CO5611126A2 - Derivados de indolinona utiles como inhibidores de la proteina cinasa - Google Patents
Derivados de indolinona utiles como inhibidores de la proteina cinasaInfo
- Publication number
- CO5611126A2 CO5611126A2 CO04070253A CO04070253A CO5611126A2 CO 5611126 A2 CO5611126 A2 CO 5611126A2 CO 04070253 A CO04070253 A CO 04070253A CO 04070253 A CO04070253 A CO 04070253A CO 5611126 A2 CO5611126 A2 CO 5611126A2
- Authority
- CO
- Colombia
- Prior art keywords
- group
- formula
- alkyl group
- hydrogen atom
- independently
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 title 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 3
- 125000005843 halogen group Chemical group 0.000 abstract 3
- 125000003386 piperidinyl group Chemical group 0.000 abstract 3
- 125000001424 substituent group Chemical group 0.000 abstract 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000004956 cyclohexylene group Chemical group 0.000 abstract 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 abstract 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 abstract 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 abstract 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 abstract 1
- 102200001405 rs377584435 Human genes 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 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)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Abstract
1.- Un compuesto de fórmula (I) en donde (i) R1 representa un átomo de hidrógeno o un grupo alquilo(C1-4); y R2 representa un grupo de fórmula -A1-NR5R6 en donde cada uno de R5 y R6 representa independientemente un átomo de hidrógeno o un grupo alquilo(C1-4) y A1 representa (CH2)m, (CH2)n-A2-(CH2)p o (CH2CH2O)qCH2CH2 en donde m es un número entero desde 2 a 10, cada uno de n y p es un número entero desde 1 a 6, A2 es CH=CH, fenileno, bifenileno, ciclohexileno o piperazinileno y q es 1, 2 ó 3; (ii) R1 y R2 juntos representan -A3-NR7-A4- en donde cada uno de A3 y A4 representan independientemente (CH2)r o (CH2CH2O)sCH2CH2 en donde r es un número entero desde 2 a 6, s es 1, 2 ó 3, y R7 representa un átomo de hidrógeno o un grupo alquilo(C1-4); (iii) R1 y R2 junto con el átomo de nitrógeno al cual están unidos representan un grupo piperidinilo, cuyo grupo piperidinilo lleva un sustituyente de fórmula -A5-R8 en la posición 4, en donde A5 representa alquileno(C1-4) y R8 representa piperidin-4-ilo; o (iv) R1 y R2 junto con el átomo de nitrógeno al cual están unidos representan un grupo pirrolidinilo, piperidinilo o morfolino; y R3 y R4 cada uno representa independientemente un átomo de hidrógeno, un átomo de halógeno, un grupo alquilo(C1-4), un grupo alcoxi(C1-4), un grupo fenilo que es insustituido o sustituido por uno o dos sustituyentes seleccionados independientemente entre un átomo de halógeno, un grupo alquilo(C1-4) y un grupo alcoxi(C1-4), un grupo de fórmula R8S(O)2NR9-, un grupo de fórmula R10N(R11)S(O)2-, un grupo de fórmula R12C(O)N(R13)- o un grupo de fórmula R14N(R15)C(O)- en donde cada uno de R8, R10, R12 y R14 representan independientemente un grupo alquilo(C1-4) o un grupo fenilo que es insustituido o sustituido por uno o dos sustituyentes seleccionados independientemente entre un átomo de halógeno, un grupo alquilo(C1-4) y un grupo alcoxi(C1-4), y cada uno de R9, R11, R13 y R15 representa independientemente un átomo de hidrógeno o un grupo alquilo(C1-4);o su sal farmacéuticamente aceptable.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34374601P | 2001-12-27 | 2001-12-27 | |
