CA2718872C - Novel tyrosine kinase inhibitors - Google Patents
Novel tyrosine kinase inhibitors Download PDFInfo
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- CA2718872C CA2718872C CA2718872A CA2718872A CA2718872C CA 2718872 C CA2718872 C CA 2718872C CA 2718872 A CA2718872 A CA 2718872A CA 2718872 A CA2718872 A CA 2718872A CA 2718872 C CA2718872 C CA 2718872C
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- dihydropyridin
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US3803208P | 2008-03-19 | 2008-03-19 | |
| US61/038,032 | 2008-03-19 | ||
| PCT/US2009/001691 WO2009117097A1 (en) | 2008-03-19 | 2009-03-18 | Novel tyrosine kinase inhibitors |
Publications (2)
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| CA2718872A1 CA2718872A1 (en) | 2009-09-24 |
| CA2718872C true CA2718872C (en) | 2016-09-13 |
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| EP (2) | EP2966076A1 (enExample) |
| JP (2) | JP5628145B2 (enExample) |
| CN (1) | CN102036990B (enExample) |
| AU (1) | AU2009226153B2 (enExample) |
| CA (1) | CA2718872C (enExample) |
| DK (1) | DK2262807T3 (enExample) |
| MX (1) | MX2010010272A (enExample) |
| WO (1) | WO2009117097A1 (enExample) |
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| US9249147B2 (en) * | 2008-03-19 | 2016-02-02 | Chembridge Corporation | Tyrosine kinase inhibitors |
| JP5628145B2 (ja) * | 2008-03-19 | 2014-11-19 | ケムブリッジ・コーポレーション | 新規チロシンキナーゼ阻害剤 |
| US8822500B2 (en) | 2008-03-19 | 2014-09-02 | Chembridge Corporation | Tyrosine kinase inhibitors |
| WO2011049625A1 (en) | 2009-10-20 | 2011-04-28 | Mansour Samadpour | Method for aflatoxin screening of products |
| JP5889795B2 (ja) | 2009-11-05 | 2016-03-22 | ライゼン・ファーマシューティカルズ・エスアー | 新規キナーゼモジュレーター |
| AU2011256380C1 (en) | 2010-05-20 | 2016-09-08 | Array Biopharma Inc. | Macrocyclic compounds as Trk kinase inhibitors |
| PH12013502240B1 (en) | 2011-05-04 | 2018-06-27 | Rhizen Pharmaceuticals Sa | Novel compounds as modulators of protein kinase |
| HK1202377A1 (en) * | 2011-11-14 | 2015-10-02 | Tesaro Inc. | Modulating certain tyrosine kinases |
| SG11201406871UA (en) | 2012-04-24 | 2014-11-27 | Chugai Pharmaceutical Co Ltd | Benzamide derivative |
| WO2013161853A1 (ja) * | 2012-04-24 | 2013-10-31 | 中外製薬株式会社 | キナゾリンジオン誘導体 |
| KR102216606B1 (ko) | 2012-07-04 | 2021-02-17 | 리젠 파마슈티컬스 소시에떼 아노님 | 선택적 pi3k 델타 억제제 |
| RU2015137610A (ru) | 2013-03-06 | 2017-04-10 | Дженентек, Инк. | Способы лечения и профилактики лекарственной резистентности злокачественных опухолей |
| CN104109168B (zh) * | 2013-04-20 | 2017-02-15 | 山东轩竹医药科技有限公司 | 四并环激酶抑制剂 |
| JP6562908B2 (ja) | 2013-10-11 | 2019-08-21 | ヤンセン バイオファーマ インク． | 置換ヌクレオシド、置換ヌクレオチドおよびその類似体 |
| CA2927830A1 (en) | 2013-10-23 | 2015-04-30 | Chugai Seiyaku Kabushiki Kaisha | Quinazolinone and isoquinolinone derivative |
| DK3103453T3 (da) * | 2014-02-04 | 2020-04-20 | Astellas Pharma Inc | Medicinsk sammensætning omfattende heterocyklisk diamino-carboxamidforbindelse som aktiv bestanddel |
| TWI680977B (zh) * | 2014-04-17 | 2020-01-01 | 美商安美基公司 | ｃ-Ｍｅｔ抑制劑之多晶形式及共晶 |
| JP2017517552A (ja) | 2014-06-13 | 2017-06-29 | ジェネンテック， インコーポレイテッド | 抗癌剤耐性の治療及び防止方法 |
| BR112017019305A2 (pt) * | 2015-03-10 | 2018-05-08 | Aurigene Discovery Technologies Limited | compostos cíclicos terapêuticos como imunomoduladores |
| AU2016279330B2 (en) | 2015-06-16 | 2020-05-14 | Jiangsu Hengrui Medicine Co., Ltd. | Piperidine derivative and preparation method and pharmaceutical use thereof |
| JP6816100B2 (ja) | 2015-07-16 | 2021-01-20 | アレイ バイオファーマ、インコーポレイテッド | ＲＥＴキナーゼ阻害物質としての置換ピラゾロ［１，５−ａ］ピリジン化合物 |
| EP3387017A1 (en) | 2015-12-11 | 2018-10-17 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or preventing growth of tumors resistant to egfr and/or erbb3 blockade |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| ES2948194T3 (es) | 2017-01-18 | 2023-09-01 | Array Biopharma Inc | Compuestos de pirazolo[1,5-a]pirazina sustituida como inhibidores de la cinasa RET |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| US10513515B2 (en) | 2017-08-25 | 2019-12-24 | Biotheryx, Inc. | Ether compounds and uses thereof |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI812649B (zh) | 2017-10-10 | 2023-08-21 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| US11603374B2 (en) | 2018-01-18 | 2023-03-14 | Array Biopharma Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| JP6997876B2 (ja) | 2018-01-18 | 2022-02-04 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての置換ピラゾリル［４，３－ｃ］ピリジン化合物 |
