September 17, 2012
Here are some new indole tau inhibitors. Tau is an intracellular protein that stabilizes microtubules and helps regulate their function, for example, in cell division. It is of interest in neurodegenerative diseases, such as Alzheimer’s disease, because of its hypothesized role in neuronal cell death. G. Griffioen and co-inventors claim a series of indoles that inhibit tau phosphorylation. Test compounds were studied for their ability to inhibit tau phosphorylation or inhibit α-synuclein in animals and in cell cultures.
Three of the 104 compounds prepared by the inventors are shown in the figure along with their half-maximal effective concentrations (EC50s) from tau-induced cytotoxicity experiments. The EC50s for the tested compounds ranged from 24 to 1078 nM. The data were reported from cell-based assays, but the specific cell-based model used to produce the data was not specified. (Catholic University of Leuven [Belgium] and reMYND NV [Leuven]. WIPO Publication WO2012080220, June 21, 2012; David P. Rotella)
This patent was originally reviewed in ACS Medicinal Chemistry Letters.