- 2-AMINOPYRIMIDINE DERIVATIVE, PREPARATION METHOD AND USE THEREOF
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The disclosure provides an aminopyrimidine derivative for preventing and treating diseases related to IDH mutation, a preparation method and use thereof. Specifically, the disclosure provides a compound of Formula I, a stereoisomer, racemate thereof, or pharmaceutically acceptable salt thereof. The compound of the general Formula I has isocitrate dehydrogenase 1 (IDH1) inhibitory activity and can treat cancer induced by IDH1 mutation.
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Paragraph 0102-0103
(2021/03/04)
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- COMBINATION THERAPY INCLUDING AN MDM2 INHIBITOR AND ONE OR MORE ADDITIONAL PHARMACEUTICALLY ACTIVE AGENTS FOR THE TREATMENT OF CANCERS
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The present invention provides combination therapy that includes an MDM2 inhibitor and one or more additional pharmaceutically active agents, particularly for the treatment of cancers. The invention also relates to pharmaceutical compositions that contain
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Page/Page column 80
(2015/05/26)
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- Discovery of AM-7209, a potent and selective 4-amidobenzoic acid inhibitor of the MDM2-p53 interaction
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Structure-based rational design and extensive structure-activity relationship studies led to the discovery of AMG 232 (1), a potent piperidinone inhibitor of the MDM2-p53 association, which is currently being evaluated in human clinical trials for the treatment of cancer. Further modifications of 1, including replacing the carboxylic acid with a 4-amidobenzoic acid, afforded AM-7209 (25), featuring improved potency (KD from ITC competition was 38 pM, SJSA-1 EdU IC50 = 1.6 nM), remarkable pharmacokinetic properties, and in vivo antitumor activity in both the SJSA-1 osteosarcoma xenograft model (ED50 = 2.6 mg/kg QD) and the HCT-116 colorectal carcinoma xenograft model (ED50 = 10 mg/kg QD). In addition, 25 possesses distinct mechanisms of elimination compared to 1.
- Rew, Yosup,Sun, Daqing,Yan, Xuelei,Beck, Hilary P.,Canon, Jude,Chen, Ada,Duquette, Jason,Eksterowicz, John,Fox, Brian M.,Fu, Jiasheng,Gonzalez, Ana Z.,Houze, Jonathan,Huang, Xin,Jiang, Min,Jin, Lixia,Li, Yihong,Li, Zhihong,Ling, Yun,Lo, Mei-Chu,Long, Alexander M.,McGee, Lawrence R.,McIntosh, Joel,Oliner, Jonathan D.,Osgood, Tao,Saiki, Anne Y.,Shaffer, Paul,Wang, Yu Chung,Wortman, Sarah,Yakowec, Peter,Ye, Qiuping,Yu, Dongyin,Zhao, Xiaoning,Zhou, Jing,Medina, Julio C.,Olson, Steven H.
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p. 10499 - 10511
(2015/02/19)
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- BENZOIC ACID DERIVATIVE MDM2 INHIBITOR FOR THE TREATMENT OF CANCER
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The present invention provides a MDM2 inhibitor compound, or a pharmaceutically acceptable salt thereof, which compound is useful as a therapeutic agent, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contains the MDM2 inhibitor.
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Paragraph 0271-0272
(2014/09/03)
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- Substituted Pteridines
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The invention relates to new pteridines which are suitable for treating respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system and cancers. This invention also relates to pharmaceutical compositions containing these compounds.
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Page/Page column 18
(2008/06/13)
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- BIPHENYLCARBOXYLIC AMIDE DERIVATIVES AS P38 KINEASE INHIBITORS
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Compounds of formula (I) or pharmaceutically acceptable derivatives thereof, and their use as pharmaceuticals, particularly as p38 kinase inhibitors.
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