99898-70-1

Upstream product

• 117411-51-5 N-carbethoxy-N¹-(4-phenyl)pyrazol-3-yl-thiourea 
• 57999-06-1 4-phenyl-1H-pyrazol-5-amine 
• 16182-04-0 Ethoxycarbonyl isothiocyanate 
• 5591-70-8 4-phenyl-1H-pyrazol-3-ylamine 

Downstream Products

• 99898-77-8 2-methylthio-4-n-butylamino-8-phenylpyrazolo<1,5-a>-s-triazine 
• 99898-79-0 4-n-butylamino-8-phenylpyrazolo<1,5-a>-s-triazine 
• 99898-74-5 2-methylthio-4-chloro-8-phenylpyrazolo<1,5-a>-s-triazine 
• 99898-73-4 2-(methylsulfanyl)-8-phenyl-pyrazolo[1,5-a][1,3,5]triazin-4(3H)-one 

Relevant academic research and scientific papers

Microwave-assisted sequential one-pot synthesis of 8-substituted pyrazolo[1,5-a][1,3,5]triazines

This paper reports a convenient sequential one-pot approach for the synthesis of an array of 14 pyrazolo[1,5-a][1,3,5]triazines, substituted in C8 by halogen (Br), various functions (CN and CO2Et)2 and alkyl or (het)aryl groups. This study conf

Chemical Validation of DegS As a Target for the Development of Antibiotics with a Novel Mode of Action

Despite the availability of hundreds of antibiotic drugs, infectious diseases continue to remain one of the most notorious health issues. In addition, the disparity between the spread of multidrug-resistant pathogens and the development of novel classes of antibiotics exemplify an important unmet medical need that can only be addressed by identifying novel targets. Herein we demonstrate, by the development of the first in vivo active DegS inhibitors based on a pyrazolo[1,5-a]-1,3,5-triazine scaffold, that the serine protease DegS and the cell envelope stress-response pathway σE represent a target for generating antibiotics with a novel mode of action. Moreover, DegS inhibition is synergistic with well-established membrane-perturbing antibiotics, thereby opening promising avenues for rational antibiotic drug design.

Synthesis of pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors of thymidine phosphorylase

Thymidine phosphorylase (TP) is an enzyme that promotes tumor growth and metastasis and therefore is an attractive druggable target. Using a reported TP inhibitor, 7-deazaxanthine (7DX), as the lead compound; this study was set up to evaluate whether pyrazolo[1,5-a][1,3,5]triazin-2,4-diones and pyrazolo[ 1,5- a][1,3,5]triazin-2-thioxo-4-ones would exhibit TP inhibitory activity. The pyrazolo[1,5-a][1,3,5] triazine nucleus was constructed using a reaction that annulated the 1,3,5-triazine ring onto a pyrazole scaffold. Among the 52 compounds synthesized and tested, it was found that 1,3-dihydro-pyrazolo[1,5-a] [1,3,5]triazin-2-thioxo-4-ones exhibited various extent of inhibitory activity against TP. The best compound 17p, which bears a para-substituted pentafluorosulfur group, showed an IC50 value of 0.04 μM, which was around 800 times more potent than the 7DX (IC50 = 32 μM) under the same bioassay conditions. The results of the study suggested that a substituent with +σ and +π properties inserted at position 4 of a phenyl ring that is attached to position 8 of the pyrazolo[1,5-a][1,3,5]triazin- 2-thioxo-4-one scaffold would give excellent TP inhibitory action. In addition, 17p was found to be a non-competitive inhibitor thus suggested that it might interact with TP at a position different from the substrate binding site.