NO20073024L - Kinaseinhibitorer - Google Patents

Kinaseinhibitorer

Info

Publication number
NO20073024L
NO20073024L NO20073024A NO20073024A NO20073024L NO 20073024 L NO20073024 L NO 20073024L NO 20073024 A NO20073024 A NO 20073024A NO 20073024 A NO20073024 A NO 20073024A NO 20073024 L NO20073024 L NO 20073024L
Authority
NO
Norway
Prior art keywords
aurora
kinase inhibitors
inhibitors
compositions
compounds
Prior art date
Application number
NO20073024A
Other languages
English (en)
Inventor
Dinesh V Patel
Xiao-Yi Xiao
Original Assignee
Miikana Therapeutics Inc
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 Miikana Therapeutics Inc filed Critical Miikana Therapeutics Inc
Publication of NO20073024L publication Critical patent/NO20073024L/no

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Beskrevet er proteinkinaseinhibitorer med Formel Ia og Ib, sammensetninger som innbefatter slike inhibitorer og fremgangsmåte for anvendelse derav. Mer spesielt er disse forbindelsene og sammensetningene inhibitorer av Aurora-A (Aurora-2) og Aurora-B (Aurora-1) proteinkinase. Også beskrevet er fremgangsmåter for anvendelse av disse forbindelsene og sammensetningene for å hindre og behandle sykdommer assosiert med proteinkinaser, særlig sykdommer assosiert med Aurora-A eller Aurora-B, slik som kreft.
NO20073024A 2004-11-17 2007-06-13 Kinaseinhibitorer NO20073024L (no)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62917604P 2004-11-17 2004-11-17
PCT/US2005/041945 WO2006055831A2 (en) 2004-11-17 2005-11-17 Kinase inhibitors

Publications (1)

Publication Number Publication Date
NO20073024L true NO20073024L (no) 2007-07-02

Family

ID=36407795

Family Applications (1)

Application Number Title Priority Date Filing Date
NO20073024A NO20073024L (no) 2004-11-17 2007-06-13 Kinaseinhibitorer

Country Status (13)

Country Link
US (1) US8153630B2 (no)
EP (1) EP1812424A4 (no)
JP (1) JP2008520713A (no)
KR (1) KR20070086188A (no)
CN (1) CN101084214A (no)
AU (1) AU2005306458B2 (no)
BR (1) BRPI0517737A (no)
CA (1) CA2587427A1 (no)
IL (1) IL183276A0 (no)
MX (1) MX2007005857A (no)
NO (1) NO20073024L (no)
RU (1) RU2007122485A (no)
WO (1) WO2006055831A2 (no)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE381566T1 (de) 2004-05-14 2008-01-15 Millennium Pharm Inc Verbindungen und verfahren zur inhibierung der mitotischen progression durch hemmung von aurorakinase
CA2587427A1 (en) 2004-11-17 2006-05-26 Miikana Therapeutics, Inc. Kinase inhibitors
ES2535854T3 (es) * 2005-09-30 2015-05-18 Miikana Therapeutics, Inc. Compuestos de pirazol sustituidos
US7948440B1 (en) 2006-09-30 2011-05-24 LHC2 Inc. Horizontally-polarized omni-directional antenna
CL2007003244A1 (es) 2006-11-16 2008-04-04 Millennium Pharm Inc Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer.
CN101638808B (zh) * 2008-07-31 2012-10-17 复旦大学 筛选加强型抗肿瘤化合物的方法
ES2468391T3 (es) 2008-12-22 2014-06-16 Millennium Pharmaceuticals, Inc. Combinación de inhibidores de cinasas Aurora y anticuerpos anti-CD20
JO3635B1 (ar) 2009-05-18 2020-08-27 Millennium Pharm Inc مركبات صيدلانية صلبة وطرق لانتاجها
MX2011013325A (es) * 2009-06-10 2012-04-30 Abbott Lab 2-(lh-pirazol-4-ilamino)-pirimidina como inhibidores de cinasa.
BR112012020557A8 (pt) 2010-02-19 2018-01-02 Millennium Pharm Inc formas cristalinas de 4-{[9-cloro-7-(2-flúor-6-metoifenil)-5h-pirimido[5,4-d][2]benzazepin-2-il]amino}-2-metoxibenzoato de sódio
RU2014141674A (ru) 2012-03-16 2016-05-10 Аксикин Фармасьютикалз, Инк. 3,5-диаминопиразоловые ингибиторы киназы
US20130303519A1 (en) 2012-03-20 2013-11-14 Millennium Pharmaceuticals, Inc. Methods of treating cancer using aurora kinase inhibitors
CA2907726A1 (en) 2013-03-22 2014-09-25 Millennium Pharmaceuticals, Inc. Combination of catalytic mtorc1/2 inhibitors and selective inhibitors of aurora a kinase
NZ631142A (en) 2013-09-18 2016-03-31 Axikin Pharmaceuticals Inc Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors
HRP20211813T1 (hr) 2014-08-11 2022-03-04 Acerta Pharma B.V. Terapeutske kombinacije inhibitora btk i inhibitora bcl-2
TW201618775A (zh) 2014-08-11 2016-06-01 艾森塔製藥公司 Ｂｔｋ抑制劑、ｐｉ３ｋ抑制劑、ｊａｋ－２抑制劑、ｐｄ－１抑制劑及／或ｐｄ－ｌ１抑制劑之治療組合物
WO2016024232A1 (en) 2014-08-11 2016-02-18 Acerta Pharma B.V. Therapeutic combinations of a btk inhibitor, a pi3k inhibitor, a jak-2 inhibitor and/or a cdk 4/6 inhibitor
US9592186B2 (en) 2014-09-30 2017-03-14 Avon Products, Inc. Topical compositions and methods for skin lightening
KR102034202B1 (ko) 2014-12-23 2019-10-18 에스엠에이 세라퓨틱스 아이엔씨. 3,5-디아미노피라졸 키나제 억제제
EP3324976A4 (en) 2015-07-21 2019-03-27 Millennium Pharmaceuticals, Inc. ADMINISTRATION OF KINASE AURORA INHIBITOR AND CHEMOTHERAPEUTIC AGENTS
CN118255713A (zh) * 2022-12-28 2024-06-28 深圳微芯生物科技股份有限公司 一种萘酰胺类化合物、其制备方法及其应用

