlorine Chemical group 0.000 claims description 12
229910052801 chlorine Inorganic materials 0.000 claims description 11
201000010099 disease Diseases 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical group 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
206010028980 Neoplasm Diseases 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 8
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 8
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
HGNFTINEEIDDLT-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxylic acid Chemical group CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=CN2 HGNFTINEEIDDLT-UHFFFAOYSA-N 0.000 claims description 7
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 7
201000011510 cancer Diseases 0.000 claims description 7
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
JENDHVLUGWDXEE-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-1,3-benzothiazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=CS2 JENDHVLUGWDXEE-UHFFFAOYSA-N 0.000 claims description 6
NTZGEBNJRQSICS-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-1,3-benzoxazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=CO2 NTZGEBNJRQSICS-UHFFFAOYSA-N 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 5
GFCWICPCSIPKGG-UHFFFAOYSA-N 7-fluoro-6-(4-iodo-2-methylanilino)-2h-benzotriazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=NN2 GFCWICPCSIPKGG-UHFFFAOYSA-N 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
238000002512 chemotherapy Methods 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
239000003112 inhibitor Substances 0.000 claims description 5
230000002062 proliferating effect Effects 0.000 claims description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims description 4
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
WULDESHELSRYQZ-UHFFFAOYSA-N 4-fluoro-5-(4-iodo-2-methylanilino)-2,1,3-benzothiadiazole-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NSN=C2C=C1C(O)=O WULDESHELSRYQZ-UHFFFAOYSA-N 0.000 claims description 4
239000004215 Carbon black (E152) Substances 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
229930195733 hydrocarbon Natural products 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
230000011278 mitosis Effects 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
208000024891 symptom Diseases 0.000 claims description 4
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 3
YKRYPAQULJMUDV-UHFFFAOYSA-N 4-fluoro-5-(4-iodo-2-methylanilino)-2,1,3-benzoxadiazole-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NON=C2C=C1C(O)=O YKRYPAQULJMUDV-UHFFFAOYSA-N 0.000 claims description 3
JWAWKFXZGAKZEU-UHFFFAOYSA-N 8-fluoro-7-(4-iodo-2-methylanilino)quinoxaline-6-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C2=NC=CN=C2C=C1C(O)=O JWAWKFXZGAKZEU-UHFFFAOYSA-N 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
210000004556 brain Anatomy 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000002757 morpholinyl group Chemical group 0.000 claims description 3
210000000056 organ Anatomy 0.000 claims description 3
201000008482 osteoarthritis Diseases 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
238000001959 radiotherapy Methods 0.000 claims description 3
208000037803 restenosis Diseases 0.000 claims description 3
ZXDUEQMOCGOOEX-UHFFFAOYSA-N 1-acetyl-7-fluoro-6-(4-iodo-2-methylanilino)benzimidazole-5-carboxylic acid Chemical compound FC1=C2N(C(=O)C)C=NC2=CC(C(O)=O)=C1NC1=CC=C(I)C=C1C ZXDUEQMOCGOOEX-UHFFFAOYSA-N 0.000 claims description 2
UXILCSZNSIYGAV-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-7-fluoro-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxylic acid Chemical compound FC1=C2NC(CCN(C)C)=NC2=CC(C(O)=O)=C1NC1=CC=C(I)C=C1C UXILCSZNSIYGAV-UHFFFAOYSA-N 0.000 claims description 2
RPZALGIZXFACEO-UHFFFAOYSA-N 7-fluoro-2-(2-hydroxyethyl)-6-(4-iodo-2-methylanilino)-3h-benzimidazole-5-carboxylic acid Chemical compound CC1=CC(I)=CC=C1NC(C(=C1)C(O)=O)=C(F)C2=C1N=C(CCO)N2 RPZALGIZXFACEO-UHFFFAOYSA-N 0.000 claims description 2
206010000830 Acute leukaemia Diseases 0.000 claims description 2
208000024827 Alzheimer disease Diseases 0.000 claims description 2
101100439665 Arabidopsis thaliana SWI2 gene Proteins 0.000 claims description 2
208000023275 Autoimmune disease Diseases 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
208000006029 Cardiomegaly Diseases 0.000 claims description 2
201000003883 Cystic fibrosis Diseases 0.000 claims description 2
208000002249 Diabetes Complications Diseases 0.000 claims description 2
206010019842 Hepatomegaly Diseases 0.000 claims description 2
208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
229930012538 Paclitaxel Natural products 0.000 claims description 2
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229960003668 docetaxel Drugs 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
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125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
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HR20010524A 1999-01-13 2001-07-12 Benzoheterocycles and their use as mek inhibitors HRP20010524A2 (en)

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US11587399P	1999-01-13	1999-01-13
US12255399P	1999-03-02	1999-03-02
PCT/US1999/030483 WO2000042022A1 (en)	1999-01-13	1999-12-21	Benzoheterocycles and their use as mek inhibitors

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CN (1)	CN1177830C (ja)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2010068738A1 (en)	2008-12-10	2010-06-17	Dana-Farber Cancer Institute, Inc.	Mek mutations conferring resistance to mek inhibitors
WO2011106298A1 (en)	2010-02-25	2011-09-01	Dana-Farber Cancer Institute, Inc.	Braf mutations conferring resistance to braf inhibitors
WO2013169858A1 (en)	2012-05-08	2013-11-14	The Broad Institute, Inc.	Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy

Families Citing this family (83)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE292462T1 (de) *	1999-01-07	2005-04-15	Warner Lambert Co	Behandlung von asthma anhand von mek-inhibitoren
US7030119B1 (en)	1999-07-16	2006-04-18	Warner-Lambert Company	Method for treating chronic pain using MEK inhibitors
HUP0202319A3 (en) *	1999-07-16	2004-12-28	Warner Lambert Co	Use of mek inhibitors for the preparation of pharmaceutical compositions treating chronic pain
US7001905B2 (en)	2000-03-15	2006-02-21	Warner-Lambert Company	Substituted diarylamines as MEK inhibitors
JP3811775B2 (ja) *	2000-07-19	2006-08-23	ワーナー−ランバートカンパニーリミティドライアビリティーカンパニー	４−ヨードフェニルアミノベンズヒドロキサム酸の酸素化エステル
CA2478534A1 (en) *	2002-03-13	2003-09-25	Array Biopharma, Inc.	N3 alkylated benzimidazole derivatives as mek inhibitors
US7235537B2 (en) *	2002-03-13	2007-06-26	Array Biopharma, Inc.	N3 alkylated benzimidazole derivatives as MEK inhibitors
AU2003218157C1 (en)	2002-03-13	2011-11-24	Array Biopharma, Inc	N3 alkylated benzimidazole derivatives as mek inhibitors
US20050004186A1 (en) *	2002-12-20	2005-01-06	Pfizer Inc	MEK inhibiting compounds
US20050049276A1 (en) *	2003-07-23	2005-03-03	Warner-Lambert Company, Llc	Imidazopyridines and triazolopyridines
CA2532067C (en)	2003-07-24	2010-12-21	Stephen Douglas Barrett	N-methyle-substituted benzamidazoles
CN103664802B (zh)	2003-08-14	2015-08-05	阿雷生物药品公司	作为受体酪氨酸激酶抑制剂的喹唑啉类似物
US7501427B2 (en)	2003-08-14	2009-03-10	Array Biopharma, Inc.	Quinazoline analogs as receptor tyrosine kinase inhibitors
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
JP4931419B2 (ja) *	2003-09-19	2012-05-16	中外製薬株式会社	新規４−フェニルアミノ−ベンズアルドオキシム誘導体並びにそのｍｅｋ阻害剤としての使用
US7781595B2 (en)	2003-09-22	2010-08-24	S*Bio Pte Ltd.	Benzimidazole derivatives: preparation and pharmaceutical applications
RU2352558C2 (ru) *	2003-10-21	2009-04-20	Уорнер-Ламберт Компани Ллс	Полиморфная форма n-[(r)-2,3-дигидроксипропокси]-3,4-дифтор-2-(2-фтор-4 йодфениламино)бензамида
US7732616B2 (en) *	2003-11-19	2010-06-08	Array Biopharma Inc.	Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof
ES2369835T3 (es)	2003-11-19	2011-12-07	Array Biopharma, Inc.	Inhibidores bicíclicos de mek y métodos de síntesis de los mismos.
