IL158649A0 - Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function - Google Patents

Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function

Info

Publication number
IL158649A0
IL158649A0 IL15864998A IL15864998A IL158649A0 IL 158649 A0 IL158649 A0 IL 158649A0 IL 15864998 A IL15864998 A IL 15864998A IL 15864998 A IL15864998 A IL 15864998A IL 158649 A0 IL158649 A0 IL 158649A0
Authority
IL
Israel
Prior art keywords
azabenzimidazole
protein kinase
based compounds
threonine protein
kinase function
Prior art date
Application number
IL15864998A
Other languages
English (en)
Original Assignee
Zentaris Gmbh
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 Zentaris Gmbh filed Critical Zentaris Gmbh
Publication of IL158649A0 publication Critical patent/IL158649A0/xx

Links

Classifications

    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
IL15864998A 1997-09-26 1998-09-23 Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function IL158649A0 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US6014597P 1997-09-26 1997-09-26
IL13510998A IL135109A0 (en) 1997-09-26 1998-09-23 Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function
PCT/US1998/019973 WO1999016438A1 (en) 1997-09-26 1998-09-23 Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function

Publications (1)

Publication Number Publication Date
IL158649A0 true IL158649A0 (en) 2004-05-12

Family

ID=22027657

Family Applications (4)

Application Number Title Priority Date Filing Date
IL15864998A IL158649A0 (en) 1997-09-26 1998-09-23 Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function
IL13510998A IL135109A0 (en) 1997-09-26 1998-09-23 Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function
IL135109A IL135109A (en) 1997-09-26 2000-03-15 Compounds based on azabenzamide, a method, their preparation and the pharmaceutical preparations containing them
IL158649A IL158649A (en) 1997-09-26 2003-10-29 Regulation of the activity of serine / threonine protein kinase using azabenzamide-based compounds

Family Applications After (3)

Application Number Title Priority Date Filing Date
IL13510998A IL135109A0 (en) 1997-09-26 1998-09-23 Azabenzimidazole-based compounds for modulating serine/threonine protein kinase function
IL135109A IL135109A (en) 1997-09-26 2000-03-15 Compounds based on azabenzamide, a method, their preparation and the pharmaceutical preparations containing them
IL158649A IL158649A (en) 1997-09-26 2003-10-29 Regulation of the activity of serine / threonine protein kinase using azabenzamide-based compounds

Country Status (28)

