122734-32-1Relevant articles and documents
Microwave-assisted synthesis and biological evaluation of novel uracil derivatives inhibiting human thymidine phosphorylase
Corelli, Federico,Botta, Maurizio,Lossani, Andrea,Pasquini, Serena,Spadari, Silvio,Focher, Federico
, p. 987 - 992 (2004)
New 5-chloro-6-substituted-uracil derivatives have been prepared by microwave assisted-synthesis and tested in vitro as thymidine phosphorylase inhibitors. One of these compounds showed potent inhibitory activity, with an IC50 value in the subm
Design and synthesis of novel PRMT1 inhibitors and investigation of their binding preferences using molecular modelling
Yang, Hao,Ouyang, Yifan,Ma, Hao,Cong, Hui,Zhuang, Chunlin,Lok, Wun-Taai,Wang, Zhe,Zhu, Xuanli,Sun, Yutong,Hong, Wei,Wang, Hao
supporting information, p. 4635 - 4642 (2017/09/29)
Protein arginine methyltransferase 1 (PRMT1) catalyses the methylation of substrate arginine by transferring the methyl group from SAM (S-adenosyl-L-methionine), which leads to the formation of S-adenosyl homocysteine (SAH) and methylated arginine. We have shown previously that the Asp84 on PRMT1 could be a potential inhibitor binding site. In the current study, 28 compounds were designed and synthesized that were predicted to bind the Asp84 and substrate arginine sites together. Among them, 6 compounds were identified as potential PRMT1 inhibitors, and showed strong inhibitory effects on cancer cell lines, especially HepG2. The most potent PRMT1 inhibitor, compound 13d, was selected for molecular dynamic simulations to investigate binding poses. Based on the free energy calculations and structural analysis, we predicted that the ethylenediamine group would tightly bind to Asp84, and the trifluoromethyl group should occupy part of substrate arginine binding site, which is consistent with our original goal. Our results show for the first time that PRMT1 inhibitors can target the Asp84 binding site, which will be helpful for future drug discovery studies.
MACROCYCLIC ACTIVIN-LIKE RECEPTOR KINASE INHIBITORS
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Page/Page column 101, (2016/10/04)
The present invention relates to macrocyclic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of Activin-like receptor kinases, more in particular ALK1 and/or ALK2 and/or mutants thereof, for use in the diagnosis, prevention and/or treatment of ALK1-kinase and/or ALK2-kinase associated diseases. Moreover, the present invention provides methods of using said compounds, for instance as a medicine or diagnostic agent.