Document Report Card

ID: ALA2150866

Journal: ACS Med Chem Lett

Title: Irreversible 4-Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease.

Authors: Prime ME, Brookfield FA, Courtney SM, Gaines S, Marston RW, Ichihara O, Li M, Vaidya D, Williams H, Pedret-Dunn A, Reed L, Schaertl S, Toledo-Sherman L, Beconi M, Macdonald D, Muñoz-Sanjuan I, Dominguez C, Wityak J.

Abstract: A new series of potent TG2 inhibitors are reported that employ a 4-aminopiperidine core bearing an acrylamide warhead. We establish the structure-activity relationship of this new series and report on the transglutaminase selectivity and in vitro ADME properties of selected compounds. We demonstrate that the compounds do not conjugate glutathione in an in vitro setting and have superior plasma stability over our previous series.

CiteXplore: 24900540

DOI: 10.1021/ml3001352