Country Link
US (2) US6093728A (zh)
EP (1) EP1017384B1 (zh)
JP (1) JP2001517699A (zh)
KR (1) KR100547929B1 (zh)
CN (1) CN1167420C (zh)
AR (1) AR017266A1 (zh)
AT (1) ATE281834T1 (zh)
AU (1) AU748849B2 (zh)
BG (1) BG64784B1 (zh)
BR (1) BR9812682A (zh)
CA (1) CA2305370C (zh)
DE (1) DE69827516T2 (zh)
DK (1) DK1017384T3 (zh)
ES (1) ES2230719T3 (zh)
HK (1) HK1032206A1 (zh)
HU (1) HUP0004024A3 (zh)
IL (4) IL158649A0 (zh)
NO (1) NO325663B1 (zh)
NZ (2) NZ503432A (zh)
PL (1) PL191618B1 (zh)
PT (1) PT1017384E (zh)
RU (1) RU2230553C2 (zh)
SK (1) SK285357B6 (zh)
TR (1) TR200001546T2 (zh)
TW (1) TW581815B (zh)
UA (1) UA72448C2 (zh)
WO (1) WO1999016438A1 (zh)
ZA (1) ZA988797B (zh)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060142236A1 (en) * 1994-05-31 2006-06-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of raf gene expression
US6919366B2 (en) * 1998-05-22 2005-07-19 Avanir Pharmaceuticals Benzimidazole derivatives as modulators of IgE
US6911462B2 (en) * 1998-05-22 2005-06-28 Avanir Pharmaceuticals Benzimidazole compounds for regulating IgE
US6384049B1 (en) * 2000-05-25 2002-05-07 The Procter & Gamble Company Cancer treatment
ATE369853T1 (de) * 2001-03-12 2007-09-15 Avanir Pharmaceuticals Benzimidazolderivate zur ige-modulierung und zellproliferationshemmung
TW200304820A (en) * 2002-03-25 2003-10-16 Avanir Pharmaceuticals Use of benzimidazole analogs in the treatment of cell proliferation
AU2003270426A1 (en) 2002-09-12 2004-04-30 Avanir Pharmaceuticals PHENYL-INDOLE COMPOUNDS FOR MODULATING IgE AND INHIBITING CELLULAR PROLIFERATION
TWI276631B (en) * 2002-09-12 2007-03-21 Avanir Pharmaceuticals Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation
JP2007501618A (ja) * 2003-08-08 2007-02-01 アバニール・ファーマシューティカルズ タンパク質輸送の選択的薬理学的阻害、および関連した、ヒト疾患を治療する方法
GB0423554D0 (en) 2004-10-22 2004-11-24 Cancer Rec Tech Ltd Therapeutic compounds
US8642278B2 (en) * 2005-11-22 2014-02-04 University Of South Florida Inhibition of cell proliferation
CA2649994A1 (en) 2006-04-26 2007-11-08 Cancer Research Technology Limited Imidazo[4,5-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds
RU2478635C2 (ru) * 2006-10-19 2013-04-10 СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи Гетероарильные соединения, содержащие их композиции и способы лечения с применением этих соединений
WO2008104979A2 (en) * 2007-02-28 2008-09-04 Yeda Research And Development Co. Ltd. Nuclear targeting sequences
CL2008001626A1 (es) * 2007-06-05 2009-06-05 Takeda Pharmaceuticals Co Compuestos derivados de heterociclos fusionados, agente farmaceutico que los comprende y su uso en la profilaxis y tratamiento del cancer.
WO2009025358A1 (ja) 2007-08-23 2009-02-26 Takeda Pharmaceutical Company Limited 複素環化合物およびその用途
EP2184285B1 (en) * 2007-08-29 2015-11-04 Takeda Pharmaceutical Company Limited Heterocyclic compound and use thereof
AU2008337286B2 (en) 2007-12-19 2014-08-07 Cancer Research Technology Limited Pyrido[2,3-b]pyrazine-8-substituted compounds and their use
GB0807609D0 (en) 2008-04-25 2008-06-04 Cancer Rec Tech Ltd Therapeutic compounds and their use
WO2010025448A2 (en) * 2008-08-29 2010-03-04 University Of South Florida Inhibition of cell proliferation
US8110578B2 (en) 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
JP5579619B2 (ja) 2008-12-01 2014-08-27 武田薬品工業株式会社 複素環化合物およびその用途
JO3101B1 (ar) 2008-12-02 2017-09-20 Takeda Pharmaceuticals Co مشتقات بنزوثيازول كعوامل مضادة للسرطان
JP2012197231A (ja) * 2009-08-06 2012-10-18 Oncotherapy Science Ltd Ｔｔｋ阻害作用を有するピリジンおよびピリミジン誘導体
MX341704B (es) 2009-10-26 2016-08-31 Signal Pharm Llc Métodos de síntesis y purificación de compuestos de heteroarilo.
EP2531502B1 (en) 2010-02-01 2014-04-02 Cancer Research Technology Limited 1-(5-tert-butyl-2-phenyl-2h-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1h-imidazo[4,5-b]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy
MY183661A (en) 2011-10-19 2021-03-05 Signal Pharm Llc Treatment of cancer with tor kinase inhibitors
WO2013082344A1 (en) 2011-12-02 2013-06-06 Signal Pharmaceuticals, Llc Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use
ES2742398T3 (es) 2012-02-24 2020-02-14 Signal Pharm Llc Métodos para tratar el cáncer de pulmón no microcítico usando una terapia de combinación de inhibidores de TOR quinasa
AU2013203714B2 (en) 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
AU2014207641A1 (en) 2013-01-16 2015-08-06 Signal Pharmaceuticals, Llc Substituted Pyrrolopyrimidine Compounds, compositions thereof, and methods of treatment therewith
WO2014145852A2 (en) 2013-03-15 2014-09-18 Knopp Biosciences Llc Imidazo(4,5-b) pyridin-2-yl amides as kv7 channel activators
US9474757B2 (en) 2013-04-17 2016-10-25 Signal Pharmaceuticals, Llc Methods for treating cancer using TOR kinase inhibitor combination therapy
BR112015026257B1 (pt) 2013-04-17 2022-12-20 Signal Pharmaceuticals, Llc Uso de um composto dihidropirazino-pirazina e enzalutamida, composição farmacêutica que os compreende, e kit
NZ631082A (en) 2013-04-17 2017-06-30 Signal Pharm Llc Methods for treating cancer using tor kinase inhibitor combination therapy
AU2014254050B2 (en) 2013-04-17 2018-10-04 Signal Pharmaceuticals, Llc Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl) pyridin-3-yl) -3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one
BR112015026238A8 (pt) 2013-04-17 2019-12-24 Signal Pharm Llc composto dihidropirazino-pirazina, composição farmacêutica que o compreende, uso do composto, métodos para inibir ou medir a fosforilação e para inibir a atividade da proteína quinase, bem como kit
MX2015014590A (es) 2013-04-17 2016-03-03 Signal Pharm Llc Tratamiento de cancer con dihidropirazino-pirazinas.
MX2015014455A (es) 2013-04-17 2016-07-21 Signal Pharm Llc Terapia de combinacion que comprende un inhibidor de tor cinasa y n-(3-(5-fluoro-2-(4-(2-metoxietoxi)fenilamino)pirimidin-4-ilamino )fenil)acrilamida para tratar cancer.
CA2912627C (en) 2013-05-29 2022-03-15 Signal Pharmaceuticals, Llc Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use
WO2015040609A1 (en) 2013-09-17 2015-03-26 Yeda Research And Development Co. Ltd. Erk-derived peptides and uses thereof
GB201320732D0 (en) 2013-11-25 2014-01-08 Cancer Rec Tech Ltd Methods of chemical synthesis
GB201320729D0 (en) 2013-11-25 2014-01-08 Cancer Rec Tech Ltd Therapeutic compounds and their use
WO2015160880A1 (en) 2014-04-16 2015-10-22 Signal Pharmaceuticals, Llc SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
NZ714742A (en) 2014-04-16 2017-04-28 Signal Pharm Llc Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
WO2015160882A1 (en) 2014-04-16 2015-10-22 Signal Pharmaceuticals, Llc SOLID FORMS COMPRISING 7-(6-(2-HYDROXYPROPAN-2YL) PYRIDIN-3-YL)-1-(TRANS)-4-METHOXYCYCLOHEXYL)-3, 4-DIHYDROPYRAZINO[2,3-b] PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
ES2823756T3 (es) 2014-04-16 2021-05-10 Signal Pharm Llc Métodos para tratar el cáncer usando terapia de combinación de inhibidores de quinasa TOR
JP2017520603A (ja) 2014-07-14 2017-07-27 シグナル ファーマシューティカルズ，エルエルシー 置換ピロロピリミジン化合物を使用するがんの治療方法及びその組成物
NZ629796A (en) 2014-07-14 2015-12-24 Signal Pharm Llc Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
ES2960991T3 (es) 2014-09-12 2024-03-07 Biohaven Therapeutics Ltd Benzoimidazol-1,2-ilamidas como activadores del canal Kv7
KR20200019229A (ko) 2017-06-22 2020-02-21 셀진 코포레이션 B형 간염 바이러스 감염을 특징으로 하는 간세포 암종의 치료

