UA80763C2 - Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors - Google Patents
Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors Download PDFInfo
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- UA80763C2 UA80763C2 UAA200512347A UAA200512347A UA80763C2 UA 80763 C2 UA80763 C2 UA 80763C2 UA A200512347 A UAA200512347 A UA A200512347A UA A200512347 A UAA200512347 A UA A200512347A UA 80763 C2 UA80763 C2 UA 80763C2
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- 238000000034 method Methods 0.000 title claims abstract description 107
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
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- 229940043355 kinase inhibitor Drugs 0.000 title 1
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- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
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- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
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- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- BJAARRARQJZURR-UHFFFAOYSA-N trimethylazanium;hydroxide Chemical compound O.CN(C)C BJAARRARQJZURR-UHFFFAOYSA-N 0.000 description 1
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- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
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- WRSWIWOVJBYZAW-UHFFFAOYSA-M zinc;methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=CC=C1 WRSWIWOVJBYZAW-UHFFFAOYSA-M 0.000 description 1
Classifications
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
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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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47266103P | 2003-05-22 | 2003-05-22 | |
| PCT/EP2004/050612 WO2004104007A1 (en) | 2003-05-22 | 2004-04-27 | Pyrazolo-quinazoline derivatives,process for their preparation and their use as kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA80763C2 true UA80763C2 (en) | 2007-10-25 |
Family
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Family Applications (1)
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| UAA200512347A UA80763C2 (en) | 2003-05-22 | 2004-04-27 | Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
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| EP (1) | EP1636236B1 (pt) |
| JP (1) | JP5043432B2 (pt) |
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| BR (2) | BR122019010200B8 (pt) |
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| TW (1) | TWI349672B (pt) |
| UA (1) | UA80763C2 (pt) |
| WO (1) | WO2004104007A1 (pt) |
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Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GEP20094664B (en) | 2003-05-22 | 2009-04-10 | Nerviano Medical Sciences Srl | Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| US7772232B2 (en) | 2004-04-15 | 2010-08-10 | Bristol-Myers Squibb Company | Quinazolinyl compounds as inhibitors of potassium channel function |
| ITMI20041033A1 (it) | 2004-05-24 | 2004-08-24 | Neuroscienze S C A R L | Composti farmaceutici |
| EP1812439B2 (en) | 2004-10-15 | 2017-12-06 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| US8119655B2 (en) | 2005-10-07 | 2012-02-21 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| EP1986632B1 (en) | 2006-02-10 | 2012-08-15 | Nerviano Medical Sciences S.R.L. | Combinations comprising a cdk inhibitor and a growth factor antibody or anti-mitotic |