US7517994B2 (en)	2003-11-19	2009-04-14	Array Biopharma Inc.	Heterocyclic inhibitors of MEK and methods of use thereof
EP1684694A2 (en)	2003-11-21	2006-08-02	Array Biopharma, Inc.	Akt protein kinase inhibitors
WO2005056547A2 (en)	2003-12-04	2005-06-23	Vertex Pharmaceuticals Incorporated	Quinoxalines useful as inhibitors of protein kinases
US20050171182A1 (en) *	2003-12-11	2005-08-04	Roger Briesewitz	Methods and compositions for use in the treatment of mutant receptor tyrosine kinase driven cellular proliferative diseases
TWI361066B (en)	2004-07-26	2012-04-01	Chugai Pharmaceutical Co Ltd	5-substituted-2-phenylamino benzamides as mek inhibitors
JP2008516939A (ja) *	2004-10-15	2008-05-22	アストラゼネカアクチボラグ	化学化合物
BRPI0518192B8 (pt)	2004-10-20	2021-05-25	Applied Res Systems Ars Holding N V	derivados de 3-arilamino piridina, seu uso e seu processo de fabricação, e composição farmacêutica
EP2361905B1 (en)	2005-05-18	2013-03-06	Array Biopharma Inc.	Heterocyclic Inhibitors of MEK and methods of use thereof
AR054623A1 (es)	2005-06-23	2007-07-04	Astrazeneca Ab	PROCESO PARA PREPARAR DERIVADOS DE BENCIMIDAZOL Y COMPUESTOS INTERMEDIARIOS DE SíNTESIS DE LOS MISMOS.
HUE043172T2 (hu)	2005-06-23	2019-08-28	Array Biopharma Inc	SNAr eljárás benzimidazol-származékok elõállítására
US8101799B2 (en)	2005-07-21	2012-01-24	Ardea Biosciences	Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK
CA3052368A1 (en)	2005-10-07	2007-04-19	Exelixis, Inc.	Azetidines as mek inhibitors
ATE446294T1 (de)	2005-11-15	2009-11-15	Array Biopharma Inc	N4-phenyl-chinazolin-4-aminderivate und verwandte verbindungen als inhibitoren der erbb-typ-i- rezeptortyrosinkinase zur behandlung hyperproliferativer krankheiten
GB0601962D0 (en)	2006-01-31	2006-03-15	Ucb Sa	Therapeutic agents
JPWO2007132867A1 (ja)	2006-05-15	2009-09-24	杉本　芳一	癌の予防及び治療剤
JP5231411B2 (ja)	2006-07-06	2013-07-10	アレイバイオファーマ、インコーポレイテッド	Ａｋｔプロテインキナーゼ阻害剤としてのジヒドロチエノピリミジン
US8329701B2 (en)	2006-07-06	2012-12-11	Array Biopharma Inc.	Dihydrofuro pyrimidines as AKT protein kinase inhibitors
US8063050B2 (en)	2006-07-06	2011-11-22	Array Biopharma Inc.	Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors
KR101527232B1 (ko)	2006-07-06	2015-06-09	어레이 바이오파마 인크.	Ａｋｔ 단백질 키나제 억제제로서의 시클로펜타〔ｄ〕피리미딘
KR101475088B1 (ko) *	2006-08-21	2014-12-23	제넨테크, 인크.	아자-벤조티오페닐 화합물 및 사용 방법
RU2444524C2 (ru) *	2006-08-21	2012-03-10	Дженентек, Инк.	Азабензотиофенильные соединения и способы применения
CA2660546A1 (en) *	2006-08-21	2008-02-28	Genentech, Inc.	Aza-benzofuranyl compounds and methods of use
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
WO2008076415A1 (en)	2006-12-14	2008-06-26	Exelixis, Inc.	Methods of using mek inhibitors
JO2985B1 (ar)	2006-12-20	2016-09-05	Takeda Pharmaceuticals Co	مثبطات كينازmapk/erk
WO2008148034A1 (en) *	2007-05-25	2008-12-04	Takeda Pharmaceutical Company Limited	Mapk/erk kinase inhibitors
ES2551352T3 (es)	2007-07-05	2015-11-18	Array Biopharma, Inc.	Pirimido ciclopentanos útiles para el tratamiento de enfermedades inflamatorias o hiperproliferativas
EP2404907B1 (en)	2007-07-05	2015-01-14	Array Biopharma, Inc.	Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
US8846683B2 (en)	2007-07-05	2014-09-30	Array Biopharma, Inc.	Pyrimidyl cyclopentanes as Akt protein kinase inhibitors
US9409886B2 (en)	2007-07-05	2016-08-09	Array Biopharma Inc.	Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
TWI441820B (zh) *	2007-12-19	2014-06-21	Genentech Inc	５－苯胺咪唑并吡啶及使用方法
CN101932564B (zh)	2008-01-09	2012-12-26	阵列生物制药公司	作为akt蛋白激酶抑制剂的羟基化嘧啶基环戊烷类
JP5539225B2 (ja)	2008-01-09	2014-07-02	アレイバイオファーマ、インコーポレイテッド	Ａｋｔタンパク質キナーゼ阻害剤としての水酸化されたピリミジルシクロペンタン
HUE027223T2 (en)	2008-08-04	2016-08-29	Merck Patent Gmbh	New Phenylamino Isonicotinamide Compounds
JP5746630B2 (ja)	2008-11-10	2015-07-08	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ＢａｙｅｒＩｎｔｅｌｌｅｃｔｕａｌＰｒｏｐｅｒｔｙＧｍｂＨ	置換スルホンアミドフェノキシベンズアミド
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
EP2491015A1 (en)	2009-10-21	2012-08-29	Bayer Pharma Aktiengesellschaft	Substituted benzosulphonamides
CA2777430A1 (en)	2009-10-21	2011-04-28	Bayer Pharma Aktiengesellschaft	Substituted benzosulphonamides
MX343368B (es)	2010-03-09	2016-11-01	The Broad Inst Inc *	Metodo de diagnostico y tratamiento de cancer en pacientes que tienen o desarrollan resistencia a una primera terapia de cancer.
