CA2705452C - Mapk/erk kinase inhibitors - Google Patents

Mapk/erk kinase inhibitors Download PDF

Info

Publication number
CA2705452C
CA2705452C CA2705452A CA2705452A CA2705452C CA 2705452 C CA2705452 C CA 2705452C CA 2705452 A CA2705452 A CA 2705452A CA 2705452 A CA2705452 A CA 2705452A CA 2705452 C CA2705452 C CA 2705452C
Authority
CA
Canada
Prior art keywords
alkyl
hetero
compound
fluoro
cycloalkyl
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 - Fee Related
Application number
CA2705452A
Other languages
English (en)
French (fr)
Other versions
CA2705452A1 (en
Inventor
Mark E. Adams
Qing Dong
Stephen W. Kaldor
Toufike Kanouni
Nicholas Scorah
Michael B. Wallace
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takeda Pharmaceutical Co Ltd
Original Assignee
Takeda Pharmaceutical Co Ltd
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.)
Filing date
Publication date
Application filed by Takeda Pharmaceutical Co Ltd filed Critical Takeda Pharmaceutical Co Ltd
Publication of CA2705452A1 publication Critical patent/CA2705452A1/en
Application granted granted Critical
Publication of CA2705452C publication Critical patent/CA2705452C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • 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
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Emergency Medicine (AREA)
  • Obesity (AREA)
  • Transplantation (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
  • Endocrinology (AREA)
  • Communicable Diseases (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CA2705452A 2007-11-12 2008-11-07 Mapk/erk kinase inhibitors Expired - Fee Related CA2705452C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US98727907P 2007-11-12 2007-11-12
US60/987,279 2007-11-12
PCT/US2008/082846 WO2009064675A1 (en) 2007-11-12 2008-11-07 Mapk/erk kinase inhibitors

Publications (2)

Publication Number Publication Date
CA2705452A1 CA2705452A1 (en) 2009-05-22
CA2705452C true CA2705452C (en) 2016-05-31

Family

ID=40340592

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2705452A Expired - Fee Related CA2705452C (en) 2007-11-12 2008-11-07 Mapk/erk kinase inhibitors

Country Status (10)

Country Link
US (1) US8022057B2 (cg-RX-API-DMAC7.html)
EP (1) EP2227469B9 (cg-RX-API-DMAC7.html)
JP (1) JP5453290B2 (cg-RX-API-DMAC7.html)
AR (1) AR069462A1 (cg-RX-API-DMAC7.html)
CA (1) CA2705452C (cg-RX-API-DMAC7.html)
CL (1) CL2008003366A1 (cg-RX-API-DMAC7.html)
ES (1) ES2456966T3 (cg-RX-API-DMAC7.html)
PE (1) PE20090998A1 (cg-RX-API-DMAC7.html)
TW (1) TW200934775A (cg-RX-API-DMAC7.html)
WO (1) WO2009064675A1 (cg-RX-API-DMAC7.html)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7723477B2 (en) 2005-10-31 2010-05-25 Oncomed Pharmaceuticals, Inc. Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth
US20100204471A1 (en) 2006-10-23 2010-08-12 Takeda Pharmaceutical Company Limited Mapk/erk kinase inhibitors
JO2985B1 (ar) * 2006-12-20 2016-09-05 Takeda Pharmaceuticals Co مثبطات كينازmapk/erk
CL2009000949A1 (es) * 2008-04-21 2010-12-24 Novartis Ag Compuestos derivados de 1,2,3,5-tetrahidro-indolizina, 6,7,8,9-tetrahidro-4h-quinolizina sustituidos, inhibidores de la actividad de cinasa de mek; su composicion farmaceutica; su uso para el tratamiento de enfermedades hiperproliferativas, tal como cancer e inflamaciones.
US7982013B2 (en) 2008-09-26 2011-07-19 Oncomed Pharmaceuticals, Inc. Frizzled-binding agents and uses thereof
KR20120028882A (ko) * 2009-04-21 2012-03-23 노파르티스 아게 Ｍｅｋ 억제제로서의 헤테로시클릭 화합물
MY156209A (en) * 2009-11-04 2016-01-29 Novartis Ag Heterocyclic sulfonamide derivatives useful mek inhibitors
WO2011067348A2 (en) 2009-12-03 2011-06-09 Novartis Ag Mek inhibitor salts and solvates thereof
CN101747300B (zh) * 2009-12-22 2012-11-07 上海大学 基于紫杉醇和氮芥的协同前药及其制备方法
TWI535445B (zh) 2010-01-12 2016-06-01 安可美德藥物股份有限公司 Ｗｎｔ拮抗劑及治療和篩選方法
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
CA2843102A1 (en) * 2011-07-27 2013-01-31 Glaxo Group Limited Bicyclic pyrimidone compounds
TWI835048B (zh) 2011-08-01 2024-03-11 美商建南德克公司 利用pd-1軸結合拮抗劑及mek抑制劑治療癌症之方法
EP2788378A4 (en) * 2011-12-09 2015-09-09 Oncomed Pharm Inc ASSOCIATION THERAPY FOR THE TREATMENT OF CANCER
WO2013109142A1 (en) 2012-01-16 2013-07-25 Stichting Het Nederlands Kanker Instituut Combined pdk and mapk/erk pathway inhibition in neoplasia
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
AU2014212081A1 (en) 2013-02-04 2015-08-13 Oncomed Pharmaceuticals, Inc. Methods and monitoring of treatment with a Wnt pathway inhibitor
JP2015003902A (ja) 2013-05-20 2015-01-08 杏林製薬株式会社 血管新生阻害剤
WO2014204263A1 (en) * 2013-06-20 2014-12-24 The Asan Foundation Substituted pyridinone compounds as mek inhibitors
EP3046557A1 (en) 2013-09-20 2016-07-27 Stichting Het Nederlands Kanker Instituut 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
US20170027940A1 (en) 2014-04-10 2017-02-02 Stichting Het Nederlands Kanker Instituut Method for treating cancer
WO2015178770A1 (en) 2014-05-19 2015-11-26 Stichting Het Nederlands Kanker Instituut Compositions for cancer treatment
WO2016011160A1 (en) 2014-07-15 2016-01-21 Genentech, Inc. Compositions for treating cancer using pd-1 axis binding antagonists and mek inhibitors
WO2017058007A1 (en) 2015-10-01 2017-04-06 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Histone deacetylase inhibitors for the use in the treatment of drug resistant melanoma
WO2017099591A1 (en) 2015-12-07 2017-06-15 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Treatment of inhibitor resistant braf-mutant cancers
WO2017204626A1 (en) 2016-05-24 2017-11-30 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Combination therapy - combined map2k4/map3k1 and mek/erk inhibition
WO2018218633A1 (en) 2017-06-02 2018-12-06 Beijing Percans Oncology Co. Ltd. Combination therapies for treating cancers
WO2019195959A1 (en) 2018-04-08 2019-10-17 Cothera Biosciences, Inc. Combination therapy for cancers with braf mutation
BR112021002622A2 (pt) 2018-08-13 2021-05-11 Beijing Percans Oncology Co. Ltd. biomarcadores para terapia de câncer
CN111662282B (zh) * 2019-03-07 2021-07-06 湖南化工研究院有限公司 氮杂环并吡啶类化合物及其中间体