| US34381301P | 2001-12-27 | 2001-12-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CO5611126A2 true CO5611126A2 (es) | 2006-02-28 |
Family
ID=26993599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CO04070253A CO5611126A2 (es) | 2001-12-27 | 2004-07-22 | Derivados de indolinona utiles como inhibidores de la proteina cinasa |
Country Status (22)
| Country | Link |
|---|---|
| US (3) | US6686362B2 (es) |
| EP (1) | EP1458713B1 (es) |
| JP (1) | JP4363985B2 (es) |
| KR (1) | KR100965519B1 (es) |
| CN (1) | CN1290844C (es) |
| AT (1) | ATE302771T1 (es) |
| AU (1) | AU2002360753B2 (es) |
| BR (1) | BR0215360A (es) |
| CA (1) | CA2470480C (es) |
| CO (1) | CO5611126A2 (es) |
| DE (1) | DE60205776T2 (es) |
| DK (1) | DK1458713T3 (es) |
| ES (1) | ES2247411T3 (es) |
| HK (1) | HK1068886A1 (es) |
| HU (1) | HUP0500111A3 (es) |
| IL (1) | IL162203A0 (es) |
| MX (1) | MXPA04006271A (es) |
| NO (1) | NO327550B1 (es) |
| NZ (1) | NZ533219A (es) |
| PL (1) | PL208283B1 (es) |
| RU (1) | RU2316554C2 (es) |
| WO (1) | WO2003057690A1 (es) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4588447B2 (ja) * | 2002-08-09 | 2010-12-01 | セラヴァンス， インコーポレーテッド | 過剰増殖および関連疾患に関連するオンコキナーゼ融合ポリペプチド、これをコードする核酸、ならびにこれを検出する方法および同定する方法 |
| US7105563B2 (en) | 2003-10-24 | 2006-09-12 | Schering Aktiengesellschaft | Indolinone derivatives and their use in treating disease-states such as cancer |
| 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 |
| 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 |
| US8071768B2 (en) | 2005-06-10 | 2011-12-06 | Janssen Pharmaceutica, N.V. | Alkylquinoline and alkylquinazoline kinase modulators |
| 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 |
| JP2009511628A (ja) | 2005-10-18 | 2009-03-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｆｌｔ３キナーゼの阻害方法 |
| JP5331681B2 (ja) | 2006-04-20 | 2013-10-30 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ｃ−ｆｍｓキナーゼの阻害剤 |
| WO2007124316A1 (en) | 2006-04-20 | 2007-11-01 | Janssen Pharmaceutica N.V. | Heterocyclic compounds as inhibitors of c-fms kinase |
| US8697716B2 (en) | 2006-04-20 | 2014-04-15 | Janssen Pharmaceutica Nv | Method of inhibiting C-KIT kinase |
| WO2008033743A1 (en) | 2006-09-11 | 2008-03-20 | Curis, Inc. | Substituted 2-indolinone as ptk inhibitors containing a zinc binding moiety |
| 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 |
| CA2786800C (en) | 2010-01-12 | 2018-02-27 | Ab Science | Thiazole and oxazole kinase inhibitors |
| JOP20180012A1 (ar) | 2012-08-07 | 2019-01-30 | Janssen Pharmaceutica Nv | عملية السلفنة باستخدام نونافلوروبوتانيسولفونيل فلوريد |
| EP2882757B1 (en) | 2012-08-07 | 2016-10-05 | Janssen Pharmaceutica, N.V. | Process for the preparation of heterocyclic ester derivatives |
| KR101738063B1 (ko) | 2012-09-21 | 2017-05-19 | 아로그 파마슈티칼스, 인코퍼레이티드 | 구조적으로 활성인 인산화된 ｆｌｔ３ 키나제의 억제 방법 |
| BR112015016282A2 (pt) | 2013-01-07 | 2017-07-11 | Arog Pharmaceuticals Inc | crenolanibe para tratamento de distúrbios proliferativos de flt3 mutado |
| 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 |
| CA2956417C (en) | 2014-07-31 | 2022-09-13 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Flt3 receptor antagonists |
| EP3254698A1 (en) | 2016-06-08 | 2017-12-13 | Universite De Montpellier | Flt3 receptor inhibitor at low dosage for the treatment of neuropathic pain |
| JP2019532011A (ja) | 2016-11-02 | 2019-11-07 | アログ・ファーマシューティカルズ・インコーポレイテッドＡｒｏｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | Ｆｌｔ３突然変異増殖性疾患および関連する突然変異を治療するためのクレノラニブ |
| AU2018269678A1 (en) | 2017-05-17 | 2019-12-12 | Biodol Therapeutics | FLT3 inhibitors for improving pain treatments by opioids |
