Synthesis of benzamide derivatives and their evaluation as antiprion agents.

Authors :: Fiorino F
Eiden M
Giese A
Severino B
Esposito A
Groschup MH
Perissutti E
Magli E
Incisivo GM
Ciano A
Frecentese F
Kretzschmar HA
Wagner J
Santagada V
Caliendo G
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2012 Aug 15; Vol. 20 (16), pp. 5001-11. Date of Electronic Publication: 2012 Jun 20.
Publication Year :: 2012
Abstract: 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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)