ZA200200783B - Purine derivatives inhibitors of tyrosine protein kinase syk. - Google Patents
Purine derivatives inhibitors of tyrosine protein kinase syk. Download PDFInfo
- Publication number
- ZA200200783B ZA200200783B ZA200200783A ZA200200783A ZA200200783B ZA 200200783 B ZA200200783 B ZA 200200783B ZA 200200783 A ZA200200783 A ZA 200200783A ZA 200200783 A ZA200200783 A ZA 200200783A ZA 200200783 B ZA200200783 B ZA 200200783B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- hydrogen
- ring
- group
- formula
- Prior art date
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- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 title description 3
- 101710104879 Tyrosine-protein kinase SYK Proteins 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 2
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 2
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
- 239000001257 hydrogen Substances 0.000 claims description 125
- 229910052739 hydrogen Inorganic materials 0.000 claims description 125
- 150000001875 compounds Chemical class 0.000 claims description 93
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 84
- 229910052757 nitrogen Inorganic materials 0.000 claims description 75
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 125000006413 ring segment Chemical group 0.000 claims description 60
- 125000000623 heterocyclic group Chemical group 0.000 claims description 53
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- -1 benzocycloalkyl Chemical group 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 43
- 150000003839 salts Chemical group 0.000 claims description 39
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
- 229910052717 sulfur Chemical group 0.000 claims description 28
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 22
- 239000011593 sulfur Substances 0.000 claims description 22
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- 125000005842 heteroatom Chemical group 0.000 claims description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 17
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 102000000551 Syk Kinase Human genes 0.000 claims description 9
- 108010016672 Syk Kinase Proteins 0.000 claims description 9
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- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/24—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one nitrogen and one sulfur atom
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9918035.8A GB9918035D0 (en) | 1999-07-30 | 1999-07-30 | Organic compounds |
Publications (1)
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|---|---|
| ZA200200783B true ZA200200783B (en) | 2003-04-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200200783A ZA200200783B (en) | 1999-07-30 | 2002-01-29 | Purine derivatives inhibitors of tyrosine protein kinase syk. |
Country Status (33)
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| US (1) | US6589950B1 (fr) |
| EP (1) | EP1200435B1 (fr) |
| JP (2) | JP2003506375A (fr) |
| KR (1) | KR100485289B1 (fr) |
| CN (1) | CN1213047C (fr) |
| AR (1) | AR029175A1 (fr) |
| AT (1) | ATE251160T1 (fr) |
| AU (1) | AU767349B2 (fr) |
| BR (1) | BR0012888A (fr) |
| CA (1) | CA2379560C (fr) |
| CO (1) | CO5180626A1 (fr) |
| CZ (1) | CZ2002299A3 (fr) |
| DE (1) | DE60005684T2 (fr) |
| DK (1) | DK1200435T3 (fr) |
| EC (1) | ECSP003589A (fr) |
| ES (1) | ES2208395T3 (fr) |
| GB (1) | GB9918035D0 (fr) |
| HK (1) | HK1046679A1 (fr) |
| HU (1) | HUP0201935A3 (fr) |
| IL (1) | IL147455A0 (fr) |
| MX (1) | MXPA02001102A (fr) |
| MY (1) | MY126862A (fr) |
| NO (1) | NO20020467L (fr) |
| NZ (1) | NZ516667A (fr) |
| PE (1) | PE20010543A1 (fr) |
| PL (1) | PL354477A1 (fr) |
| PT (1) | PT1200435E (fr) |
| RU (1) | RU2248977C2 (fr) |
| SK (1) | SK285730B6 (fr) |
| TR (1) | TR200200234T2 (fr) |
| TW (2) | TWI274754B (fr) |
| WO (1) | WO2001009134A1 (fr) |
| ZA (1) | ZA200200783B (fr) |
Families Citing this family (110)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1941501A (en) * | 1999-11-30 | 2001-06-12 | Parker Hughes Institute | Syk localized at centrosome |
| FR2802091A1 (fr) * | 1999-12-08 | 2001-06-15 | Oreal | Compositions pour la teinture des fibres keratiniques contenant des derives de paraphenylenediamine a groupement azetidinyle |
| CA2422488A1 (fr) | 2000-09-20 | 2002-03-28 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | 4-amino-quinazolines |
| MXPA03005696A (es) * | 2000-12-21 | 2003-10-06 | Glaxo Group Ltd | Pirimidinaminas como moduladores de angiogenesis. |
| GB0101686D0 (en) * | 2001-01-23 | 2001-03-07 | Cancer Res Campaign Tech | Cyclin dependent kinase inhibitors |
| US7829566B2 (en) | 2001-09-17 | 2010-11-09 | Werner Mederski | 4-amino-quinazolines |
| US7176312B2 (en) * | 2001-10-12 | 2007-02-13 | The Scripps Research Institute | Kinase inhibitor scaffolds and methods for their preparation |
| US20030158195A1 (en) * | 2001-12-21 | 2003-08-21 | Cywin Charles L. | 1,6 naphthyridines useful as inhibitors of SYK kinase |
| ES2305435T3 (es) | 2002-01-10 | 2008-11-01 | Bayer Healthcare Ag | Inhibidores de la rho-quinasa. |
| MXPA04007191A (es) | 2002-01-23 | 2005-03-31 | Bayer Pharmaceuticals Corp | Derivados de pirimidina como inhibidores de rho-quinasa. |
| CA2473910C (fr) | 2002-01-23 | 2011-03-15 | Bayer Pharmaceuticals Corporation | Derives de pyrimidine en tant qu'inhibiteurs de la rho-kinase |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| US7501417B2 (en) | 2002-03-13 | 2009-03-10 | Janssen Pharmaceutica, N.V. | Aminocarbonyl-derivatives as novel inhibitors of histone deacetylase |
| PL214279B1 (pl) | 2002-03-13 | 2013-07-31 | Janssen Pharmaceutica Nv | Pochodna sulfonyloaminowa, sposób jej wytwarzania i zastosowanie oraz kompozycja farmaceutyczna i sposób jej wytwarzania |
| US6897307B2 (en) | 2002-03-28 | 2005-05-24 | Novartis Ag | Process for preparing 2,6-diaminopurine derivatives |
| US6855724B2 (en) | 2002-04-08 | 2005-02-15 | Agouron Pharmaceuticals, Inc. | Tropane derivatives useful in therapy |
| CN1688553A (zh) * | 2002-06-17 | 2005-10-26 | 史密丝克莱恩比彻姆公司 | 化学方法 |
| CN101423497A (zh) * | 2002-07-19 | 2009-05-06 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的6-氨基-1h-吲唑和4-氨基苯并呋喃化合物 |
