CL2009000882A1 - Un compuesto n-(4-cloro-3-(piridin-2-il)fenil)-4-(2-hidroxi-2-metilpropilsulfonil)-2-metilbenzamida, inhibidor de la via de señalización hedgehog; composición farmacéutica que comprende a dicho compuesto; y su uso para tratar el cancer. - Google Patents

Un compuesto n-(4-cloro-3-(piridin-2-il)fenil)-4-(2-hidroxi-2-metilpropilsulfonil)-2-metilbenzamida, inhibidor de la via de señalización hedgehog; composición farmacéutica que comprende a dicho compuesto; y su uso para tratar el cancer.

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Publication number
CL2009000882A1
CL2009000882A1 CL2009000882A CL2009000882A CL2009000882A1 CL 2009000882 A1 CL2009000882 A1 CL 2009000882A1 CL 2009000882 A CL2009000882 A CL 2009000882A CL 2009000882 A CL2009000882 A CL 2009000882A CL 2009000882 A1 CL2009000882 A1 CL 2009000882A1
Authority
CL
Chile
Prior art keywords
compound
methylbenzamide
pyridin
chloro
hydroxy
Prior art date
Application number
CL2009000882A
Other languages
English (en)
Inventor
Georgette Castanedo
Mark S Stanley
Liang Bao
Janet L Gunzner
Daniel P Sutherlin
Rebecca L Lalonde
Shumei Wang
Mark E Reynolds
Scott J Savage
Kimberly Malesky
Michael S Dina
Original Assignee
Genentech Inc
Curis Inc
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41162633&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CL2009000882(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Genentech Inc, Curis Inc filed Critical Genentech Inc
Publication of CL2009000882A1 publication Critical patent/CL2009000882A1/es

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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
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  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

UN COMPUESTO N-(4-CLORO-3-(PIRIDIN-2-IL)FENIL)-4-(2-HIDROXI-2-METILPROPILSULFONIL)-2-METILBENZAMIDA QUE TIENE LA FÓRMULA:<br /> UNA COMPOSICIÓN FARMACÉUTICA QUE COMPRENDE DICHO COMPUESTO Y UN VEHÍCULO FARMACÉUTICAMENTE ACEPTABLE. USO DE DICHO COMPUESTO PARA PREPARAR UN MEDICAMENTO ÚTIL PARA TRATAR EL CÁNCER EN UN MAMÍFERO.<br />  
CL2009000882A 2008-04-11 2009-04-13 Un compuesto n-(4-cloro-3-(piridin-2-il)fenil)-4-(2-hidroxi-2-metilpropilsulfonil)-2-metilbenzamida, inhibidor de la via de señalización hedgehog; composición farmacéutica que comprende a dicho compuesto; y su uso para tratar el cancer. CL2009000882A1 (es)