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU616916B2 (en) 1987-11-20 1991-11-14 Kissei Pharmaceutical Co. Ltd. 4h-quinolizin-4-one compounds exhibiting therapeutic activities
JPH0670044B2 (ja) * 1987-11-20 1994-09-07 キッセイ薬品工業株式会社 ４ｈ―キノリジン―４―オン誘導体
AU5610398A (en) 1997-02-28 1998-09-18 Warner-Lambert Company Method of treating or preventing septic shock by administering a mek inhibitor
BR9916857A (pt) 1999-01-13 2001-12-04 Warner Lambert Co 4 heteroaril diarilaminas
US7235537B2 (en) 2002-03-13 2007-06-26 Array Biopharma, Inc. N3 alkylated benzimidazole derivatives as MEK inhibitors
CA2478534A1 (en) 2002-03-13 2003-09-25 Array Biopharma, Inc. N3 alkylated benzimidazole derivatives as mek inhibitors
TWI350285B (en) 2002-03-13 2011-10-11 Array Biopharma Inc N3 alkylated benzimidazole derivatives as mek inhibitors
WO2005000818A1 (en) * 2003-06-27 2005-01-06 Warner-Lambert Company Llc 5-substituted-4-`(substituted phenyl)!amino!-2-pyridone deviatives for use as mek inhibitors
US20050049276A1 (en) 2003-07-23 2005-03-03 Warner-Lambert Company, Llc Imidazopyridines and triazolopyridines
ATE442847T1 (de) 2003-07-24 2009-10-15 Warner Lambert Co Benzimidazol-derivate als mek-hemmer
US7144907B2 (en) 2003-09-03 2006-12-05 Array Biopharma Inc. Heterocyclic 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
ES2369835T3 (es) 2003-11-19 2011-12-07 Array Biopharma, Inc. Inhibidores bicíclicos de mek y métodos de síntesis de los mismos.
RS50569B (sr) 2004-06-11 2010-05-07 Japan Tobacco Inc. Derivati 5-amino-2,4,7-triokso-3,4,7,8-tetrahidro-2h-pirido (2,3-d)pirimidina i slična jedinjenja za lečenje raka
CA2587178A1 (en) 2004-11-24 2006-06-01 Laboratoires Serono S.A. Novel 4-arylamino pyridone derivatives as mek inhibitors for the treatment of hyperproliferative disorders
JP2008521858A (ja) 2004-12-01 2008-06-26 ラボラトワール セローノ ソシエテ アノニム 過増殖性疾患を処置するための［１，２，４］トリアゾロ［４，３−ａ］ピリジン誘導体
EP2361905B1 (en) * 2005-05-18 2013-03-06 Array Biopharma Inc. Heterocyclic Inhibitors of MEK and methods of use thereof
US20100204471A1 (en) 2006-10-23 2010-08-12 Takeda Pharmaceutical Company Limited Mapk/erk kinase inhibitors
US7943659B2 (en) 2006-10-31 2011-05-17 Takeda Pharmaceutical Company Limited MAPK/ERK kinase inhibitors
JO2985B1 (ar) 2006-12-20 2016-09-05 Takeda Pharmaceuticals Co مثبطات كينازmapk/erk
CL2009000949A1 (es) * 2008-04-21 2010-12-24 Novartis Ag Compuestos derivados de 1,2,3,5-tetrahidro-indolizina, 6,7,8,9-tetrahidro-4h-quinolizina sustituidos, inhibidores de la actividad de cinasa de mek; su composicion farmaceutica; su uso para el tratamiento de enfermedades hiperproliferativas, tal como cancer e inflamaciones.
KR20120028882A (ko) 2009-04-21 2012-03-23 노파르티스 아게 Ｍｅｋ 억제제로서의 헤테로시클릭 화합물

Also Published As

Publication number Publication date
CL2008003366A1 (es) 2009-05-29
AR069462A1 (es) 2010-01-27
WO2009064675A1 (en) 2009-05-22
EP2227469B1 (en) 2014-01-08
EP2227469A1 (en) 2010-09-15
CA2705452A1 (en) 2009-05-22
PE20090998A1 (es) 2009-08-12
TW200934775A (en) 2009-08-16
JP5453290B2 (ja) 2014-03-26
EP2227469B9 (en) 2014-09-10
US8022057B2 (en) 2011-09-20
ES2456966T3 (es) 2014-04-24
JP2011503099A (ja) 2011-01-27
US20090124595A1 (en) 2009-05-14

Similar Documents

Publication Publication Date Title
CA2705452C (en) Mapk/erk kinase inhibitors
CA2673647C (en) Mapk/erk kinase inhibitors
EP2150544B1 (en) Mapk/erk kinase inhibitors
EP2113500A1 (en) MAPK/ERK kinase inhibitors
US7943626B2 (en) Substituted 1,3-dialkyl-2,4-dioxo-6-(pyridylamino)-1,2,3,4-tetrahydropyrimidine-5-hydroxamic acid inhibitors of MAPK/ERK kinase
US20090246198A1 (en) Mapk/erk kinase inhibitors and methods of use thereof
US20080312307A1 (en) Mapk/erk kinase inhibitors

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20131106

MKLA Lapsed

Effective date: 20171107