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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| WO2015172747A1 (en) * | 2014-05-16 | 2015-11-19 | Zhaoyin Wang | Spirocyclic molecules as mth1 inhibitors |
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| CA2976415A1 (en) | 2015-02-13 | 2016-08-18 | Merck Patent Gmbh | Pyrimidine derivatives for use in the treatment 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 |
| WO2017190050A1 (en) * | 2016-04-28 | 2017-11-02 | 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 |
| TW201900180A (zh) | 2017-05-18 | 2019-01-01 | 瑞士商愛杜西亞製藥有限公司 | 嘧啶衍生物 |
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| AU2018268311B2 (en) | 2017-05-18 | 2022-02-10 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives as PGE2 receptor modulators |
| JP7093791B2 (ja) | 2017-05-18 | 2022-06-30 | 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ベンゾフラン及びベンゾチオフェン誘導体 |
| 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 |
| CA3091951A1 (en) | 2018-03-01 | 2019-09-06 | Thomas Helledays Stiftelse For Medicinsk Forskning | Substituted benzodiazoles and use thereof in therapy |
| 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 |
| CN114450277A (zh) * | 2019-09-30 | 2022-05-06 | 豪夫迈·罗氏有限公司 | 用于治疗和预防乙型肝炎病毒感染的经取代的嘧啶 |
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| 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 |
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Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB681712A (en) * | 1949-09-14 | 1952-10-29 | Burroughs Wellcome Co | Improvements in or relating to therapeutically useful pyrimidine compounds |
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| 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 |
| EP1678147B1 (en) | 2003-09-15 | 2012-08-08 | 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 |
| WO2006078886A2 (en) | 2005-01-18 | 2006-07-27 | Irm Llc | Compounds and compositions as wnt signaling pathway modulators |
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| US8268846B2 (en) | 2008-07-11 | 2012-09-18 | Abbott Laboratories | Amino heterocyclic linked pyrimidine derivatives |
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| CA2789229A1 (en) * | 2010-02-10 | 2011-08-18 | Lexicon Pharmaceuticals, Inc. | Tryptophan hydroxylase inhibitors for the treatment of metastatic bone disease |
| US20140031547A1 (en) | 2010-12-14 | 2014-01-30 | Electrophoretics Limited | CASEIN KINASE 1delta (CK 1delta) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODE-GENERATIVE DISEASES SUCH AS TAUOPATHIES |
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