CA2470480C - Indolinone derivatives useful as protein kinase inhibitors - Google Patents
Indolinone derivatives useful as protein kinase inhibitors Download PDFInfo
- Publication number
- CA2470480C CA2470480C CA2470480A CA2470480A CA2470480C CA 2470480 C CA2470480 C CA 2470480C CA 2470480 A CA2470480 A CA 2470480A CA 2470480 A CA2470480 A CA 2470480A CA 2470480 C CA2470480 C CA 2470480C
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- compound
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- dimethyl
- pyrrol
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- 239000005720 sucrose Substances 0.000 description 1
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- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- QHQATUUBFDYJOC-UHFFFAOYSA-N tert-butyl 4-[3-[2,4-dimethyl-5-[(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoyl]piperazine-1-carboxylate Chemical compound CC=1NC(C=C2C3=CC=CC=C3NC2=O)=C(C)C=1CCC(=O)N1CCN(C(=O)OC(C)(C)C)CC1 QHQATUUBFDYJOC-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34381301P | 2001-12-27 | 2001-12-27 | |
| US34374601P | 2001-12-27 | 2001-12-27 | |
| US60/343,746 | 2001-12-27 | ||
| US60/343,813 | 2001-12-27 | ||
| PCT/US2002/041252 WO2003057690A1 (en) | 2001-12-27 | 2002-12-20 | Indolinone derivatives useful as protein kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2470480A1 CA2470480A1 (en) | 2003-07-17 |
| CA2470480C true CA2470480C (en) | 2010-12-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2470480A Expired - Fee Related CA2470480C (en) | 2001-12-27 | 2002-12-20 | Indolinone derivatives useful as protein kinase inhibitors |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US6686362B2 (https=) |
| EP (1) | EP1458713B1 (https=) |
| JP (1) | JP4363985B2 (https=) |
| KR (1) | KR100965519B1 (https=) |
| CN (1) | CN1290844C (https=) |
| AT (1) | ATE302771T1 (https=) |
| AU (1) | AU2002360753B2 (https=) |
| BR (1) | BR0215360A (https=) |
| CA (1) | CA2470480C (https=) |
| CO (1) | CO5611126A2 (https=) |
| DE (1) | DE60205776T2 (https=) |
| DK (1) | DK1458713T3 (https=) |
| ES (1) | ES2247411T3 (https=) |
| HU (1) | HUP0500111A3 (https=) |
| IL (1) | IL162203A0 (https=) |
| MX (1) | MXPA04006271A (https=) |
| NO (1) | NO327550B1 (https=) |
| NZ (1) | NZ533219A (https=) |
| PL (1) | PL208283B1 (https=) |
| RU (1) | RU2316554C2 (https=) |
| WO (1) | WO2003057690A1 (https=) |
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| US7195876B2 (en) * | 2002-08-09 | 2007-03-27 | Theravance, Inc. | Oncokinase fusion polypeptides associated with hyperproliferative and related disorders, nucleic acids encoding the same and methods for detecting and identifying the same |
| RU2006117635A (ru) * | 2003-10-24 | 2007-12-10 | Шеринг Акциенгезельшафт (De) | Производные индолинона и их применение для лечения патологических состояний, таких как злокачественное новообразование |
| 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 |
| SE0401790D0 (sv) * | 2004-07-07 | 2004-07-07 | Forskarpatent I Syd Ab | Tamoxifen response in pre- and postmenopausal breast cancer patients |
| US7825244B2 (en) | 2005-06-10 | 2010-11-02 | Janssen Pharmaceutica Nv | Intermediates useful in the synthesis of alkylquinoline and alkylquinazoline kinase modulators, and related methods of synthesis |
| US8071768B2 (en) | 2005-06-10 | 2011-12-06 | Janssen Pharmaceutica, N.V. | Alkylquinoline and alkylquinazoline kinase modulators |
| US20060281788A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using a flt3 inhibitor and a farnesyl transferase inhibitor |
| AU2006304897B2 (en) | 2005-10-18 | 2012-07-12 | Janssen Pharmaceutica N.V. | Method of inhibiting FLT3 kinase |
