Synthesis and biological evaluation of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamides as pyruvate dehydrogenase kinase 1 (PDK1) inhibitors to reduce the growth of cancer cells was written by Zhang, Shao-Lin;Zhang, Wen;Yang, Zheng;Hu, Xiaohui;Tam, Kin Yip. And the article was included in European Journal of Pharmaceutical Sciences in 2017.Application of 2103-99-3 This article mentions the following:
Most cancer cells exhibit a high rate of glycolysis and reduced capacity in mitochondrial oxidative phosphorylation. The expression of pyruvate dehydrogenase kinases (PDKs) was found to be increased in many cancer cells. Inhibition of PDKs increases the oxidative phosphorylation of glucose, which may disrupt the balance between the demand and supply of oxygen in cancer cell, thus leading to cell death. Several reports suggested that compounds containing (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide group could inhibit PDKs in pyruvate dehydrogenase primary enzymic assay. However, none of them were capable of reducing the growth of cancer cells. Herein, we report the synthesis and biol. evaluation of some novel PDK1 inhibitors containing the (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide warhead. Excitingly, these novel PDK1 inhibitors exhibited good potency to reduce the growth of cancer cells. We have demonstrated that these compounds could phys. associate with PDK1 and activate pyruvate dehydrogenase in low micromolar levels. In the experiment, the researchers used many compounds, for example, 4-(4-Chlorophenyl)thiazol-2-amine (cas: 2103-99-3Application of 2103-99-3).
4-(4-Chlorophenyl)thiazol-2-amine (cas: 2103-99-3) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity.Various laboratory methods exist for the organic synthesis of thiazoles. For example, 2,4-dimethylthiazole is synthesized from thioacetamide and chloroacetone.Application of 2103-99-3
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica