52199-07-2

Upstream product

• 78158-84-6 6-{N'-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-hydrazino}-1,3-dimethyl-5-phenylazo-1H-pyrimidine-2,4-dione 
• 62758-20-7 6,8-dimethyl-3,5,7-trioxo-2,3,5,6,7,8-hexahydropyrimido[5,4-e][1,2,4]-triazine-4-oxide 
• 123-11-5 4-methoxy-benzaldehyde 
• 52421-35-9 4-methoxy-benzaldehyde (1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-methyl-hydrazone 
• 42748-13-0 4-methoxy-benzaldehyde (1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl)-hydrazone 
• 42747-84-2 3-methyl-6-(1-methylhydrazinyl)pyrimidine-2,4(1H,3H)-dione 
• 42748-18-5 6-(2-(4-methoxybenzylidene)-1-methylhydrazinyl)-3-methylpyrimidine-2,4(1H,3H)-dione 
• 4318-56-3 3-methyl-6-chlorouracil 
• 52348-60-4 3-(4-methoxyphenyl)-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione 

Downstream Products

• 118214-96-3 2,4a,5,6,7,8-hexahydro-3-(p-methoxyphenyl)-4a-(3-indolyl)-6,8-dimethylpyrimido<5,4-e><1,2,4>triazine-5,7-dione 

Relevant academic research and scientific papers

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.

N-Bromosuccinimide in Heterocyclic Synthesis. Synthesis of Pyrazolopyrimidines, Pyrimido-as-triazines, and Pyrimidopyridazines from 6-Arylidenehydrazino-1,3-dimethyluracil Derivatives

Reactions of 6-arylidenehydrazino-1,3-dimethyluracil derivatives with N-bromosuccinimide leading to pyrazolopyrimidines, pyrimido-as-triazines, and pyrimidopyridazines are described.

A NEW SYNTHESIS OF PYRIMIDO-as-TRIAZINE DERIVATIVES

The reaction of 5-arylazo-6-arylidenehydrazino-1,3-dimethyluracils (II), prepared by the diazotization of 6-arylidenehydrazino-1,3-dimethyluracils (I), with dimethylformamide dimethylacetal afforded the corresponding 3-arylfervenulins (3-aryl-6,8-dimethylpyrimido-as-triazine-5,7(6H,8H)-diones) (V).