ES2438509T3 - Inhibidores de la esfingosina quinasa - Google Patents

Inhibidores de la esfingosina quinasa Download PDF

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Publication number
ES2438509T3
ES2438509T3 ES10782202.5T ES10782202T ES2438509T3 ES 2438509 T3 ES2438509 T3 ES 2438509T3 ES 10782202 T ES10782202 T ES 10782202T ES 2438509 T3 ES2438509 T3 ES 2438509T3
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atoms
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substituted
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nr18r18
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Frank Stieber
Dirk Wienke
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Merck Patent GmbH
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Merck Patent GmbH
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Abstract

Compuestos según la fórmula (I) en la que representan, independiente entre sí: R1, R2, R3, R4, R5, R6 , R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 H, D (Deuterio), A, OR18, CN, F, Cl y NR18R18'; donde R1 y R2, R3 y R4, R5 y R6, R10 y R11, R12 y R13, R14 y R15, R16 y R17 pueden formar en cada casotambién >=O (oxígeno carbonílico); donde R9 y R1, R1 y R2, R2 y R3, R3 y R4, R4 y R5, R5 y R6, R6 y R7, R7 y R8, R10 y R11, R11 y R12, R12 y R13 ,R14 y R15, R15 y R16, R16 y R17 pueden formar en cada caso también alquilos cíclicos con 3, 4, 5, 6 o 7átomos de C o Het con 3, 4, 5, 6 o 7 átomos en el anillo; donde R10 y R19, si Y1 >= CR19, R11 y R12, R13 y R19, si Y2 >= CR19, R14 y R19, si Y1 >= CR19, R15 y R16, R17 yR19, si Y2 >= CR19 pueden formar en cada caso también con el enlace sencillo y los átomos de C a los quese unen, un doble enlace C>=C; R18, R18' H, D o A; R19, R19' H, D, A, OR18, NR18R18', F, Cl, Br, CN o Het; M1, M2, M3, M4 CR19 o N; Y1, Y2 CR19 o N; V C(R19)(R19'), NR19 o está ausente; W [C(R19)(R19')]pZ, CO-[C(R19)(R19')]pZ, [C(R19)(R19')]pN(R19)-Z, CO-N(R19)-[C(R19)(R19')]pZ, N(R19)-CO-[C(R19)(R19')]pZ, CO-O-[C(R19)(R19')]pZ, C(O)OR18, OR18, H o D; donde V, W y Y2 pueden estar formados en cada caso también por alquilo cíclico con 3, 4, 5, 6 o 7 átomos deC, pudiéndose sustituir preferentemente 1, 2, 3, 4, 5, 6 o 7 átomos de H por F, Cl, Br, CN y/o OH, OR19,OC(O)R19, NR19C(O)OZ, C(O)OR19, C(O)N(R19)(R19') o N(R19)(R19'25 ); o Het con 3, 4, 5, 6 o 7 átomos en elanillo, en el que Het representa preferentemente un heterociclo saturado, insaturado o aromático con 1 a4 átomos de N, O y/o S, que puede no estar sustituido o estarlo una, dos o tres veces por Hal, F, Cl, Br,CN, A, OR18, W, SR18, NO2, N(R19)(R19'), NR18COOZ, OCONHZ, NR18SO2Z, SO2N(R18)Z, S(O)mZ, COZ,CHO, COZ, >=S, >=NH, >=NA, Oxi (-O-) y/o >=O (oxígeno carbonílico); Z Het, Ar o A; A alquilo no ramificado o ramificado con 1, 2, 3, 4, 5, 6, 7, 8, 9 o 10 átomos de C, donde 1, 2, 3, 4, 5, 6 o 7átomos de H pueden estar sustituidos por F, Cl, Br, CN y/o OH, OR19, OC(O)R19, NR19C(O)OZ, C(O)OR19,C(O)N(R19)(R19') o N(R19)(R19'); y/o en el que uno o dos grupos CH2 pueden estar sustituidos por O, S, SO, SO2, CO, COO, NR18,NR18CO, CONR1835 , alquilo cíclico con 3, 4, 5, 6 o 7 átomos de C, CH>=CH y/o grupos CHºCH.
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Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201020161D0 (en) * 2010-11-26 2011-01-12 Almac Discovery Ltd Pharmaceutical compounds
CN104093730A (zh) * 2011-12-19 2014-10-08 沙特基础工业公司 用于制备茂金属络合物的方法
PT2800754T (pt) * 2011-12-19 2017-08-18 Saudi Basic Ind Corp (Sabic) Processo para a preparação de complexos metalocenos
US9840489B2 (en) * 2013-12-20 2017-12-12 Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China Piperidine carboxamide compound, preparation method, and usage thereof
JP6902040B2 (ja) 2016-01-28 2021-07-14 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 免疫チェックポイント阻害剤の効力を増強する方法
MX388576B (es) 2016-06-07 2025-03-20 Jacobio Pharmaceuticals Co Ltd Derivados heterociclicos novedosos utiles como inhibidores de shp2.
EA202190196A1 (ru) 2017-03-23 2021-08-31 Джакобио Фармасьютикалс Ко., Лтд. Новые гетероциклические производные, применимые в качестве ингибиторов shp2
CN108079303A (zh) * 2017-12-14 2018-05-29 广东药科大学 鞘氨醇激酶抑制剂在制备治疗肝纤维化药物中的应用
EP3756012A1 (en) 2018-02-21 2020-12-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of sk1 as biomarker for predicting response to immunecheckpoint inhibitors
BR112020018094A2 (pt) 2018-03-08 2020-12-22 Incyte Corporation Compostos de aminopirazina diol como inibidores de pi3k-¿
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
US20210393623A1 (en) 2018-09-26 2021-12-23 Jacobio Pharmaceuticals Co., Ltd. Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors
JP2023539463A (ja) 2020-08-17 2023-09-14 アリゴス セラピューティクス インコーポレイテッド Ｐｄ－ｌ１を標的とするための方法及び組成物

