JP2016504289A5 - - Google Patents
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- JP2016504289A5 JP2016504289A5 JP2015544036A JP2015544036A JP2016504289A5 JP 2016504289 A5 JP2016504289 A5 JP 2016504289A5 JP 2015544036 A JP2015544036 A JP 2015544036A JP 2015544036 A JP2015544036 A JP 2015544036A JP 2016504289 A5 JP2016504289 A5 JP 2016504289A5
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| PL2925744T3 (pl) * | 2012-11-27 | 2021-06-14 | Thomas Helledays Stiftelse För Medicinsk Forskning | Pochodne pirymidyno-2,4-diaminy do leczenia nowotworu |
| WO2015172747A1 (en) * | 2014-05-16 | 2015-11-19 | Zhaoyin Wang | Spirocyclic molecules as mth1 inhibitors |
| WO2015187088A1 (en) * | 2014-06-04 | 2015-12-10 | Thomas Helledays Stiftelse För Medicinsk Forskning | Mth1 inhibitors for treatment of cancer |
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| AU2015274285C1 (en) | 2014-06-13 | 2021-07-01 | The Brigham And Women's Hospital, Inc. | Pyrimidine compounds and methods using the same |
| CN104292213A (zh) * | 2014-09-08 | 2015-01-21 | 湖南华腾制药有限公司 | 一种嘧啶衍生物的制备方法 |
| JP6533997B2 (ja) * | 2014-12-26 | 2019-06-26 | 株式会社ヤクルト本社 | Znf143阻害活性を有する化合物およびその利用 |
| WO2016128140A1 (en) | 2015-02-13 | 2016-08-18 | Merck Patent Gmbh | Pyrimidine derivatives for use in the treatment of cancer |
| WO2016135139A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | 2,3-dihydrocyclopenta[b]quinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135137A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Substituted 4-(phenylamino)quinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135138A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Oxoquinoline derivatives as mth1 inhibitors for the therapy of cancer |
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| WO2016145383A1 (en) * | 2015-03-11 | 2016-09-15 | Board Of Regents, University Of Texas System | Mth1 inhibitors for treating disease |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| CN106928192B (zh) * | 2015-12-29 | 2020-11-13 | 中国科学院广州生物医药与健康研究院 | 一种嘧啶类化合物及其制备方法和应用 |
| CN105732516A (zh) * | 2016-03-09 | 2016-07-06 | 哈尔滨医科大学 | 一种合成mth1蛋白抑制剂th287的方法 |
| US10981899B2 (en) | 2016-04-28 | 2021-04-20 | Cornell University | Inhibitors of soluble adenylyl cyclase |
| KR101876514B1 (ko) * | 2016-11-08 | 2018-07-10 | 한국화학연구원 | 신규한 피리미딘화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 암 및 염증질환의 예방 또는 치료용 약학적 조성물 |
| JP7159214B2 (ja) | 2017-05-18 | 2022-10-24 | イドーシア ファーマシューティカルズ リミテッド | Pge2レセプター調節剤としてのフェニル誘導体 |
| JP7159215B2 (ja) | 2017-05-18 | 2022-10-24 | イドーシア ファーマシューティカルズ リミテッド | Pge2レセプター調節剤としてのピリミジン誘導体 |
| TW201900179A (zh) | 2017-05-18 | 2019-01-01 | 瑞士商愛杜西亞製藥有限公司 | 作為pge2受體調節劑之苯并呋喃及苯并噻吩衍生物 |
| EP3625223B1 (en) | 2017-05-18 | 2021-08-11 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives |
| CN111065635B (zh) * | 2018-01-04 | 2022-07-22 | 无锡安万生物科技有限公司 | 作为mth1抑制剂的新型嘧啶衍生物 |
| CN112074511B (zh) | 2018-03-01 | 2024-04-26 | 托马斯·黑勒戴药物研究基金会 | 取代的苯并二唑及其在治疗中的用途 |
