761440-34-0Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel pteridinone derivatives as potent dual inhibitors of PLK1 and BRD4
Gong, Ping,Hou, Yunlei,Hu, Tao,Li, Zhiwei,Liu, Yajing,Qi, Yinliang,Qin, Mingze,Xu, Le,Yin, Bixi,Zhao, Yanfang
, p. 16477 - 16490 (2020/10/14)
To develop novel simultaneous inhibition of PLK1 and BRD4 bromodomain by a single molecule, three series of novel pteridinone derivatives were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against A549, HCT116, PC-3 and MCF-7 cell lines. The most promising compound III4 showed high antiproliferative effects on four cell lines with IC50 values of 1.27 μM, 1.36 μM, 3.85 μM and 4.06 μM, respectively. The enzymatic assay identified III4 as a potent PLK1 and BRD4 dual inhibitor with % inhibition values of 96.6 and 59.1, respectively. Furthermore, to clarify the anticancer mechanism of the target compounds, explorations in the bioactivity were conducted. The results showed that compound III4 obviously inhibited the proliferation of HCT-116 cell lines, induced a great decrease in the mitochondrial membrane potential leading to apoptosis of cancer cells, suppressed the migration of tumor cells, and arrested the S phase of HCT116 cells.
SUBSTITUTED PYRIMIDINES USEFUL AS EGFR-T790M KINASE INHIBITORS
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Page/Page column 15; 16, (2015/09/23)
The present invention is directed to novel pyrimidines, their derivatives, pharmaceutically acceptable salts, solvates and hydrates thereof. The compounds and compositions of the present invention have protein kinases inhibitory activities and are expecte
5 OXO-5,8-DIHYDROPYRIDO[2,3-d]PYRIMIDINE DERIVATIVES AS CAMKII KINASE INHIBITORS FOR TREATING CARDIOVASCULAR DISEASES
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Page/Page column 25, (2012/11/08)
The present invention relates to 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine derivatives, to their preparation and to their therapeutic use.
PYRIMIDINYL ARYL UREA DERIVATIVES BEING FGF INHIBITORS
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Page/Page column 85, (2008/06/13)
The invention relates to heteroaryl aryl ureas of the formula (IA), wherein the radicals and symbols have the meanings as defined herein, the use of such compounds in the treatment of protein kinase dependent diseases; to pharmaceutical preparations comprising said heteroaryl aryl ureas, to processes for the manufacture of such novel compounds and to methods of treatment comprising the use of such heteroaryl aryl ureas.
2, 4- DI (PHENYLAMINO) PYRIMIDINES USEFUL IN THE TREATMENT OF NEOPLASTIC DISEASES, INFLAMMATORY AND IMMUNE SYSTEM DISORDERS
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Page 118; 121, (2010/02/08)
Novel pyrimidine derivatives of formula (I), to processes for their production, their use as pharmaceuticals in the treatment of neoplastic diseases, inflammatory and immune system disorders and to pharmaceutical compositions comprising them.