| CN1678321A (zh) | 2002-07-29 | 2005-10-05 | 里格尔药品股份有限公司 | 用2,4－嘧啶二胺化合物治疗或者预防自体免疫性疾病的方法 |
| EP1444982A1 (fr) * | 2003-02-06 | 2004-08-11 | Merckle Gmbh | Utilisation des dérivés de purine comme inhibiteurs sélectifs de kinases |
| US7122542B2 (en) | 2003-07-30 | 2006-10-17 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds |
| AU2004264419B2 (en) * | 2003-08-15 | 2009-01-15 | Irm Llc | 6-substituted anilino purines as RTK inhibitors |
| CN100475815C (zh) * | 2003-09-25 | 2009-04-08 | 詹森药业有限公司 | 抑制hiv复制的嘌呤衍生物 |
| JP2007510671A (ja) * | 2003-11-06 | 2007-04-26 | セルジーン・コーポレーション | アスベスト関連疾患および障害の治療および管理のための、ｊｎｋ阻害剤の使用方法およびそれを含む組成物 |
| WO2005047524A2 (fr) * | 2003-11-10 | 2005-05-26 | The Scripps Research Institute | Compositions et procedes pour induire la differenciation cellulaire |
| GB0407723D0 (en) * | 2004-04-05 | 2004-05-12 | Novartis Ag | Organic compounds |
| US8057815B2 (en) * | 2004-04-19 | 2011-11-15 | Portola Pharmaceuticals, Inc. | Methods of treatment with Syk inhibitors |
| WO2005118543A1 (fr) * | 2004-06-03 | 2005-12-15 | Ono Pharmaceutical Co., Ltd. | Inhibiteur des kinases et utilisation de cet inhibiteur |
| US7173031B2 (en) * | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| US7439246B2 (en) | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US7626021B2 (en) * | 2004-07-27 | 2009-12-01 | Sgx Pharmaceuticals, Inc. | Fused ring heterocycle kinase modulators |
| EP2264033A1 (fr) | 2004-07-27 | 2010-12-22 | SGX Pharmaceuticals, Inc. | DÉRIVÉS PYRROLO[2,3b]PYRIDINE, 3,5-DIPHÉNYL SUBSTITUÉS, EN TANT QU'INHIBITEURS DE KINASES |
| US7361764B2 (en) * | 2004-07-27 | 2008-04-22 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| US7709645B2 (en) * | 2004-07-27 | 2010-05-04 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
| JP2008508304A (ja) | 2004-07-27 | 2008-03-21 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | 縮合環ヘテロ環キナーゼ調節因子 |
| KR101261305B1 (ko) | 2004-07-28 | 2013-05-08 | 얀센 파마슈티카 엔.브이. | 히스톤 디아세틸라제의 신규한 저해제로의 치환된 인돌릴알킬 아미노 유도체 |
| WO2006027377A1 (fr) * | 2004-09-10 | 2006-03-16 | Altana Pharma Ag | Combinaison de ciclesonide et d'inhibiteur de syk et procedes d'utilisation |
| DK1814878T3 (da) | 2004-11-24 | 2012-05-07 | Rigel Pharmaceuticals Inc | Spiro-2, 4-pyrimidindiamin-forbindelser og anvendelser deraf |
| CN100526315C (zh) * | 2005-06-16 | 2009-08-12 | 浙江医药股份有限公司新昌制药厂 | N2-喹啉或异喹啉取代的嘌呤衍生物及其制备方法和其用途 |
| JP2009511528A (ja) * | 2005-10-13 | 2009-03-19 | グラクソ グループ リミテッド | Ｓｙｋ阻害物質としてのピロロピリミジン誘導体群 |
| WO2007053776A1 (fr) * | 2005-11-03 | 2007-05-10 | Sgx Pharmaceuticals, Inc. | Modulateurs de kinase de type pyrimidinylthiophène |
| CA2633035C (fr) | 2005-12-15 | 2016-05-10 | Rigel Pharmaceuticals, Inc. | Inhibiteurs de kinase et leurs utilisations |
| JP5225104B2 (ja) * | 2006-01-19 | 2013-07-03 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 新しい、ヒストンデアセチラーゼのインヒビターとしてのアミノフェニル誘導体 |
| AU2007206950B2 (en) * | 2006-01-19 | 2012-02-02 | Janssen Pharmaceutica N.V. | Substituted indolyl-alkyl-amino-derivatives as inhibitors of histone deacetylase |
