MX2013001427A - 2-sustituido-8-alquil-7-oxo-7,8-dihidropirido[2,3-d]pirimidina-6- carbonitrilos y sus usos. - Google Patents
2-sustituido-8-alquil-7-oxo-7,8-dihidropirido[2,3-d]pirimidina-6- carbonitrilos y sus usos.Info
- Publication number
- MX2013001427A MX2013001427A MX2013001427A MX2013001427A MX2013001427A MX 2013001427 A MX2013001427 A MX 2013001427A MX 2013001427 A MX2013001427 A MX 2013001427A MX 2013001427 A MX2013001427 A MX 2013001427A MX 2013001427 A MX2013001427 A MX 2013001427A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- formula
- cancer
- further characterized
- pyrimidine
- Prior art date
Links
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Classifications
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Rheumatology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37094610P | 2010-08-05 | 2010-08-05 | |
| PCT/US2011/044807 WO2012018540A1 (en) | 2010-08-05 | 2011-07-21 | 2-substituted-8-alkyl-7-oxo-7,8-dihydropyrido[2,3-d] pyrimidine-6-carbonitriles and uses thereof |
Publications (1)
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|---|---|
| MX2013001427A true MX2013001427A (es) | 2013-06-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| MX2013001427A MX2013001427A (es) | 2010-08-05 | 2011-07-21 | 2-sustituido-8-alquil-7-oxo-7,8-dihidropirido[2,3-d]pirimidina-6- carbonitrilos y sus usos. |
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| EP (1) | EP2600719B1 (https=) |
| JP (1) | JP5512894B2 (https=) |
| KR (1) | KR101434841B1 (https=) |
| CN (1) | CN103200822B (https=) |
| AU (1) | AU2011286282B2 (https=) |
| BR (1) | BR112013002375B1 (https=) |
| CA (1) | CA2807498C (https=) |
| DK (1) | DK2600719T3 (https=) |
| EA (1) | EA022527B1 (https=) |
| ES (1) | ES2525866T3 (https=) |
| IL (1) | IL224555A (https=) |
| MX (1) | MX2013001427A (https=) |
| NZ (1) | NZ606281A (https=) |
| PL (1) | PL2600719T3 (https=) |
| PT (1) | PT2600719E (https=) |
| WO (1) | WO2012018540A1 (https=) |
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| CA2807498C (en) * | 2010-08-05 | 2017-02-07 | Temple University-Of The Commonwealth System Of Higher Education | 2-substituted-8-alkyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitriles and uses thereof |
| WO2014031571A1 (en) * | 2012-08-21 | 2014-02-27 | Icahn School Of Medicine At Mount Sinai | Treatment of viral infections |
| WO2014151682A1 (en) | 2013-03-14 | 2014-09-25 | Icahn School Of Medicine At Mount Sinai | Pyrimidine compounds as kinase inhibitors |
| KR102359214B1 (ko) | 2014-04-04 | 2022-02-07 | 델 마 파마슈티컬스 | 폐의 비소세포 암종 및 난소암을 치료하기 위한 디안하이드로갈락티톨 및 이의 유사체 또는 유도체 |
| KR20170032244A (ko) | 2014-07-26 | 2017-03-22 | 선샤인 레이크 파르마 컴퍼니 리미티드 | Cdk 저해제로서 2-아미노-피리도[2,3-d]피리미딘-7(8h)-온 유도체 및 그 용도 |
| CN104447739B (zh) * | 2014-11-07 | 2016-02-17 | 郑州泰基鸿诺药物科技有限公司 | 一种氘代Palbociclib衍生物、制备方法及应用 |
| CN104496983B (zh) | 2014-11-26 | 2016-06-08 | 苏州明锐医药科技有限公司 | 一种帕博西尼的制备方法 |
