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
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 |
|---|---|---|---|---|
| EP1576129A4 (en) * | 2002-08-09 | 2008-01-23 | Theravance Inc | ONCOKINASE FUSION POLYPEPTIDES ASSOCIATED WITH HYPERPROLIFERATIVE DISORDERS, NUCLEIC ACIDS ENCODING THESE POLYPEPTIDES AND METHODS OF DETECTION AND IDENTIFICATION THEREOF |
| WO2005040116A2 (en) * | 2003-10-24 | 2005-05-06 | Schering Aktiengesellschaft | Indolinone derivatives and their use in treating disease-states such as cancer |
| JP2007513967A (ja) * | 2003-12-11 | 2007-05-31 | セラヴァンス， インコーポレーテッド | 変異レセプターチロシンキナーゼが駆動する細胞増殖性疾患の処置において使用するための組成物 |
| 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 |
| CN101340909B (zh) | 2005-10-18 | 2012-01-11 | 詹森药业有限公司 | 抑制flt3激酶的方法 |
| DK2021335T3 (da) | 2006-04-20 | 2011-09-05 | Janssen Pharmaceutica Nv | Heterocykliske forbindelser som C-FMS-kinasehæmmere |
| US8697716B2 (en) | 2006-04-20 | 2014-04-15 | Janssen Pharmaceutica Nv | Method of inhibiting C-KIT kinase |
| PE20080074A1 (es) | 2006-04-20 | 2008-02-11 | Janssen Pharmaceutica Nv | Derivados de amida como agentes inhibidores de la quinasa c-fms |
| CA2663147A1 (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 |
| US9109227B2 (en) | 2010-01-05 | 2015-08-18 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | FLT3 receptor antagonists for the treatment or the prevention of pain disorders |
| WO2011086085A1 (en) | 2010-01-12 | 2011-07-21 | Ab Science | Thiazole and oxazole kinase inhibitors |
| IN2015DN00659A (es) | 2012-08-07 | 2015-06-26 | Janssen Pharmaceutica Nv | |
| JOP20180012A1 (ar) | 2012-08-07 | 2019-01-30 | Janssen Pharmaceutica Nv | عملية السلفنة باستخدام نونافلوروبوتانيسولفونيل فلوريد |
| JP6407504B2 (ja) | 2012-09-21 | 2018-10-17 | 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． | 恒常的に活性であるリン酸化型ｆｌｔ３キナーゼの阻害方法 |
| 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 |
| WO2016016370A1 (en) | 2014-07-31 | 2016-02-04 | INSERM (Institut National de la Santé et de la Recherche Médicale) | 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 |
| CN108778276A (zh) | 2016-11-02 | 2018-11-09 | 安罗格制药有限责任公司 | 用于治疗flt3突变型增殖性疾患相关突变的克莱拉尼 |
| US20200171022A1 (en) | 2017-05-17 | 2020-06-04 | Inserm (Institut National De La Santé Et Da La Recherche Médicale) | 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 |
| 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 |
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 |
| CA2314156C (en) | 1998-05-29 | 2010-05-25 | Sugen, Inc. | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| TR200101860T2 (tr) * | 1998-12-17 | 2001-12-21 | F.Hoffmann-La Roche Ag | Sikline bağlı kinaz inhibitörleri olarak 4-alkenil (ve alkinil) oksidoller |
| BR9916735A (pt) | 1998-12-31 | 2001-09-25 | Sugen Inc | Compostos de 3-heteroarilidenil-2-indolinona para a modulação da atividade das cinases protéicas e para uso na quimioterapia do cancêr |
| DE19924401A1 (de) | 1999-05-27 | 2000-11-30 | Boehringer Ingelheim Pharma | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| EP1212318B1 (de) | 1999-08-27 | 2006-01-25 | Boehringer Ingelheim Pharma GmbH & Co.KG | Substituierte indolinone als tyrosinkinase inhibitoren |
| JP5036112B2 (ja) | 1999-10-06 | 2012-09-26 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | チロシンキナーゼのインヒビターとして有益な複素環化合物 |
| DE19949209A1 (de) | 1999-10-13 | 2001-04-19 | Boehringer Ingelheim Pharma | In 5-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| 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 |
| AU2576501A (en) | 1999-12-08 | 2001-06-18 | Advanced Medicine, Inc. | Protein kinase inhibitors |
| NZ520640A (en) | 2000-02-15 | 2005-04-29 | Upjohn Co | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| AU2001270260A1 (en) | 2000-06-30 | 2002-01-14 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| NZ524461A (en) | 2000-08-18 | 2004-12-24 | Millennium Pharm Inc | Quinazoline derivatives as kinase inhibitors |
| PE20020776A1 (es) | 2000-12-20 | 2002-08-22 | Sugen Inc | Indolinonas 4-aril sustituidas |
| EP1576129A4 (en) | 2002-08-09 | 2008-01-23 | Theravance Inc | ONCOKINASE FUSION POLYPEPTIDES ASSOCIATED WITH HYPERPROLIFERATIVE DISORDERS, NUCLEIC ACIDS ENCODING THESE POLYPEPTIDES AND METHODS OF DETECTION AND IDENTIFICATION THEREOF |
| JP2007513967A (ja) * | 2003-12-11 | 2007-05-31 | セラヴァンス， インコーポレーテッド | 変異レセプターチロシンキナーゼが駆動する細胞増殖性疾患の処置において使用するための組成物 |
-
2002
- 2002-12-20 RU RU2004122918/04A patent/RU2316554C2/ru not_active IP Right Cessation
- 2002-12-20 CA CA2470480A patent/CA2470480C/en not_active Expired - Fee Related
- 2002-12-20 WO PCT/US2002/041252 patent/WO2003057690A1/en active IP Right Grant
- 2002-12-20 KR KR1020047010148A patent/KR100965519B1/ko not_active IP Right Cessation
- 2002-12-20 MX MXPA04006271A patent/MXPA04006271A/es active IP Right Grant
- 2002-12-20 AT AT02796035T patent/ATE302771T1/de active
- 2002-12-20 DK DK02796035T patent/DK1458713T3/da active
- 2002-12-20 CN CNB028261399A patent/CN1290844C/zh not_active Expired - Fee Related
- 2002-12-20 NZ NZ533219A patent/NZ533219A/en not_active IP Right Cessation
- 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 HU HU0500111A patent/HUP0500111A3/hu unknown
- 2002-12-20 ES ES02796035T patent/ES2247411T3/es not_active Expired - Lifetime
- 2002-12-20 DE DE60205776T patent/DE60205776T2/de not_active Expired - Lifetime
- 2002-12-20 IL IL16220302A patent/IL162203A0/xx unknown
- 2002-12-20 US US10/327,385 patent/US6686362B2/en not_active Expired - Lifetime
- 2002-12-20 BR BR0215360-2A patent/BR0215360A/pt not_active IP Right Cessation
- 2002-12-20 EP EP02796035A patent/EP1458713B1/en not_active Expired - Lifetime
- 2002-12-20 PL PL369602A patent/PL208283B1/pl not_active IP Right Cessation
-
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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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FC | Application refused |