| WO2007128820A1 (en) * | 2006-05-09 | 2007-11-15 | Novartis Ag | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof |
| WO2007149395A2 (en) * | 2006-06-20 | 2007-12-27 | Amphora Discovery Corporation | 2,5-substituted oxazole derivatives as protein kinase inhibitors for the treatment of cancer |
| US7517882B2 (en) * | 2006-09-18 | 2009-04-14 | Polaris Group | Protein kinase inhibitors |
| EA200970361A1 (ru) | 2006-10-09 | 2010-02-26 | Такеда Фармасьютикал Компани Лимитед | Ингибиторы киназы |
| EP2125822B1 (en) * | 2006-12-21 | 2014-11-19 | Nerviano Medical Sciences S.R.L. | Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
| UA102219C2 (ru) * | 2006-12-21 | 2013-06-25 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Замещенные пиразолохиназолиновые производные, способ их получения и их применения как ингибиторов киназы |
| JPWO2009054332A1 (ja) | 2007-10-23 | 2011-03-03 | 萬有製薬株式会社 | ピリドン置換ジヒドロピラゾロピリミジノン誘導体 |
| WO2009085185A1 (en) * | 2007-12-19 | 2009-07-09 | Amgen Inc. | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
| WO2009126584A1 (en) * | 2008-04-07 | 2009-10-15 | Amgen Inc. | Gem-disubstituted and spirocyclic amino pyridines/pyrimidines as cell cycle inhibitors |
| TWI426074B (zh) * | 2008-04-30 | 2014-02-11 | Nerviano Medical Sciences Srl | ５－（２－胺基－嘧啶－４－基）－２－芳基－１ｈ－吡咯－３－羧醯胺之製造方法 |
| JP5542133B2 (ja) * | 2008-06-26 | 2014-07-09 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | ピラゾロ−キナゾリン |
| ES2622559T3 (es) * | 2008-07-29 | 2017-07-06 | Nerviano Medical Sciences S.R.L. | Combinación terapéutica que comprende un inhibidor de cdk y un agente antineoplásico |
| CN102105151B (zh) * | 2008-07-29 | 2013-12-18 | 内尔维阿诺医学科学有限公司 | Cdk抑制剂在治疗神经胶质瘤中的应用 |
| JP5579724B2 (ja) * | 2008-10-17 | 2014-08-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ホスファチジルイノシトール−３−キナーゼ（ｐｉ−３キナーゼ）阻害剤としてのテトラ−アザ−複素環 |
| CN102223885B (zh) * | 2008-11-24 | 2013-04-03 | 内尔维阿诺医学科学有限公司 | 用于治疗间皮瘤的cdk抑制剂 |
| IT1395724B1 (it) * | 2009-02-25 | 2012-10-19 | Neuroscienze Pharmaness S C A R L | Composti farmaceutici |
| US8580793B2 (en) * | 2009-03-20 | 2013-11-12 | Nerviano Medical Services S.R.L. | Use of kinase inhibitor for the treatment of thymoma |
| EP2421872B1 (en) * | 2009-04-22 | 2015-06-10 | Boehringer Ingelheim International GmbH | Thia-triaza-as-indacenes as pi3-kinases inhibitors for the treatment of cancer |
| CN102428086B (zh) * | 2009-04-29 | 2014-08-20 | 内尔维阿诺医学科学有限公司 | Cdk抑制剂的盐类 |
| AR076784A1 (es) | 2009-05-26 | 2011-07-06 | Nerviano Medical Sciences Srl | Combinacion terapeutica que comprende un inhibidor de plk1 y un agente antineoplasico |
| CN103626777B (zh) * | 2009-07-29 | 2015-10-21 | 内尔维阿诺医学科学有限公司 | Plk抑制剂的盐类 |
| MX336731B (es) * | 2010-01-28 | 2016-01-28 | Harvard College | Composiciones y metodos para potenciar la actividad de proteasoma. |
| US8735386B2 (en) | 2010-07-23 | 2014-05-27 | Boehringer Ingelheim International Gmbh | Aminopyrazoloquinazolines |
| WO2012013557A1 (en) | 2010-07-30 | 2012-02-02 | Nerviano Medical Sciences S.R.L. | Isoxazolo-quinazolines as modulators of protein kinase activity |
| EP2619181A1 (en) | 2010-09-23 | 2013-07-31 | Syngenta Participations AG | Novel microbiocides |
| CN106967074A (zh) * | 2010-10-25 | 2017-07-21 | G1治疗公司 | Cdk抑制剂 |
| EP2614065B1 (en) * | 2010-12-17 | 2017-04-19 | Nerviano Medical Sciences S.r.l. | Substituted pyrazolo-quinazoline derivatives as kinase inhibitors |