| AU2007206942B2 (en) | 2006-01-19 | 2012-08-23 | Janssen Pharmaceutica N.V. | Pyridine and pyrimidine derivatives as inhibitors of histone deacetylase |
| US8008481B2 (en) * | 2006-03-31 | 2011-08-30 | Ericsson Anna M | Indazole compounds |
| AU2007309149C1 (en) | 2006-10-23 | 2013-04-04 | Sgx Pharmaceuticals, Inc. | Bicyclic triazoles as protein kinase modulators |
| US20080139531A1 (en) * | 2006-12-04 | 2008-06-12 | Alcon Manufacturing Ltd. | Use of connective tissue mast cell stabilizers to facilitate ocular surface re-epithelization and wound repair |
| EA019966B1 (ru) | 2006-12-08 | 2014-07-30 | АйАрЭм ЭлЭлСи | Соединения и композиции в качестве ингибиторов протеинкиназы |
| CN103641833A (zh) * | 2006-12-08 | 2014-03-19 | Irm责任有限公司 | 作为蛋白激酶抑制剂的化合物和组合物 |
| EP2123654A4 (fr) | 2006-12-28 | 2011-05-11 | Taisho Pharmaceutical Co Ltd | Composé pyrazolopyridimidine |
| US8404674B2 (en) | 2007-03-07 | 2013-03-26 | Boehringer Ingelheim International Gmbh | Substituted 9H-purin-2-YL compounds, compositions thereof and uses thereof |
| EP2078020A4 (fr) | 2007-04-10 | 2011-10-19 | Sgx Pharmaceuticals Inc | Modulateurs hétérocycliques à cycles fusionnés pour les kinases |
| CN101289449A (zh) * | 2007-04-20 | 2008-10-22 | 浙江医药股份有限公司新昌制药厂 | 2,6-二含氮取代的嘌呤衍生物及其制备方法和应用 |
| WO2008135232A1 (fr) * | 2007-05-02 | 2008-11-13 | Riccardo Cortese | Utilisation et compositions de dérivés de purine pour le traitement de troubles prolifératifs |
| EA200971077A1 (ru) * | 2007-05-21 | 2010-04-30 | ЭсДжиЭкс ФАРМАСЬЮТИКАЛЗ, ИНК. | Гетероциклические модуляторы киназы |
| TW200908968A (en) * | 2007-05-29 | 2009-03-01 | Sgx Pharmaceuticals Inc | Substituted pyrrolopyridines and pyrazolopyridines as kinase modulators |
| US7705004B2 (en) | 2007-08-17 | 2010-04-27 | Portola Pharmaceuticals, Inc. | Protein kinase inhibitors |
| FR2929851B1 (fr) * | 2008-04-09 | 2012-11-30 | Centre Nat Rech Scient | Molecules inhibant une voie metabolique impliquant la proteine tyrosine kinase syk et procede d'identification de ces molecules |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| ES2546502T3 (es) | 2008-04-16 | 2015-09-24 | Portola Pharmaceuticals, Inc. | 2,6-Diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o JAK quinasas |
| AU2009238590A1 (en) * | 2008-04-22 | 2009-10-29 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| MX2010012703A (es) | 2008-05-21 | 2010-12-21 | Ariad Pharma Inc | Derivados fosforosos como inhibidores de cinasa. |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| WO2010003084A2 (fr) * | 2008-07-02 | 2010-01-07 | Memory Pharmaceuticals Corporation | Inhibiteurs de la phosphodiestérase 4 |
| WO2010111406A2 (fr) * | 2009-03-24 | 2010-09-30 | Myriad Pharmaceuticals, Inc. | Composés et leurs utilisations thérapeutiques |
| JP5242857B2 (ja) * | 2009-12-17 | 2013-07-24 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｓｙｋ阻害剤としてのアミノピリミジン類 |
| EP3825316A1 (fr) | 2009-12-23 | 2021-05-26 | Takeda Pharmaceutical Company Limited | Pyrrolidinones hétéroaromatiques fusionnés comme inhibiteurs du syk |