| US8697716B2 (en) | 2006-04-20 | 2014-04-15 | Janssen Pharmaceutica Nv | Method of inhibiting C-KIT kinase |
| WO2007124319A1 (en) | 2006-04-20 | 2007-11-01 | Janssen Pharmaceutica N.V. | Inhibitors of c-fms kinase |
| PL2021335T3 (pl) | 2006-04-20 | 2011-10-31 | Janssen Pharmaceutica Nv | Związki heterocykliczne jako inhibitory kinazy C-FMS |
| JP2010502741A (ja) * | 2006-09-11 | 2010-01-28 | キュリス，インコーポレイテッド | Ｐｔｋインヒビターとしての亜鉛結合部分を含む置換２−インドリノン |
| JO3240B1 (ar) | 2007-10-17 | 2018-03-08 | Janssen Pharmaceutica Nv | c-fms مثبطات كيناز |
| FR2948940B1 (fr) * | 2009-08-04 | 2011-07-22 | Servier Lab | Nouveaux derives dihydroindolones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| HUE045270T2 (hu) | 2010-01-05 | 2019-12-30 | Inst Nat Sante Rech Med | FLT3 receptor anatgonisták fájdalom rendellenességek kezelésére |
| ES2539170T3 (es) | 2010-01-12 | 2015-06-26 | Ab Science | Inhibidores de quinasas de oxazol |
| CN104870454B (zh) | 2012-08-07 | 2020-03-03 | 詹森药业有限公司 | 用于制备杂环酯衍生物的方法 |
| ES2658773T3 (es) | 2012-08-07 | 2018-03-12 | Janssen Pharmaceutica N.V. | Procedimiento de sulfonilación usando fluoruro de nonafluorobutanosulfonilo |
| KR101738063B1 (ko) | 2012-09-21 | 2017-05-19 | 아로그 파마슈티칼스, 인코퍼레이티드 | 구조적으로 활성인 인산화된 ｆｌｔ３ 키나제의 억제 방법 |
| BR112015016282A2 (en) | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals, Inc. | crenolanib for treatment of mutated flt3 proliferative disorders |
| FR3008411B1 (fr) * | 2013-07-12 | 2015-07-03 | Servier Lab | Nouveau sel de la 3-[(3-{[4-(4-morpholinylmethyl)-1h-pyrrol-2-yl]methylene}-2-oxo-2,3-dihydro-1h-indol-5-yl)methyl]-1,3-thiazolidine-2,4-dione, sa preparation, et les formulations qui le contiennent |
| US10463658B2 (en) | 2013-10-25 | 2019-11-05 | Videra Pharmaceuticals, Llc | Method of inhibiting FLT3 kinase |
| BR112017002001B1 (pt) | 2014-07-31 | 2022-10-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compostos e composição farmacêutica |
| EP3254698A1 (en) | 2016-06-08 | 2017-12-13 | Universite De Montpellier | Flt3 receptor inhibitor at low dosage for the treatment of neuropathic pain |
| US12534764B2 (en) | 2016-11-02 | 2026-01-27 | Arog Pharmaceuticals, Inc. | Crenolanib for treating FLT3 mutated proliferative disorders associated mutations |
| EA201991078A1 (ru) | 2016-11-02 | 2019-11-29 | Креноланиб для лечения пролиферативных расстройств, связанных с мутацией flt3 | |
| JP2020519665A (ja) | 2017-05-17 | 2020-07-02 | アンセルム（アンスティテュト ナショナル ド ラ サンテ エ ド ラ ルシェルシュ メディカル） | オピオイドによる痛みの処置を改善する為のｆｌｔ３阻害剤 |
| WO2019057649A1 (en) | 2017-09-19 | 2019-03-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA |
| WO2022019998A1 (en) | 2020-07-20 | 2022-01-27 | Arog Pharmaceuticals, Inc. | Crystal forms of crenolanib and methods of use thereof |
| US11969420B2 (en) | 2020-10-30 | 2024-04-30 | Arog Pharmaceuticals, Inc. | Combination therapy of crenolanib and apoptosis pathway agents for the treatment of proliferative disorders |
| WO2022090547A1 (en) | 2020-10-30 | 2022-05-05 | Dsm Ip Assets B.V. | Production of carotenoids by fermentation |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MC2096A1 (fr) * | 1989-02-23 | 1991-02-15 | Hoffmann La Roche | Pyrroles substitues |
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| CO4950519A1 (es) | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| SK287132B6 (sk) * | 1998-05-29 | 2009-12-07 | Sugen, Inc. | Farmaceutická kompozícia obsahujúca pyrolom substituovaný 2-indolinón, súprava obsahujúca uvedenú kompozíciu a použitie pyrolom substituovaného 2-indolinónu |
| BR9916327A (pt) * | 1998-12-17 | 2001-09-18 | Hoffmann La Roche | Oxindóis de 4-alquenila (e alquinila) como inibidores de cinases dependentes de ciclina, em particular, cdk2 |
