Identification of pyrido[1,2-α]pyrimidine-4-ones as new molecules improving the transcriptional functions of estrogen-related receptor α.

The nuclear estrogen-related receptor α (ERRα) plays a central role in the regulation of expression of the genes involved in mitochondrial biogenesis and oxidative metabolism. We have successfully identified a series of pyrido[1,2-a]pyrimidin-4-ones as new agonists enhancing the transcriptional functions of ERRα. The compounds potently elevated the mRNA levels and the protein levels of ERRα downstream targets. Consequently, the compounds improved the glucose and fatty acid uptake in C2C12 muscle cells.