Family Cites Families (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57203072A (en) 1981-06-05 1982-12-13 Sankyo Co Ltd 4-anilinopyrimidine derivative, its preparation, antidepressant comprising it as active ingredient
JPH0665237A (ja) 1992-05-07 1994-03-08 Nissan Chem Ind Ltd 置換ピラゾール誘導体および農園芸用殺菌剤
US5453414A (en) 1993-05-20 1995-09-26 Rohm And Haas Company 2-arylpyrimidines and herbicidal use thereof
DK0640599T3 (da) 1993-08-26 1998-09-28 Ono Pharmaceutical Co 4-Aminopyrimidin-derivater
ES2219670T3 (es) * 1994-11-10 2004-12-01 Millennium Pharmaceuticals, Inc. Utilizacion de compuestos de pirazola para el tratamiento de la glomerulonefritis, cancer, ateroesclerosis o restenosis.
DE19511562A1 (de) 1995-03-29 1996-10-02 Hoechst Schering Agrevo Gmbh Cyclohexylamino- und alkoxy-Stickstoff-Heterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Schädlingsbekämpfungsmittel und Fungizide
US6716575B2 (en) 1995-12-18 2004-04-06 Sugen, Inc. Diagnosis and treatment of AUR1 and/or AUR2 related disorders
US6432947B1 (en) * 1997-02-19 2002-08-13 Berlex Laboratories, Inc. N-heterocyclic derivatives as NOS inhibitors
EA200000840A1 (ru) * 1998-02-17 2001-02-26 Туларик, Инк. Антивирусные производные пиримидина
CN1161352C (zh) 1998-10-08 2004-08-11 阿斯特拉曾尼卡有限公司 喹唑啉衍生物
GB9828511D0 (en) 1998-12-24 1999-02-17 Zeneca Ltd Chemical compounds
US20020065270A1 (en) 1999-12-28 2002-05-30 Moriarty Kevin Joseph N-heterocyclic inhibitors of TNF-alpha expression
JP4739632B2 (ja) 2000-02-05 2011-08-03 バーテックス ファーマシューティカルズ インコーポレイテッド Ｅｒｋのインヒビターとして有用なピラゾール組成物
HUP0301117A3 (en) 2000-02-17 2004-01-28 Amgen Inc Thousand Oaks Imidazole derivatives kinase inhibitors, their use, process for their preparation and pharmaceutical compositions containing them
GB0004887D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
JP2004501083A (ja) * 2000-04-18 2004-01-15 アゴーロン・ファーマシューティカルズ・インコーポレイテッド プロテインキナーゼを阻害するためのピラゾール
ES2346513T3 (es) * 2000-07-24 2010-10-18 Krenitsky Pharmaceuticals, Inc. 5-alquinil pirimidinas sustituidas que tienen actividad neurotrofica.
BR0113574A (pt) 2000-08-31 2003-07-22 Pfizer Prod Inc Derivados de pirazol e uso dos mesmos como inibidores de proteìna quinase
US6613776B2 (en) 2000-09-15 2003-09-02 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6660731B2 (en) * 2000-09-15 2003-12-09 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US7473691B2 (en) 2000-09-15 2009-01-06 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
JP4105948B2 (ja) * 2000-09-15 2008-06-25 バーテックス ファーマシューティカルズ インコーポレイテッド プロテインキナーゼインヒビターとして有用なピラゾール化合物
US6610677B2 (en) 2000-09-15 2003-08-26 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
CN1474815A (zh) 2000-09-20 2004-02-11 Ĭ��ר���ɷ����޹�˾ 4-氨基-喹唑啉
US20020137755A1 (en) 2000-12-04 2002-09-26 Bilodeau Mark T. Tyrosine kinase inhibitors
US6716851B2 (en) * 2000-12-12 2004-04-06 Cytovia, Inc. Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof
KR100909665B1 (ko) * 2000-12-21 2009-07-29 버텍스 파마슈티칼스 인코포레이티드 단백질 키나제 억제제로서 유용한 피라졸 화합물 및 이를 포함하는 약제학적 조성물
EP1389206B1 (en) * 2001-04-13 2006-09-13 Vertex Pharmaceuticals Incorporated Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases
CA2446864C (en) * 2001-05-16 2011-02-15 Vertex Pharmaceuticals Incorporated Inhibitors of src and other protein kinases
MXPA03010961A (es) 2001-05-31 2004-02-27 Vertex Pharma Compuestos de tiazol utiles como inhibidores de proteinas cinasas.