| EP2668188B1 (en) * | 2011-01-26 | 2016-05-18 | Nerviano Medical Sciences S.r.l. | Tricyclic derivatives, process for their preparation and their use as kinase inhibitors |
| ES2602791T3 (es) * | 2011-01-26 | 2017-02-22 | Nerviano Medical Sciences S.R.L. | Derivados de pirrolo tricíclicos, proceso para su preparación y su uso como inhibidores de cinasa |
| WO2012117021A2 (en) | 2011-03-03 | 2012-09-07 | Syngenta Participations Ag | Novel microbiocidal oxime ethers |
| EP2688887B1 (en) | 2011-03-23 | 2015-05-13 | Amgen Inc. | Fused tricyclic dual inhibitors of cdk 4/6 and flt3 |
| US9556166B2 (en) | 2011-05-12 | 2017-01-31 | Proteostasis Therapeutics, Inc. | Proteostasis regulators |
| WO2013092460A1 (en) | 2011-12-20 | 2013-06-27 | Syngenta Participations Ag | Cyclic bisoxime microbicides |
| US9150578B2 (en) | 2012-01-23 | 2015-10-06 | Boehringer Ingelheim International Gmbh | 5,8-dihydro-6H-pyrazolo[3,4-h]quinazolines as IGF-1R/IR inhibitors |
| EP2641901A1 (en) | 2012-03-22 | 2013-09-25 | Syngenta Participations AG. | Novel microbiocides |
| CN104870446B (zh) | 2012-11-07 | 2019-08-13 | 内尔维阿诺医学科学有限公司 | 取代的嘧啶基和吡啶基吡咯并吡啶酮类、其制备方法及其作为激酶抑制剂的用途 |
| WO2014116228A1 (en) | 2013-01-25 | 2014-07-31 | President And Fellows Of Harvard College | Usp14 inhibitors for treating or preventing viral infections |
| US20140271460A1 (en) | 2013-03-15 | 2014-09-18 | G1 Therapeutics, Inc. | Highly Active Anti-Neoplastic and Anti-Proliferative Agents |
| EP2968291A4 (en) | 2013-03-15 | 2016-09-28 | G1 Therapeutics Inc | HSPC-PROOF TREATMENTS FOR RB-POSITIVE ABNORMAL CELLULAR PROLIFERATION |
| WO2015073528A1 (en) | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
| USRE50082E1 (en) | 2014-04-07 | 2024-08-20 | Netherlands Translational Research Center B.V. | (5,6-dihydro)pyrimido[4,5-e]indolizines |
| US20150297606A1 (en) | 2014-04-17 | 2015-10-22 | G1 Therapeutics, Inc. | Tricyclic Lactams for Use in the Protection of Hematopoietic Stem and Progenitor Cells Against Ionizing Radiation |
| ES2873959T3 (es) | 2014-05-28 | 2021-11-04 | Piramal Entpr Ltd | Combinación farmacéutica que comprende un inhibidor de CDK y un inhibidor de tiorredoxina reductasa para el tratamiento del cáncer |
| WO2016040848A1 (en) | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Treatment of rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors |
| EP3191098A4 (en) | 2014-09-12 | 2018-04-25 | G1 Therapeutics, Inc. | Combinations and dosing regimes to treat rb-positive tumors |
| CN108348486A (zh) | 2015-07-17 | 2018-07-31 | 巴斯德研究院 | 用作卫星细胞自我更新和/或分化的启动子的5-羟色胺1b受体激动剂 |
| BR112019000706A8 (pt) | 2016-07-15 | 2022-12-06 | Pasteur Institut | Agente de estímulo do receptor 1b de 5-hidroxitriptamina para reparo de pele e/ou cabelo |
| JP6905069B2 (ja) * | 2016-11-11 | 2021-07-21 | 上海海雁醫藥科技有限公司 | ピリジルアミノ置換へテロ三環式化合物並びにその製造方法及び医薬用途 |
| JP7178401B2 (ja) * | 2017-07-11 | 2022-11-25 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | コリンキナーゼ阻害剤としてのピラゾロキナゾリン誘導体 |
| CN107383019B (zh) * | 2017-07-28 | 2019-10-15 | 江苏艾凡生物医药有限公司 | 吡唑并[4,3-h]喹唑啉类化合物及其用途 |
| EP3666774B1 (en) * | 2017-08-11 | 2022-05-11 | Shengke Pharmaceuticals (Jiangsu) Ltd. | 1h-pyrazolo[4,3-h]quinazoline compound serving as protein kinase inhibitor |
| CN114423765B (zh) * | 2019-09-05 | 2024-09-20 | 成都赛璟生物医药科技有限公司 | 异𫫇唑并[5,4-h]喹唑啉类化合物作为蛋白激酶抑制剂 |
| WO2021084541A1 (en) * | 2019-10-31 | 2021-05-06 | Sol-Gel Technologies Ltd. | Treatment of hair loss disorders with a topical egfr inhibitor |
