2020 Volume 30 Issue 1 Pages 43-46
Discovery of CNS penetrant HDAC inhibitors has attracted medicinal chemists’ attentions because inhibition of HDAC in CNS is a potent treatment of neurodegenerative diseases such as Alzheimer’s disease. We designed and synthesized a pyrilamine derivative 1 as a selective class I HDAC inhibitor focusing on pyrilamine-sensitive proton-coupled organic cation antiporter (PYSOCA) expressed at the blood brain barrier (BBB). Synthesized compound 1 inhibited class I HDACs selectively and our BBB transport study showed that compound 1 is a substrate of PYSOCA. In addition, compound 1 showed higher BBB permeability than CI-994 in rats.