| WO2011153553A2 (fr) | 2010-06-04 | 2011-12-08 | The Regents Of The University Of California | Méthodes et compositions pour l'inhibition de kinases |
| EP2489663A1 (fr) | 2011-02-16 | 2012-08-22 | Almirall, S.A. | Composés en tant qu'inhibiteurs de la syk kinase |
| AU2012250517B2 (en) | 2011-05-04 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| WO2012154518A1 (fr) | 2011-05-10 | 2012-11-15 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines en tant qu'inhibiteurs de syk |
| AU2012253886A1 (en) | 2011-05-10 | 2013-10-31 | Merck Sharp & Dohme Corp. | Pyridyl aminopyridines as Syk inhibitors |
| MX2013013090A (es) | 2011-05-10 | 2013-12-16 | Merck Sharp & Dohme | Aminopirimidinas como inhibidores de tirosina cinaza del bazo. |
| EP2713737B1 (fr) * | 2011-06-01 | 2016-04-20 | Janus Biotherapeutics, Inc. | Nouveaux modulateurs du système immunitaire |
| WO2012177714A1 (fr) | 2011-06-22 | 2012-12-27 | Takeda Pharmaceutical Company Limited | Dérivés de 6-aza-isoindolin-1-one substitués |
| WO2013052391A1 (fr) | 2011-10-05 | 2013-04-11 | Merck Sharp & Dohme Corp. | Inhibiteurs de tyrosine kinase de la rate (syk) contenant un phényl carboxamide |
| WO2013052394A1 (fr) | 2011-10-05 | 2013-04-11 | Merck Sharp & Dohme Corp. | Inhibiteurs de tyrosine kinase de la rate (syk) contenant un 2-pyridyl carboxamide |
| US8987456B2 (en) | 2011-10-05 | 2015-03-24 | Merck Sharp & Dohme Corp. | 3-pyridyl carboxamide-containing spleen tyrosine kinase (SYK) inhibitors |
| MX363551B (es) | 2011-11-23 | 2019-03-27 | Portola Pharmaceuticals Inc Star | Compuestos derivados de pirazina como inhibidores de cinasa. |
| AR090650A1 (es) * | 2012-04-12 | 2014-11-26 | Alcon Res Ltd | Tratamiento para respuestas inflamatorias inducidas por microbios en el ojo |
| JP6469567B2 (ja) | 2012-05-05 | 2019-02-13 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物 |
| EP2863913B1 (fr) | 2012-06-20 | 2018-09-12 | Merck Sharp & Dohme Corp. | Analogues d'imidazolyle en tant qu'inhibiteurs de syk |
| WO2013192125A1 (fr) | 2012-06-20 | 2013-12-27 | Merck Sharp & Dohme Corp. | Dérivés de pyrazolyle en tant qu'inhibiteurs de syk |
| WO2013192088A1 (fr) | 2012-06-22 | 2013-12-27 | Merck Sharp & Dohme Corp. | Inhibiteurs de tyrosine kinase splénique (syk) diazines et triazines substituées |
| WO2013192098A1 (fr) | 2012-06-22 | 2013-12-27 | Merck Sharp & Dohme Corp. | Inhibiteurs à pyridine substituée de la tyrosine kinase de la rate (syk) |
| US9353066B2 (en) | 2012-08-20 | 2016-05-31 | Merck Sharp & Dohme Corp. | Substituted phenyl-Spleen Tyrosine Kinase (Syk) inhibitors |
| EP2900665B1 (fr) | 2012-09-28 | 2018-01-03 | Merck Sharp & Dohme Corp. | Dérivés triazolyle en tant qu'inhibiteurs de la syk |
| EP2931281B1 (fr) | 2012-12-12 | 2018-01-17 | Merck Sharp & Dohme Corp. | Inhibiteurs de tyrosine kinase splénique contenant une aminopyridine |
| EP2934525B1 (fr) | 2012-12-21 | 2019-05-08 | Merck Sharp & Dohme Corp. | Aminopyridines substituées par thiazole en tant qu'inhibiteurs de la tyrosine kinase de la rate |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| WO2014176216A1 (fr) | 2013-04-26 | 2014-10-30 | Merck Sharp & Dohme Corp. | Aminopyrimidines substituées par thiazole utilisées en tant qu'inhibiteurs de tyrosine kinase splénique |
