UA72448C2 - Azabenzimidazole-based compounds, methods for their synthesis and pharmaceutical composition, method for modulating function of serine/threonine protein kinases with azabenzimidazole-based compounds, method for identifying compounds modulating functioning of serine/threonine protein kinase, method for preventing and treating serine/threonine protein kinase-related abnormal conditions with azabenzimidazole-based compounds - Google Patents
Azabenzimidazole-based compounds, methods for their synthesis and pharmaceutical composition, method for modulating function of serine/threonine protein kinases with azabenzimidazole-based compounds, method for identifying compounds modulating functioning of serine/threonine protein kinase, method for preventing and treating serine/threonine protein kinase-related abnormal conditions with azabenzimidazole-based compounds Download PDFInfo
- Publication number
- UA72448C2 UA72448C2 UA2000042349A UA2000042349A UA72448C2 UA 72448 C2 UA72448 C2 UA 72448C2 UA 2000042349 A UA2000042349 A UA 2000042349A UA 2000042349 A UA2000042349 A UA 2000042349A UA 72448 C2 UA72448 C2 UA 72448C2
- Authority
- UA
- Ukraine
- Prior art keywords
- meml
- trifluoromethyl
- eml
- protein kinase
- phenyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 201
- 238000000034 method Methods 0.000 title claims abstract description 138
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 102100030011 Endoribonuclease Human genes 0.000 title claims abstract description 30
- 101710199605 Endoribonuclease Proteins 0.000 title claims abstract description 30
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 title claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- 230000015572 biosynthetic process Effects 0.000 title claims description 15
- 238000003786 synthesis reaction Methods 0.000 title claims description 5
- 230000002159 abnormal effect Effects 0.000 title abstract description 10
- 108060006633 protein kinase Proteins 0.000 claims description 120
- 102000001253 Protein Kinase Human genes 0.000 claims description 119
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 77
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 75
- -1 Azabenzimidazole compound Chemical class 0.000 claims description 73
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 54
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 33
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 33
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- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 201000010099 disease Diseases 0.000 claims description 29
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- 208000035475 disorder Diseases 0.000 claims description 25
- 239000000758 substrate Substances 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
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- 230000008859 change Effects 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 19
- 102100028921 Serine/threonine-protein kinase MARK1 Human genes 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 18
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 17
- 230000003993 interaction Effects 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 17
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 16
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- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 16
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
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Classifications
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6014597P | 1997-09-26 | 1997-09-26 | |
| 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 |
|---|---|
| UA72448C2 true UA72448C2 (en) | 2005-03-15 |
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| UA2000042349A UA72448C2 (en) | 1997-09-26 | 1998-09-23 | Azabenzimidazole-based compounds, methods for their synthesis and pharmaceutical composition, method for modulating function of serine/threonine protein kinases with azabenzimidazole-based compounds, method for identifying compounds modulating functioning of serine/threonine protein kinase, method for preventing and treating serine/threonine protein kinase-related abnormal conditions with azabenzimidazole-based compounds |
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| EP (1) | EP1017384B1 (pt) |
| JP (1) | JP2001517699A (pt) |
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| AT (1) | ATE281834T1 (pt) |
