ES2718218T3 - Derivados de 4,5,6,7-tetrahidropirazolo[1,5-a]pirazina sustituidos como inhibidores de caseína cinasa 1 D/E - Google Patents
Derivados de 4,5,6,7-tetrahidropirazolo[1,5-a]pirazina sustituidos como inhibidores de caseína cinasa 1 D/E Download PDFInfo
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- ES2718218T3 ES2718218T3 ES14802796T ES14802796T ES2718218T3 ES 2718218 T3 ES2718218 T3 ES 2718218T3 ES 14802796 T ES14802796 T ES 14802796T ES 14802796 T ES14802796 T ES 14802796T ES 2718218 T3 ES2718218 T3 ES 2718218T3
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- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- ZODMDGQSPVUKOB-UHFFFAOYSA-N tert-butyl n-[3-[tert-butyl(dimethyl)silyl]oxy-2-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC(O)CO[Si](C)(C)C(C)(C)C ZODMDGQSPVUKOB-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
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- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
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- 229960003087 tioguanine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
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- WIOADUFWOUUQCV-UHFFFAOYSA-N triphenylphosphanium dichloride Chemical compound [Cl-].[Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 WIOADUFWOUUQCV-UHFFFAOYSA-N 0.000 description 1
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- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
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- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07D487/10—Spiro-condensed systems
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Hematology (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361904116P | 2013-11-14 | 2013-11-14 | |
| PCT/US2014/065599 WO2015073767A1 (en) | 2013-11-14 | 2014-11-14 | Substituted 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine derivatives as casein kinase 1 d/e inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2718218T3 true ES2718218T3 (es) | 2019-06-28 |
Family
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Family Applications (2)
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|---|---|---|---|
| ES14802796T Active ES2718218T3 (es) | 2013-11-14 | 2014-11-14 | Derivados de 4,5,6,7-tetrahidropirazolo[1,5-a]pirazina sustituidos como inhibidores de caseína cinasa 1 D/E |
| ES14806145T Active ES2744636T3 (es) | 2013-11-14 | 2014-11-14 | Derivados de 4,5,6,7-tetrahidropirazolo[1,5-a]pirazina sustituidos como inhibidores de caseína quinasa 1 D/E |
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| Application Number | Title | Priority Date | Filing Date |
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| ES14806145T Active ES2744636T3 (es) | 2013-11-14 | 2014-11-14 | Derivados de 4,5,6,7-tetrahidropirazolo[1,5-a]pirazina sustituidos como inhibidores de caseína quinasa 1 D/E |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US9273058B2 (https=) |
| EP (2) | EP3068784B1 (https=) |
| JP (2) | JP6494624B2 (https=) |
| CN (2) | CN105916856B (https=) |
| AR (1) | AR098414A1 (https=) |
| ES (2) | ES2718218T3 (https=) |
| TW (1) | TW201605859A (https=) |
| UY (1) | UY35834A (https=) |
| WO (2) | WO2015073763A1 (https=) |
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| AR098414A1 (es) | 2013-11-14 | 2016-05-26 | Bristol Myers Squibb Co | PIPERAZINAS DE PIRAZOLO SUSTITUIDO COMO INHIBIDORES DE CASEÍNA QUINASA 1 d/e |
| JP6513075B2 (ja) * | 2014-02-27 | 2019-05-15 | 国立大学法人 東京大学 | オートタキシン阻害活性を有する縮合ピラゾール誘導体 |
