- NOVEL PYRIDO[3,4-D]PYRIMIDIN-8-ONE DERIVATIVE HAVING PROTEIN KINASE INHIBITORY ACTIVITY, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING, ALLEVIATING, OR TREATING CANCER, COMPRISING SAME
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The present disclosure relates to a pyrido[3,4-d]pyrimidin-8-one derivative compound exhibiting excellent anti-proliferative effects against cancer cells, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a stereoisomer thereof, a production method therefor, a pharmaceutical composition for preventing, alleviating or treating cancer metastasis and proliferative disease containing the same as an active ingredient, and an anticancer composition against cancer cells. The compound exhibits excellent cancer cell inhibitory activity and anti-proliferative effects, and thus is effective in inhibiting cancer cells, preventing cancer metastasis and proliferative diseases or treating cancer.
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- IMIDAZOPYRIMIDINES AS EED INHIBITORS AND THE USE THEREOF
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The present disclosure provides compounds represented by Formula (I) wherein R1, R2, R3, and R4 are as defined in the specification, and the salts and solvates thereof. Compounds of Formula (I) are FED inhibitors. FED inhibitors are useful for the treatment of cancer and other diseases.
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Paragraph 0464-0466
(2021/02/12)
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- CRYSTAL OF PYRIDO[3,4-D]PYRIMIDINE DERIVATIVE OR SOLVATE THEREOF
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Provided is a crystal of a novel pyrido[3, 4-d]pyrimidine derivative having excellent CDK 4/6 inhibitory activity. A crystal of a compound represented by formula (I). In the formula, R1 represents a hydrogen atom or a C1-3 alkyl group; R2 represents a hydrogen atom or an oxo group; L represents a single bond or a C1-3 alkylene group; and X represents CH or N.
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Paragraph 0111-0112
(2021/09/10)
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- Photoinduced and Palladium-Catalyzed Remote Desaturation of Amide Derivatives
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A photoinduced and palladium-catalyzed remote desaturation of O-acyl hydroxamides to unsaturated amides under mild conditions has been achieved. The formation of the alkyl Pd(II) intermediate by the recombination of alkyl radical and Pd(I) species is critical to achieve this efficient and selective desaturation of alkanes. This reaction features good site-selectivity, is terminal oxidant-free, and produces moderate to excellent yields for a variety of unsaturated amides. Remarkably, this approach enables late-stage desaturation of complex and biologically important molecules.
- Jin, Weiwei,Yu, Shouyun
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supporting information
p. 6931 - 6935
(2021/09/11)
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- EEDi-5285: An Exceptionally Potent, Efficacious, and Orally Active Small-Molecule Inhibitor of Embryonic Ectoderm Development
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Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20 pM and 0.5 nM in the Pfeiffer and KARPAS422 lymphoma cell lines, respectively, carrying an EZH2 mutation. EEDi-5285 is approximately 100 times more potent than EED226 in binding to EED and >300 times more potent than EED226 in inhibition of cell growth in the KARPAS422 cell line. EEDi-5285 has excellent pharmacokinetics and achieves complete and durable tumor regression in the KARPAS422 xenograft model in mice with oral administration. The cocrystal structure of EEDi-5285 in a complex with EED defines the precise structural basis for their high binding affinity. EEDi-5285 is the most potent and efficacious EED inhibitor reported to date.
- Rej, Rohan Kalyan,Wang, Changwei,Lu, Jianfeng,Wang, Mi,Petrunak, Elyse,Zawacki, Kaitlin P.,McEachern, Donna,Fernandez-Salas, Ester,Yang, Chao-Yie,Wang, Lu,Li, Ruiting,Chinnaswamy, Krishnapriya,Wen, Bo,Sun, Duxin,Stuckey, Jeanne,Zhou, Yunlong,Chen, Jianyong,Tang, Guozhi,Wang, Shaomeng
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p. 7252 - 7267
(2020/07/14)
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- FGFR4 inhibitor and preparation method and application thereof
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The invention relates to an FGFR4 inhibitor and a preparation method and application thereof, in particular to a medicine composition of the FGFR4 inhibitor with a structure shown in the formula (I).The medicine composition has a high inhibiting effect on FGFR4 kinase activity, and can be widely applied to preparation of medicine for treating cancers including the liver cancer, the stomach cancer, the prostatic cancer, the skin cancer, the ovarian cancer, the lung cancer, the breast cancer and the colon cancer.