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3590045A (en) * 1969-09-25 1971-06-29 Smith Kline French Lab Certain substituted imidazo (4,5-b)pyridines
BE788065A (fr) 1971-08-26 1973-02-26 Degussa Nouvelles aza-benzimidazoles et procede pour leur preparation
SE422799B (sv) 1975-05-28 1982-03-29 Merck & Co Inc Analogiforfarande for framstellning av 1,3-dihydroimidazo (4,5-b)pyridin-2-oner
ES473201A1 (es) * 1977-09-26 1979-03-16 Degussa Procedimiento para la preparacion de 7-azabencimidazoles
US5217999A (en) * 1987-12-24 1993-06-08 Yissum Research Development Company Of The Hebrew University Of Jerusalem Styryl compounds which inhibit EGF receptor protein tyrosine kinase
ES2064101T3 (es) * 1990-04-02 1995-01-16 Pfizer Compuestos de acido bencilfosfonico inhibidores de la quinasa de tirosina.
US5302606A (en) * 1990-04-16 1994-04-12 Rhone-Poulenc Rorer Pharmaceuticals Inc. Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase
WO1992020642A1 (en) * 1991-05-10 1992-11-26 Rhone-Poulenc Rorer International (Holdings) Inc. Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase
JPH06503095A (ja) * 1991-05-29 1994-04-07 ファイザー・インコーポレーテッド 三環式ポリヒドロキシ系のチロシンキナーゼ阻害薬
AU661533B2 (en) * 1992-01-20 1995-07-27 Astrazeneca Ab Quinazoline derivatives
AU672224B2 (en) * 1992-08-06 1996-09-26 Warner-Lambert Company 2-thioindoles (selenoindoles) and related disulfides (selenides) which inhibit protein tyrosine kinases and whichhave antitumor properties
US5330992A (en) * 1992-10-23 1994-07-19 Sterling Winthrop Inc. 1-cyclopropyl-4-pyridyl-quinolinones
GB9226855D0 (en) * 1992-12-23 1993-02-17 Erba Carlo Spa Vinylene-azaindole derivatives and process for their preparation
US5582995A (en) 1993-06-11 1996-12-10 The General Hospital Corporation Methods of screening for compounds which inhibit the direct binding of Ras to Raf
US5645982A (en) * 1993-08-19 1997-07-08 Systemix, Inc. Method for screening potential therapeutically effective antiviral agents
GB9501567D0 (en) * 1995-01-26 1995-03-15 Pharmacia Spa Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors
US5880141A (en) * 1995-06-07 1999-03-09 Sugen, Inc. Benzylidene-Z-indoline compounds for the treatment of disease