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Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20170001725A (ko) 2004-09-02 2017-01-04 제넨테크, 인크. 헤지호그 신호전달에 대한 피리딜 억제제
WO2010059618A1 (en) 2008-11-21 2010-05-27 High Point Pharmaceuticals, Llc Adamantyl benzamide compounds
AU2010223919B2 (en) 2009-03-13 2016-03-31 Les Laboratoires Servier Methods and compositions for cell-proliferation-related disorders
SG10201403696UA (en) 2009-06-29 2014-10-30 Agios Pharmaceuticals Inc Therapeutic compounds and compositions
JP2013508350A (ja) * 2009-10-20 2013-03-07 ファイザー・インク ガンマ−セクレターゼモジュレーターとしての新規なヘテロアリールイミダゾールおよびヘテロアリールトリアゾール
WO2011050210A1 (en) 2009-10-21 2011-04-28 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
SG186229A1 (en) 2010-06-07 2013-01-30 Novomedix Llc Furanyl compounds and the use thereof
ES2543151T3 (es) * 2010-10-20 2015-08-17 Pfizer Inc Derivados de 2-piridina como moduladores del receptor Smoothened
EP2468726B1 (en) 2010-12-06 2013-08-28 Siena Biotech S.p.A. Compound for the treatment of tumours and tumour metastases
US9708299B2 (en) 2011-01-03 2017-07-18 Genentech, Inc. Hedgehog antagonists having zinc binding moieties
TWI574687B (zh) * 2011-01-03 2017-03-21 古利斯股份有限公司 具有鋅結合部份之刺蝟拮抗劑
BR112013028422B8 (pt) 2011-05-03 2022-01-11 Agios Pharmaceuticals Inc Ativadores de piruvato cinase para uso em terapia
WO2012151544A1 (en) 2011-05-05 2012-11-08 Wisconsin Alumni Research Foundation Micelles for the solubilization of gossypol
CN102827073A (zh) * 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
FR2980477B1 (fr) 2011-09-23 2013-10-18 Centre Nat Rech Scient Nouveaux composes modulateurs de la voie de signalisation des proteines hedgehog, leurs formes marquees, et applications
US8809372B2 (en) 2011-09-30 2014-08-19 Asana Biosciences, Llc Pyridine derivatives
US9474779B2 (en) 2012-01-19 2016-10-25 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their methods of use
US9505728B2 (en) 2012-03-09 2016-11-29 Inception 2, Inc. Triazolone compounds and uses thereof
CN103570625A (zh) * 2012-07-19 2014-02-12 南京英派药业有限公司 N-(3-杂芳基芳基)-4-芳基芳基甲酰胺和类似物作为Hedgehog通路抑制剂及其应用
US20140057920A1 (en) 2012-08-23 2014-02-27 Boehringer Ingelheim International Gmbh Substituted 4-pyridones and their use as inhibitors of neutrophil elastase activity
CA2888360A1 (en) 2012-10-15 2014-04-24 Agios Pharmaceuticals, Inc. Therapeutic compounds and compositions
CN103864770B (zh) * 2012-12-10 2019-06-11 江苏先声药业有限公司 作为Hedgehog信号传导的嘧啶胺类和吡啶胺类抑制剂
CN104918922B (zh) 2012-12-20 2017-04-26 因森普深2公司 ***酮化合物及其用途
CN103910672B (zh) * 2013-01-08 2016-10-05 连云港润众制药有限公司 Vismodegib的制备方法
WO2014147504A2 (en) * 2013-03-22 2014-09-25 Shilpa Medicare Limited Process for preparation of 2-chloro-n-(4-chloro-3-pyridin-2-ylphenyl)-4-methylsulfonylbenzamide solid forms
TW201512171A (zh) 2013-04-19 2015-04-01 Pfizer Ltd 化學化合物
CN103254124A (zh) * 2013-04-23 2013-08-21 镇江圣安医药有限公司 N-[4-氯-3–(吡啶-2-基)苯基]-2-氯-4–(甲磺酰基)-苯甲酰胺衍生物及其应用
CN104177363B (zh) * 2013-05-24 2018-06-05 江苏先声药业有限公司 双环杂环胺类Hedgehog信号通路抑制剂
CN105593215B (zh) 2013-07-11 2019-01-15 安吉奥斯医药品有限公司 用于治疗癌症的作为idh2突变体抑制剂的2,4-或4,6-二氨基嘧啶化合物
WO2015003360A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US9579324B2 (en) 2013-07-11 2017-02-28 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
WO2015003355A2 (en) 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US20150031627A1 (en) 2013-07-25 2015-01-29 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
EA201690230A1 (ru) 2013-09-06 2016-07-29 Инсепшн 2, Инк. Соединения триазолона и их применения
EA036325B1 (ru) 2014-03-14 2020-10-27 Аджиос Фармасьютикалз, Инк. Фармацевтическая композиция на основе твердой дисперсии ингибитора idh1
WO2015169269A1 (en) 2014-05-05 2015-11-12 Zentiva, K.S. Salts of 2-chloro-n-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide
WO2015170218A1 (en) 2014-05-07 2015-11-12 Pfizer Inc. Tropomyosin-related kinase inhibitors