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Paragraph 0256; 0257; 0258; 0259
(2019/05/28)
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- PYRIDO[3, 4-D]PYRIMIDINE DERIVATIVE AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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The purpose of the present invention is to provide a compound that has excellent CDK4/6 inhibitory activity. The present invention is a compound represented by formula (I) or a pharmaceutically acceptable salt of the compound.
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Paragraph 0170; 0171
(2019/10/16)
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- PYRIDO[3,4-d]PYRIMIDINE DERIVATIVE AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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The purpose of the present invention is to provide a compound having an excellent CDK4/6 inhibiting activity. The present invention is a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof.
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Paragraph 0167; 0168
(2018/04/19)
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- Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy
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Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2MUT preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.
- Huang, Ying,Zhang, Jeff,Yu, Zhengtian,Zhang, Hailong,Wang, Youzhen,Lingel, Andreas,Qi, Wei,Gu, Justin,Zhao, Kehao,Shultz, Michael D.,Wang, Long,Fu, Xingnian,Sun, Yongfeng,Zhang, Qiong,Jiang, Xiangqing,Zhang, Jiangwei,Zhang, Chunye,Li, Ling,Zeng, Jue,Feng, Lijian,Zhang, Chao,Liu, Yueqin,Zhang, Man,Zhang, Lijun,Zhao, Mengxi,Gao, Zhenting,Liu, Xianghui,Fang, Douglas,Guo, Haibing,Mi, Yuan,Gabriel, Tobias,Dillon, Michael P.,Atadja, Peter,Oyang, Counde
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supporting information
p. 2215 - 2226
(2017/04/03)
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- IMIDAZOPYRIMIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER
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A compound of Formula (IA), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein A, R3, R4, R6, and R7 are as defined herein.
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Paragraph 00284
(2018/04/12)
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- Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors
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The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer's disease.[Figure presented]
- Katz, Jason D.,Haidle, Andrew,Childers, Kaleen K.,Zabierek, Anna A.,Jewell, James P.,Hou, Yongquan,Altman, Michael D.,Szewczak, Alexander,Chen, Dapeng,Harsch, Andreas,Hayashi, Mansuo,Warren, Lee,Hutton, Michael,Nuthall, Hugh,Su, Hua-Poo,Munshi, Sanjeev,Stanton, Matt G.,Davies, Ian W.,Munoz, Ben,Northrup, Alan
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p. 114 - 120
(2016/12/09)
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- N2-PHENYL-PYRIDO[3,4-D]PYRIMIDINE-2,8-DIAMINE DERIVATIVES AND THEIR USE AS MPS1 INHIBITORS
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The present invention relates to compounds of formula (I) wherein R1, R2, R3 and R4 are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 –also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.
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Page/Page column 117-118
(2015/09/28)
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- INHIBITOR COMPOUNDS
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The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 - also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them
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Paragraph 00149; 0046-0050
(2014/03/26)
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- Novel potent pyrimido[4,5-c]quinoline inhibitors of protein kinase CK2: SAR and preliminary assessment of their analgesic and anti-viral properties
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We describe the discovery of novel potent substituted pyrimido[4,5-c] quinoline ATP-competitive inhibitors of protein kinase CK2. A binding model of the inhibitors with the protein was elaborated on the basis of SAR and revealed various modes of interacti
- Pierre, Fabrice,O'Brien, Sean E.,Haddach, Mustapha,Bourbon, Pauline,Schwaebe, Michael K.,Stefan, Eric,Darjania, Levan,Stansfield, Ryan,Ho, Caroline,Siddiqui-Jain, Adam,Streiner, Nicole,Rice, William G.,Anderes, Kenna,Ryckman, David M.
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p. 1687 - 1691
(2011/05/05)
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- THERAPEUTIC KINASE MODULATORS
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The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, and modulating protein kinase activity. Molecules of the invention can modulate casein kinase (CK) activity. The invention also relates in part to methods for using such molecules.
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Page/Page column 33
(2009/04/24)
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- PROTEIN KINASE MODULATORS
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The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and/or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.
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Page/Page column 44
(2009/10/01)
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- SERINE-THREONINE PROTEIN KINASE AND PARP MODULATORS
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The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.
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Page/Page column 78
(2008/06/13)
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- 7H-PYRIDO[3,4-D]PYRIMIDIN-8-ONES, THEIR MANUFACTURE AND USE AS PROTEIN KINASE INHIBITORS
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Objects of the present invention are the compounds of formula (I) their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above compounds, medicaments containing them and their manufacture, as we
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Page/Page column 31
(2008/06/13)
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