| WO2014176210A1 (fr) | 2013-04-26 | 2014-10-30 | Merck Sharp & Dohme Corp. | Composés aminohétéroaryle à substitution thiazole inhibiteurs de tyrosine kinase splénique |
| CN104418858B (zh) * | 2013-08-30 | 2018-12-11 | 浙江医药股份有限公司新昌制药厂 | 2,6-二含氮取代的嘌呤衍生物及其制备方法和其药物组合物与应用 |
| EP3083559B1 (fr) | 2013-12-20 | 2021-03-10 | Merck Sharp & Dohme Corp. | Composés aminohétéroaryles à substitution thiazole utilisés comme inhibiteurs de la tyrosine kinase splénique |
| US9670196B2 (en) | 2013-12-20 | 2017-06-06 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as Spleen Tyrosine Kinase inhibitors |
| US9783531B2 (en) | 2013-12-20 | 2017-10-10 | Merck Sharp & Dohme Corp. | Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors |
| WO2015138273A1 (fr) | 2014-03-13 | 2015-09-17 | Merck Sharp & Dohme Corp. | Composés 2-pyrazine carboxamide utiles comme inhibiteurs de la tyrosine kinase splénique |
| WO2015162518A1 (fr) | 2014-04-25 | 2015-10-29 | Pfizer Inc. | Composes hetero-aromatiques et leur utilisation comme ligands d1 de la dopamine |
| RU2570113C1 (ru) * | 2014-12-08 | 2015-12-10 | Федеральное государственное бюджетное учреждение науки Институт органического синтеза им. И.Я. Постовского Уральского отделения Российской академии наук | N-(2-ацетамидопурин-6-ил)глицин, обладающий противотуберкулезной активностью |
| CA2976109A1 (fr) * | 2015-02-13 | 2016-08-18 | Dana-Farber Cancer Institute, Inc. | Pyrrolopyrimidine substituee, pyrazolopyrimidine et derives de purine, et utilisation connexe comme inhibiteurs de lrrk2 |
| CA2993288A1 (fr) * | 2015-07-24 | 2017-02-02 | Glaxo Group Limited | Traitement du vitiligo |
| WO2017181285A1 (fr) | 2016-04-21 | 2017-10-26 | The Royal Institution For The Advancement Of Learning/Mcgill University | Composés de purine et méthode pour le traitement du cancer |
| WO2018075937A1 (fr) | 2016-10-21 | 2018-04-26 | Nimbus Lakshmi, Inc. | Inhibiteurs de tyk2 et leurs utilisations |
| BR112020007679A2 (pt) | 2017-10-19 | 2020-10-20 | Bayer Animal Health Gmbh | uso de pirrolidonas heteroaromáticas fundidas para tratamento e prevenção de doenças em animais. |
| WO2019241896A1 (fr) * | 2018-06-22 | 2019-12-26 | The Royal Institution For The Advancement Of Learning/Mcgill University | Composés de purine et procédé pour letraitement du cancer |
| EP3894392A4 (fr) * | 2018-12-11 | 2022-08-24 | Duke University | Compositions et procédés pour le traitement du cancer |
| CA3129665A1 (fr) | 2019-03-21 | 2020-09-24 | Onxeo | Molecule dbait associee a un inhibiteur de kinase pour le traitement du cancer |
| CN114761006A (zh) | 2019-11-08 | 2022-07-15 | Inserm(法国国家健康医学研究院) | 对激酶抑制剂产生耐药性的癌症的治疗方法 |
| WO2021148581A1 (fr) | 2020-01-22 | 2021-07-29 | Onxeo | Nouvelle molécule dbait et son utilisation |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3529497A1 (de) | 1985-08-17 | 1987-02-26 | Boehringer Mannheim Gmbh | N(pfeil hoch)6(pfeil hoch)-disubstituierte purinderivate, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| JPH08828B2 (ja) * | 1992-02-19 | 1996-01-10 | ファイザー・インコーポレーテッド | 抗腫瘍活性を高めるための複素環化合物 |