| US10988479B1 (en) | 2020-06-15 | 2021-04-27 | G1 Therapeutics, Inc. | Morphic forms of trilaciclib and methods of manufacture thereof |
| CN114685520B (zh) * | 2020-12-25 | 2024-08-30 | 武汉誉祥医药科技有限公司 | 三并环化合物及其药物组合物和应用 |
| WO2022143576A1 (zh) * | 2020-12-31 | 2022-07-07 | 恒元生物医药科技(苏州)有限公司 | 一种吡唑并喹唑啉类化合物、其制备方法及应用 |
| WO2022166725A1 (zh) * | 2021-02-08 | 2022-08-11 | 南京明德新药研发有限公司 | 5，6-二氢噻吩并[3，4-h]喹唑啉类化合物 |
| CN113527310B (zh) * | 2021-07-30 | 2022-09-23 | 上海市肺科医院 | 用于减轻自身免疫性疾病患者不良炎性反应的小分子化合物及其应用 |
| EP4446325A1 (en) * | 2021-12-10 | 2024-10-16 | Shandong Luye Pharmaceutical Co., Ltd. | Protein kinase inhibitor, preparation method therefor, and application thereof |
| WO2024153110A1 (zh) * | 2023-01-17 | 2024-07-25 | 北京哲源科技有限责任公司 | 吡唑并喹唑啉类化合物的立体异构体和氘代衍生物及应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2119975A (en) * | 1936-08-26 | 1938-06-07 | Beatrice S Nazel | Fluid pressure hammer |
| JP3907220B2 (ja) * | 1994-06-30 | 2007-04-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 複素環含有化合物 |
| MX9709867A (es) | 1995-06-07 | 1998-03-31 | Pfizer | Derivados de pirimidina condensados con un anillo heterociclico, composiciones que contienen los mismos, y uso de los mismos. |
| WO1998028281A1 (en) | 1996-12-23 | 1998-07-02 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives, their preparation and their use as protein tyrosine kinase inhibitors |
| GB9713087D0 (en) | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9911053D0 (en) | 1999-05-12 | 1999-07-14 | Pharmacia & Upjohn Spa | 4,5,6,7-tetrahydroindazole derivatives process for their preparation and their use as antitumour agents |
| US6387900B1 (en) | 1999-08-12 | 2002-05-14 | Pharmacia & Upjohn S.P.A. | 3(5)-ureido-pyrazole derivatives process for their preparation and their use as antitumor agents |
| JP2003507329A (ja) | 1999-08-12 | 2003-02-25 | フアルマシア・イタリア・エツセ・ピー・アー | ３（５）−アミノ−ピラゾール誘導体、それらの製造方法および抗腫瘍薬としてのそれらの使用 |
| PT1320531E (pt) | 2000-08-10 | 2010-10-27 | Pfizer Italia Srl | Biciclo-pirazoles activos como inibidores da cinase, processo para a sua preparação e composições farmacêuticas compreendendo estes |
| CA2417635C (en) * | 2000-08-11 | 2008-02-05 | Boehringer Ingelheim Pharmaceuticals, Inc. | Heterocyclic compounds useful as inhibitors of tyrosine kinases |
| AU2002215053A1 (en) | 2000-11-27 | 2002-06-24 | Pharmacia Italia S.P.A. | Phenylacetamido- pyrazole derivatives and their use as antitumor agents |
| EP1379524A2 (en) | 2001-01-26 | 2004-01-14 | Pharmacia Italia S.p.A. | Chromane derivatives, process for their preparation and their use as antitumor agents |
| WO2003013655A2 (en) * | 2001-08-10 | 2003-02-20 | Pharmacia Corporation | Carbonic anhydrase inhibitors |
| US20030100594A1 (en) * | 2001-08-10 | 2003-05-29 | Pharmacia Corporation | Carbonic anhydrase inhibitor |
| JP4542338B2 (ja) | 2001-09-26 | 2010-09-15 | ファイザー イタリア ソシエタ ア レスポンサビリタ リミタータ | キナーゼ阻害因子として活性なアミノインダゾール誘導体、それらの製造方法及びそれらを含有する医薬組成物 |
| EP1476431A1 (en) * | 2002-02-19 | 2004-11-17 | Pharmacia Corporation | Tricyclic pyrazole derivatives for the treatment of inflammation |
| GEP20094664B (en) * | 2003-05-22 | 2009-04-10 | Nerviano Medical Sciences Srl | Pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
| EP2125822B1 (en) * | 2006-12-21 | 2014-11-19 | Nerviano Medical Sciences S.R.L. | Substituted pyrazolo-quinazoline derivatives, process for their preparation and their use as kinase inhibitors |
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