| MXPA01006742A (es) | 1998-12-31 | 2004-04-21 | Sugen Inc | Compuestos 3-heteroarilidenil-2-indolinona para modular la actividad de la quinasa de proteina y para utilizarse en la quimioterapia de cancer. |
| DE19924401A1 (de) | 1999-05-27 | 2000-11-30 | Boehringer Ingelheim Pharma | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| CA2381821A1 (en) | 1999-08-27 | 2001-03-08 | Boehringer Ingelheim Pharma Kg | Substituted indolinones, their manufacture and their use as medicaments |
| CA2384378C (en) | 1999-10-06 | 2011-05-24 | Boehringer Ingelheim Pharmaceuticals, Inc. | Heterocyclic compounds useful as inhibitors of tyrosine kinases |
| UA75054C2 (uk) | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
| DE19949209A1 (de) | 1999-10-13 | 2001-04-19 | Boehringer Ingelheim Pharma | In 5-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| WO2001042243A2 (en) | 1999-12-08 | 2001-06-14 | Advanced Medicine, Inc. | Protein kinase inhibitors |
| JP3663382B2 (ja) * | 2000-02-15 | 2005-06-22 | スージェン・インコーポレーテッド | ピロール置換２−インドリノン蛋白質キナーゼ阻害剤 |
| WO2002002551A1 (en) | 2000-06-30 | 2002-01-10 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| PT1315715E (pt) | 2000-08-18 | 2008-10-30 | Millennium Pharm Inc | Derivados de quianazolina utilizados como inibidores de quinase |
| WO2002055517A2 (en) | 2000-12-20 | 2002-07-18 | Jingrong Cui | 4-(hetero)aryl substituted indolinones |
| US7195876B2 (en) | 2002-08-09 | 2007-03-27 | Theravance, Inc. | Oncokinase fusion polypeptides associated with hyperproliferative and related disorders, nucleic acids encoding the same and methods for detecting and identifying the same |
| 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 |
-
2002
- 2002-12-20 EP EP02796035A patent/EP1458713B1/en not_active Expired - Lifetime
- 2002-12-20 AT AT02796035T patent/ATE302771T1/de active
- 2002-12-20 IL IL16220302A patent/IL162203A0/xx unknown
- 2002-12-20 BR BR0215360-2A patent/BR0215360A/pt not_active IP Right Cessation
- 2002-12-20 NZ NZ533219A patent/NZ533219A/en not_active IP Right Cessation
- 2002-12-20 DE DE60205776T patent/DE60205776T2/de not_active Expired - Lifetime
- 2002-12-20 CA CA2470480A patent/CA2470480C/en not_active Expired - Fee Related
- 2002-12-20 KR KR1020047010148A patent/KR100965519B1/ko not_active Expired - Fee Related
- 2002-12-20 HU HU0500111A patent/HUP0500111A3/hu unknown
- 2002-12-20 DK DK02796035T patent/DK1458713T3/da active
- 2002-12-20 ES ES02796035T patent/ES2247411T3/es not_active Expired - Lifetime
- 2002-12-20 MX MXPA04006271A patent/MXPA04006271A/es active IP Right Grant
- 2002-12-20 RU RU2004122918/04A patent/RU2316554C2/ru not_active IP Right Cessation
- 2002-12-20 US US10/327,385 patent/US6686362B2/en not_active Expired - Lifetime
- 2002-12-20 AU AU2002360753A patent/AU2002360753B2/en not_active Ceased
- 2002-12-20 JP JP2003558005A patent/JP4363985B2/ja not_active Expired - Fee Related
- 2002-12-20 CN CNB028261399A patent/CN1290844C/zh not_active Expired - Fee Related
- 2002-12-20 WO PCT/US2002/041252 patent/WO2003057690A1/en not_active Ceased
- 2002-12-20 PL PL369602A patent/PL208283B1/pl not_active IP Right Cessation
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2003
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2004
- 2004-07-08 NO NO20042926A patent/NO327550B1/no not_active IP Right Cessation
- 2004-07-22 CO CO04070253A patent/CO5611126A2/es not_active Application Discontinuation
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2006
- 2006-02-21 US US11/358,305 patent/US7223783B2/en not_active Expired - Lifetime
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