Synthesis of benzamide derivatives and their evaluation as antiprion agents.
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.
Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Ferdinando
F
Fiorino
Martin
M
Eiden
Armin
A
Giese
Beatrice
B
Severino
Antonella
A
Esposito
Martin H
MH
Groschup
Elisa
E
Perissutti
Elisa
E
Magli
Giuseppina Maria
GM
Incisivo
Antonio
A
Ciano
Francesco
F
Frecentese
Hans A
HA
Kretzschmar
Jens
J
Wagner
Vincenzo
V
Santagada
Giuseppe
G
Caliendo
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011328:Prions / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012608:Scrapie / Q000188:drug therapy / Q000378:metabolism; D013329:Structure-Activity Relationship
D001549:Benzamides; D011328:Prions; D011994:Recombinant Proteins; C037689:benzamide