| 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 |
| US11713310B2 (en) | 2020-07-20 | 2023-08-01 | 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 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| DK2020408T3 (da) * | 1998-05-29 | 2013-09-30 | Sugen Inc | Pyrrol-substitueret 2-indolinon som proteinkinaseinhibitor |
| TR200101860T2 (tr) * | 1998-12-17 | 2001-12-21 | F.Hoffmann-La Roche Ag | Sikline bağlı kinaz inhibitörleri olarak 4-alkenil (ve alkinil) oksidoller |
| WO2000038519A1 (en) | 1998-12-31 | 2000-07-06 | Sugen, Inc. | 3-heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy |
| DE19924401A1 (de) | 1999-05-27 | 2000-11-30 | Boehringer Ingelheim Pharma | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| JP3952369B2 (ja) | 1999-08-27 | 2007-08-01 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | 新規な置換インドリノン類、その製造及びその薬剤としての使用 |
| MXPA02003364A (es) | 1999-10-06 | 2002-08-23 | Boehringer Ingelheim Pharma | Compuestos heterociclicos utiles como inhibidores de las cinasas de tirosina. |
| 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 |
| CA2399358C (en) | 2000-02-15 | 2006-03-21 | Sugen, Inc. | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| US6635640B2 (en) | 2000-06-30 | 2003-10-21 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| KR100831116B1 (ko) | 2000-08-18 | 2008-05-20 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 키나아제 억제제로서의 퀴나졸린 유도체 |
| PE20020776A1 (es) | 2000-12-20 | 2002-08-22 | Sugen Inc | Indolinonas 4-aril sustituidas |
| JP4588447B2 (ja) | 2002-08-09 | 2010-12-01 | セラヴァンス， インコーポレーテッド | 過剰増殖および関連疾患に関連するオンコキナーゼ融合ポリペプチド、これをコードする核酸、ならびにこれを検出する方法および同定する方法 |
| 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 US US10/327,385 patent/US6686362B2/en not_active Expired - Lifetime
- 2002-12-20 CA CA2470480A patent/CA2470480C/en not_active Expired - Fee Related
- 2002-12-20 JP JP2003558005A patent/JP4363985B2/ja not_active Expired - Fee Related
- 2002-12-20 HU HU0500111A patent/HUP0500111A3/hu unknown
- 2002-12-20 CN CNB028261399A patent/CN1290844C/zh not_active Expired - Fee Related
- 2002-12-20 ES ES02796035T patent/ES2247411T3/es not_active Expired - Lifetime
- 2002-12-20 EP EP02796035A patent/EP1458713B1/en not_active Expired - Lifetime
- 2002-12-20 RU RU2004122918/04A patent/RU2316554C2/ru not_active IP Right Cessation
- 2002-12-20 MX MXPA04006271A patent/MXPA04006271A/es active IP Right Grant
- 2002-12-20 AU AU2002360753A patent/AU2002360753B2/en not_active Ceased
- 2002-12-20 BR BR0215360-2A patent/BR0215360A/pt not_active IP Right Cessation
- 2002-12-20 KR KR1020047010148A patent/KR100965519B1/ko not_active IP Right Cessation
- 2002-12-20 IL IL16220302A patent/IL162203A0/xx unknown
- 2002-12-20 NZ NZ533219A patent/NZ533219A/en not_active IP Right Cessation
- 2002-12-20 PL PL369602A patent/PL208283B1/pl not_active IP Right Cessation
- 2002-12-20 DK DK02796035T patent/DK1458713T3/da active
- 2002-12-20 AT AT02796035T patent/ATE302771T1/de active
- 2002-12-20 DE DE60205776T patent/DE60205776T2/de not_active Expired - Lifetime
- 2002-12-20 WO PCT/US2002/041252 patent/WO2003057690A1/en active IP Right Grant
-
2003
- 2003-10-22 US US10/691,094 patent/US7060703B2/en not_active Expired - Lifetime
-
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
-
2005
- 2005-02-23 HK HK05101511A patent/HK1068886A1/xx not_active IP Right Cessation
-
2006
- 2006-02-21 US US11/358,305 patent/US7223783B2/en not_active Expired - Lifetime
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