WO2016196879A1 (en) 2015-06-05 2016-12-08 Dana-Farber Cancer Institute, Inc. Compounds and methods for treating cancer
LT3307271T (lt) 2015-06-11 2023-10-25 Agios Pharmaceuticals, Inc. Piruvatkinazės aktyvatorių panaudojimo būdai
CN104926714B (zh) * 2015-07-02 2017-07-28 天津大学 2‑氯‑n‑(4‑氯‑3‑(2‑吡啶基)苯基)‑4‑甲基砜苯基苯甲酰胺的制备方法
AU2016338552B2 (en) 2015-10-15 2022-04-28 Les Laboratoires Servier Combination therapy for treating malignancies
PL3362066T3 (pl) 2015-10-15 2022-05-02 Les Laboratoires Servier Terapia skojarzona do leczenia nowotworów złośliwych
JP6750177B2 (ja) * 2015-12-11 2020-09-02 ロート製薬株式会社 アントラニルアミド誘導体およびそれを含有するｔｌｒ３が関与する疾患の治療剤
EP3536320A4 (en) * 2016-11-04 2020-07-29 Impact Therapeutics, Inc APPLICATION OF A HEDGEHOG SIGNALWAY INHIBITOR FOR TREATING FIBROTIC DISEASES
WO2018133114A1 (en) * 2017-01-23 2018-07-26 Shenzhen University Novel natrural algicide with low toxicity to non-target organisms
GB2560903A (en) 2017-03-27 2018-10-03 Azad Pharmaceutical Ingredients Ag New synthetic path to pharmaceutically acceptable vismodegib
CN107556289A (zh) * 2017-06-22 2018-01-09 天津国际生物医药联合研究院 一种氯苯‑吡啶类化合物及其应用
CN111818915B (zh) 2018-01-31 2024-05-24 德西费拉制药有限责任公司 治疗胃肠道间质瘤的组合疗法
CN117903140A (zh) 2018-02-27 2024-04-19 因赛特公司 作为a2a/a2b抑制剂的咪唑并嘧啶和***并嘧啶
MA52940A (fr) 2018-05-18 2021-04-28 Incyte Corp Dérivés de pyrimidine fusionnés utilisés en tant qu'inhibiteurs de a2a/a2b
US10980788B2 (en) 2018-06-08 2021-04-20 Agios Pharmaceuticals, Inc. Therapy for treating malignancies
JP7490631B2 (ja) 2018-07-05 2024-05-27 インサイト・コーポレイション Ａ２ａ／ａ２ｂ阻害剤としての縮合ピラジン誘導体
TWI829857B (zh) 2019-01-29 2024-01-21 美商英塞特公司 作為a2a / a2b抑制劑之吡唑并吡啶及***并吡啶
WO2021030405A1 (en) 2019-08-12 2021-02-18 Deciphera Pharmaceuticals, Llc Ripretinib for treating gastrointestinal stromal tumors
EP4013412A1 (en) 2019-08-12 2022-06-22 Deciphera Pharmaceuticals, LLC Ripretinib for treating gastrointestinal stromal tumors
IL293866A (en) 2019-12-30 2022-08-01 Deciphera Pharmaceuticals Llc Compositions of amorphous kinase inhibitors and methods of using them
KR20220123058A (ko) 2019-12-30 2022-09-05 데시페라 파마슈티칼스, 엘엘씨. 1-(4-브로모-5-(1-에틸-7-(메틸아미노)-2-옥소-1,2-디히드로-1,6-나프티리딘-3-일)-2-플루오로페닐)-3-페닐우레아의 조성물
CN113968804B (zh) * 2020-07-22 2022-12-02 中国农业大学 莫奈太尔砜的半抗原、人工抗原及其制备方法与应用
US11779572B1 (en) 2022-09-02 2023-10-10 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4323916A1 (de) * 1993-07-16 1995-01-19 Basf Ag Substituierte 2-Phenylpyridine
WO1995009846A1 (en) * 1993-10-06 1995-04-13 E.I. Du Pont De Nemours And Company Herbicidal heteroaryl substituted anilides
TW467902B (en) * 1996-07-31 2001-12-11 Bristol Myers Squibb Co Diphenyl heterocycles as potassium channel modulators
ATE297904T1 (de) 1997-04-15 2005-07-15 Genentech Inc Halo-alkoxycarbonylverbindungen
US7223782B2 (en) * 2001-11-01 2007-05-29 Icagen, Inc. Pyrazole-amides and -sulfonamides
DE60334651D1 (de) * 2002-02-12 2010-12-02 Glaxosmithkline Llc Nicotinamide und deren Verwendung als P38 Inhibitoren
AU2003297431A1 (en) * 2002-12-20 2004-07-22 Pharmacia Corporation Mitogen activated protein kinase-activated protein kinase-2 inhibiting compounds
KR20070005736A (ko) * 2004-04-30 2007-01-10 제넨테크, 인크. 헤지호그 신호전달 경로의 퀴녹살린 억제제
KR20170001725A (ko) * 2004-09-02 2017-01-04 제넨테크, 인크. 헤지호그 신호전달에 대한 피리딜 억제제
US7638928B2 (en) * 2005-06-30 2009-12-29 Intel Corporation Piezo actuator for cooling
UA93548C2 (uk) * 2006-05-05 2011-02-25 Айерем Елелсі Сполуки та композиції як модулятори хеджхогівського сигнального шляху
TW200918521A (en) * 2007-08-31 2009-05-01 Astrazeneca Ab Heterocyclic amides and methods of use thereof

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WO2009126863A3 (en) 2009-12-23
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US20120094980A1 (en) 2012-04-19
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US20090281089A1 (en) 2009-11-12
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