Synthesis of benzamide derivatives and their evaluation as antiprion agents

Fiorino, F.; Eiden, Martin GND; Giese, A.; Severino, B.; Esposito, A.; Groschup, Martin H. GND; Perissutti, E.; Magli, E.; Incisivo, G.M.; Ciano, A.; Frecentese, F.; Kretzschmar, H.A.; Wagner, J.; Santagada, V.; Caliendo, G.

A new set of 5-(2-(pyrrolidin-1-yl)acetamido)-N-butyl-2-(substituted)benzamide and 5-(2-(piperidin-1-yl)acetamido)-N-butyl-2-(substituted) benzamide derivatives were synthesized in which as structural features the 2-(1-pyrrolidinyl)- or 2-(1-piperidyl)acetylamino group or a diphenylether moiety are associated to a benzamide scaffold. Their binding affinity for human PrP C and inhibition of its conversion into PrP Sc were determined in vitro; moreover, the antiprion activity was assayed by inhibition of PrP Sc accumulation in scrapie-infected mouse neuroblastoma cells (ScN2a) and scrapie mouse brain (SMB) cells. The results clearly indicate the benzamide derivatives as attractive lead compounds for the development of potential therapeutic agents against prion disease.

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Fiorino, F. / Eiden, Martin / Giese, A. / et al: Synthesis of benzamide derivatives and their evaluation as antiprion agents. 2012.

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