| MA41338B1 (fr) * | 2015-01-16 | 2019-07-31 | Hoffmann La Roche | Composés de pyrazine pour le traitement de maladies infectieuses |
| JP6904970B2 (ja) | 2016-03-07 | 2021-07-21 | エナンタ ファーマシューティカルズ インコーポレイテッド | Ｂ型肝炎抗ウイルス剤 |
| WO2017156071A1 (en) | 2016-03-09 | 2017-09-14 | Blade Therapeutics, Inc. | Cyclic keto-amide compounds as calpain modulators and methods of production and use thereof |
| EP3458455B1 (en) * | 2016-05-20 | 2021-06-16 | F. Hoffmann-La Roche AG | Novel pyrazine compounds with oxygen, sulfur and nitrogen linker for the treatment of infectious diseases |
| EP3481835A4 (en) | 2016-07-05 | 2020-02-26 | Blade Therapeutics, Inc. | CALPAIN MODULATORS AND THERAPEUTIC USE THEREOF |
| EP3484886B1 (en) * | 2016-07-14 | 2020-03-04 | Hoffmann-La Roche AG | 6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine and 6,7-dihydro-4h-triazolo[1,5-a]pyrazine compounds for the treatment of infectious diseases |
| BR112019006110A2 (pt) | 2016-09-28 | 2019-09-10 | Blade Therapeutics Inc | moduladores de calpaína e usos terapêuticos dos mesmos |
| TWI782056B (zh) * | 2017-07-14 | 2022-11-01 | 日商鹽野義製藥股份有限公司 | 具有ｍｇａｔ２抑制活性的縮合環衍生物 |
| CA3070004A1 (en) | 2017-07-27 | 2019-01-31 | Jiangsu Hengrui Medicine Co., Ltd. | Piperazine heteroaryl derivative, preparation method therefor and use of same in medicine |
| US10952978B2 (en) | 2017-08-28 | 2021-03-23 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| US11292791B2 (en) | 2017-09-15 | 2022-04-05 | Forma Therapeutics, Inc. | Tetrahydro-imidazo quinoline compositions as CBP/P300 inhibitors |
| PE20201170A1 (es) | 2017-11-01 | 2020-10-28 | Bristol Myers Squibb Co | Compuestos biciclicos en puente como moduladores del receptor farnesoide x |
| US11058678B2 (en) | 2018-01-22 | 2021-07-13 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| WO2019191166A1 (en) * | 2018-03-29 | 2019-10-03 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| CN111484442B (zh) * | 2018-06-01 | 2021-11-09 | 杭州阿诺生物医药科技有限公司 | 一种具有抗肿瘤活性的csf1r抑制剂中间体的制备方法 |
| IL279734B2 (en) | 2018-06-29 | 2024-11-01 | Forma Therapeutics Inc | Inhibiting creb binding protein (cbp) |
| UY38383A (es) | 2018-09-21 | 2020-04-30 | Enanta Pharm Inc | Heterociclos funcionalizados como agentes antivirales |
| US11198693B2 (en) | 2018-11-21 | 2021-12-14 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| CA3126334A1 (en) | 2019-01-11 | 2020-07-16 | Shionogi & Co., Ltd. | Dihydropyrazolopyrazinone derivative having mgat2 inhibitory activity |
| AU2020210998A1 (en) * | 2019-01-25 | 2021-09-16 | Jiangsu Hengrui Medicine Co., Ltd. | Crystal form of 1,2,3-triazolo(1,5-a)pyrazines derivative and preparation method for crystal form |
| CN111484497B (zh) * | 2019-01-25 | 2021-07-02 | 江苏恒瑞医药股份有限公司 | 咪唑并[1,5-a]吡嗪类衍生物的可药用盐、晶型及其制备方法 |
| CN111484498B (zh) * | 2019-01-25 | 2021-05-14 | 江苏恒瑞医药股份有限公司 | 咪唑并[1,5-a]吡嗪类化合物的晶型及其制备方法 |
| CA3128946A1 (en) | 2019-02-07 | 2020-08-13 | Bayer Aktiengesellschaft | 3-amino-2-[2-(acylamino)pyridin-4-yl]-1,5,6,7-tetrahydro-4h-pyrrolo[3,2-c]pyridin-4-one as csnk1 inhibitors |
| US12351577B2 (en) | 2019-03-15 | 2025-07-08 | Forma Therapeutics, Inc. | Inhibiting cyclic AMP-responsive element-binding protein (CREB) |
| WO2020247444A1 (en) | 2019-06-03 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| WO2020247561A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| WO2020247575A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| US11738019B2 (en) | 2019-07-11 | 2023-08-29 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| US11236108B2 (en) | 2019-09-17 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| WO2021188414A1 (en) | 2020-03-16 | 2021-09-23 | Enanta Pharmaceuticals, Inc. | Functionalized heterocyclic compounds as antiviral agents |