ATE432929T1 (de) 2001-06-15 2009-06-15 Vertex Pharma 5-(2-aminopyrimidin-4-yl)benzisoxazole als proteinkinasehemmer
US6825198B2 (en) 2001-06-21 2004-11-30 Pfizer Inc 5-HT receptor ligands and uses thereof
WO2003011854A1 (en) 2001-08-03 2003-02-13 Vertex Pharmaceuticals Incorporated Pyrazole-derived kinase inhibitors and uses thereof
RU2323215C2 (ru) 2001-12-24 2008-04-27 Астразенека Аб Замещенные производные хиназолина как ингибиторы ауроракиназы
WO2003078427A1 (en) 2002-03-15 2003-09-25 Vertex Pharmaceuticals, Inc. Azolylaminoazines as inhibitors of protein kinases
AU2003225800A1 (en) 2002-03-15 2003-09-29 Hayley Binch Azolylaminoazine as inhibitors of protein kinases
WO2003078423A1 (en) 2002-03-15 2003-09-25 Vertex Pharmaceuticals, Inc. Compositions useful as inhibitors of protein kinases
WO2003077921A1 (en) 2002-03-15 2003-09-25 Vertex Pharmaceuticals, Inc. Azinylaminoazoles as inhibitors of protein kinases
US6677337B2 (en) * 2002-03-19 2004-01-13 The Procter & Gamble Company 1,2-dihydropyrazol-3-ones which controls inflammatory cytokines
US20030207873A1 (en) * 2002-04-10 2003-11-06 Edmund Harrington Inhibitors of Src and other protein kinases
ES2340475T3 (es) 2002-05-01 2010-06-04 Vertex Pharmaceuticals Incorporated Estructura cristalizada de proteina aurora-2 y sus bolsillos de union.
MY141867A (en) 2002-06-20 2010-07-16 Vertex Pharma Substituted pyrimidines useful as protein kinase inhibitors
EP1554269A1 (en) * 2002-07-09 2005-07-20 Vertex Pharmaceuticals Incorporated Imidazoles, oxazoles and thiazoles with protein kinase inhibiting activities
US20040023977A1 (en) 2002-07-15 2004-02-05 Larsen Robert D. Process for making substituted thiazolyl-amino pyrimidinyl
DE60318219T2 (de) 2002-08-24 2009-01-15 Astrazeneca Ab PYRIMIDINDERIVATE ALS MODULATOREN DER AKTIVITuT VON CHEMOKINREZEPTOREN
WO2004037814A1 (en) 2002-10-25 2004-05-06 Vertex Pharmaceuticals Incorporated Indazolinone compositions useful as kinase inhibitors
ES2308182T3 (es) 2003-06-02 2008-12-01 Astrazeneca Ab Derivadosde (3-((quinazolin-4-il)amino)-1h-pirazol-1-il)acetamida y compuestos relacionados como inhibidores de quinasas aurora para el tratamiento de enfermedades proliferativas tales como el cancer.
DE602004022187D1 (de) 2003-10-17 2009-09-03 Astrazeneca Ab 4-(pyrazol-3-ylamino)pyrimidinderivate zur verwendung bei der behandlung von krebs
MXPA06005735A (es) 2003-11-24 2006-08-17 Hoffmann La Roche Pirazolil e imidazolil pirimidinas.
US7244735B2 (en) 2003-12-02 2007-07-17 Vertex Pharmaceuticals Inc. Heterocyclic protein kinase inhibitors and uses thereof
AR049418A1 (es) 2004-02-27 2006-08-02 Bayer Pharmaceuticals Corp Derivados de heteroarilaminopirazol y composiciones farmaceuticas para el tratamiento de la diabetes.
AR050948A1 (es) 2004-09-24 2006-12-06 Hoffmann La Roche Derivados de ftalazinona; su obtencion y su utilizacion en la fabricacion de medicamentos para el tratamiento del cancer.
US7713973B2 (en) 2004-10-15 2010-05-11 Takeda Pharmaceutical Company Limited Kinase inhibitors
US7491720B2 (en) 2004-10-29 2009-02-17 Banyu Pharmaceutical Co., Ltd. Aminopyridine derivatives having Aurora A selective inhibitory action
CA2587427A1 (en) 2004-11-17 2006-05-26 Miikana Therapeutics, Inc. Kinase inhibitors
AU2005316599A1 (en) 2004-12-14 2006-06-22 Vertex Pharmaceuticals Incorporated Pyrimidine inhibitors of ERK protein kinase and uses therof