WO2011131748A2 (en)	2010-04-21	2011-10-27	Probiodrug Ag	Novel inhibitors
US9045429B2 (en)	2010-10-29	2015-06-02	Bayer Intellectual Property Gmbh	Substituted phenoxypyridines
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
ES2620644T3 (es)	2011-04-01	2017-06-29	Genentech, Inc.	Combinaciones de compuestos inhibidores de AKT y agentes quimioterapéuticos, y métodos de uso
TR201815685T4 (tr)	2011-04-01	2018-11-21	Genentech Inc	Kanser tedavisi için akt ve mek inhibe edici bileşiklerin kombinasyonları.
WO2012160130A1 (en)	2011-05-25	2012-11-29	Universite Paris Descartes	Erk inhibitors for use in treating spinal muscular atrophy
ES2396764B1 (es)	2011-11-02	2013-12-19	Universidad Autónoma de Madrid	FÁRMACOS INHIBIDORES DE p38 Y APLICACIONES.
CN103204822B (zh)	2012-01-17	2014-12-03	上海科州药物研发有限公司	作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途
BR112014029338A2 (pt)	2012-05-31	2017-06-27	Bayer Pharma AG	biomarcadores para determinação da resposta eficaz dos tratamentos de pacientes com carcinoma hepatocelular (hcc)
PL2909188T3 (pl)	2012-10-12	2018-08-31	Exelixis, Inc.	Nowy sposób wytwarzania związków do stosowania w leczeniu raka
BR112015008623B1 (pt) *	2012-10-19	2022-10-25	Novartis Ag	Processos de preparação de (2-hidroxietióxi)-amida do ácido 6-(4-bromo-2-fluorfenilamino) -7-flúor-3-metil-3h-benzoimidazol-5-carboxílico cristalizado e seus intermediários
WO2015038704A1 (en)	2013-09-11	2015-03-19	The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone	Compositions for preparing cardiomyocytes
CN104774188B (zh) *	2014-01-15	2019-10-11	江苏恒瑞医药股份有限公司	苯并杂环类或苯并杂芳环类衍生物、其制备方法及其在医药上的应用
CN105384754B (zh) *	2014-09-02	2018-04-20	上海科州药物研发有限公司	作为蛋白激酶抑制剂的杂环类化合物及其制备方法和用途
AU2015328411C1 (en)	2014-10-06	2022-03-03	Dana-Farber Cancer Institute, Inc.	Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response
MA41866A (fr)	2015-03-31	2018-02-06	Massachusetts Gen Hospital	Molécules à auto-assemblage pour l'administration ciblée de médicaments
WO2017033113A1 (en)	2015-08-21	2017-03-02	Acerta Pharma B.V.	Therapeutic combinations of a mek inhibitor and a btk inhibitor
AU2016370846B2 (en) *	2015-12-18	2022-08-25	Ignyta, Inc.	Combinations for the treatment of cancer
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
EA202192575A1 (ru)	2019-03-21	2022-01-14	Онксео	Соединения dbait в сочетании с ингибиторами киназ для лечения рака
US20220401436A1 (en)	2019-11-08	2022-12-22	INSERM (Institute National de la Santé et de la Recherche Médicale)	Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
WO2021148581A1 (en)	2020-01-22	2021-07-29	Onxeo	Novel dbait molecule and its use
CN114478447A (zh) *	2020-11-13	2022-05-13	江苏恒瑞医药股份有限公司	苯并含氧环类衍生物、其制备方法及其在医药上的应用
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

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
WO1998037881A1 (en) *	1997-02-28	1998-09-03	Warner Lambert Company	Method of treating or preventing septic shock by administering a mek inhibitor
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