| WO2020210521A2 (en) * | 2019-04-12 | 2020-10-15 | The Regents Of The University Of California | Compositions and methods for increasing muscle mass and oxidative metabolism |
| EP4038065A1 (en) * | 2019-09-30 | 2022-08-10 | F. Hoffmann-La Roche AG | Substituted pyrimidine for the treatment and prophylaxis of hepatitis b virus infection |
| KR20220101138A (ko) * | 2019-11-13 | 2022-07-19 | 제넨테크, 인크. | 치료적 화합물 및 사용 방법 |
| CN110872291B (zh) * | 2019-11-26 | 2021-06-25 | 五邑大学 | 一种四氢吡啶并嘧啶类化合物及其制备方法和应用 |
| CN111557940A (zh) * | 2020-05-28 | 2020-08-21 | 青岛大学附属医院 | Mth1抑制剂th588在制备治疗多发性骨髓瘤的药物中的应用 |
| US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
| GB202108249D0 (en) * | 2021-06-09 | 2021-07-21 | Univ Of Sussex | Compounds |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| US2691655A (en) * | 1952-05-24 | 1954-10-12 | Burroughs Wellcome Co | 2-amino-4-substituted amino-6-aryl pyrimidines and process of preparing same |
| EP0210228A1 (en) | 1985-02-05 | 1987-02-04 | The Upjohn Company | 4-substituted-6-aryl pyrimidine compounds |
| US6169086B1 (en) | 1997-01-27 | 2001-01-02 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
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| WO2002096867A2 (en) | 2001-05-30 | 2002-12-05 | Lg Biomedical Institute | Inhibitors of protein kinase for the treatment of disease |
| HRP20040098B1 (en) | 2001-08-13 | 2012-08-31 | Janssen Pharmaceutica N.V. | 2,4,5-TRlSUBSTITUTED THIAZOLYL DERIVATIVES AND THEIR ANTIINFLAMMATORY ACTIVITY |
| US7419984B2 (en) | 2002-10-17 | 2008-09-02 | Cell Therapeutics, Inc. | Pyrimidines and uses thereof |
| WO2004080979A1 (en) * | 2003-03-14 | 2004-09-23 | Lg Life Sciences Ltd. | Novel 3-(2-amino-4-pyrimidinyl)-4-hydroxyphenyl ketone derivatives |
| US8084457B2 (en) | 2003-09-15 | 2011-12-27 | Lead Discovery Center Gmbh | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| EP1735319B1 (en) | 2004-03-26 | 2017-05-03 | MethylGene Inc. | Inhibitors of histone deacetylase |
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| EP2254415B1 (en) * | 2008-02-19 | 2013-01-23 | Janssen Pharmaceutica, N.V. | Aryl-hydroxyethylamino-pyrimidines and triazines as modulators of fatty acid amide hydrolase |
| US8268846B2 (en) | 2008-07-11 | 2012-09-18 | Abbott Laboratories | Amino heterocyclic linked pyrimidine derivatives |
| JP5743897B2 (ja) * | 2008-11-20 | 2015-07-01 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーGlaxoSmithKline LLC | 化合物 |
| US20120316171A1 (en) * | 2009-11-05 | 2012-12-13 | Tamas Oravecz | Tryptophan Hydroxylase Inhibitors for the Treatment of Cancer |
| EP2533778A1 (en) * | 2010-02-10 | 2012-12-19 | Lexicon Pharmaceuticals, Inc. | Tryptophan hydroxylase inhibitors for the treatment of metastatic bone disease |
| CN103298460B (zh) | 2010-12-14 | 2016-06-01 | 电泳有限公司 | 酪蛋白激酶1δ(CK1δ)抑制剂 |
| GB201215502D0 (en) | 2012-08-31 | 2012-10-17 | Chalkiadakis Spyridon | Medical use |
| PL2925744T3 (pl) * | 2012-11-27 | 2021-06-14 | Thomas Helledays Stiftelse För Medicinsk Forskning | Pochodne pirymidyno-2,4-diaminy do leczenia nowotworu |
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