| CN104447743B (zh) * | 2014-11-26 | 2016-03-02 | 苏州明锐医药科技有限公司 | 帕博西尼的制备方法 |
| CN104478874B (zh) * | 2014-12-08 | 2016-03-02 | 新发药业有限公司 | 一种帕博赛布的制备方法 |
| CN104610254B (zh) * | 2015-01-26 | 2017-02-01 | 新发药业有限公司 | 一种帕博赛布的低成本制备方法 |
| CN105111205B (zh) * | 2015-09-12 | 2017-01-04 | 山东罗欣药业集团股份有限公司 | 一种帕博西尼的制备方法 |
| EP3556758B1 (en) | 2016-12-16 | 2024-07-17 | Cstone Pharmaceuticals (Suzhou) Co., Ltd. | 1,2-dihydro-1,6-naphthyridin-2-one derivatives as cdk4/6 inhibitors |
| WO2019161224A1 (en) | 2018-02-15 | 2019-08-22 | GiraFpharma LLC | Heterocyclic compounds as kinase inhibitors |
| KR102286701B1 (ko) * | 2018-09-28 | 2021-08-06 | 재단법인 대구경북첨단의료산업진흥재단 | 피리도[2,3-d]피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조성물 |
| TWI818930B (zh) * | 2018-11-12 | 2023-10-21 | 美商昂可諾法治療股份有限公司 | 8-環戊基-7-側氧基-2-(4-哌嗪-1-基-苯基胺基)-7,8-二氫-吡啶[2,3-d]嘧啶-6-氰基及其用於治療增生性疾病的用途 |
| US20220002293A1 (en) * | 2018-11-12 | 2022-01-06 | Onconova Therapeutics, Inc. | 8-cyclopentyl-7-oxo-2-(4-piperazin-1-yl-phenylamino)-7, 8-dihydro-pyrido [2,3-d]pyrimidine-6-carbonitrile and uses thereof in treating proliferative disorders |
| WO2020140055A1 (en) * | 2018-12-28 | 2020-07-02 | Spv Therapeutics Inc. | Cyclin-dependent kinase inhibitors |
| WO2020140053A1 (en) * | 2018-12-28 | 2020-07-02 | Spv Therapeutics Inc. | Cyclin-dependent kinase inhibitors |
| US20220273659A1 (en) * | 2019-07-02 | 2022-09-01 | Nuvation Bio Inc. | Heterocyclic compounds as kinase inhibitors |
| CN114901659A (zh) | 2019-11-26 | 2022-08-12 | 施万生物制药研发Ip有限责任公司 | 作为jak抑制剂的稠合嘧啶吡啶酮化合物 |
| US20230132667A1 (en) * | 2020-05-28 | 2023-05-04 | University Of Washington | Drug-like molecules and methods for the therapeutic targeting of viral rna structures |
| CA3237696A1 (en) | 2021-11-08 | 2023-05-11 | Progentos Therapeutics, Inc. | Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof |
| EP4433061A4 (en) * | 2021-11-18 | 2025-09-03 | Onconova Therapeutics Inc | METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER |
| JP2024540529A (ja) * | 2021-11-18 | 2024-10-31 | オンコノヴァ セラピューティクス， インコーポレイテッド | がんを処置するための方法および組成物 |
| WO2023230288A1 (en) * | 2022-05-25 | 2023-11-30 | Onconova Therapeutics, Inc. | Methods and compositions for treating cancer |
| WO2024107730A1 (en) * | 2022-11-14 | 2024-05-23 | Onconova Therapeutics, Inc. | Methods and compositions for treating cancer |
| WO2024107955A1 (en) * | 2022-11-17 | 2024-05-23 | Onconova Therapeutics, Inc. | Methods and compositions for treating cancer |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5620981A (en) | 1995-05-03 | 1997-04-15 | Warner-Lambert Company | Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| US6498163B1 (en) * | 1997-02-05 | 2002-12-24 | Warner-Lambert Company | Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation |
| AU763839B2 (en) * | 1998-05-26 | 2003-07-31 | Warner-Lambert Company | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