HUP0003731A3 (en)	1997-07-01	2002-11-28	Warner Lambert Co	4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as mek inhibitors
JP2000204079A (ja) *	1999-01-13	2000-07-25	Warner Lambert Co	ジアリ―ルアミン

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2010068738A1 (en)	2008-12-10	2010-06-17	Dana-Farber Cancer Institute, Inc.	Mek mutations conferring resistance to mek inhibitors
WO2011106298A1 (en)	2010-02-25	2011-09-01	Dana-Farber Cancer Institute, Inc.	Braf mutations conferring resistance to braf inhibitors
EP3028699A1 (en)	2010-02-25	2016-06-08	Dana-Farber Cancer Institute, Inc.	Braf mutations conferring resistance to braf inhibitors
WO2013169858A1 (en)	2012-05-08	2013-11-14	The Broad Institute, Inc.	Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy

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EE200100373A (et)	2002-10-15
OA11746A (en)	2005-05-13
AU2203700A (en)	2000-08-01
IS5976A (is)	2001-06-22
MA26771A1 (fr)	2004-12-20
ID30439A (id)	2001-12-06
CZ20012498A3 (cs)	2002-08-14
JP4621355B2 (ja)	2011-01-26
NO20013452L (no)	2001-07-12
CA2355470C (en)	2008-09-30
GEP20032922B (en)	2003-03-25
KR20020002370A (ko)	2002-01-09
EA200100772A1 (ru)	2002-02-28
DE69926800D1 (de)	2005-09-22
ATE302193T1 (de)	2005-09-15
BG105800A (en)	2002-03-29
YU49401A (sh)	2004-07-15
EP1144385A1 (en)	2001-10-17
DE69926800T2 (de)	2006-05-18
JP2002534510A (ja)	2002-10-15
CN1177830C (zh)	2004-12-01
EP1144385B1 (en)	2005-08-17
NO20013452D0 (no)	2001-07-12
BR9916904A (pt)	2001-10-30
NZ513433A (en)	2003-05-30
US6469004B1 (en)	2002-10-22
TR200102030T2 (tr)	2002-01-21
HUP0105113A2 (hu)	2002-04-29
IL144214A0 (en)	2002-05-23
SK9832001A3 (en)	2003-02-04
CN1333754A (zh)	2002-01-30
CA2355470A1 (en)	2000-07-20
ES2247859T3 (es)	2006-03-01
WO2000042022A1 (en)	2000-07-20
HK1041697A1 (zh)	2002-07-19
AP2001002224A0 (en)	2001-09-30
HUP0105113A3 (en)	2004-11-29

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Publication	Publication Date	Title
HRP20010524A2 (en)	2002-08-31	Benzoheterocycles and their use as mek inhibitors
US6455582B1 (en)	2002-09-24	Sulohydroxamic acids and sulohyroxamates and their use as MEK inhibitors
US6506798B1 (en)	2003-01-14	4-Arylamino, 4-aryloxy, and 4-arylthio diarylamines and derivatives thereof as selective MEK inhibitors
US6440966B1 (en)	2002-08-27	Benzenesulfonamide derivatives and their use as MEK inhibitors
US6545030B1 (en)	2003-04-08	1-heterocycle substituted diarylamines
US7001905B2 (en)	2006-02-21	Substituted diarylamines as MEK inhibitors
JP2002534446A (ja)	2002-10-15	４′ヘテロアリールジアリールアミン
JP2002534491A (ja)	2002-10-15	選択的ｍｅｋ阻害剤としての４−アリールアミノ、４−アリールオキシ、及び４−アリールチオジアリールアミン及びそれらの誘導体
JP2003527379A (ja)	2003-09-16	Ｍｅｘ阻害物質としての５−アミド置換ジアリールアミン類
CA2377092A1 (en)	2001-01-25	Method for treating chronic pain using mek inhibitors
JP2000204079A (ja)	2000-07-25	ジアリ―ルアミン
JP2000212141A (ja)	2000-08-02	ジアリ―ルアミン
JP2001055376A (ja)	2001-02-27	ジアリールアミン
JP2000212157A (ja)	2000-08-02	ジアリ―ルアミン
MXPA01006568A (es)	2002-03-26	Benzoheterociclos y su uso como inhibidores de mek