Also Published As

Publication number Publication date
WO2006055831A2 (en) 2006-05-26
MX2007005857A (es) 2007-10-10
EP1812424A2 (en) 2007-08-01
AU2005306458A1 (en) 2006-05-26
BRPI0517737A (pt) 2008-10-21
KR20070086188A (ko) 2007-08-27
RU2007122485A (ru) 2008-12-27
EP1812424A4 (en) 2009-07-08
WO2006055831A3 (en) 2006-12-07
CA2587427A1 (en) 2006-05-26
US20080200485A1 (en) 2008-08-21
IL183276A0 (en) 2007-10-31
US8153630B2 (en) 2012-04-10
JP2008520713A (ja) 2008-06-19
AU2005306458B2 (en) 2011-02-17
CN101084214A (zh) 2007-12-05

Similar Documents

Publication Publication Date Title
NO20073024L (no) Kinaseinhibitorer
NO20081952L (no) Substituerte pyrazolforbindelser
NO20084435L (no) C-MET proteinkinaseinhibitorer
TW200801008A (en) Protein kinase inhibitors
NO20072567L (no) Triazoler nyttige som proteinkinase-inhibitorer
NO20080785L (no) Behandling av kreft
NO20082508L (no) Aminopyrimidiner anvendelige som kinaseinhibitorer
EA200801291A1 (ru) Карбониламинопирролопиразолы в качестве эффективных ингибиторов киназ
DE602007007985D1 (de) Als inhibitoren von proteinkinasen geeignete aminopyrimidine
MX2010006203A (es) Derivados de pirazol y uso de los mismos como inhibidores de cinasas dependientes de ciclina.
GEP20135785B (en) Pyrrolopyrimidine compounds as cdk inhibitors
NO20045677L (no) Inhibitorer av JAK- og CDK2-proteinkinaser
MX2009013077A (es) Derivados dde benzoxazolona.
NO20073140L (no) Pyrrolopyraziner og pyralopyraziner som er nyttige som inhibitorer av proteinkinaser
DE602006004844D1 (de) Pyrrolopyrimidine verwendbar als protein kinase inhibitoren
ATE493401T1 (de) Als proteinkinaseinhibitoren geeignete diaminotriazolverbindungen
EA201000093A1 (ru) Производные пиридазинона
SG170828A1 (en) Deazapurines useful as inhibitors of janus kinases
NO20081893L (no) 4-(3-aminopyrazol)pyrimidinderivater til anvendelse som tyrosin-kinaseinhibitorer i behandling av kreft
WO2007067781A3 (en) 9-membered heterobicyclic compounds as inhibitors of protein kinases
ATE554087T1 (de) Neue kinaseinhibitoren
EA201070395A1 (ru) Ингибиторы polo-подобных киназ
NO20091326L (no) Indazolderivater som modulatorer av interleukin-1-reseptor-assosiert kinase
ATE548363T1 (de) 3,5-disubstituierte pyrid-2-one, die sich als inhibitoren der tec-familie von nicht-rezeptor- tyrosinkinasen eignen
NO20061194L (no) Mitotiske kinesininbibitorer

Legal Events

Date Code Title Description
FC2A Withdrawal, rejection or dismissal of laid open patent application