| TW201938169A (zh) | 2018-01-18 | 2019-10-01 | 美商亞雷生物製藥股份有限公司 | 作為RET激酶抑制劑之經取代吡唑并[3,4-d]嘧啶化合物 |
| EP3830093A1 (en) | 2018-07-27 | 2021-06-09 | Biotheryx, Inc. | Bifunctional compounds as cdk modulators |
| CA3111984A1 (en) | 2018-09-10 | 2020-03-19 | Array Biopharma Inc. | Fused heterocyclic compounds as ret kinase inhibitors |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A Dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| US11897930B2 (en) | 2020-04-28 | 2024-02-13 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
| CN116096715A (zh) | 2020-07-06 | 2023-05-09 | 泰科根公司 | 用于精神障碍或精神增强的有益苯并噻吩组合物 |
| TW202220965A (zh) | 2020-08-06 | 2022-06-01 | 美商塔朵根公司 | 用於心理疾患或心理增強之２－胺基茚滿化合物 |
Family Cites Families (23)
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| US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
| US5073543A (en) | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
| IT1229203B (it) | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
| US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
| US5733566A (en) | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
| US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
| EP0600830A1 (de) * | 1992-11-27 | 1994-06-08 | Ciba-Geigy Ag | Substituierte Derivate von Diaminophthalimid als Protein-Tyrosin-Kinase-Hemmer |
| US5591767A (en) | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
| IT1270594B (it) | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
| WO2004063151A2 (en) | 2003-01-03 | 2004-07-29 | Bristol-Myers Squibb Company | Novel tyrosine kinase inhibitors |
| BRPI0409873A (pt) | 2003-04-28 | 2006-05-16 | Tibotec Pharm Ltd | inibidores da integrase do hiv |
| AU2004259012C1 (en) * | 2003-07-23 | 2012-08-02 | Exelixis, Inc. | Anaplastic lymphoma kinase modulators and methods of use |
| CN101160312A (zh) * | 2005-04-14 | 2008-04-09 | 霍夫曼-拉罗奇有限公司 | 三环吡咯衍生物、它们的制备和作为药剂的应用 |
| US20090005396A1 (en) * | 2005-04-27 | 2009-01-01 | Astrazeneca Ab | Use of Pyrazolyl-Pyrimidine Derivatives in the Treatment of Pain |
| US20080062003A1 (en) * | 2006-08-07 | 2008-03-13 | Christian Paetz | Wireless controllable power control device molded into a power cable |
| US8063225B2 (en) * | 2006-08-14 | 2011-11-22 | Chembridge Corporation | Tricyclic compound derivatives useful in the treatment of neoplastic diseases, inflammatory disorders and immunomodulatory disorders |
| WO2008022747A1 (en) * | 2006-08-21 | 2008-02-28 | F. Hoffmann-La Roche Ag | Tricyclic lactam derivatives, their manufacture and use as pharmaceutical agents |
| JP5628145B2 (ja) * | 2008-03-19 | 2014-11-19 | ケムブリッジ・コーポレーション | 新規チロシンキナーゼ阻害剤 |
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- 2009-03-18 JP JP2011500801A patent/JP5628145B2/ja not_active Expired - Fee Related
- 2009-03-18 CN CN200980118256.XA patent/CN102036990B/zh not_active Expired - Fee Related
- 2009-03-18 US US12/922,891 patent/US8815906B2/en not_active Expired - Fee Related
- 2009-03-18 DK DK09721981.0T patent/DK2262807T3/en active
- 2009-03-18 CA CA2718872A patent/CA2718872C/en not_active Expired - Fee Related
- 2009-03-18 MX MX2010010272A patent/MX2010010272A/es active IP Right Grant
- 2009-03-18 EP EP15177176.3A patent/EP2966076A1/en not_active Withdrawn
- 2009-03-18 WO PCT/US2009/001691 patent/WO2009117097A1/en not_active Ceased
- 2009-03-18 AU AU2009226153A patent/AU2009226153B2/en not_active Ceased
- 2009-03-18 EP EP09721981.0A patent/EP2262807B1/en not_active Not-in-force
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2013
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2718872A1 (en) | 2009-09-24 |
| JP2011515397A (ja) | 2011-05-19 |
| CN102036990A (zh) | 2011-04-27 |
| CN102036990B (zh) | 2015-09-30 |
| AU2009226153A1 (en) | 2009-09-24 |
| EP2262807A1 (en) | 2010-12-22 |
| JP2013082744A (ja) | 2013-05-09 |
| US8815906B2 (en) | 2014-08-26 |
| EP2262807B1 (en) | 2015-08-12 |
| US20130053376A1 (en) | 2013-02-28 |
| AU2009226153B2 (en) | 2014-02-20 |
| EP2966076A1 (en) | 2016-01-13 |
| JP5628145B2 (ja) | 2014-11-19 |
| DK2262807T3 (en) | 2015-11-30 |
| MX2010010272A (es) | 2011-05-25 |
| WO2009117097A1 (en) | 2009-09-24 |
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