Design, Synthesis, and Structure-Activity Relationship of Indole-3-glyoxylamide Libraries Possessing Highly Potent Activity in a Cell Line Model of Prion Disease

Transmissible spongiform encephalopathies (TSEs) are a family of invariably fatal neurodegenerative disorders for which no effective Curative therapy currently exists. We report here the synthesis of a library of indole-3-glyoxylamides and their evaluation as potential antiprion agents. A number of compounds demonstrated submicromolar activity ill it cell line model of prion disease together with it defined structure-activity relationship, permitting the design of more potent compounds that effected clearance of scrapie ill the low nanomolar range. Thus, the indole-3-glyoxylamides described herein constitute ideal candidates to progress to further development as potential therapeutics for the family of human prion disorders.