| WO2022023341A1 (en) | 2020-07-29 | 2022-02-03 | Bayer Aktiengesellschaft | Substituted 1 h-pyrrolo[3,2-b]pyridin compounds and methods of use thereof |
| CN114057745A (zh) * | 2020-07-29 | 2022-02-18 | 江苏恒瑞医药股份有限公司 | 一种三氮唑并[1,5-a]吡嗪制备方法及其应用 |
| JP2023541465A (ja) * | 2020-09-17 | 2023-10-02 | ヤンセン ファーマシューティカ エヌ．ベー． | カゼインキナーゼ１デルタモジュレーター |
| US11795168B2 (en) | 2020-09-23 | 2023-10-24 | Forma Therapeutics, Inc. | Inhibiting cyclic amp-responsive element-binding protein (CREB) binding protein (CBP) |
| US11801243B2 (en) | 2020-09-23 | 2023-10-31 | Forma Therapeutics, Inc. | Bromodomain inhibitors for androgen receptor-driven cancers |
| WO2022166778A1 (zh) * | 2021-02-04 | 2022-08-11 | 江苏恒瑞医药股份有限公司 | 一种衣壳蛋白抑制剂的药物组合物及其制备方法 |
| EP4469457A4 (en) * | 2022-01-27 | 2026-01-21 | Broad Inst Inc | CSNK1 SUBSTITUTE HETEROCYCLIC INHIBITORS |
| AU2023296166A1 (en) * | 2022-06-13 | 2024-11-28 | Shionogi & Co., Ltd. | Crystal of dihydropyridinone derivative or solvate thereof |
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| IL160915A0 (en) * | 2001-09-19 | 2004-08-31 | Aventis Pharma Sa | Indolizines inhibiting kinase proteins |
| DE602004020685D1 (de) * | 2003-12-11 | 2009-05-28 | Aventis Pharma Inc | Substituierte 1h-pyrroloä3,2-b, 3,2-c und 2,3-cüpyridin-2-carbonsäureamide und verwandte analoga als inhibitoren von caseinkinase-i-epsilon |
| US20050222171A1 (en) * | 2004-01-22 | 2005-10-06 | Guido Bold | Organic compounds |
| US20070155738A1 (en) | 2005-05-20 | 2007-07-05 | Alantos Pharmaceuticals, Inc. | Heterobicyclic metalloprotease inhibitors |
| CN101417999A (zh) | 2007-10-25 | 2009-04-29 | 上海恒瑞医药有限公司 | 哌嗪类衍生物,其制备方法及其在医药上的应用 |
| EP2085398A1 (en) | 2008-02-01 | 2009-08-05 | Merz Pharma GmbH & Co. KGaA | Pyrazolopyrimidines, a process for their preparation and their use as medicine |
| CN102223798A (zh) | 2008-09-24 | 2011-10-19 | 巴斯夫欧洲公司 | 用于防治无脊椎动物害虫的吡唑化合物 |
| US8703778B2 (en) | 2008-09-26 | 2014-04-22 | Intellikine Llc | Heterocyclic kinase inhibitors |
| WO2010059836A1 (en) | 2008-11-20 | 2010-05-27 | Decode Genetics Ehf | Substituted aza-bridged bicyclics for cardiovascular and cns disease |
| TW201035102A (en) | 2009-03-04 | 2010-10-01 | Gruenethal Gmbh | Sulfonylated tetrahydroazolopyrazines and their use as medicinal products |
| FR2960876B1 (fr) * | 2010-06-03 | 2012-07-27 | Sanofi Aventis | Derives de 3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1h)-dicarboxamide leur preparation et leur application en therapeutique. |
| CN102372716A (zh) | 2010-08-09 | 2012-03-14 | 江苏恒瑞医药股份有限公司 | 酞嗪酮类衍生物、其制备方法及其在医药上的应用 |
| US9226929B2 (en) | 2011-03-02 | 2016-01-05 | Bayer Intellectual Property Gmbh | Pharmaceutically active disubstituted triazine derivatives |
| AR098414A1 (es) | 2013-11-14 | 2016-05-26 | Bristol Myers Squibb Co | PIPERAZINAS DE PIRAZOLO SUSTITUIDO COMO INHIBIDORES DE CASEÍNA QUINASA 1 d/e |
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| CN105916855A (zh) | 2016-08-31 |
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| US20160311824A1 (en) | 2016-10-27 |
| ES2744636T3 (es) | 2020-02-25 |
| TW201605859A (zh) | 2016-02-16 |
| CN105916855B (zh) | 2019-03-15 |
| JP2016537369A (ja) | 2016-12-01 |
| EP3068784B1 (en) | 2019-02-20 |
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