Also Published As

Publication number Publication date
EP1017384B1 (en) 2004-11-10
SK4152000A3 (en) 2002-02-05
ZA988797B (en) 1999-12-02
KR20010015623A (ko) 2001-02-26
US6093728A (en) 2000-07-25
EP1017384A1 (en) 2000-07-12
IL135109A (en) 2007-07-04
NZ503432A (en) 2002-11-26
TR200001546T2 (tr) 2000-10-23
UA72448C2 (en) 2005-03-15
PT1017384E (pt) 2005-03-31
ATE281834T1 (de) 2004-11-15
WO1999016438A1 (en) 1999-04-08
CN1278172A (zh) 2000-12-27
HUP0004024A3 (en) 2001-10-29
PL339744A1 (en) 2001-01-02
AU9578198A (en) 1999-04-23
CA2305370A1 (en) 1999-04-08
HK1032206A1 (en) 2001-07-13
SK285357B6 (sk) 2006-11-03
BG104356A (en) 2000-12-29
AU748849B2 (en) 2002-06-13
NO20001555L (no) 2000-03-24
ES2230719T3 (es) 2005-05-01
BR9812682A (pt) 2000-08-22
CA2305370C (en) 2006-11-28
TW581815B (en) 2004-04-01
AR017266A1 (es) 2001-09-05
NZ517808A (en) 2003-07-25
HUP0004024A2 (hu) 2001-04-28
DE69827516T2 (de) 2005-12-01
US6855723B2 (en) 2005-02-15
KR100547929B1 (ko) 2006-02-02
PL191618B1 (pl) 2006-06-30
JP2001517699A (ja) 2001-10-09
CN1167420C (zh) 2004-09-22
DE69827516D1 (de) 2004-12-16
IL158649A (en) 2006-12-10
BG64784B1 (bg) 2006-04-28
NO20001555D0 (no) 2000-03-24
DK1017384T3 (da) 2005-01-31
IL135109A0 (en) 2001-05-20
NO325663B1 (no) 2008-07-07
US20030181480A1 (en) 2003-09-25
RU2230553C2 (ru) 2004-06-20

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