1173081-96-3Relevant articles and documents
Identification of potent, selective, cell-Active inhibitors of the histone lysine methyltransferase EZH2
Verma, Sharad K.,Tian, Xinrong,Lafrance, Louis V.,Duquenne, Céline,Suarez, Dominic P.,Newlander, Kenneth A.,Romeril, Stuart P.,Burgess, Joelle L.,Grant, Seth W.,Brackley, James A.,Graves, Alan P.,Scherzer, Daryl A.,Shu, Art,Thompson, Christine,Ott, Heidi M.,Van Aller, Glenn S.,MacHutta, Carl A.,Diaz, Elsie,Jiang, Yong,Johnson, Neil W.,Knight, Steven D.,Kruger, Ryan G.,McCabe, Michael T.,Dhanak, Dashyant,Tummino, Peter J.,Creasy, Caretha L.,Miller, William H.
, p. 1091 - 1096 (2012)
The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-Active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.
5-Hydroxyindole-based EZH2 inhibitors assembled via TCCA-catalyzed condensation and Nenitzescu reactions
Chen, Guoliang,Du, Fangyu,Sun, Wenjiao,Wang, Lihui,Wu, Chunfu,Yang, Cheng,Zhou, Qifan
, (2020/05/16)
5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L–04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC50 = 52.6 μM). These findings revealed that compound L–04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we discovered that trichloroisocyanuric acid (TCCA) is a novel catalyst which demonstrates condensation-promoting effects. To gain insight into the reaction, in situ React IR technology was used to confirm the reactivity. Different amines were condensed in high yields with β-diketones or β-ketoesters in the presence of TCCA to afford the corresponding products in a short time (10~20 min), which displayed some advantages and provided an alternative condensation strategy.
Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents
Zhou, Qifan,Jia, Lina,Du, Fangyu,Dong, Xiaoyu,Sun, Wanyu,Wang, Lihui,Chen, Guoliang
supporting information, p. 2247 - 2255 (2020/02/20)
Zeste enhancer homolog 2 (EZH2) is highly expressed in various malignant tumors, which could silence tumor suppressor genes via trimethylation of H3K27. Herein was first reported a novel series of pyrrole-3-carboxamide derivatives carrying a pyridone fragment as EZH2 inhibitors. By combining computational modeling, in vitro cellular assays and further rational structure-activity relationship exploration and optimization, compound DM-01 showed powerful inhibition towards EZH2. DM-01 was found to have significant ability to reduce the cellular H3K27me3 level in K562 cells in the Western blot test. Meanwhile, our data showed that knockdown EZH2 in A549 cells resulted in a decrease of cell sensitivity to DM-01 at 50 and 100 μM. DM-01 could also increase the transcription expression of DIRAS3 in a dose-dependent manner, a tumor suppressor in the downstream of EZH2, suggesting it was worth investigating further as a lead compound.
Pyrrole-3-formamide compound as well as preparation method and application thereof
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, (2019/02/25)
The invention belongs to the technical field of medicines, and relates to a pyrrole-3-formamide compound as well as a preparation method and application thereof, in particular to a pyrrole-3-formamidecompound shown as a formula (I) or (II) and a pharmaceutically-acceptable salt thereof, wherein R to R and X are defined in the claims and description. The preparation of the compound mainly comprises performing Knorr pyrrole synthesis, Hantzsch pyrrole synthesis, decarboxylation, alkylation, hydrolysis, condensation, cyclization and reduction on ethyl acetoacetate or tert-butyl acetoacetate serving as the raw material. The pyrrole-3-formamide compound and the pharmaceutically-acceptable salt thereof have good treatment effects on tumors, and can be applied to the preparation of anti-tumor drugs. (The formulas (I) and (II) are shown in the description).
EZH2 inhibitor as well as preparation of EZH2 inhibitor and application of EZH2 inhibitor in anti-tumor treatment
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Paragraph 0104-0106, (2019/08/20)
The invention discloses an EZH2 inhibitor as well as preparation of the EZH2 inhibitor and application of the EZH2 inhibitor in anti-tumor treatment. The EZH2 inhibitor has a structure represented bya general formula I shown in the description, wherein de
INDOLE DERIVATIVES AS MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Paragraph 00174; 00177, (2015/02/25)
Agents of formulas (l)/(ll)/(lll) for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
SUBSTITUTED BICYCLIC COMPOUNDS AS INHIBITORS OF EZH2
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Page/Page column 53; 54; 55; 56, (2014/10/15)
The present invention provides compounds of formula 1, isotopic forms, stereoisomers or tautomers thereof, or pharmaceutically acceptable salts, solvates, N-oxides, S-oxides and polymorphs thereof, and processes for their preparation. The invention further relates to pharmaceutical compositions containing said compounds and their use in the treatment of diseases or disorders mediated by EZH2 (enhancer of zeste homolog 2), particularly cancer.
MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Paragraph 00155, (2014/10/04)
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
ARYL AND HETEROARYL FUSED LACTAMS
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Paragraph 0786; 0790, (2014/07/08)
This invention relates to compounds of general formula (I) in which R1, R2, U, V, L, M, R5, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.
Substituted Benzene Compounds
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, (2014/05/07)
The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
