Document Report Card

ID: ALA1156119

Journal: J Med Chem

Title: Design, synthesis, and structure-activity relationship of indole-3-glyoxylamide libraries possessing highly potent activity in a cell line model of prion disease.

Authors: Thompson MJ, Borsenberger V, Louth JC, Judd KE, Chen B.

Abstract: 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 in a cell line model of prion disease together with a defined structure-activity relationship, permitting the design of more potent compounds that effected clearance of scrapie in 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.

CiteXplore: 19842664

DOI: 10.1021/jm900920x