SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease.

Abstract

We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.

• Authors: John Wityak, Michael E Prime, Frederick A Brookfield, Stephen M Courtney, Sayeh Erfan, Siw Johnsen, Peter D Johnson, Marie Li, Richard W Marston, Laura Reed, Darshan Vaidya, Sabine Schaertl, Anna Pedret-Dunn, Maria Beconi, Douglas Macdonald, Ignacio Muñoz-Sanjuan, Celia Dominguez
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 3 Issue 12 Pg. 1024-8 (Dec 13 2012) ISSN: 1948-5875 [Print] United States
• PMID: 24900424 (Publication Type: Journal Article)