Irreversible 4‑Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease

Irreversible 4‑Aminopiperidine Transglutaminase 2 Inhibitors for Huntington's Disease

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...

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Bibliographic Details
Published in:ACS medicinal chemistry letters Vol. 3; no. 9; pp. 731 - 735
Main Authors: Prime, Michael E, Brookfield, Frederick A, Courtney, Stephen M, Gaines, Simon, Marston, Richard W, Ichihara, Osamu, Li, Marie, Vaidya, Darshan, Williams, Helen, Pedret-Dunn, Anna, Reed, Laura, Schaertl, Sabine, Toledo-Sherman, Leticia, Beconi, Maria, Macdonald, Douglas, Muñoz-Sanjuan, Ignacio, Dominguez, Celia, Wityak, John
Format: Journal Article
Language:English
Published: United States American Chemical Society 13-09-2012
Subjects:
Letter
Celiac disease
plasma stability
SAR
ADME
computer-aided drug design
acrylamides
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Summary: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.
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ISSN:1948-5875
1948-5875
DOI:10.1021/ml3001352