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| BR (1) | BR9812682A (pt) |
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| TR (1) | TR200001546T2 (pt) |
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| US20060142236A1 (en) * | 1994-05-31 | 2006-06-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| US6911462B2 (en) * | 1998-05-22 | 2005-06-28 | Avanir Pharmaceuticals | Benzimidazole compounds for regulating IgE |
| US6919366B2 (en) * | 1998-05-22 | 2005-07-19 | Avanir Pharmaceuticals | Benzimidazole derivatives as modulators of IgE |
| US6384049B1 (en) * | 2000-05-25 | 2002-05-07 | The Procter & Gamble Company | Cancer treatment |
| PT1368028E (pt) * | 2001-03-12 | 2007-11-26 | Avanir Pharmaceuticals | Compostos de benzimidazole para modulação de ige e inibição da proliferação celular |
| TW200304820A (en) * | 2002-03-25 | 2003-10-16 | Avanir Pharmaceuticals | Use of benzimidazole analogs in the treatment of cell proliferation |
| TWI276631B (en) * | 2002-09-12 | 2007-03-21 | Avanir Pharmaceuticals | Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
| WO2004024655A2 (en) | 2002-09-12 | 2004-03-25 | Avanir Pharmaceuticals | Phenyl-indole 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 |
| CA2630920A1 (en) * | 2005-11-22 | 2007-05-31 | University Of South Florida | Inhibition of cell proliferation |
| JP2009534457A (ja) | 2006-04-26 | 2009-09-24 | キャンサー・リサーチ・テクノロジー・リミテッド | がん治療用化合物としてのイミダゾ［４，５−ｂ］ピリジン−２−オンおよびオキサゾロ［４，５−ｂ］ピリジン−２−オン化合物およびその類似体 |
| ES2627352T3 (es) * | 2006-10-19 | 2017-07-27 | Signal Pharmaceuticals, Llc | Compuestos heteroarilo, sus composiciones y su uso como inhibidores de proteínas quinasas |
| EP2839839B1 (en) * | 2007-02-28 | 2018-01-17 | Yeda Research And Development Company Limited | Nuclear targeting sequences |
| US8304557B2 (en) | 2007-06-05 | 2012-11-06 | Takeda Pharmaceutical Company Limited | Fused heterocycle derivatives and use thereof |
| JP5270553B2 (ja) | 2007-08-23 | 2013-08-21 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
| WO2009028629A1 (ja) | 2007-08-29 | 2009-03-05 | Takeda Pharmaceutical Company Limited | 複素環化合物およびその用途 |
| WO2009077766A1 (en) | 2007-12-19 | 2009-06-25 | 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 |
| WO2010064611A1 (ja) | 2008-12-01 | 2010-06-10 | 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 |
| BR112012009751A2 (pt) | 2009-10-26 | 2020-09-24 | Signal Pharmaceuticals, Llc | métodos de síntese e purificação de heteroarila |
| ES2469367T3 (es) | 2010-02-01 | 2014-06-18 | Cancer Research Technology Limited | 1-(5-Terc-butil-2-fenil-2H-pirazol-3-il)-3-[2-fluoro-4-(1-metil-2-oxo-2,3-dihidro-1H-imidazo[4,5-b]piridin-7-iloxi)-fenil]-urea y compuestos relacionados y su uso en terapia |
| TWI758746B (zh) | 2011-10-19 | 2022-03-21 | 美商標誌製藥公司 | 以tor激酶抑制劑治療癌症 |
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| 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 |
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| CN113831345A (zh) | 2013-05-29 | 2021-12-24 | 西格诺药品有限公司 | 二氢吡嗪并吡嗪化合物的药物组合物、其固体形式和它们的用途 |
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| AU2018289539B2 (en) | 2017-06-22 | 2024-07-04 | Celgene Corporation | Treatment of hepatocellular carcinoma characterized by hepatitis B virus infection |
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| 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 |
| CA2078214C (en) * | 1990-04-02 | 1995-03-28 | Robert Lee Dow | Benzylphosphonic acid tyrosine kinase inhibitors |
| US5302606A (en) * | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
| CA2102780C (en) * | 1991-05-10 | 2007-01-09 | Alfred P. Spada | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| WO1992021660A1 (en) * | 1991-05-29 | 1992-12-10 | Pfizer, Inc. | Tricyclic polyhydroxylic tyrosine kinase inhibitors |
| GB9300059D0 (en) * | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| WO1994003427A1 (en) * | 1992-08-06 | 1994-02-17 | Warner-Lambert Company | 2-thioindoles (selenoindoles) and related disulfides (selenides) which inhibit protein tyrosine kinases and which have 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 |
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1998
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- 1998-09-23 DK DK98949464T patent/DK1017384T3/da active
- 1998-09-23 WO PCT/US1998/019973 patent/WO1999016438A1/en active IP Right Grant
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