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9624482D0 (en) 1995-12-18 1997-01-15 Zeneca Phaema S A Chemical compounds
DE69720965T2 (de) 1996-02-13 2004-02-05 Astrazeneca Ab Chinazolinderivate und deren verwendung als vegf hemmer
NZ331191A (en) 1996-03-05 2000-03-27 Zeneca Ltd 4-anilinoquinazoline derivatives and pharmaceutical compositions thereof
GB9718972D0 (en) 1996-09-25 1997-11-12 Zeneca Ltd Chemical compounds
GB9714249D0 (en) 1997-07-08 1997-09-10 Angiogene Pharm Ltd Vascular damaging agents
ATE404539T1 (de) * 1997-10-02 2008-08-15 Eisai R&D Man Co Ltd Kondensierte pyridinderivate
GB9900334D0 (en) 1999-01-07 1999-02-24 Angiogene Pharm Ltd Tricylic vascular damaging agents
GB9900752D0 (en) 1999-01-15 1999-03-03 Angiogene Pharm Ltd Benzimidazole vascular damaging agents
DE19945594A1 (de) * 1999-09-23 2001-03-29 Boehringer Ingelheim Pharma Substituierte Piperazinderivate, ihre Herstellung und ihre Verwendung als Arzneimittel
AU2001258628A1 (en) 2000-05-31 2001-12-11 Astrazeneca Ab Indole derivatives with vascular damaging activity
MXPA02012905A (es) 2000-07-07 2004-07-30 Angiogene Pharm Ltd Derivados de colquinol como agentes de dano vascular..
MXPA02012903A (es) 2000-07-07 2004-07-30 Angiogene Pharm Ltd Derivados de colquinol como inhibidores de angiogenesis.
CA2432409A1 (en) * 2000-12-26 2002-07-11 Research Foundation Itsuu Laboratory Tropolone derivative
EP1485381B8 (en) 2002-03-15 2010-05-12 Vertex Pharmaceuticals Incorporated Azolylaminoazine as inhibitors of protein kinases
US6846928B2 (en) 2002-03-15 2005-01-25 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of protein kinases
DE60332433D1 (de) 2002-03-15 2010-06-17 Vertex Pharma Azolylaminoazine als proteinkinasehemmer
US20040009981A1 (en) 2002-03-15 2004-01-15 David Bebbington Compositions useful as inhibitors of protein kinases
UA77526C2 (en) 2002-06-07 2006-12-15 Sanofi Aventis Substituted derivatives of 1-piperazineacylpiperidine, a method for the preparation thereof and their use in therapy
AU2003291403A1 (en) 2002-11-08 2004-06-03 Neurogen Corporation 3-substituted-6-aryl pyridined as ligands of c5a receptors
DE60335827D1 (de) 2002-12-20 2011-03-03 Merck Sharp & Dohme 1-(amino)indane als edg-rezeptoragonisten
WO2005023261A1 (en) 2003-09-09 2005-03-17 F. Hoffmann-La Roche Ag 1-benzoyl-piperazine derivatives as glycine uptake inhibitors for the treatment of psychoses
TW200526626A (en) 2003-09-13 2005-08-16 Astrazeneca Ab Chemical compounds
ATE414689T1 (de) * 2003-12-08 2008-12-15 Galderma Res & Dev Biphenylderivate, die sich als rar-rezeptor- aktivierende liganden eignen, verfahren zu deren herstellung und deren verwendung in der humanmedizin und in kosmetika
JP2007518719A (ja) 2003-12-26 2007-07-12 アラーガン　インコーポレイテッド ＲＡＲγレチノイド受容体アンタゴニスト活性を有する二置換カルコンオキシム
US7476673B2 (en) 2003-12-30 2009-01-13 Allergan, Inc. Disubstituted chalcone oximes as selective agonists of RARγ retinoid receptors
ES2528451T3 (es) 2005-06-17 2015-02-10 Apogee Biothechnology Corporation Inhibidores de esfingosina cinasa
US20070032531A1 (en) 2005-08-04 2007-02-08 Apogee Biotechnology Corporation Sphingosine kinase inhibitors and methods of their use
US7250510B2 (en) * 2005-08-24 2007-07-31 Total Synthesis, Ltd. Transition metal complexes of N-heterocyclic carbenes, method of preparation and use in transition metal catalyzed organic transformations
JP2009528280A (ja) 2006-02-16 2009-08-06 シェーリング コーポレイション Ｅｒｋインヒビターとしてのピロリジン誘導体
WO2007100610A2 (en) * 2006-02-23 2007-09-07 Merck & Co., Inc. Pyridine, pyrimidine and pyrazine derivatives as cxcr3 receptor modulators
PL2639226T3 (pl) * 2007-09-17 2017-02-28 Abbvie Bahamas Ltd. Pirymidyny o działaniu przeciw zakaźnym oraz ich zastosowania
WO2009146112A1 (en) * 2008-04-02 2009-12-03 University Of Virginia Patent Foundation Compositions and methods for inhibiting sphingosine kinase
GB0822425D0 (en) * 2008-12-09 2009-01-14 Glaxo Group Ltd Compounds
US20120015942A1 (en) * 2010-07-19 2012-01-19 Millennium Pharmaceuticals, Inc. Substituted hydroxamic acids and uses thereof
GB201020161D0 (en) * 2010-11-26 2011-01-12 Almac Discovery Ltd Pharmaceutical compounds

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