Structure-activity relationship study of prion inhibition by 2-aminopyridine-3, 5-dicarbonitrile-based compounds: parallel synthesis, bioactivity, and in vitro …

…, JA Zorn, J Witkop, J Sherrill, AC Wallace…

Index: May, Barnaby C. H.; Zorn, Julie A.; Witkop, Juanita; Sherrill, John; Wallace, Andrew C.; Legname, Giuseppe; Prusiner, Stanley B.; Cohen, Fred E. Journal of Medicinal Chemistry, 2007 , vol. 50, # 1 p. 65 - 73

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Citation Number: 75

Abstract

2-Aminopyridine-3, 5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6- aminopyridine-3, 5-dicarbonitrile scaffold. We identify compounds with significantly improved bioactivity (approximately 40-fold) against replication of the infectious prion ...