| KR20020070520A (ko) * | 2000-01-27 | 2002-09-09 | 워너-램버트 캄파니 | 신경퇴행성 질병의 치료를 위한 피리도피리미디논 유도체 |
| JP4064671B2 (ja) * | 2000-02-25 | 2008-03-19 | エフ．ホフマン−ラ ロシュ アーゲー | アデノシン受容体モジュレーター |
| PL358271A1 (pl) * | 2000-03-06 | 2004-08-09 | Warner-Lambert Company | 5-alkilopirydo[2,3-D]pirymidyny jako inhibitory kinazy tyrozyny |
| ES2251677T3 (es) | 2002-01-22 | 2006-05-01 | Warner-Lambert Company Llc | 2-(piridin-2-ilamino)-pirido(2,3-d)pirimidin-7-onas. |
| BRPI0507852A (pt) | 2004-02-18 | 2007-07-10 | Warner Lambert Co | 2-(piridin-3-ilamino)-pirido[2,3-d]pirimidin-7-onas |
| WO2005105097A2 (en) | 2004-04-28 | 2005-11-10 | Gpc Biotech Ag | Pyridopyrimidines for treating inflammatory and other diseases |
| US20060142312A1 (en) | 2004-12-23 | 2006-06-29 | Pfizer Inc | C6-aryl and heteroaryl substituted pyrido[2,3-D] pyrimidin-7-ones |
| RU2007128961A (ru) * | 2004-12-30 | 2009-02-10 | 4 Аза Ип Ив (Be) | ПИРИДО(3,2-d)ПИРИМИДИНЫ И ФАРМАЦЕВТИЧЕСКИЕ ПРЕПАРАТЫ, ПОЛЕЗНЫЕ ДЛЯ КОНСЕРВАТИВНОГО ЛЕЧЕНИЯ |
| GB0428475D0 (en) * | 2004-12-30 | 2005-02-02 | 4 Aza Bioscience Nv | Pyrido(3,2-D)pyrimidine derivatives and pharmaceutical compositions useful as medicines for the treatment of autoimmune disorders |
| US8232278B2 (en) * | 2005-06-24 | 2012-07-31 | Gilead Sciences, Inc. | Pyrido(3,2-D)pyrimidines and pharmaceutical compositions useful for treating hepatitis C |
| CN101395155A (zh) * | 2005-10-07 | 2009-03-25 | 埃克塞里艾克西斯公司 | PI3Kα的吡啶并嘧啶酮抑制剂 |
| US8247408B2 (en) * | 2005-10-07 | 2012-08-21 | Exelixis, Inc. | Pyridopyrimidinone inhibitors of PI3Kα for the treatment of cancer |
| CA2659746A1 (en) | 2006-08-02 | 2008-02-07 | Temple University - Of The Commonwealth System Of Higher Education | Aryl vinyl sulfides, sulfones, sulfoxides and sulfonamides, derivatives thereof and therapeutic uses thereof |
| BRPI0715566A2 (pt) | 2006-10-16 | 2013-07-02 | Gpc Biotech Inc | composto, prà-droga, composiÇço farmacÊutica, uso de um composto, mÉtodo para inibir a proliferaÇço de cÉlulas e mÉtodo para sintetizar um composto |
| WO2008150260A1 (en) | 2007-06-06 | 2008-12-11 | Gpc Biotech, Inc. | 8-oxy-2-aminopyrido (2, 3-d) pyrimidin-7-one derivatives as kinase inhibitors and anticancer agents |
| US8889696B2 (en) | 2009-12-18 | 2014-11-18 | Temple University—Of the Commonwealth System of Higher Education | Substituted pyrido[2,3-d]pyrimidin-7(8H)-ones and therapeutic uses thereof |
| CA2807498C (en) * | 2010-08-05 | 2017-02-07 | Temple University-Of The Commonwealth System Of Higher Education | 2-substituted-8-alkyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitriles and uses thereof |
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| PT2600719E (pt) | 2014-12-22 |
| ES2525866T3 (es) | 2014-12-30 |
| EA201390199A1 (ru) | 2013-07-30 |
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