| PT633886E (pt) * | 1992-04-03 | 2001-03-30 | Upjohn Co | Aminas biciclicas-heterociclicas farmaceuticamente activas |
| US5550132A (en) | 1994-06-22 | 1996-08-27 | University Of North Carolina | Hydroxyalkylammonium-pyrimidines or purines and nucleoside derivatives, useful as inhibitors of inflammatory cytokines |
| ES2196181T3 (es) * | 1995-11-01 | 2003-12-16 | Novartis Ag | Derivados de purina y proceso para su preparacion. |
| US5866702A (en) * | 1996-08-02 | 1999-02-02 | Cv Therapeutics, Incorporation | Purine inhibitors of cyclin dependent kinase 2 |
| US6255485B1 (en) | 1997-08-07 | 2001-07-03 | The Regents Of The University Of California | Purine inhibitors of protein kinases, G proteins and polymerases |
| GB9903762D0 (en) * | 1999-02-18 | 1999-04-14 | Novartis Ag | Organic compounds |
-
1999
- 1999-07-30 GB GBGB9918035.8A patent/GB9918035D0/en not_active Ceased
-
2000
- 2000-07-20 TW TW94101835A patent/TWI274754B/zh not_active IP Right Cessation
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- 2000-07-25 PE PE2000000744A patent/PE20010543A1/es not_active Application Discontinuation
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- 2000-07-28 AU AU65677/00A patent/AU767349B2/en not_active Ceased
- 2000-07-28 BR BR0012888-0A patent/BR0012888A/pt not_active Application Discontinuation
- 2000-07-28 RU RU2002103305/04A patent/RU2248977C2/ru not_active IP Right Cessation
- 2000-07-28 EP EP00953112A patent/EP1200435B1/fr not_active Expired - Lifetime
- 2000-07-28 SK SK126-2002A patent/SK285730B6/sk not_active IP Right Cessation
- 2000-07-28 MX MXPA02001102A patent/MXPA02001102A/es active IP Right Grant
- 2000-07-28 DK DK00953112T patent/DK1200435T3/da active
- 2000-07-28 WO PCT/EP2000/007311 patent/WO2001009134A1/fr not_active Application Discontinuation
- 2000-07-28 US US10/048,577 patent/US6589950B1/en not_active Expired - Lifetime
- 2000-07-28 PT PT00953112T patent/PT1200435E/pt unknown
- 2000-07-28 NZ NZ516667A patent/NZ516667A/en unknown
- 2000-07-28 JP JP2001514337A patent/JP2003506375A/ja not_active Withdrawn
- 2000-07-28 AT AT00953112T patent/ATE251160T1/de not_active IP Right Cessation
- 2000-07-28 DE DE60005684T patent/DE60005684T2/de not_active Expired - Fee Related
- 2000-07-28 ES ES00953112T patent/ES2208395T3/es not_active Expired - Lifetime
- 2000-07-28 MY MYPI20003444 patent/MY126862A/en unknown
- 2000-07-28 CA CA002379560A patent/CA2379560C/fr not_active Expired - Fee Related
- 2000-07-28 CN CNB008110263A patent/CN1213047C/zh not_active Expired - Fee Related
- 2000-07-28 KR KR10-2002-7001276A patent/KR100485289B1/ko not_active IP Right Cessation
-
2002
- 2002-01-29 ZA ZA200200783A patent/ZA200200783B/en unknown
- 2002-01-29 NO NO20020467A patent/NO20020467L/no not_active Application Discontinuation
- 2002-09-25 HK HK02107013.6A patent/HK1046679A1/zh unknown
-
2007
- 2007-05-16 JP JP2007130684A patent/JP2007217426A/ja active Pending
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