5909-24-0Relevant articles and documents
Developing novel classes of protein kinase CK1δ inhibitors by fusing [1,2,4]triazole with different bicyclic heteroaromatic systems
Grieco, Ilenia,Bissaro, Maicol,Tiz, Davide Benedetto,Perez, Daniel I.,Perez, Conception,Martinez, Ana,Redenti, Sara,Mariotto, Elena,Bortolozzi, Roberta,Viola, Giampietro,Cozza, Giorgio,Spalluto, Giampiero,Moro, Stefano,Federico, Stephanie
, (2021/03/16)
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.
Method for synthesizing high-purity 4-chloro-2-methylthiopyrimidine-5-ethyl carboxylate
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Paragraph 0015-0018, (2018/06/26)
The invention discloses a method for synthesizing high-purity 4-chloro-2-methylthiopyrimidine-5-ethyl carboxylate. The method comprises the following steps: reacting S-methylisothiourea sulfate and diethyl ethoxy-methylene malonate in an ethanol-sodium hydroxide solution, concentrating to remove ethanol and regulating the pH to be acidic to obtain an intermediate, namely 4-hydroxy-2-hydroxyhydroxypyrimidine-5-carboxylic acid ethyl ester, wherein the molar ratio of the S-methylisothiourea sulfate to the diethyl ethoxy-methylene malonate is 1 to 1.9-2.4; enabling the obtained 4-hydroxy-2-hydroxyhydroxy pyrimidine-5-carboxylic acid ethyl ester to react with thionyl chloride to obtain a target product, wherein the molar ratio of the 4-hydroxy-2-hydroxyhydroxy pyrimidine-5-carboxylic acid ethyl ester to the thionyl chloride is 1 to 1-1.8. The improved method provided by the invention can improve the yield, increase the reaction safety and reduce the cost.
Synthesis and Antifungal Activity Evaluation of Novel Substituted Pyrimidine-5-Carboxamides Bearing the Pyridine Moiety
Wang, Shi-Chun,Wan, Fu-Xian,Liu, Si,Zhang, Shuai,Jiang, Lin
, p. 445 - 451 (2018/01/15)
A series of novel N-(substituted phenyl/benzyl)-2-methylthio-4-((pyridin-3-ylmethyl)amino)pyrimidine-5-carboxamides were synthesized by multistep reactions. The structures of the target compounds were characterized by IR, 1H NMR, 13C NMR, and elemental analysis. Their in vitro antifungal activities against two kinds of plant pathogenic fungi were evaluated by the mycelial growth rate method. The result showed that at the dosage of 100 μg/mL, several of these compounds exhibited moderate activity against Botrytis cinerea with inhibition rates of ~70%, and most compounds (e.g., 5a, 5c, 5e, 5f, and 5h) possessed excellent activity against Sclerotinia Sclerotiorum with more than 90% inhibition rate.
