Discovery and Preliminary SAR of Arylpiperazines as Novel, Brainpenetrant Antiprion Compounds.

ABSTRACT: Prion diseases are a group of fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) and kuru in humans, BSE in cattle, and scrapie in sheep. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrP^Sc) of a normally benign, host cellular protein, denoted PrP^C. We employed high-throughput screening (HTS) ELISAs to evaluate compounds for their ability to reduce the level of PrP^Sc in Rocky Mountain Laboratory (RML) prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1, 7, 13, and 19, displayed moder

SUBMITTER: Li Z 

PROVIDER: S-EPMC3704178 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature