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• 78514-88-2 C₁₆H₁₈N₄O₃S 
• 67280-21-1 C₁₀H₁₃N₃OS 
• 94-05-3 ethyl (ethoxymethylene)cyanoacetate 
• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

Developing novel classes of protein kinase CK1δ inhibitors by fusing [1,2,4]triazole with different bicyclic heteroaromatic systems

Protein kinase CK1δ expression and activity is involved in different pathological situations that include neuroinflammatory and neurodegenerative diseases. For this reason, protein kinase CK1δ has become a possible therapeutic target for these conditions. 5,6-fused bicyclic heteroaromatic systems that resemble adenine of ATP represent optimal scaffolds for the development of a new class of ATP competitive CK1δ inhibitors. In particular, a new series of [1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-a][1,3,5]triazines was developed. Some crucial interactors have been identified, such as the presence of a free amino group able to interact with the residues of the hinge region at the 5- and 7- positions of the [1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-a][1,3,5]triazine scaffolds, respectively; or the presence of a 3-hydroxyphenyl or 3,5-dihydroxyphenyl moiety at the 2- position of both nuclei. Molecular modeling studies identified the key interactions involved in the inhibitor-protein recognition process that appropriately fit with the outlined structure-activity relationship. Considering the fact that the CK1 protein kinase is involved in various pathologies in particular of the central nervous system, the interest in the development of new inhibitors permeable to the blood-brain barrier represents today an important goal in the pharmaceutical field. The best potent compound of the series is the 5-(7-amino-5-(benzylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)benzen-1,3-diol (compound 51, IC50 = 0.18 μM) that was predicted to have an intermediate ability to cross the membrane in our in vitro assay and represents an optimal starting point to both studies the therapeutic value of protein kinase CK1δ inhibition and to develop new more potent derivatives.

Cyclization of Isothiosemicarbazones. 5. Triazolopyrimidines

The 4--3-methylisothiosemicarbazones of aromatic aldehydes underwent cyclization upon being heated in 1-butanol, N,N-dimethylformamide, dioxane, or pyridine to give 2,5-disubstituted triazolopyrimidine-8-carboxylates in moderate yields.Competitive formation of ethyl 4-amino-2-(methylthio)pyrimidine-5-carboxylate occured in this cyclization with elimination of benzonitriles probably through a nonionic pathway.Treatment of the aromatic ketone analogues with hot acetic acid or pyridine gave 2,2,5-trisubstituted 2,3-dihydrotriazolopyrimidine-8-carboxylates by intramolecular cycloaddition.These compounds exist as a chain-ring tautomeric mixture in pyridine at elevated temperatures and gradually lose the substituents at the 2-position to give the same bicyclic pyrimidines as those from aldehyde isothiosemicarbazones.A mechanism was proposed in which the ring closure of the 2,3,5,9-tetraaza-1,3,6-nonatrien-8-yne systems may involve a ten-electron cyclic transition state.