52348-60-4

Basic information

• Product Name: Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-dione, 3-(4-methoxyphenyl)-1,6-dimethyl-
• Synonyms: 3-(p-Anisyl)-toxoflavin;3-(4-Methoxy-phenyl)-1,6-dimethyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione;3-p-Methoxyphenyl-toxoflavin;3-p-Anisyltoxoflavin;3-(4-Methoxyphenyl)toxoflavin;3-(4-Methoxyphenyl) toxoflavin
• CAS NO: 52348-60-4
• Molecular Formula: C14H13N5O3
• Molecular Weight: 299.289
• Mol File: 52348-60-4.mol
• Article Data: 7

Chemical Properties

• Melting Point: 244 °C (decomp)
• Boiling Point: 415.3±47.0 °C(Predicted)
• Density: 1.44±0.1 g/cm3(Predicted)
• CAS DataBase Reference: Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-dione, 3-(4-methoxyphenyl)-1,6-dimethyl-(CAS DataBase Reference)
• NIST Chemistry Reference: Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-dione, 3-(4-methoxyphenyl)-1,6-dimethyl-(52348-60-4)
• EPA Substance Registry System: Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-dione, 3-(4-methoxyphenyl)-1,6-dimethyl-(52348-60-4)

Safety Data

• Hazardous Substances Data: 52348-60-4(Hazardous Substances Data)

Upstream product

• 42748-18-5 6-(2-(4-methoxybenzylidene)-1-methylhydrazinyl)-3-methylpyrimidine-2,4(1H,3H)-dione 
• 42747-84-2 3-methyl-6-(1-methylhydrazinyl)pyrimidine-2,4(1H,3H)-dione 
• 4318-56-3 3-methyl-6-chlorouracil 

Downstream Products

• 61602-21-9 3-(4-methoxyphenyl)-1,5-dimethyl-1H-imidazo[4,5-e][1,2,4]triazin-6(5H)-one 
• 52199-07-2 5,6,7,8-tetrahydro-3-(p-methoxyphenyl)-6,8-dimethylpyrimido<5,4-e><1,2,4>triazine-5,7-dione 

Relevant articles and documents

Rational design, synthesis and biological profiling of new KDM4C inhibitors

The human histone demethylases of the KDM4 family have been related to diseases such as prostate and breast cancer. Majority of currently known inhibitors suffer from the low permeability and low selectivity between the enzyme isoforms. In this study, toxoflavin motif was used to design and synthesize new KDM4C inhibitors with improved biological activity and in vitro ADME properties. Inhibitors displayed good passive cellular permeability and metabolic stability. However, diminishing of redox liability and consequently non-specific influence on cell viability still remains a challenge.

Investigation of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7-diones as small molecule antagonists of β-catenin/TCF transcription

Nearly all colorectal cancers (CRCs) and varied subsets of other cancers have somatic mutations leading to β-catenin stabilization and increased β-catenin/TCF transcriptional activity. Inhibition of stabilized β-catenin in CRC cell lines arrests their growth and highlights the potential of this mechanism for novel cancer therapeutics. We have pursued efforts to develop small molecules that inhibit β-catenin/TCF transcriptional activity. We used xanthothricin, a known β-catenin/TCF antagonist of microbial origin, as a lead compound to synthesize related analogues with drug-like features such as low molecular weight and good metabolic stability. We studied a panel of six candidate Wnt/β-catenin/Tcf- regulated genes and found that two of them (Axin2, Lgr5) were reproducibly activated (9-10 fold) in rat intestinal epithelial cells (IEC-6) following β-catenin stabilization by Wnt-3a ligand treatment. Two previously reported β-catenin/TCF antagonists (calphostin C, xanthothricin) and XAV939 (tankyrase antagonist) inhibited Wnt-activated genes in a dose-dependent fashion. We found that four of our compounds also potently inhibited Wnt-mediated activation in the panel of target genes. We investigated the mechanism of action for one of these (8c) and demonstrated these novel small molecules inhibit β-catenin transcriptional activity by degrading β-catenin via a proteasome-dependent, but GSK3β-, APC-, AXIN2- and βTrCP-independent, pathway. The data indicate the compounds act at the level of β-catenin to inhibit Wnt/β-catenin/TCF function and highlight a robust strategy for assessing the activity of β-catenin/TCF antagonists.

PYRIMIDOTRIAZINEDIONES AND PYRIMIDOPYRIMIDINEDIONES AND METHODS OF USING THE SAME

The present disclosure is directed to pyrimidotriazinediones and pyrimidopyrimidinediones having a formula (I), (II), or (III), or a mixture or pharmaceutically acceptable salt or hydrate thereof, and to methods of treating cancer comprising administering